Abnormal Labor

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    To define abnormal labor, a definition of normal labor must be understood and accepted. Normal labor is defined as uterine contractions that result in progressive dilation and effacement of the cervix. By following thousands of labors resulting in uncomplicated vaginal deliveries, time limits and progress milestones have been identified that define normal labor. Failure to meet these milestones defines abnormal labor, which suggests an increased risk of an unfavorable outcome. Thus, abnormal labor alerts the obstetrician to consider alternative methods for a successful delivery that minimize risks to both the mother and the infant.

    Dystocia of labor is defined as difficult labor or abnormally slow progress of labor. Other terms that are often used interchangeably with dystocia are dysfunctional labor, failure to progress (lack of progressive cervical dilatation or lack of descent), and cephalopelvic disproportion (CPD).

    Friedman’s original research in 1955 defined the following three stages of labor [1] :

    The first stage starts with uterine contractions leading to complete cervical dilation and is divided into latent and active phases. In the latent phase, irregular uterine contractions occur with slow and gradual cervical effacement and dilation. The active phase is demonstrated by an increased rate of cervical dilation and fetal descent. The active phase usually starts at 3-4 cm cervical dilation and is subdivided into the acceleration, maximum slope, and deceleration phases.

    The second stage of labor is defined as complete dilation of the cervix to the delivery of the infant.

    The third stage of labor involves delivery of the placenta.

    See images below for the normal labor curves of both nulliparas and multiparas. The following table shows abnormal labor indicators.

    Table. Abnormal Labor Indicators (Open Table in a new window)

    Indication

    Nullipara

    Multipara

    Prolonged latent phase

    >20 h

    >14 h

    Average second stage

    50 min

    20 min

    Prolonged second stage without (with) epidural

    >2 h (>3 h)

    >1 h (>2 h)

    Protracted dilation

    < 1.2 cm/h

    < 1.5 cm/h

    Protracted descent

    < 1 cm/h

    < 2 cm/h

    Arrest of dilation*

    >2 h

    >2 h

    Arrest of descent*

    >2 h

    >1 h

    Prolonged third stage

    >30 min

    >30 min

    *Adequate contractions >200 Montevideo units [MVU] per 10 minutes for 2 hours. (Please refer to the Pathophysiology for information regarding adequate contractions.)

     

    Abnormal labor constitutes any findings that fall outside the accepted normal labor curve. However, the authors hesitate to apply the diagnosis of abnormal labor during the latent phase because it is easy to confuse prodromal contractions for latent labor. In addition, the original labor curve, as defined by Friedman, may not be completely applicable today. [2, 3, 4, 5]

    Contemporary practice with supporting data suggest that the duration of labor appears longer today than in the past. For both nulliparous and multiparous women, labor may take longer than 6 hours to progress from 4 cm to 5 cm and longer than 3 hours to progress from 5 cm to 6 cm of dilation. Cervical dilation of 6 cm appears to be a better landmark for the start of the active phase. The 95th percentile for duration of the second stage in a nulliparous woman with conduction anesthesia is closer to 4 hours. [6] Note the charts below.

    As stated above, first stage of labor is divided into latent and active phases. According to Friedman et al., latent stage considered to be prolonged if takes >20 hours for nulliparous women and >14 hours for multiparous women. However, prolonged latent phase does not usually lead to any clinically significant adverse events for mother or the infant. Therefore, diagnosis of abnormal labor during the latent phase is uncommon and is not relevant for clinical practice.

    Around the time uterine contractions cause the cervix to become 3-4 cm dilated, the patient usually enters the active phase of the first stage of labor, according to the traditional definition. Abnormalities of cervical dilation (protracted dilation and arrest of dilation) as well as descent abnormalities (protracted descent and arrest of descent) as described historically are outlined in the Table above.

    Both American College of Obstetrics and Gynecology (ACOG) and the Consortium on Safe Labor have proposed extending the minimum period before diagnosing active-phase arrest. The Consortium on Safe Labor defines 6 hours as the 95th percentile of time to go from 4 cm to 5 cm dilation, with the active phase defined as beginning at 6 cm (instead of 4 cm). According to this study, the 95th percentile of rate of dilation in active phase is 0.5 cm/hr to 0.7 cm/hr for nulliparous women and from 0.5 cm/h to 1.3cm/hr for multiparous women. [7]   ACOG has also stated that extending the time from 2 to 4 hours with oxytocin augmentation appears effective. Irrespective of the duration, maternal and fetal well-being status must be confirmed. In another study it was found that extending oxytocin augmentation for an additional 4 hours, up to 8 hours total, in patients who were dilated at least 3cm and had unsatisfactory progress resulted in a greater number of vaginal deliveries (38% delivered vaginally) without any evidence of fetal compromise. [8]

    According to the most recent evidence, arrest of labor in the first stage should be defined as more than or equal to 6cm dilation with ruptured membranes and one of the following: 4 hours or more of adequate contractions (>200 MVU) or 6 hours or more of inadequate contractions and no cervical change. [9]

    The maternal risk of a first stage greater than the 95th percentile (>30 h) is associated with a higher cesarean delivery rate (adjusted odds ratio [aOR]: 2.28) and chorioamnionitis (aOR: 1.58). The neonatal risk is associated with a higher incidence of neonatal ICU admissions in the absence of any other of the major morbidities (aOR: 1.53). [6] These results were again confirmed by another study, which established that prolonged first stage of labor lead to increased risks of a prolonged second stage, maternal fever, shoulder dystocia, and admission to a level 2-3 nursery [10]  

    The Consortium on Safe Labor also addressed the 95th percentile for the second stage for nulliparous women; it was 2.8 hours (168 min) without regional anesthesia and 3.6 hours (216 min) with regional anesthesia. For multiparous women, the 95th percentiles for second-stage duration with and without regional anesthesia remained around 2 hours and 1 hour, respectively. [6, 7] However, other studies demonstrate the risks of both maternal and perinatal adverse outcomes rising with increased duration of the second stage, particularly for durations longer than 3 hours in nulliparous women and 2 hours in multiparous women. [11] One study found that if nulliparous women delivered after prolonged second stage, they were twice as likely to have operative vaginal delivery, three times as likely to develop chorioamnionitis, have higher odds of having episiotomy and 3rd or 4th degree lacerations, and one day longer median hospital stay. [12] .Thus, careful clinical assessment of fetal and maternal well-being must be confirmed when extending the duration of the first and second stages of labor.

    The third stage of labor is the time from delivery of the infant to placental delivery. Historically, the duration of a normal third stage of labor was defined as less than 30min. This threshold was established by the study conducted by Combs et al. in 1991, in which 75% of placentas were delivered by 10 minutes and maternal morbidity and mortality increased if the third stage was increased beyond 30 min. However, a recently published article by Frolova et al, puts this definition into a question. In this study, the researchers found that in a modern cohort, 90% of placentas are delivered within 10 minutes and the risk of postpartum hemorrhage almost doubles by the time the duration of third stage reaches twenty minutes. [13]  Therefore, the traditional definition of prolonged third stage being >30 min, may be outdated and in need of revision.

     

    In general, abnormal labor is the result of problems with one of the following three P’ s:

    Passenger (infant size, fetal presentation [occiput anterior, posterior, or transverse])

    Pelvis or passage (size, shape, and adequacy of the pelvis)

    Power (uterine contractility)

    A prolonged latent phase may result from oversedation or from entering labor early with a thickened or uneffaced cervix. It may be misdiagnosed in the face of frequent prodromal contractions. Protraction of active labor is more easily diagnosed and is dependent upon the 3 P’ s.

    The first P, the passenger, may produce abnormal labor because of the infant’s size (eg, macrosomia) or from malpresentation.

    The second P, the pelvis, can cause abnormal labor because its contours may be too small or narrow to allow passage of the infant. Both the passenger and pelvis cause abnormal labor by a mechanical obstruction, referred to as mechanical dystocia.

    With the third P, the power component, the frequency of uterine contraction may be adequate, but the intensity may be inadequate. Disruption of communication between adjacent segments of the uterus may also exist, resulting from surgical scarring, fibroids, or other conduction disruption. Whatever the cause, the contraction pattern fails to result in cervical effacement and dilation. This is called functional dystocia. Uterine contractile force can be quantified by the use of an intra-uterine pressure catheter. Use of this device allows for direct measurement and calculation of uterine contractility per each contraction and is reported in Montevideo units (MVUs). For uterine contractile force to be considered adequate, the force produced must exceed 200 MVUs during a 10-minute contraction period. Arrest disorders cannot be properly diagnosed until the patient is in the active phase and had no cervical change for 2 or more hours with the contraction pattern exceeding 200 MVUs. Uterine contractions must be considered adequate to correctly diagnose arrest of dilation. [14]

    United States

    Of all cephalic deliveries, 8-11% are complicated by an abnormal first stage of labor. Dystocia occurs in 12% of deliveries in women without a history of prior cesarean delivery. Dystocia may account for as many as 60% of cesarean deliveries.

    Both maternal and fetal mortality and morbidity rates increase with abnormal labor. This is probably an effect-effect relationship rather than a cause-effect relationship. Nonetheless, identification of abnormal labor and initiation of appropriate actions to reduce the risks are matters of some urgency.

    Friedman EA. Primigravid labor; a graphicostatistical analysis. Obstet Gynecol. 1955 Dec. 6(6):567-89. [Medline].

    Zhang J, Troendle JF, Yancey MK. Reassessing the labor curve in nulliparous women. Am J Obstet Gynecol. 2002 Oct. 187(4):824-8. [Medline].

    Rouse DJ, Owen J, Hauth JC. Criteria for failed labor induction: prospective evaluation of a standardized protocol. Obstet Gynecol. 2000 Nov. 96(5 Pt 1):671-7. [Medline].

    Cheng YW, Hopkins LM, Caughey AB. How long is too long: Does a prolonged second stage of labor in nulliparous women affect maternal and neonatal outcomes?. Am J Obstet Gynecol. 2004 Sep. 191(3):933-8. [Medline].

    Rinehart BK, Terrone DA, Hudson C, Isler CM, Larmon JE, Perry KG Jr. Lack of utility of standard labor curves in the prediction of progression during labor induction. Am J Obstet Gynecol. 2000 Jun. 182(6):1520-6. [Medline].

    El-Sayed YY. Diagnosis and management of arrest disorders: duration to wait. Semin Perinatol. 2012 Oct. 36(5):374-8. [Medline].

    Zhang J, Landy HJ, Branch DW, et al. Contemporary patterns of spontaneous labor with normal neonatal outcomes. Obstet Gynecol. 2010 Dec. 116(6):1281-7. [Medline]. [Full Text].

    Arulkumaran S, Koh CH, Ingemarsson I, Ratnam SS. Augmentation of labour–mode of delivery related to cervimetric progress. Aust N Z J Obstet Gynaecol. 1987 Nov. 27 (4):304-8. [Medline].

    American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine. Obstetric care consensus no. 1: safe prevention of the primary cesarean delivery. Obstet Gynecol. 2014 Mar. 123 (3):693-711. [Medline].

    Harper LM, Caughey AB, Roehl KA, Odibo AO, Cahill AG. Defining an abnormal first stage of labor based on maternal and neonatal outcomes. Am J Obstet Gynecol. 2014 Jun. 210 (6):536.e1-7. [Medline].

    Allen VM, Baskett TF, O’Connell CM, McKeen D, Allen AC. Maternal and perinatal outcomes with increasing duration of the second stage of labor. Obstet Gynecol. 2009 Jun. 113(6):1248-58. [Medline].

    Laughon SK, Berghella V, Reddy UM, Sundaram R, Lu Z, Hoffman MK. Neonatal and maternal outcomes with prolonged second stage of labor. Obstet Gynecol. 2014 Jul. 124 (1):57-67. [Medline].

    Frolova AI, Stout MJ, Tuuli MG, López JD, Macones GA, Cahill AG. Duration of the Third Stage of Labor and Risk of Postpartum Hemorrhage. Obstet Gynecol. 2016 May. 127 (5):951-6. [Medline].

    Cunningham FG, Leveno KL, Bloom SL, et al. Abnormal labor. Williams Obstetrics. 22nd ed. Appleton & Lange; 2007. 415-434.

    Anim-Somuah M, Smyth R, Howell C. Epidural versus non-epidural or no analgesia in labour. Cochrane Database Syst Rev. 2005 Oct 19. CD000331. [Medline].

    Gabbe SJ, O’Brien WF, Cefalo RC. Labor and delivery. Obstetrics: Normal and Problem Pregnancies. 5th ed. 2007. 322-326.

    Sanchez-Ramos L, Quillen MJ, Kaunitz AM. Randomized trial of oxytocin alone and with propranolol in the management of dysfunctional labor. Obstet Gynecol. 1996 Oct. 88(4 Pt 1):517-20. [Medline].

    Mitrani A, Oettinger M, Abinader EG, Sharf M, Klein A. Use of propranolol in dysfunctional labour. Br J Obstet Gynaecol. 1975 Aug. 82(8):651-5. [Medline].

    Roth C, Dent SA, Parfitt SE, Hering SL, Bay RC. Randomized Controlled Trial of Use of the Peanut Ball During Labor. MCN Am J Matern Child Nurs. 2016 May-Jun. 41 (3):140-6. [Medline].

    Tussey CM, Botsios E, Gerkin RD, Kelly LA, Gamez J, Mensik J. Reducing Length of Labor and Cesarean Surgery Rate Using a Peanut Ball for Women Laboring With an Epidural. J Perinat Educ. 2015. 24 (1):16-24. [Medline].

    Cheng YW, Kaimal AJ, Snowden JM, Nicholson JM, Caughey AB. Induction of labor compared to expectant management in low-risk women and associated perinatal outcomes. Am J Obstet Gynecol. 2012 Dec. 207(6):502.e1-8. [Medline].

    Smyth RM, Alldred SK, Markham C. Amniotomy for shortening spontaneous labour. Cochrane Database Syst Rev. 2007 Oct 17. CD006167. [Medline].

    Le Ray C, Serres P, Schmitz T, Cabrol D, Goffinet F. Manual rotation in occiput posterior or transverse positions: risk factors and consequences on the cesarean delivery rate. Obstet Gynecol. 2007 Oct. 110 (4):873-9. [Medline].

    Shaffer BL, Cheng YW, Vargas JE, Caughey AB. Manual rotation to reduce caesarean delivery in persistent occiput posterior or transverse position. J Matern Fetal Neonatal Med. 2011 Jan. 24 (1):65-72. [Medline].

    Mollberg M, Hagberg H, Bager B, Lilja H, Ladfors L. Risk factors for obstetric brachial plexus palsy among neonates delivered by vacuum extraction. Obstet Gynecol. 2005 Nov. 106(5 Pt 1):913-8. [Medline].

    Mehta SH, Bujold E, Blackwell SC, Sorokin Y, Sokol RJ. Is abnormal labor associated with shoulder dystocia in nulliparous women?. Am J Obstet Gynecol. 2004 Jun. 190(6):1604-7; discussion 1607-9. [Medline].

    Shields SG, Ratcliffe SD, Fontaine P, Leeman L. Dystocia in nulliparous women. Am Fam Physician. 2007 Jun 1. 75(11):1671-8. [Medline].

    Oppenheimer LW, Labrecque M, Wells G, et al. Prostaglandin E vaginal gel to treat dystocia in spontaneous labour: a multicentre randomised placebo-controlled trial. BJOG. 2005 May. 112(5):612-8. [Medline].

    Butchart AG, Mathews M, Surendran A. Complex regional pain syndrome following protracted labour*. Anaesthesia. 2012 Nov. 67(11):1272-4. [Medline].

    Treacy A, Robson M, O’Herlihy C. Dystocia increases with advancing maternal age. Am J Obstet Gynecol. 2006 Sep. 195(3):760-3. [Medline].

    Zhu BP, Grigorescu V, Le T, et al. Labor dystocia and its association with interpregnancy interval. Am J Obstet Gynecol. 2006 Jul. 195(1):121-8. [Medline].

    Zuo Z, Goel S, Carter JE. Association of cervical cytology and HPV DNA status during pregnancy with placental abnormalities and preterm birth. Am J Clin Pathol. 2011 Aug. 136(2):260-5. [Medline].

    Cheng YW, Hopkins LM, Laros RK Jr, Caughey AB. Duration of the second stage of labor in multiparous women: maternal and neonatal outcomes. Am J Obstet Gynecol. 2007 Jun. 196(6):585.e1-6. [Medline].

    Friedman EA. Labor in multiparas; a graphicostatistical analysis. Obstet Gynecol. 1956 Dec. 8(6):691-703. [Medline].

    Hoffman MK, Vahratian A, Sciscione AC, Troendle JF, Zhang J. Comparison of labor progression between induced and noninduced multiparous women. Obstet Gynecol. 2006 May. 107(5):1029-34. [Medline].

    Vahratian A, Hoffman MK, Troendle JF, Zhang J. The impact of parity on course of labor in a contemporary population. Birth. 2006 Mar. 33(1):12-7. [Medline].

    Wood S, Ross S, Sauve R. Cesarean section and subsequent stillbirth, is confounding by indication responsible for the apparent association? An updated cohort analysis of a large perinatal database. PLoS One. 2015. 10(9):e0136272. [Medline].

    Chaiworapongsa T, Romero R, Whitten AE, et al. The use of angiogenic biomarkers in maternal blood to identify which SGA fetuses will require a preterm delivery and mothers who will develop pre-eclampsia. J Matern Fetal Neonatal Med. 2015 Aug 25. 1-15. [Medline].

    Indication

    Nullipara

    Multipara

    Prolonged latent phase

    >20 h

    >14 h

    Average second stage

    50 min

    20 min

    Prolonged second stage without (with) epidural

    >2 h (>3 h)

    >1 h (>2 h)

    Protracted dilation

    < 1.2 cm/h

    < 1.5 cm/h

    Protracted descent

    < 1 cm/h

    < 2 cm/h

    Arrest of dilation*

    >2 h

    >2 h

    Arrest of descent*

    >2 h

    >1 h

    Prolonged third stage

    >30 min

    >30 min

    *Adequate contractions >200 Montevideo units [MVU] per 10 minutes for 2 hours. (Please refer to the Pathophysiology for information regarding adequate contractions.)

    Nina S Olsen, MD Resident Physician, Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine

    Nina S Olsen, MD is a member of the following medical societies: American Academy of Family Physicians, American College of Obstetricians and Gynecologists, American College of Physicians, Virginia Academy of Family Physicians

    Disclosure: Nothing to disclose.

    Nicole W Karjane, MD Associate Professor, Department of Obstetrics and Gynecology, Virginia Commonwealth University Medical Center

    Nicole W Karjane, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of Professors of Gynecology and Obstetrics, North American Society for Pediatric and Adolescent Gynecology

    Disclosure: Received income in an amount equal to or greater than $250 from: Merck<br/>Served as Nexplanon trainer for: Merck.

    Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

    Disclosure: Received salary from Medscape for employment. for: Medscape.

    John G Pierce, Jr, MD Associate Professor, Departments of Obstetrics/Gynecology and Internal Medicine, Medical College of Virginia at Virginia Commonwealth University

    John G Pierce, Jr, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of Professors of Gynecology and Obstetrics, Christian Medical and Dental Associations, Medical Society of Virginia, Society of Laparoendoscopic Surgeons

    Disclosure: Nothing to disclose.

    Ronald M Ramus, MD Professor of Obstetrics and Gynecology, Director, Division of Maternal-Fetal Medicine, Virginia Commonwealth University School of Medicine

    Ronald M Ramus, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Medical Society of Virginia, Society for Maternal-Fetal Medicine

    Disclosure: Nothing to disclose.

    Robert K Zurawin, MD Associate Professor, Chief, Section of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Baylor College of Medicine

    Robert K Zurawin, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Society of Laparoendoscopic Surgeons, Texas Medical Association, AAGL, Harris County Medical Society, North American Society for Pediatric and Adolescent Gynecology

    Disclosure: Received consulting fee from Ethicon for consulting; Received consulting fee from Bayer for consulting; Received consulting fee from Hologic for consulting.

    Deborah Lyon, MD Director, Division of Gynecology, Associate Professor, Department of Obstetrics and Gynecology, University of Florida Health Science Center at Jacksonville

    Deborah Lyon, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of American Medical Colleges, Association of Professors of Gynecology and Obstetrics, Florida Medical Association

    Disclosure: Nothing to disclose.

    Saju Joy, MD, MS Associate Director, Division Chief of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Carolinas Medical Center

    Saju Joy, MD, MS is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Society for Maternal-Fetal Medicine, American Medical Association

    Disclosure: Nothing to disclose.

    Patricia L Scott, MD Tennessee Maternal-Fetal Medicine

    Patricia L Scott, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, Tennessee Medical Association

    Disclosure: Nothing to disclose.

    Abnormal Labor

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    CBD Benefits, Crack Drown and Everything You Need to Know

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    CBD Benefits, Crack Drown and Everything You Need to Know

    There has been a rise in the use of CBD in the last couple of years. CBD has shown tremendous success when used as an alternative treatment for common ailments. The boom has come with its own challenges. New York City, in particular, has been at the center of the CBD boom but it might come to an end as there have been crackdowns by health officials. New York City’s Department of Health paid a visit to one of the biggest CBD-infused pastry shops that sell bakery products.

    According to the Eater, the officials from the health department confiscated edibles worth around $1000 from Cat Fat Kitchen. The problem is not isolated to New York alone. According to Maines health officials, CBD edibles have been banned as it is not a federally approved food additive. The component itself is still legal to sell and includes oil, lotion, and vape.

    The use of CBD is currently in a grey area when it comes to legality in most states. The Drug Enforcement Agency still insists that CBD is illegal since it is derived from Cannabis. This is a contrasting opinion with that of the Food and Drug Administration Authority which has approved the use of CBD prescription drug that is legally sold in North America. FDA is clear on the use of CBD oil. It states that CBD can’t be used as a dietary supplement. It also can’t be sold in foods deemed to be crossing state lines.

    The fact that the law is very clear on what shouldn’t be sold doesn’t mean it doesn’t happen. New York, for example, is full of restaurants where you can get CBD-laden smoothies, coffee, and sometimes even dog treats. There are no formal regulations in place which is likely to result in chaos. It is surprising that most of the CBD products are not sold in secret. Some places even advertise the products that they’re offering.

    In both Maine and New York, CBD can be sold legally as long as it is not in an edible form. Most cities and states across the country are very interested in regulating CBD when it comes to the edible form. Fat Cat Kitchen is not going to be the last crackdown as there are many establishments that openly sell CBD edibles.

    CBD has become a popular topic especially in states where Marijuana use is legalized. CBD oil has been credited as a treatment for many medical ailments. Despite the lack of proper regulations in place, CBD has the potential to be a reliable alternative treatment for many diseases.

    CBD (Cannabidiol) is extracted from buds and flowers of the hemp or marijuana plant. It does not contain any form of intoxication which is synonymous with Marijuana. CBD oils use is currently legal in 30 States. There are 17 additional states that have CBD specific laws on the books.

    CBD has been touted as a multipurpose molecule. It has the potential for being an alternative treatment for people who don’t like the harsh side effects of pharmaceutical drugs. CBD synchs with how the human body function on a biological level. It can provide relief from depression, inflammation, anxiety, and chronic pain. There has been extensive research some sponsored by the U.S. government which shows the potential use of CBD as a treatment option for a wide range of maladies.

    CBD interacts with the body differently compared to THC. One way the CBD interacts with the human body is through mimicking endogenous cannabinoids compounds which are naturally occurring. The discovery of the endocannabinoid system has helped doctors understand diseases better. As a result, the implication is a better understanding of how THC and CBD interact with the body.

    The endocannabinoid system plays a crucial role in regulating the most important physiological processes that are crucial and affect our everyday experience. It can alter the mood, intestinal fortitude, blood pressure, bone density, immune activity, pain experience, glucose metabolism and so much more.

    When the endocannabinoid system is not functioning well, a person is more susceptible to diseases. Regulating the endocannabinoid system can prevent a lot of diseases experienced by the human body. CBD helps in regulating the endocannabinoid system by slowing and in some cases stopping the disease progression.

    There has been a lot of excitement on pharmaceutical CBD and the potential it presents. It was not until 25th July 2018 when the FDA recognized CBD as real medicine when they approved the use of Epidiolex. The drug is almost pure in the formulation and is used to treat Dravet syndrome and seizure disorders. Cannabis and CBD oil are still on the FDA’s list of schedule 1 which contains illegal narcotics. Epidiolex could be seen as expensive and people would rather look for alternatives elsewhere.

    The use of CBD oil is another grey area when it comes to jurisdiction in law. The dilemma currently being witnessed in Texas goes to show the altercation between legal authorities and sellers. CBD oil sellers continue to trade despite having been warned by the chief Tarrant County prosecutor.

    According to the Tarrant District Attorney’s office, the use of CBD oil is only allowed to be used by those who suffer from intractable epilepsy. Those who are selling or buying CBD oil are breaking the law according to District Attorney Sharen Wilson. The sellers have vowed to continue engaging in the trade and are not afraid of being arrested.

    CBD oil is made by extracting from the cannabis plant the diluting it with a carrier like hemp seed oil or coconut oil. It has been gaining momentum in the wellness and health world with some studies showing that it can provide relief from chronic pain. Below are some of the benefits you could get from using CBD oil

    CBD oil can provide almost immediate pain relief from major ailments. The parent plant has been used to provide relief since time immemorial. Recent studies have shown that components like CBD in Marijuana are the ones responsible for providing relief. CBD reduces pain interacting with the endocannabinoid receptor activity and with the neurotransmitters as well.

    The endocannabinoid system is responsible for the mood of a person. Depression and anxiety are some of the common mental disorders that affect millions of Americans every year. According to statistics from the World Health Organization, depression is the biggest contributor to disability in the world. Treating anxiety and depression might not work and they could also have adverse side effects. CBD oil has been effectively used to treat children with insomnia and post-traumatic stress disorder. CBD oil is also not as addictive as other pharmaceutical treatment options.

    CBD oil can be used to alleviate cancer-related symptoms and also help in coping with the side effects that come with treatment like vomiting, nausea, and constant pain. There are drugs that are recommended for distressing the symptoms but they are not always effective. That is why some people would opt for alternative options like CBD oil. CBD oil helps in reducing the vomiting and nausea that comes as a result of chemotherapy.

    Acne can become a menace to treat and affects close to 9% of the population. Some of the common causes of acne include underlying inflammation problems, excessive production of sebum, genetics, bacteria, and oily secretions which may lead to skin blockage.

    Studies have shown that CBD oil can be used as an acne treatment due to its anti-inflammatory properties. There was a test tube study that was done which found out CBD helped in preventing the sebaceous glands from producing excessive sebum by exerting anti-inflammatory actions. Even though the results look promising, a lot more studies need to be done.

    There are some studies that have shown that CBD oil could benefit heart health. High blood pressure comes with a number of hazardous health conditions like metabolic syndrome, stroke, and heart attack. CBD act as a natural treatment for high blood pressure since it directly impacts the endocannabinoid system in the body. Studies have shown that CBD oil has a much better effect when it comes to reducing blood pressure compared to placebo. The stress and anxiety-reducing properties can also help in reducing high blood pressure in the body.

    CBD can be used as a therapeutic alternative when it comes to substance abuse treatment. The non- psychoactive element is sometimes overlooked when choosing CBD as an alternative treatment. There are studies that show CBD can modify circuits in the brain that contribute to substance abuse. CBD oil has the ability to reduce morphine and heroin dependence. It can also be used to prevent relapses which is common among drug addicts. It has little side effects and the fact that it is not addictive makes a good therapy option for substance abuse treatment.

    Many people see CBD as a miracle alternative, which is not the case. As much as a lot of people could benefit from using CBD, legal access still remains a challenge. There is also the concern that CBD alone might not be as effective as a treatment alternative. Hemp has been fully legalized and there are some people who are of the opinion the same applies to CBD. There is a thin line between what’s legal and what’s not when it comes to state jurisdiction.

    The majority of the states have legalized CBD products but not cannabis or THC in general. Marijuana is illegal on the federal level but legal in some states. This means that businesses that deal with cannabis cannot transport related products across state lines. Companies that deal with CBD products usually supply them in the form of lotions, pills, or oils. The DEA has been cracking down on companies and issuing “cease and desist” letters from making claims that CBD is a dietary supplement. The reason why the DEA has refused to acknowledge CBD as a dietary supplement is because the parent plant has been authorized for investigation.

    Even with the scientifically proven benefits of CBD, the rules and regulation are not very clear for both sellers and buyers. The recent crackdown on CBD edibles goes to show how why it is important to put lasting legal frameworks in place. A lot more research also needs to be done on the benefits of CBD oil. It has the potential to treat a myriad of ailments.

    CBD Benefits, Crack Drown and Everything You Need to Know

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    Pelvic Inflammatory Disease Organism-Specific Therapy 

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    Pelvic Inflammatory Disease Organism-Specific Therapy 

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    All drug regimens used to treat pelvic inflammatory disease (PID) should be effective against Neisseria gonorrhoeae and Chlamydia trachomatis. [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15]

    There is no agreement amongst experts on whether treatment of pelvic inflammatory disease should include anaerobic coverage. Outpatient regimens provided below have moderate coverage, while inpatient regimens have excellent coverage. Some experts recommend that all women should be covered for anaerobes, while others recommend that only women with severe disease requiring hospitalization, or those with tubo-ovarian abscesses should be covered. 

    See the list below:

    Doxycycline 100 mg IV or PO q12h for 14d or

    Azithromycin 500 mg IV for 1-2 doses, followed by 250 mg PO for 5-6d

    See the list below:

    Uncomplicated gonorrhea [5] : Ceftriaxone 250 mg IM plus  either azithromycin 1 g PO as a single dose or doxycycline 100 mg PO q12h for 7d or

    Ceftriaxone 1 g IV q24h or

    Cefoxitin 2 g IV q6h or

    Cefotetan 2 g IV q12h

    If N gonorrhoeae is the suspected pathogen, fluoroquinolones are no longer recommended secondary to increased resistance

    Cefixime is no longer recommended at any dose as first-line treatment of gonococcal infections [4, 5] ; if used as an alternative agent, cefixime 400 mg PO plus  either azithromycin 1 g PO as a single dose or doxycycline 100 mg PO q12h × 7 days (Patients should return in 1 week for a test-of-cure at the infection site.) [5]

    See the list below:

    Cefoxitin 2 g IV q6h or

    Cefotetan 2 g IV q12h or

    Metronidazole 500 mg PO q12h or

    Ampicillin-sulbactam 3 g IV q6h

    See the list below:

    Cefoxitin 2 g IV q6h or

    Cefotetan 2 g IV q12h or

    Gentamicin IV or IM 2 mg/kg loading dose, followed by 1.5 mg/kg q8h maintenance dose

    Bevan CD, Ridgway GL, Rothermel CD. Efficacy and safety of azithromycin as monotherapy or combined with metronidazole compared with two standard multidrug regimens for the treatment of acute pelvic inflammatory disease. J Int Med Res. 2003 Jan-Feb. 31(1):45-54. [Medline].

    Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Recomm Rep. 2002 May 10. 51(RR-6):1-78. [Medline].

    Centers for Disease Control and Prevention. Update to CDC’s sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep. 2007 Apr 13. 56(14):332-6. [Medline].

    [Guideline] Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec 17. 59:1-110. [Medline]. [Full Text].

    Centers for Disease Control and Prevention (CDC). Update to CDC’s Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012 Aug 10. 61(31):590-4. [Medline].

    Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec 17. 59:1-110. [Medline].

    U.S. Preventive Services Task Force. Screening for chlamydial infection: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2007 Jul 17. 147(2):128-34. [Medline].

    Ness RB, Soper DE, Holley RL, et al. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial. Am J Obstet Gynecol. 2002 May. 186(5):929-37. [Medline].

    Savaris RF, Teixeira LM, Torres TG, et al. Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial. Obstet Gynecol. 2007 Jul. 110(1):53-60. [Medline].

    Walker CK, Wiesenfeld HC. Antibiotic therapy for acute pelvic inflammatory disease: the 2006 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. Clin Infect Dis. 2007 Apr 1. 44 Suppl 3:S111-22. [Medline].

    Asicioglu O, Gungorduk K, Ozdemir A, Ertas IE, Yildirim G, Sanci M, et al. Single daily dose of moxifloxacin versus ofloxacin plus metronidazole as a new treatment approach to uncomplicated pelvic inflammatory disease: a multicentre prospective randomized trial. Eur J Obstet Gynecol Reprod Biol. 2013 Nov. 171(1):116-21. [Medline].

    Chen C, Chen Y, Wu P, Chen B. Update on new medicinal applications of gentamicin: evidence-based review. J Formos Med Assoc. 2014 Feb. 113(2):72-82. [Medline].

    Haggerty CL, Totten PA, Tang G, Astete SG, Ferris MJ, Norori J, et al. Identification of novel microbes associated with pelvic inflammatory disease and infertility. Sex Transm Infect. 2016 Sep. 92 (6):441-6. [Medline]. [Full Text].

    Savaris RF, Fuhrich DG, Duarte RV, Franik S, Ross J. Antibiotic therapy for pelvic inflammatory disease. Cochrane Database Syst Rev. 2017 Apr 24. 4:CD010285. [Medline]. [Full Text].

    Das BB, Ronda J, Trent M. Pelvic inflammatory disease: improving awareness, prevention, and treatment. Infect Drug Resist. 2016. 9:191-7. [Medline]. [Full Text].

    Ritu Kumar, MD Resident, Department of Emergency Medicine, Hospital of the University of Pennsylvania

    Ritu Kumar, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Student Association/Foundation, Society for Academic Emergency Medicine, Emergency Medicine Residents’ Association

    Disclosure: Nothing to disclose.

    Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

    Disclosure: Received salary from Medscape for employment. for: Medscape.

    Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

    Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

    Disclosure: Nothing to disclose.

    Pelvic Inflammatory Disease Organism-Specific Therapy 

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    Pelvic Inflammatory Disease Empiric Therapy 

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    Pelvic Inflammatory Disease Empiric Therapy 

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    Empiric treatment for pelvic inflammatory disease (PID) should be initiated in sexually active young women and women at risk for sexually transmitted diseases if they are experiencing lower abdominal pain and pelvic tenderness. [1, 2, 3, 4, 5, 6, 7, 8, 9]

    In addition, PID empiric therapy is warranted if one or more of the following are present on pelvic examination; cervical motion tenderness, uterine tenderness, or adnexal tenderness.

    Empiric therapy should be broad spectrum and should include regiments that are effective against Neisseria gonorrhoeae and Chlamydia trachomatis.

    There is no agreement amongst experts on whether treatment of PID should include anaerobic coverage. Outpatient regimens provided below have moderate coverage, while inpatient regimens have excellent coverage. Some experts recommend that all women should be covered for anaerobes, while others recommend that only women with severe disease requiring hospitalization, or those with tubo-ovarian abscesses should be covered. 

    Recommended by the CDC. Results in cure in > 90% of patients: 

    Cefoxitin 2 grams IV every 6 hours plus doxycycline 100 mg IV or orally every 12 hours or

    Cefotetan 2 grams IV every 12 hours plus  doxycycline 100 mg IV or orally every 12 hours or

    Clindamycin 900 mg IV every 8 hours plus gentamicin loading dose 2 mg/kg IV, followed by a maintenance dose of 1.5 mg/kg every 8 hours. Single daily dosing of gentamicin (3-5 mg/kg) can be substituted for three times daily dosing.

    Alternative regimen per CDC with limited data:

    Ampicillin-sulbactam 3 grams IV every 6 hours plus doxycycline 100 mg IV or orally every 12 hours

    Note: If patient able to tolerate oral medication, oral doxycycline preferred to IV secondary to discomfort from IV administration. Patients should complete 14 day course of doxycycline (100mg twice daily). If a pelvic abscess is also present, patients should also be treated with oral clindamycin 450mg every 6 hours or metronidazole 500mg every 8 hours for 14 days, in addition to doxycycline. 

    As recommended by the CDC:

    Ceftriaxone 250 mg intramuscularly in a single dose plus  doxycycline 100 mg orally twice a day for 14 days, with or without metronidazole 500 mg orally twice a day for 14 days or

    Cefotaxime 1 gram intramuscularly in a single dose or ceftizoxime 1 gram intramuscularly in a single dose plus doxycycline 100 mg orally twice a day for 14 days.

    Of the regimens listed above for treatment of mild to moderate PID, ceftriaxone has the best coverage against gonococcal disease and this is the preferred antibiotic in conjunction with doxycycline. Metronidazole should be added for women with trichomonas vaginalis or bacterial vaginosis.

     

    Alternative oral therapy for penicillin- or cephalosporin-allergic patients

    Patients with a history of a severe penicillin allergy who cannot tolerate cephalosporins or a known cephalosporin allergy may be prescribed fluoroquinolones (levofloxacin 500 mg orally daily or ofloxacin 400 mg orally twice a day for 14days), with or without metronidazole (500 mg orally twice a day for 14 days). This regimen should only be used for individuals in whom suspicion of N gonorrhoeae is low or resistance in the community is less than 5%.

    If N gonorrhoeae is the suspected pathogen, fluoroquinolones are no longer recommended secondary to increased resistance.

    If considering a fluoroquinolone, the patient must be cultured for N gonorrhoeae.

     

     

     

    Bevan CD, Ridgway GL, Rothermel CD. Efficacy and safety of azithromycin as monotherapy or combined with metronidazole compared with two standard multidrug regimens for the treatment of acute pelvic inflammatory disease. J Int Med Res. 2003 Jan-Feb. 31(1):45-54. [Medline].

    Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR Recomm Rep. 2002 May 10. 51(RR-6):1-78. [Medline].

    Centers for Disease Control and Prevention. Update to CDC’s sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep. 2007 Apr 13. 56(14):332-6. [Medline].

    Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec 17. 59:1-110. [Medline].

    U.S. Preventive Services Task Force. Screening for chlamydial infection: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2007 Jul 17. 147(2):128-34. [Medline].

    Ness RB, Soper DE, Holley RL, et al. Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) Randomized Trial. Am J Obstet Gynecol. 2002 May. 186(5):929-37. [Medline].

    Savaris RF, Teixeira LM, Torres TG, et al. Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial. Obstet Gynecol. 2007 Jul. 110(1):53-60. [Medline].

    Walker CK, Wiesenfeld HC. Antibiotic therapy for acute pelvic inflammatory disease: the 2006 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines. Clin Infect Dis. 2007 Apr 1. 44 Suppl 3:S111-22. [Medline].

    [Guideline] Centers for Disease Control and Prevention. Update to CDC’s Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no loner a recommended treatment for gonococcal infections. MMR Morb Mortal Wkly Rep. Aug/2012. 61:91-95. [Medline].

    Ritu Kumar, MD Resident, Department of Emergency Medicine, Hospital of the University of Pennsylvania

    Ritu Kumar, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Student Association/Foundation, Society for Academic Emergency Medicine, Emergency Medicine Residents’ Association

    Disclosure: Nothing to disclose.

    Jasmeet Anand, PharmD, RPh Adjunct Instructor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

    Disclosure: Nothing to disclose.

    Nicole W Karjane, MD Associate Professor, Department of Obstetrics and Gynecology, Virginia Commonwealth University Medical Center

    Nicole W Karjane, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of Professors of Gynecology and Obstetrics, North American Society for Pediatric and Adolescent Gynecology

    Disclosure: Received income in an amount equal to or greater than $250 from: Merck<br/>Served as Nexplanon trainer for: Merck.

    Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

    Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

    Disclosure: Nothing to disclose.

    Pelvic Inflammatory Disease Empiric Therapy 

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    HIV in Pregnancy

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    HIV in Pregnancy

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    The reduction in mother-to-child transmission of human immunodeficiency virus (HIV) is regarded as one of the most effective public health initiatives in the United States. In the absence of treatment, the risk of vertical transmission of HIV is as high as 25-30%. With the implementation of HIV testing, counseling, antiretroviral medication, delivery by cesarean section prior to onset of labor, and discouraging breastfeeding, the mother-to-infant transmission has decreased to less than 2% in the United States.

    Before the current treatment era, approximately 2000 babies were infected with HIV each year in the United States alone. [1] That figure now stands at less than 200 infants per year since 2010 (there were 86 perinatal transmissions in the US in 2015).

    The rapid clinical implementation of research findings directed toward decreasing perinatal transmission is credited as the key to this accomplishment. In 1994, the Pediatric AIDS Clinical Trials Group (PACTG) protocol 076 demonstrated that the administration of zidovudine during pregnancy and labor and then to the newborn decreased the risk of perinatal transmission of HIV by 68%, from 25.5% to 8.3%. [2] In the late 1990s, the combined use of 3 or more antiretroviral medications was found to be highly successful at suppressing viral replication.

    The exact mechanism of mother-to-child transmission of HIV remains unknown. Transmission may occur during intrauterine life, delivery, or breastfeeding. The greatest risk factor for vertical transmission is thought to be advanced maternal disease, likely due to a high maternal HIV viral load. [3] Unfortunately, it has been reported that 30% of pregnant women are not tested for HIV during pregnancy, and another 15-20% receive no or minimal prenatal care, thereby allowing for potential newborn transmission. [4]

    Early in the acquired immunodeficiency syndrome (AIDS) epidemic, women were rarely diagnosed with HIV or AIDS, but by 2005, women represented 27% of the estimated 45,669 new diagnosis of HIV/AIDS, with the greatest rise among young women. [5] About 74% of new cases in women in the United States are contracted through heterosexual intercourse, 23% by contaminated needles, and most of the remaining cases by maternal-child transmission. Testing of donated blood has essentially eliminated blood transfusions as a source of infection.

    Of women with AIDS, 71% were diagnosed between the ages of 25 and 44, implying that many of them may have been infected as adolescents. In the United States, African American and Hispanic women represent 25% of the female population but account for 76% of the total number of women with AIDS. Furthermore, the rate of HIV diagnosis is 15 times higher in African-American women compared to white women. Women of color account for 80% of newly diagnosed HIV/AIDS cases in the United States. [6]

    The Joint United Nations Programme on HIV/AIDS (UNAIDS) has estimated that in 2017, approximately 36.7 million people worldwide (1% of the global adult population aged 15-49 y) were infected with HIV, of which 1.8 million people were newly infected; 64% of all people living with HIV worldwide live in sub-Saharan Africa. New HIV infection rates are declining globally as a result of efforts to strengthen HIV prevention and treatment programs. Worldwide, new infections among children declined 47% since 2010 as coverage of ART provided to pregnant women rose 29% in the same time period. Unfortunately, young women in high-prevalence areas of the world, such as sub-Saharan Africa, continue to remain at high risk for HIV with 26% of new infections occurring in women aged 15-24 years despite this age group making up only 10% of the population. In 2016, AIDS claimed an estimated 1 million lives; of which 120,000 were children. [7]

     

    The Antiretroviral Pregnancy Registry, where clinicians should report cases of exposure to antiviral therapy in pregnancy, contains approximately 18,000 reported exposures and notes no increase in the congenital malformation rate with exposure to antiretroviral medications, even in the first trimester, with the exception of didanosine and nelfinavir. First trimester exposure to efavirenz was previously reported to be associated with neural tube defects, however further meta-analyses and studies have been reassuring and the WHO continues to recommend efavirenz as an alternative in resource-poor settings.

    ART may increase the incidence of adverse pregnancy outcomes. Several studies have shown that zidovudine monotherapy had no negative effect on pregnancy.

    Although initial data from cohorts in the United States have not shown an increased risk of preterm birth with combination therapy, a European collaborative study showed an increased risk of preterm labor in women infected with HIV who were taking combination antiretroviral therapy, with an odds ratio for preterm birth of 1.8 for combination therapy without a protease inhibitor and 2.6 for combination therapy that included a protease inhibitor. [8]

    The Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, published in 2016, was a well-designed randomized controlled trial of 3,490 mostly African women that reported women who initiated ART in pregnancy were more likely to deliver preterm (9</ref>

    In another US study of pregnant women infected with HIV, the overall rate of adverse pregnancy outcome, including prematurity, low birth weight, stillbirth, and abnormal Apgar scores, was similar in women who received antiretroviral therapy during pregnancy and those who did not. [10] Of the 2123 women in the study, 1590 received monotherapy, 396 received combination therapy without a protease inhibitor, and 137 received combination therapy with a protease inhibitor; 1143 did not receive antiretroviral therapy.

    Rates of prematurity and extreme prematurity did not differ significantly according to antiretroviral regimen. Although the risk of low and very low birth weight was greater in the group receiving a protease inhibitor, the results did not reach statistical significance. Furthermore, this may be a reflection of higher viral load or advanced stage of disease rather than exposure to protease inhibitors. [10]

    In a more recent retrospective study (2004-2012) that evaluated US infant growth patterns during their first year of life among those born to perinatally HIV-infected (PHIV) (32 infants, 25 mothers) and nonperinatally HIV-infected (NPHIV) mothers (120 infants, 99 mothers) who received care, infants of PHIV mothers had lower mean length-for-age z-scores (LAZ) that were associated with birth length. Other small-for-gestational age anthropometric parameter associations included those of birth weight and weight-for-age z-scores (WAZ) and those of both birth length and weight with weight-for-length z-scores (WLZ). The investigators also reported an association between delivery HIV RNA level below 400 copies/mL with increased WAZ and WLZ. [11]

    A large meta-analysis that included articles from several countries between 1998 and 2006 showed that overall, highly active antiretroviral therapy (HAART) did not increase the risk of prematurity; however, the use of regimens with protease inhibitors seemed to increase prematurity slightly. [12]

    A possible association exists between HAART and preeclampsia. [13]

    The development of glucose intolerance may be more common in pregnant women with HIV. Originally thought to be associated with protease inhibitors, gestational diabetes appears to be somewhat increased regardless of the medication regimen. As such, during pregnancy, women should be screened and monitored for glucose intolerance. [14]

    Preliminary data suggest that women with HIV may suffer from subfertility. Conception in couples who have never conceived may occur in a median of 6 months with 2 acts of intercourse during the ovulatory period of the cycle. With each act, the risk of sexual transmission must be considered even in the presence of an undetectable viral load.

    In couples planning a pregnancy where only the female is HIV-infected, assisted insemination at home or with a treatment provider with her partner’s semen is the safest conception option after ART (antiretroviral therapy) has been initiated and maximum viral suppression has been attained.

    In couples planning a pregnancy where only the male partner is infected, natural conception carries a risk of sexual transmission to the uninfected female and alternatives to natural conception are the safest options. Safe alternative options include adoption or sperm donation with assisted reproduction techniques. If a couple cannot or declines alternatives to natural conception, counseling regarding pre-exposure prophylaxis(PreP), sperm analysis, sperm washing, and transmission risks should be reviewed. While antiretroviral therapy can reduce viral load in the blood to undetectable levels, semen analysis is recommended prior to attempting conception as HIV-infected men can still have a substantial viral concentration in semen in the presence of an undetectable plasma viral load. If HIV viral load cannot be suppressed, semen washing can be considered with appropriate counseling as it may decrease the HIV RNA and DNA to undetectable levels. After processing and rechecking for residual contamination, the spermatozoa can be used for intrauterine insemination or in vitro fertilization.

    Pregnancy does not appear to influence the progression of HIV disease. [15] A large cohort of French women with known seroconversion dates noted a pregnancy-adjusted relative risk of progression from HIV to AIDS of 0.7. [16] Furthermore, pregnancy does not seem to affect survival of women infected with HIV. [17]

    For concordant couples (both partners are HIV-infected) who wish to conceive, both partners should attain maximum viral suppression and be screened and treated for genital tract infections before attempting conception. For serodiscordant couples who want to conceive, in addition to above, counseling should include the recommendation to only attempt conception once antiretroviral therapy (ART) is started and viral loads are undetectable. Additionally, NIH guidelines include educating patients regarding PrEP in serodiscordant couples. Recommendations regarding periconception administration of antiretroviral PrEP for HIV-uninfected partners are an additional tool to reduce the risk of sexual transmission and are continually evolving. The current guidelines include information on counseling, laboratory testing, and monitoring of individuals on PrEP and the importance of reporting uninfected women who become pregnant on PrEP to the Antiretroviral Pregnancy Registry. FDA labeling information and perinatal ART guidelines permit off-label using in pregnancy, however safety data regarding teratogenicity are limited. [18, 19, 20]

    HIV-infection risk-reduction strategies in conjunction with relatively inexpensive fertility awareness methods (FAMs) may be useful for counseling HIV-serodiscordant couples who want to conceive. [21] Such methods include use of accessible and highly sensitive, but poorly specific, strategies like the calendar method, basal body temperature measurements, and cervicovaginal mucus secretion features. Urinary luteinizing hormone testing has high specificity and cost with less sensitivity. Timed condomless sex has low cost but necessitates understanding how to precisely predict the fertile period in a menstrual cycle. [21]

    Approximately 30% of women in the United States are not tested for HIV during pregnancy. Reasons for declining should be explored and patients counseled appropriately. Testing strategies also include reoffering screening in the third trimester to women who declined first-trimester screening or who are in high-risk groups. The Centers for Disease Control and Prevention (CDC) recommends routine third-trimester screening in women with high-risk behaviors or who exhibit signs or symptoms of the disease. [4]

    Clinicians who care for women with HIV need to provide family planning services and counseling regarding optimizing health status. This includes making a primary treatment goal of attaining an undetectable viral load prior to conception. Preconception care should include modifying current ART regimens to optimize viral suppression, encouraging compliance to medication regimens, cessation of smoking, and updating immunizations. Stressing the importance of taking their medication regularly to decrease the possibility of developing antiretroviral drug resistance may encourage women to comply with therapy. Cigarette smoking, concurrent use of drugs (cocaine, heroin), and unprotected intercourse have been associated with increased risk of perinatal transmission.

    It is encouraging to note there has been a substantial reduction in substance use in the past 2 decades. [22] In a retrospective study over a 23-year period (1990-2012) that evaluated data from two prospective cohort studies (Women and Infants Transmission Study, Surveillance Monitoring for Antiretroviral Therapy Toxicities Study), investigators noted a dramatic decrease in substance use among 5451 HIV-infected pregnant women (1990: 82%; 2012: 23%). There was a significant decline in use of each substance between 1990 and 2006, when it reached a plateau, which the investigators suggested may have been caused by an epidemiologic transition of the HIV epidemic among US women. [22] Substance use was inversely associated with receiving antiretroviral therapy. Women with multiple pregnancies with substance use in their previous pregnancy were at higher risk of substance use in their next pregnancy. [22]

    Unfortunately, 15% of women infected with HIV receive no or minimal prenatal care, and 20% do not initiate prenatal care until late in the third trimester. Even in the absence of antepartum treatment, intrapartum and early neonatal prophylaxis can reduce the mother-to-child transmission risk. Women with HIV should be extensively counseled regarding the ability to decrease the risk of perinatal transmission with ART. In women of reproductive age who are being treated with ART, the current regimen’s effectiveness, an individual’s hepatitis B (HBV) status, the potential for teratogenicity, and possible adverse outcomes for mother and fetus should all be considered.

    All women who do not desire pregnancy should be counseled regarding contraceptive methods, including hormonal contraception and long-term reversible contraceptive methods. Emergency contraception options should be reviewed and made available to HIV-infected women who do not desire contraception.

    In pregnancy, the initial history should assess the status of the patient’s HIV disease (eg, CD4+ T-cell count, viral load), the need for beginning or altering antiretroviral medication, and ways to reduce perinatal transmission. A careful review of the medical and surgical history, gynecologic history, high-risk habits, and previous obstetric history should be done at the first prenatal visit. Women with HIV should be screened for current and past exposure to intimate partner violence and depression and referral made to supportive and mental health services if indicated.

    During pregnancy, a complete physical examination must be performed. Knowledge of the normal physiologic changes of pregnancy, such as an enlarged thyroid gland and a systolic murmur, is important to differentiate from disease process. HIV infection can affect essentially all body systems.

    The American Congress of Obstetrics and Gynecology (ACOG) recommends routine HIV screening for women aged 19-64 years and targeted screening for at-risk women outside of this age reference. All pregnant women should have their HIV serostatus evaluated when they first present for prenatal care.

    Women should have the right to refuse testing after being informed that HIV testing will be drawn as part of their routine prenatal panel. This opt-out approach to prenatal screening, as advocated by the Institute of Medicine and the National Institute of Health, is associated with higher testing rates among pregnant women. However, some states have laws that prohibit this approach and mandate that patients sign consent forms for testing, known as the opt-in approach. [23]

    The most common screening test is an enzyme-linked immunosorbent assay (ELISA), which looks for the presence of antibodies. If this test result is positive, the ELISA is repeated to eliminate laboratory error prior to proceeding to a confirmatory test by Western blot. The ELISA has 98% sensitivity. False-negative results may occur early in the disease, and false-positive results have been reported after certain vaccines. Repeat testing several months later usually confirms seronegativity in such cases. A positive test is sent for Western blot.

    For the Western blot, specific viral proteins are separated by electrophoresis, and reaction of antibody to 3 proteins must occur for the test to be considered positive. Indeterminate results occur when 1 or 2 of the proteins are present. In low-risk populations, indeterminate results usually revert to negative over several months. Western blot has a false-positive rate of 1 in 20,000.

    For pregnant women infected with HIV, in addition to the standard prenatal assessment, continued assessment of HIV status is important. A complete blood count to assess anemia and white blood cell count as well as renal and liver function tests should be included. Initial evaluation includes CD4+ counts, which help determine the degree of immunodeficiency.

    Viral load, determined by plasma HIV RNA copy number (copies/mL) assesses the risk of disease progression. The viral load is important in decisions regarding maternal treatment and delivery management; however, because perinatal HIV transmission can occur even at low or undetectable HIV RNA copy numbers, the viral load is not used to decide whether to start antiretroviral medications. Moreover, newer guidelines now recommend initiation of ART for all HIV-infected individuals, regardless of CD4 count, to reduce the morbidity and mortality associated with HIV infection and the risk for all modes of transmission.

    If a viral load is detected, antiretroviral drug resistance studies (HIV genotype) should be sent but providers should not wait for results before initiation of ART. In general, pregnancy has not been associated with a risk of rapid progression of HIV. [17] With appropriate therapy, the viral load should drop by 1 log within the first month and become nondetectable within 6 months after initiating treatment. The higher the viral load, the longer the decrease may take; however, if the viral load persists or increases at 6 months, treatment failure must be considered.

    Other laboratory studies should include a lipid profile, which is not usually obtained in pregnancy. Although cholesterol normally increases in pregnancy, baseline values are required, as certain medications have been associated with increased triglyceride and cholesterol levels.

    Initial obstetric ultrasonography for viability and dating is important for determining treatment and planning delivery. Potential teratogenicity is highest during the first trimester, and some patients may consider delaying treatment until after the first 12 weeks of pregnancy. In women who are severely ill, the risks and benefits of this delay must be weighed. A targeted ultrasonography may be warranted depending on medication exposure.

    Hepatitis B surface antigen status testing is recommended for all pregnant women. HIV-infected pregnant women who screen negative for HBV (i.e., HBsAg-negative, anti-HBc-negative, and anti-HBs-negative) should receive the HBV vaccine series. In the case of acute hepatitis B infection (HBV), the risk of vertical transmission also varies with gestational age, with an 80-90% risk of transmission to the offspring if the infection occurs in the third trimester. [23] Women who are co-infected with HIV and chronic hepatitis B may require different management in pregnancy.  Current guidelines recommend tenofovir disoproxil fumarate plus lamivudine or emtricitabine. [24]

    Co-infection with HIV and hepatitis C virus (HCV) is common and may range from 17-54%. [25] The diagnosis of hepatitis C is confirmed by identification of the hepatitis C antibody via an ELISA test. False-negative HCV test results may occur if the CD4 count is very low. More specific tests, (eg, hepatitis C viral RNA detection by polymerase chain reaction) are available. High maternal viral titers have been associated with an increased risk of vertical transmission.

    Chronic carriers of HBV or HCV should receive education on the importance of informing sexual partners, household contacts, and needle-sharing contacts and review precautions to decrease transmission.

    Evaluation of opportunistic infectious disease states should be performed in accordance with current guidelines. Assessment of the need for prophylaxis against Pneumocystis jiroveci pneumonia (PCP),Mycobacterium avium complex (MAC) infection, and reactivation toxoplasmosis is necessary based on CD4 counts. Though routine toxoplasmosis titers are not recommended for all pregnant women in the United States, baseline titers should be obtained for HIV-infected women and suppressive therapy is recommended in women with low CD4 counts and a positive IgG. For women with low CD4 counts, prophylaxis for PCP is with trimethoprim-sulfamethoxazole (TMP-SMX). Due to potential teratogenicity, aerosolized pentamidine may be substituted in the first trimester, as it is not absorbed systemically. Atovaquone administration is also an oral alternative to TMP-SMX in the first trimester. For prophylaxis of MAC, azithromycin is used in place of clarithromycin because of potential teratogenicity. Cytomegalovirus should not be routinely screened for in HIV-infected pregnant patients, however assessment for re-infection or reactivation of disease is the same as for non-pregnant HIV-infected individuals.  

    Screening for other maternal sexually transmitted diseases is recommended in pregnancy. For example, screening for maternal syphilis is important not only for the prevention of congenital syphilis but also because maternal syphilis has been associated with an increased risk of mother-to-child transmission of HIV. [26]

    Vaginal speculum examination should be performed to obtain cervical cytology smear and assays for gonorrhea and chlamydia as vaginal swabs are preferred over testing other sites in HIV-infected individuals. All sexually transmitted diseases should be treated promptly. Genital warts and vulvar intraepithelial neoplasia are more common among HIV-seropositive than HIV-seronegative women, but wart regression is as common in women with HIV as those without and cancer is infrequent. [27] Women infected with HIV have a higher incidence of cervical dysplasia.

    Vaccinations should be kept updated. During pregnancy, live attenuated vaccines (eg, measles-mumps-rubella [MMR], varicella, Bacille Calmette-Guérin [BCG] vaccines) should be avoided. Inactivated annual influenza, H1N1, and tetanus vaccines should be administered to all pregnant women, including women who are HIV positive. Hepatitis A and B vaccines (if non-immune) and pneumococcal vaccines should be administered to HIV-positive pregnant women.

    Co-infection with HIV and tuberculosis is very common in developing nations. Immunosuppression from HIV infection contributes not only to a higher rate of tuberculosis reactivation but also to an increased disease severity.

    Tuberculosis skin testing should be performed and a 5-mm purified protein derivative (PPD) result interpreted as positive. Alternatively, interferon (IFN)-gamma release assays have been shown to be safe and reliable in pregnancy to screen for latent tuberculosis. [41] If screening test is positive, chest radiography can be performed during pregnancy because radiation risk is exceedingly low.

    For women who present in labor and have not had prenatal testing, rapid testing should be offered. Unlike the ELISA, the rapid HIV test is a blood or saliva antibody test and results are usually available within an hour. The rapid test is reported to have a high negative predictive value (100%) and to be highly sensitive and specific (approaching 100%); however, the positive predictive value in pregnancy varies from 44-100%. [4] Patients who test positive in labor by ELISA should be treated as HIV positive until confirmatory results are available.

    Mother-to-child transmission is linked to viral load. As such, antepartum antiretroviral therapy should be offered to all pregnant women infected with HIV to reduce the risk of perinatal transmission to below 2%. [28] Combination antiretroviral therapy should be offered in all cases.

    If a pregnant woman has received antiretroviral medication in the past but is not currently on any medication, the choice of regimen may vary according to the history of prior use, the indication for stopping treatment in the past, gestational age, and resistance testing. In this setting, if there is no resistance to the drugs and the regimen suppressed viral load, antiretroviral medication can be used again, but avoid drugs with teratogenic potential or adverse maternal effects.

    If a patient who is on an ART regimen presents for prenatal care, continuing her treatment during the first trimester is reasonable, provided that care is taken to avoid medications that are contraindicated in early pregnancy (stavudine, didanosine, full-dose ritonavir). HIV antiretroviral drug resistance testing is recommended if a viral load is detectable. Considerations of drugs not usually used early in pregnancy may be necessary if drug resistance is confirmed and the patient receives extensive counseling regarding risk and benefits.

    In an HIV-infected pregnant woman who has never been exposed to antiretroviral medication, ART regimen determination is similar to non-pregnant patients however certain medications should be avoided (dolutegravir, elvitegravir, and tenofovir alafenamide). ART should be started as soon as possible, including during the first trimester. Again, recommendations are for drug-resistance testing and care to avoid medications that may potentially cause adverse maternal and fetal effects.

    If prenatal HIV testing was not performed and a rapid HIV test returns preliminarily positive, the patient should be treated and managed as high-risk for transmission. Certainly, the gestational age and obstetrical scenario may dictate the treatment options available, but as the exposure risk to antiretroviral medication is minimal to both mother and fetus, antiretroviral therapy should be initiated. [4]

    The patient with a positive rapid test must be counseled regarding the possibility of a false-positive screen, and the results should be documented as preliminary in the medical chart. If this test was performed on arrival in labor, treatment with the ZDV protocol through labor is recommended, followed by avoiding breastfeeding and administration to the neonate until confirmatory testing on the mother becomes available.

    Treatment of women infected with HIV should not be withheld because of pregnancy. Although the decision regarding starting or maintaining current antiretroviral therapy is based on the same criteria as in nonpregnant patients, several considerations must be taken into account because of potential effects on the fetus.

    The regimen chosen should also take into account prior therapy and response to that regimen, as well as resistance testing. Gestational age and potential fetal and neonatal toxicity must also be taken into account when selecting a regimen.

    The mechanism of action with which these drugs reduce perinatal transmission includes lowering maternal viral load; however, as these drugs cross the placenta, there appears to be prenatal prophylaxis as well. The third component, prophylaxis of the newborn, further decreases the risk of perinatal transmission.

    The antiretroviral drugs used in pregnancy fall broadly into 3 categories: the nucleoside and nucleotide analogue reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs).   Additionally, raltegravir is an integrase inhibitor with a growing body of data that is reassuring in pregnancy. There are insufficient data to allow recommendations regarding the use of entry inhibitors in pregnancy.

    Guidelines for perinatal ART were revised in January 2017 regarding which agents are considered preferred, alternative, or to be used under special circumstances. Combination regimens, usually including 2 NRTIs with either an NNRTI or 1 or more protease inhibitors (PIs) are recommended. For further information, see Table 1 and refer to updated guidelines (published annually).

    Table 1. ART agents during pregnancy [18] (Open Table in a new window)

    ART Class

    Preferred*

    Alternate

    Special Circumstances

    Insufficient Data to Recommend

    NRTIs

    tenofovir disoproxil fumarate + emtricitabine or lamivudine

    abacavir + lamivudine

    zidovudine + lamivudine

    didanosine (not recommended)

     

    stavudine (not recommended)

     

    tenofovir alafenamide

    NNRTIs

     

    efavirenz

    rilpivirine

    nevirapine (not recommended, ART naive)

     

    etravirine

     

    PIs

    atazanavir + ritonavir

    darunavir + ritonavir

    lopinavir + ritonavir

    indinavir

    nelfinavir

    saquinavir

    darunavir + cobicistat

    atazanavir + cobicistat

    fosamprenavir

    tipranavir

    dolutegravir

    elvitegravir/ cobicistat

    elvitegravir/ cobicistat/ emtricitabine/ tenofovir

    alafenamide 

    Entry and Fusion Inhibitors

    enfuvirtide

    maraviroc

    Pharmacoenhancers

    ritonavir

     

    cobicistat

     

    Nucleotide analogue reverse transcriptase inhibitors

    The NRTIs are generally well tolerated and cross the placenta with a variable safety profile depending on the agent used. These drugs do bind to mitochondrial DNA gamma polymerase and may cause mitochondrial dysfunction manifesting as cardiomyopathy, neuropathy, lactic acidosis, and liver dysfunction. Genetic susceptibility to these drugs may play a role, and the effects usually resolve with cessation of the medication. [1]

    The combination of didanosine and stavudine has been associated with lactic acidosis and hepatic failure leading to fatalities and should be used with caution or only in cases where other NRTIs cannot be used due to resistance or toxicity. Finally, ZDV and stavudine have overlapping toxicities and are antagonistic and should be avoided in combination. [28]

    Non-nucleoside reverse transcriptase inhibitors

    Five NNRTIs are FDA approved: delavirdine (Rescriptor), efavirenz (Sustiva), etravirine (Intelence), nevirapine (Viramune), and rilpivirine (Edurant). Although less information is available regarding NNRTI use in pregnancy, nevirapine and efavirenz both cross the placenta. The most common side effect is rash, which can occur in up to 17% of patients on nevirapine.

    Use of efavirenz was previously not recommended in the first trimester because of reported cases of fetal neural tube defects, however, based on additional data the NIH now classifies this drug as an acceptable alternative agent.

    Severe nevirapine-associated skin rash and hepatic toxicity have been reported in pregnancy. The potentially fatal hepatotoxicity appears to be increased in women, during pregnancy, and in patients with a CD4+ T-cell count greater than 250 cells/mL. Because of these significant complications, nevirapine should not be used as first-line therapy unless no other option is available.

    In women whose CD4+ T-cell counts were below 200 cells/mL and who were previously exposed to peripartum single-dose nevirapine, ritonavir-boosted lopinavir plus tenofovir-emtricitabine was superior to nevirapine plus tenofovir-emtricitabine for initial antiretroviral therapy. [29]

    In children previously exposed to single-dose nevirapine for perinatal prevention of HIV transmission, zidovudine and lamivudine plus ritonavir-boosted lopinavir for antiretroviral treatment resulted in better outcomes than treatment with zidovudine and lamivudine plus nevirapine. [30]

    Protease inhibitors

    Protease inhibitors do not cross the placenta easily, and no teratogenic effects have been noted in animals.

    Also see the Medscape Drugs & Diseases topic Antiretroviral Therapy for HIV Infection.

    In any pregnant woman infected with HIV who presents in labor, every effort should be made to continue her ART regimen on schedule in the peripartum period as much as possible to provide maximal virologic effect and to minimize the chance of developing drug resistance. All HIV-infected women with HIV RNA >1,000 copies/mL (or unknown HIV RNA) near delivery should be administered IV zidovudine (ZDV) during labor, in addition to their regular antepartum regimen and regardless of mode of delivery. IV ZDV is no longer required for HIV-infected women receiving combination ART regimens who have HIV RNA ≤1,000 copies/mL near delivery. [18]

    ZDV is given intravenously during labor at a dose of 2 mg/kg infused over 1 hour, followed by a continuous infusion of 1 mg/kg throughout labor. This regimen, along with maternal antepartum and infant zidovudine, reduced perinatal transmission by 66% overall. [18] If the patient is having a planned cesarean delivery, the IV infusion should begin 3 hours before the procedure. [28, 31]

    Women with documented drug resistance to ZDV or whose antepartum regimen did not include ZDV should still be given the intravenous ZDV protocol during labor and delivery or before cesarean delivery. [31] Furthermore, the other antiretroviral agents must be continued on schedule throughout the intrapartum or preoperative period. Stavudine is the only agent that can antagonize ZDV and should be stopped prior to the IV infusion of ZDV. [28]

    In patients attempting a vaginal delivery, amniotomy performed in the setting of ART and virologic suppression is not associated with increased risk of perinatal transmission and can be performed for standard obstetric indications.   Amniotomy in the setting of viremia, routine use of fetal scalp electrodes for fetal heart rate monitoring, operative delivery with vacuum devices or forceps and episiotomy are generally avoided given the potential increased risk of transmission.

    ART is now recommended for all HIV-infected individuals to reduce the risk of disease progression and to prevent HIV sexual transmission.  Antepartum ART regimens in general should be continued postpartum, however decisions regarding continuation should be made in consultation with the patient and her HIV care provider.  Such decision-making should occur in the outpatient setting and careful documented before delivery given the immediate postpartum period poses its own unique challenges to medication adherence.

    Infant ART prophylaxis  [18]

    All HIV-exposed infants should receive zidovudine in the following doses for the first six weeks of life:

    < 30 weeks’ gestation: 2 mg/kg PO BID; after age 4 weeks, advance to 3 mg/kg PO BID

    >30 to < 35 weeks’ gestation: 2 mg/kg PO BID; after age 2 weeks, advance to 3 mg/kg PO BID

    >35 weeks’ gestation: 4 mg/kg PO BID

    Initiate as soon after delivery as possible (preferably within 6-12 hours) and continue through age 6 weeks and administer birth through 6 weeks. For infants unable to tolerate IV doses, the IV dose is 75% of the oral dose while maintaining the same dosing interval. A simplified weight-band dosing for infants ≥ 35 weeks is also published and available via the NIH guidelines.

    Additional prophylaxis with nevirapine is needed for HIV-exposed infants of women who did not receive antepartum ART at the following weights and dosages:

    Birth weight 1.5-2 kg: 8 mg/dose PO

    Birth weight >2 kg: 12 mg/dose PO

    Administer 3 doses in the first week of life; 1st dose 48 hours after birth, give 2nd dose 48 hours after 1st dose, and 3rd dose 96 hours after 2nd dose.

    Three-drug infant combined ART prophylaxis regimens are under investigation, however some experts are already using these in clinical practice (please refer to current guidelines available via the NIH).

    The current recommendation for treating women co-infected with HIV and HBV is to treat these women with tenofovir, lamivudine, telbivudine or emtricitabine. [32] All four have shown activity against HBV. A meta-analysis found that the use of lamivudine effectively prevents mother-to-child transmission, even in pregnant women who have a high degree of HBV infectiousness in late pregnancy. [33]

    Women receiving treatment should be advised of the signs and symptoms of liver toxicity, and regular follow-up of transaminase levels is warranted. The infant should receive hepatitis B immunoglobulin and start the 3-dose series of hepatitis B vaccine within the first 12 hours of life. [18]

    Pregnancy does not appear to alter the course of HCV infection; however, co-infection with HIV does appear to increase the risk of perinatal transmission of HCV. As such, a 3-drug antiviral combination is recommended regardless of the viral load. As with HBV co-infection, patients should be made aware of the signs and symptoms of liver toxicity, and transaminases should be assessed according to current guidelines.

    As with HIV, prolonged rupture of membranes may increase the risk of perinatal HCV transmission; however, the data remain inconclusive regarding the use of cesarean section delivery to decrease the risk of transmission. As such, delivery recommendations are based on the HIV status. Infants can be evaluated by testing HCV RNA at 2 and 6 months of age or HCV antibody after 15 months of age. [18]

    Cesarean delivery must be discussed and the patient counseled regarding the possibility of an unnecessary surgical procedure should the final HIV result be negative. [18] Care should be individualized according to clinical scenario.

    Early studies regarding cesarean delivery and transmission risk showed conflicting results. Cesarean delivery before the onset of labor may prevent microtransfusion that occurs with uterine contractions, and avoiding vaginal delivery eliminates exposure to virus in the cervicovaginal secretions and blood at time of delivery.

    In the late 1990s, prospective cohort studies noted a decrease in mother-to-child transmission in women on zidovudine (ZDV) who underwent elective cesarean delivery compared with women who did not take ZDV prophylaxis. [34, 35] In 1999, results from a large meta-analysis of individual patient data from 15 prospective cohort studies demonstrated a 50% reduction of vertical transmission with the use of elective cesarean delivery for women with HIV, after adjusting for antiretroviral therapy, maternal stage of disease, and infant birth weight.

    Of note, vertical transmission risk did not change when the study group was limited to those women who had rupture of membranes shortly before surgery. The transmission risk was decreased by about 80% for women who had both an elective cesarean delivery and were taking antiretroviral medication. [36]

    In the same year, ACOG issued an opinion that elective cesarean delivery should be discussed and offered to all pregnant women who were HIV positive at 38 weeks’ gestation to avoid the potential risk of spontaneous labor and rupture of membranes. [31]

    These studies did not adjust for viral load and were performed before HAART came into use. In patients on HAART with an undetectable viral load (< 1000 copies), the risk of transmission is very low, and whether cesarean delivery offers any further benefit remains unknown.

    This led to an updated ACOG statement in 2000, stating that women infected with HIV whose viral loads are greater than 1,000 copies/mL should be counseled regarding the potential benefit of scheduled cesarean delivery to further reduce the risk of vertical transmission of HIV beyond that achieved with antiretroviral therapy alone. [31] However, data are insufficient to demonstrate a benefit for neonates of women with viral loads less than 1,000 copies/mL.

    Longer duration of ruptured membranes may be associated with a higher rate of mother-to-child transmission. The International Perinatal HIV group meta-analysis found that the risk of vertical transmission increased by 2% for every increase of 1 hour in the duration of ruptured membranes. If cesarean delivery is performed after the onset of labor or rupture of membranes, the benefit of surgery is likely lost as available data indicate no reduction in the transmission rate if cesarean delivery is performed after the onset of labor or rupture of membranes.  In this scenario, a decision regarding the route of delivery should be individualized. [31, 36]

    Operative risk may outweigh the potential benefit of further reducing HIV transmission. In a study by Louis et al that compared the outcome of cesarean section in 378 women infected with HIV and in more than 54,000 uninfected women, HIV-infected women had a higher rate of intraoperative need for blood transfusion as well as increased incidence of postpartum endometritis, sepsis, pneumonia, admission to the intensive care unit, and maternal death. [37]

    In the HIV-infected group, morbidity and mortality were associated with infection and related to immune function, with the greatest risk being for women with a CD4 count less than 200 cells/mL. [37]

    Because morbidity is increased in women infected with HIV who undergo cesarean delivery, prophylactic antibiotics should be administered. Scheduled cesarean delivery should be discussed and recommended for women with viral loads greater than 1000 copies/mL, whether or not they are taking antiretroviral therapy.

    Discussion of the recommendation of scheduled cesarean delivery in women with high viral loads should begin as early as possible in pregnancy with every pregnant woman infected with HIV, to give her an adequate opportunity to consider the recommendations and plan for the procedure. The risks, which appear to be greater for the mother, must be balanced with the benefits expected for the neonate. The patient’s autonomy must be respected when making the decision to perform a cesarean delivery, because the potential for maternal morbidity is significant.

    Consultation and follow-up with specialists in infectious disease and maternal-fetal medicine is recommended.

    During pregnancy, a healthy, well-balanced diet is recommended, and this recommendation is not altered by HIV. Certain foods need to be limited and avoided during all pregnancies. Alcohol should be avoided. Generally, eating fish low in mercury content is recommended. Caffeine must also be limited, as well as foods high in nitrites and soft cheeses. Current available evidence suggests that vitamin A supplementation during pregnancy (not to exceed 10,000 IU in the first trimester) improves birth weight. [38] Light exercise is recommended in pregnancy, and this recommendation is not altered by HIV infection. Walking and swimming are excellent programs during pregnancy. Women should discuss their exercise routine with their physician.

    Currently, no vaccine is available for HIV; therefore, prevention is crucial to decreasing the risk of transmission. [39] Women must be counseled on methods to avoid transmission to others, including safe sex practice and avoiding donation of blood or organs.

    Regular use of latex condoms and avoidance of unprotected intercourse is important. Treatment of genital tract infections and inflammation in both partners is important to avoid mucosal breaks. The frequent use of nonoxyynol-9 vaginal gel has been associated with increased risk of HIV acquisition in the high-risk population. Women should not share toothbrushes or razors, as small amounts of blood may be present.

    In areas of the world where safe alternatives are available, breastfeeding is not recommended. This also applies to women on antiretroviral therapy. [5] Passage of antiretrovirals into breast milk has been shown for several agents, including zidovudine and lamivudine. [18]

    Brinkman K, ter Hofstede HJ, Burger DM, Smeitink JA, Koopmans PP. Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS. 1998 Oct 1. 12(14):1735-44. [Medline].

    Connor EM, Sperling RS, Gelber R, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994 Nov 3. 331(18):1173-80. [Medline].

    Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burchett SK, et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. N Engl J Med. 1999 Aug 5. 341 (6):394-402. [Medline].

    Rahangdale L, Cohan D. Rapid human immunodeficiency virus testing on labor and delivery. Obstet Gynecol. 2008 Jul. 112(1):159-63. [Medline].

    Centers for Disease Control and Prevention (CDC). Epidemiology of HIV/AIDS–United States, 1981-2005. MMWR Morb Mortal Wkly Rep. 2006 Jun 2. 55(21):589-92. [Medline].

    Committee on Health Care for Underserved Women, The American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 536: Human immunodeficiency virus and acquired immunodeficiency syndrome and women of color. Obstet Gynecol. 2012 Sep. 120 (3):735-9. [Medline].

    Joint United Nations Programme on HIV/AIDS (UNAIDS). Ending AIDS: Progress Towards the 90-90-90 Targets. Available at http://www.unaids.org/sites/default/files/media_asset/Global_AIDS_update_2017_en.pdf. 2017; Accessed: September 5, 2017.

    Combination antiretroviral therapy and duration of pregnancy. AIDS. 2000 Dec 22. 14(18):2913-20. [Medline].

    Fowler MG, Qin M, Fiscus SA, et al. Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention. N Engl J Med. 2016 Nov 3. 375 (18):1726-1737. [Medline].

    Tuomala RE, Shapiro DE, Mofenson LM, Bryson Y, Culnane M, Hughes MD. Antiretroviral therapy during pregnancy and the risk of an adverse outcome. N Engl J Med. 2002 Jun 13. 346(24):1863-70. [Medline]. [Full Text].

    Jao J, Agwu A, Mhango G, et al. Growth patterns in the first year of life differ in infants born to perinatally vs. nonperinatally HIV-infected women. AIDS. 2015 Jan 2. 29(1):111-6. [Medline].

    Kourtis AP, Schmid CH, Jamieson DJ, Lau J. Use of antiretroviral therapy in pregnant HIV-infected women and the risk of premature delivery: a meta-analysis. AIDS. 2007 Mar 12. 21(5):607-15. [Medline].

    Thorne C, Newell ML. The safety of antiretroviral drugs in pregnancy. Expert Opin Drug Saf. 2005 Mar. 4(2):323-35. [Medline].

    Hitti J, Anderson J, McComsey G, et al. Effect of protease inhibitor-based antiretroviral therapy on glucose tolerance in pregnancy. Abstract. 13th Conference on Retroviruses and Opportunistic Infections. 2006 Feb.

    Minkoff H, Hershow R, Watts DH, Frederick M, Cheng I, Tuomala R. The relationship of pregnancy to human immunodeficiency virus disease progression. Am J Obstet Gynecol. 2003 Aug. 189(2):552-9. [Medline].

    Saada M, Le Chenadec J, Berrebi A, Bongain A, Delfraissy JF, Mayaux MJ. Pregnancy and progression to AIDS: results of the French prospective cohorts. SEROGEST and SEROCO Study Groups. AIDS. 2000 Oct 20. 14(15):2355-60. [Medline].

    French R, Brocklehurst P. The effect of pregnancy on survival in women infected with HIV: a systematic review of the literature and meta-analysis. Br J Obstet Gynaecol. 1998 Aug. 105(8):827-35. [Medline].

    [Guideline] Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1 Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. National Institutes of Health. Available at https://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf. Accessed: September 5, 2017.

    Centers for Disease Control and Prevention: US Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the United States. MMWR Morb Mortal Wkly Rep. September 2017. [Full Text].

    Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012 Aug 2. 367(5):399-410. [Medline].

    Liao C, Wahab M, Anderson J, Coleman JS. Reclaiming fertility awareness methods to inform timed intercourse for HIV serodiscordant couples attempting to conceive. J Int AIDS Soc. 2015. 18(1):19447. [Medline].

    Rough K, Tassiopoulos K, Kacanek D, et al. Dramatic decline in substance use by HIV-infected pregnant women in the United States from 1990 to 2012. AIDS. 2015 Jan 2. 29(1):117-23. [Medline]. [Full Text].

    American College of Obstetrics and Gynecology. ACOG Committee Opinion No. 389, December 2007. Human immunodeficiency virus. Obstet Gynecol. 2007 Dec. 110(6):1473-8. [Medline].

    Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States: Special Populations: HIV/Hepatitis B Virus Coinfection. US Department of Health and Human Services. Available at https://aidsinfo.nih.gov/guidelines/html/3/perinatal-guidelines/159/hiv-hepatitis-b-virus-coinfection. October 26, 2016; Accessed: September 6, 2017.

    Thomas SL, Newell ML, Peckham CS, Ades AE, Hall AJ. A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection. Int J Epidemiol. 1998 Feb. 27(1):108-17. [Medline].

    Mwapasa V, Rogerson SJ, Kwiek JJ, et al. Maternal syphilis infection is associated with increased risk of mother-to-child transmission of HIV in Malawi. AIDS. 2006 Sep 11. 20(14):1869-77. [Medline].

    Massad LS, Xie X, Darragh T, et al. Genital Warts and Vulvar Intraepithelial Neoplasia: Natural History and Effects of Treatment and Human Immunodeficiency Virus Infection. Obstet Gynecol. 2011 Oct. 118(4):831-839. [Medline]. [Full Text].

    Minkoff H. Human immunodeficiency virus infection in pregnancy. Obstet Gynecol. 2003 Apr. 101(4):797-810. [Medline].

    Lockman S, Hughes MD, McIntyre J, Zheng Y, Chipato T, Conradie F, et al. Antiretroviral therapies in women after single-dose nevirapine exposure. N Engl J Med. 2010 Oct 14. 363(16):1499-509. [Medline].

    Palumbo P, Lindsey JC, Hughes MD, Cotton MF, Bobat R, Meyers T, et al. Antiretroviral treatment for children with peripartum nevirapine exposure. N Engl J Med. 2010 Oct 14. 363(16):1510-20. [Medline].

    American College of Obstetrics and Gynecology. Scheduled cesarean delivery and the prevention of vertical transmission of HIV infection. No. 234. Obstet Gynecol. 2000 (Reaffirmed 2015).

    [Guideline] American College of Obstetrics and Gynecology. ACOG Practice Bulletin No. 86: Viral hepatitis in pregnancy. Obstet Gynecol. 2007 Oct. 110(4):941-56. [Medline].

    Shi Z, Yang Y, Ma L, Li X, Schreiber A. Lamivudine in late pregnancy to interrupt in utero transmission of hepatitis B virus: a systematic review and meta-analysis. Obstet Gynecol. 2010 Jul. 116(1):147-59. [Medline].

    Kind C, Rudin C, Siegrist CA, Wyler CA, Biedermann K, Lauper U. Prevention of vertical HIV transmission: additive protective effect of elective Cesarean section and zidovudine prophylaxis. Swiss Neonatal HIV Study Group. AIDS. 1998 Jan 22. 12(2):205-10. [Medline].

    Mandelbrot L, Landreau-Mascaro A, Rekacewicz C, et al. Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1. JAMA. 2001 Apr 25. 285(16):2083-93. [Medline].

    The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1–a meta-analysis of 15 prospective cohort studies. The International Perinatal HIV Group. N Engl J Med. 1999 Apr 1. 340(13):977-87. [Medline].

    Louis J, Landon MB, Gersnoviez RJ, Leveno KJ, Spong CY, Rouse DJ. Perioperative morbidity and mortality among human immunodeficiency virus infected women undergoing cesarean delivery. Obstet Gynecol. 2007 Aug. 110(2 Pt 1):385-90. [Medline].

    Wiysonge CS, Shey M, Kongnyuy EJ, Sterne JA, Brocklehurst P. Vitamin A supplementation for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev. 2011 Jan 19. CD003648. [Medline].

    Fowler MG, Lampe MA, Jamieson DJ, Kourtis AP, Rogers MF. Reducing the risk of mother-to-child human immunodeficiency virus transmission: past successes, current progress and challenges, and future directions. Am J Obstet Gynecol. 2007 Sep. 197(3 Suppl):S3-9. [Medline].

    Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry International Interim Report for 1 January 1989 through 31 January 2017. Wilmington, NC: Registry Coordinating Center; 2017; [Full Text].

    Lighter-Fisher J, Surette AM. Performance of an interferon-gamma release assay to diagnose latent tuberculosis infection during pregnancy. Obstet Gynecol. 2012 Jun. 119 (6):1088-95. [Medline].

    ART Class

    Preferred*

    Alternate

    Special Circumstances

    Insufficient Data to Recommend

    NRTIs

    tenofovir disoproxil fumarate + emtricitabine or lamivudine

    abacavir + lamivudine

    zidovudine + lamivudine

    didanosine (not recommended)

     

    stavudine (not recommended)

     

    tenofovir alafenamide

    NNRTIs

     

    efavirenz

    rilpivirine

    nevirapine (not recommended, ART naive)

     

    etravirine

     

    PIs

    atazanavir + ritonavir

    darunavir + ritonavir

    lopinavir + ritonavir

    indinavir

    nelfinavir

    saquinavir

    darunavir + cobicistat

    atazanavir + cobicistat

    fosamprenavir

    tipranavir

    dolutegravir

    elvitegravir/ cobicistat

    elvitegravir/ cobicistat/ emtricitabine/ tenofovir

    alafenamide 

    Entry and Fusion Inhibitors

    enfuvirtide

    maraviroc

    Pharmacoenhancers

    ritonavir

     

    cobicistat

     

    Ashley T Peterson, MD Fellow in Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Tufts Medical Center; Clinical Instructor, Department of Obstetrics and Gynecology, Tufts University School of Medicine

    Ashley T Peterson, MD is a member of the following medical societies: American Congress of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Massachusetts Medical Society, Society for Maternal-Fetal Medicine

    Disclosure: Nothing to disclose.

    Linda C Kleeman, MD Assistant Professor, Department of Obstetrics and Gynecology, Tufts Medical Center; Course Director, Maternal-Fetal Medicine Acting Internship, Tufts University School of Medicine

    Linda C Kleeman, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine

    Disclosure: Nothing to disclose.

    Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

    Disclosure: Received salary from Medscape for employment. for: Medscape.

    Ronald M Ramus, MD Professor of Obstetrics and Gynecology, Director, Division of Maternal-Fetal Medicine, Virginia Commonwealth University School of Medicine

    Ronald M Ramus, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Medical Society of Virginia, Society for Maternal-Fetal Medicine

    Disclosure: Nothing to disclose.

    Teresa Marino, MD Assistant Professor, Attending Physician, Division of Maternal-Fetal Medicine, Tufts Medical Center

    Disclosure: Nothing to disclose.

    HIV in Pregnancy

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    Gynecologic Care of Women With HIV Management Overview

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    Gynecologic Care of Women With HIV Management Overview

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    As the human immunodeficiency virus (HIV) epidemic progressed and women represented an increasing proportion of cases, concerns arose about possible clinically significant gynecologic manifestations of HIV infection and acquired immunodeficiency syndrome (AIDS). To address those concerns, the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) funded 2 large, multisite, prospective cohort studies, respectively: the Women’s Interagency HIV Study (WIHS) [1] and the HIV Epidemiology Research Study (HERS). [2]

    WIHS and HERS have contributed greatly to the understanding of HIV infection in women. Findings from these and other studies indicate that there are subtle differences between HIV disease in men and women, although these differences are less pronounced than originally predicted.

    WIHS, which began in 1994 and is ongoing, was established to follow the natural history of HIV infection and related health conditions among 2,058 women with HIV and 568 women without HIV. [1] In HERS, 871 women with HIV and 439 women without infection who were at-risk, aged 16–55, were enrolled at 4 US sites between 1993 and 1995 and were followed prospectively until 2000 to evaluate medical and psychosocial events associated with the clinical course of HIV infection. [2]

    As therapies continue to improve, women with HIV can expect to live longer. Consequently, health care providers must be aware of the special needs of women with HIV/AIDS. The American College of Obstetricians and Gynecologists has released clinical management guidelines for practitioners who care for women infected with HIV. [3]

    Globally, nearly half of all adults living with AIDS are women. In the United States, women accounted for 19% of the new HIV cases in 2016. [4] Black and Hispanic women account for 77% of HIV cases among women in the United States, although they represent less than 31% of people in the US; these disparities remain poorly explained. [5, 4, 6] Approximately 12% of new HIV infections in women are related to injection drug use but the number increases to 28% among white women. [4]

    Overwhelmingly, women who contract HIV infection are diagnosed during their reproductive years, and most (87%) become infected through high-risk heterosexual contact: sex with multiple partners, bisexual males, male injection drug users, or males with unidentified risk factors. [4]

    Disparities in survival by race and sex have been identified in studies: blacks and women have poorer outcomes compared with whites and men. [7]

    Among black women in the United States, HIV/AIDS was the sixth leading cause of death among women aged 25-34 and the fourth leading cause of death among women aged 35–44 in 2014. [4, 8]

    Findings from several studies indicate that differential use of highly active antiretroviral therapy (HAART) explains much of the disparity. [7] Lemly et al found that black patients presented with more advanced stages of HIV, were slower to initiate HAART, and were less likely to receive HAART while in care. [9]

    Studies have clearly demonstrated sex and race differences in HAART prescription and use among patients with access to therapy. Other studies have demonstrated higher rates of discontinuation and virologic failure among blacks and other minorities. [10] Women have been found to be less likely to use HAART, but even after correction for HAART use, women still have poorer outcomes. [9]

    The reasons for differential use of HAART are unclear. Substance abuse, mental illness, gaps in public insurance coverage (ie, Medicaid), and psychosocial stressors may be contributing factors.

    For other discussions on of HIV infection, see HIV Disease, Pediatric HIV Infection, and Antiretroviral Therapy for HIV Infection, as well as HIV in Pregnancy.

    Menstrual dysfunction is relatively common in the general population of reproductive-aged women. Studies have not established a consistent association between HIV infection and menstrual abnormalities. Additionally, no clear relationship has been established between menstrual dysfunction (particularly amenorrhea) and the use of highly active antiretroviral therapy (HAART).

    The few studies that have evaluated menstrual disorders or complaints in women with or without HIV have not found significant differences in amenorrhea, menstrual cycle length, or variability by HIV serostatus, unless advanced immunodeficiency (eg, CD4+ lymphocyte count < 200 cells/mL) is present. [11] Women with HIV should receive the same workup and treatment for menstrual disorders (including evaluation of risk factors) as women without HIV.

    The HIV Epidemiology Research Study (HERS) [2] and other studies have not found significant differences in the prevalence of chlamydial infection, gonorrhea, trichomoniasis, or syphilis in women by HIV serostatus. [12, 13] However, the presence of new or recurrent sexually transmitted infections (STIs) indicates high-risk behavior and warrants further counseling. Because the presence of STIs increases HIV shedding (which may increase the risk of HIV transmission to partners), [14] STIs should be treated aggressively in women with HIV.

    Many STIs are asymptomatic; therefore, sexually active women with HIV should be screened at least annually for curable STIs (eg, syphilis, trichomoniasis, gonorrhea, chlamydia). [15, 16] More frequent STI screening may be indicated based on symptoms and risk behaviors.

    The diagnosis and treatment of gonorrhea, chlamydial infection, and trichomoniasis are the same diagnosed and treated in HIV-positive women as in HIV-negative women. However, closer monitoring after treatment for syphilis is warranted for HIV-infected women. [15, 16]

    Herpes simplex virus type 2 (HSV2) is the most common cause of genital ulcer disease worldwide. While the prevalence of HSV2 varies by geographic location, it is consistently present in high percentages (50–90%) among persons infected with HIV. Among those co-infected with HIV and HSV2, more shedding of HSV2 and HIV in the genital tract occurs than in those infected with HIV or HSV2 alone. [17]

    Co-infection with HSV increases the risk of HIV acquisition by nearly twofold. Women with HIV may have recurrent problems with herpetic outbreaks and may benefit from episodic or suppressive therapy. highly active antiretroviral therapy (HAART) may decrease HSV shedding, although the data are inconsistent. The CDC’s Sexually Transmitted Diseases Treatment Guidelines provide recommendations for both episodic and suppressive HSV therapy in women with HIV. [15]

    Vulvovaginal candidiasis (VVC) is a common cause of vaginitis among women. In both women with and without HIV, the most common cause of VVC is Candida albicans. Studies have consistently found that both vaginal colonization and VVC are more frequent among women with HIV infection. [18, 19] The clinical spectrum of signs and symptoms and the severity of disease, however, do not appear to differ between those infected and those uninfected with HIV.

    The frequency of vaginal yeast colonization is inversely related to CD4+ counts, which may predispose the subgroup of women with HIV and low CD4+ counts to more frequent or severe infections. [20] Since the clinical and microbiological spectrum of VVC appears similar for women with and without HIV, the treatment decision should be based on the clinical indications. [15, 20, 21] VVC is associated with increased HIV cervicovaginal shedding; in women with HIV, however, the effect of treatment for VVC on HIV transmission is unknown.

    Bacterial vaginosis (BV) is the most common cause of vaginal discharge among women of reproductive age. Several clinical studies have found that the prevalence of BV in women with HIV is similar to that among women without HIV. [22, 23] However, evaluation of HERS concluded that BV is more prevalent among women with HIV, primarily because of more persistent infections rather than more incident (ie, frequent) infections. [22]

    Women who are immunocompromised (CD4+ T-cell count < 200 cells/mL) have a higher prevalence of BV than women with HIV with higher CD4+ counts. Women with HIV may require longer or more frequent treatment. Otherwise, the treatment regimens for BV in women with HIV infection are the same as for those not infected.

    Few data suggest that the course of pelvic inflammatory disease (PID) in women with HIV is worse than that in women without HIV. Thus, women should be managed according to the standard treatment criteria. Tubo-ovarian abscesses may be more common in women infected with HIV, but these appear to respond equally as well as uninfected women to standard IV and oral antibiotic therapies. [15]

    Human papillomavirus (HPV) causes cervical cytologic abnormalities (such as atypical squamous cells of undetermined significance [ASCUS] and squamous intraepithelial neoplasia [SIL]) and cervical cancer. More than 40 types of HPV cause genital infection; the types are typically grouped as low-risk (eg, 6, 11) or high-risk (eg, 16, 18) for development of cervical cancer. Persistent infection with a high-risk HPV type is necessary for progression to high-grade SIL and invasive cervical cancer, while both low-risk and high-risk HPV types can cause ASCUS and low-grade SIL. Nearly 70% of invasive cervical cancer is caused by HPV types 16 and 18.

    HPV infections are common, frequent, and generally transient and asymptomatic in the general population of sexually active young women. Approximately 70% of new HPV infections in young women without HIV clear spontaneously within 1 year, and up to 91% clear within 2 years. [24]

    Among women with HIV, HPV infection is more prevalent and persistent, the distribution of high-risk types is different, and cytologic abnormalities are more prevalent. High-risk HPV types have been found to have lower clearance rates than low-risk types, but there does not appear to be a difference by HIV serostatus. [25] The degree of immunosuppression correlates inversely with the frequency and severity of cytologic abnormalities.

    The relationship between HIV infection and invasive cervical cancer is less clear. Some studies have reported that although HIV infection increases the risk of abnormal cervical cytology, most abnormalities are low-grade. High-grade lesions and invasive cancers are rare (ie, similar to that among women without HIV) [26, 27] ; however, it appears that women with HIV and invasive cervical cancer have a greater degree of immunosuppression than women with HIV who are immunocompetent. [28]

    Highly active antiretroviral therapy (HAART) has improved the length and quality of life among women with HIV infection. Consequently, researchers have hypothesized that HAART could reduce the risk of cervical dysplasia and progression to invasive cervical cancer by decreasing HIV replication, but this hypothesis has not been proven. A 2009 HERS publication reported that HAART was associated with enhanced HPV clearance but not with Papanicolaou test abnormality regression. [29]

    More than 20% of people who are infected with HIV in the United States are estimated to be unaware of their HIV status. The CDC and ACOG recommend HIV screening in health care settings for all patients aged 13-64 years. [30, 31]

    Because they often provide primary health care for women, obstetrician-gynecologists are well positioned to encourage HIV screening for women. The CDC recommends that all pregnant women be screened with consent for HIV infection as part of routine prenatal testing as early in the pregnancy as possible. [30, 32] Retesting is recommended in the third trimester (preferably ≤ 36 weeks’ gestation) in pregnant women at high-risk of HIV infection. [32]

    Unless she declines, perform rapid HIV screening for women in labor who have an undocumented HIV status. [32] For women with positive rapid HIV test results, administer antiretroviral prophylaxis without waiting for results from more confirmatory tests. [32]

    After initial diagnosis, women with HIV should provide a complete history of previous cervical disease, and they should receive a comprehensive gynecologic examination. [15, 16]

    A Papanicolaou test should be performed twice during the first year. If the results of both tests are normal, subsequent Papanicolaou tests should be performed annually. Otherwise, subsequent care should be administered according to the American Society of Colposcopy and Cervical Pathology (ASCCP) 2006 Consensus Guidelines for Management of Abnormal Cervical Cytology. [33]

    Women infected with HIV who have cytologic abnormalities, regardless of CD4+ count or antiretroviral treatment status, should undergo colposcopy and directed biopsy. Conversely, women with HIV with normal cervical cytology should not receive colposcopy and biopsy.

    Because of the increased prevalence of abnormal cervical cytology, more women with HIV may undergo hysterectomy for high-grade squamous intraepithelial neoplasia (SIL) or carcinoma in situ. HERS found that 63% of women with HIV with evidence of cervical intraepithelial neoplasia (CIN) before or at hysterectomy experienced SIL vaginal cytology during follow-up, a level that is significantly higher than in women in the general population. [34] Low CD4+ counts and high viral load appear to also be predictors of SIL during follow-up.

    Women with HIV have higher rates of intraepithelial neoplasia of the vulvar, vaginal, and anal regions than women without HIV, and these lesions may be present in the absence of squamous intraepithelial lesions of the cervix. Risk factors for development of vulvar, vaginal, and anal intraepithelial neoplasia include CD4+ counts less than 200 cells/mL, HPV positivity, and high-risk HPV positivity.

    When women with HIV receive routine pelvic examinations, the vulva, vagina, and anus should be carefully examined. When colposcopy is indicated, the entire lower genital tract should be evaluated, including biopsies as needed. [35]

    The CDC, [30, 32] the American Congress of Obstetricians and Gynecologists (ACOG), [36] and several other national organizations recommend preconception counseling for all women of childbearing age, including women who are HIV positive. [37, 38] The goals of preconception care are to provide education and counseling targeted to the individual’s needs, identify risk factors for adverse maternal or fetal outcomes, and initiate interventions to optimize outcomes.

    Most women with HIV infection are of reproductive age, and 70-80% are sexually active. With highly active antiretroviral therapy (HAART), women with HIV are living longer, healthier lives; consequently more women with HIV may desire their own biologic children.

    By suppressing viral load, HAART significantly decreases mother-to-child transmission. To maximize outcomes and minimize risk, physicians should encourage women to plan their pregnancies, to use an effective form of contraception until they are ready to conceive, and to reduce risky behaviors (ie, smoking, substance use) and use folic acid.

    In addition, physicians should counsel women regarding the risk of transmitting infection through unprotected intercourse with an uninfected male partner. Intravaginal or intrauterine insemination may be feasible to reduce the risk of HIV transmission to an uninfected male partner.

    Nearly 50% of all pregnancies in the United States are unintended. Women with HIV should be counseled regarding the need to avoid unintended pregnancy as well as the need to protect themselves against sexually transmitted infections (STIs) and to protect their uninfected male partner(s) from infection. [39]

    Highly effective contraceptive methods (eg, hormonal methods, intrauterine devices [IUDs]) should be recommended when appropriate. Depomedroxyprogesterone acetate (DMPA) is considered safe and effective in women with HIV without known interactions with antiretroviral therapy. [40, 41]

    Combined oral contraceptives (COCs) are not recommended for women with HIV on certain HAART regimens because of potential alterations in safety and effectiveness of both the hormonal contraceptive and the antiretroviral drug. [42, 43] Specifically, for women taking ritonavir-boosted protease inhibitors, COCs are generally not recommended. [43] Women on HAART who are interested in using COCs should consistently use condoms (ie, dual method).

    IUDs are considered safe and effective for women with HIV, [44] but IUD insertion is not recommended for women with AIDS unless they are clinically stable on antiretroviral therapy. [43] Although data on surgical sterilization of women with HIV are scant, no specific recommendations or concerns different from those regarding women without HIV have been described.

    Correct, consistent condom use is essential for protection of an uninfected male partner and for protection of the woman from STIs, which can increase viral shedding. Studies have reported decreased condom use among women with HIV on HAART [45] , and among women without HIV whose partners have HIV. [46]

    There is little published information on gynecologic surgery in women with HIV; most information is from studies of postoperative complications after cesarean section. The limited available data on gynecologic surgery suggest that no differences in the clinical management of women with HIV undergoing routine gynecologic procedures are required.

    Two limited studies found no significant differences in postoperative complications between immunocompetent women with HIV and women without HIV. [47, 48] A larger, retrospective study concluded that women with HIV who undergo abdominal surgery or uterine curettage appear to be at risk for increased infectious morbidity such as postoperative fever (either transient or fever requiring antibiotic therapy). [49] Complications are more likely in women with HIV who are immunocompromised. [48, 49]

    In a more recent study at a single institution, investigators reported that low preoperative levels of serum albumin in HIV-infected women were associated with an increased risk of surgical site infections following abdominal hysterectomy. [50]

    Because of improved antiretroviral therapies, women with HIV are living longer, healthier lives. In addition, the HIV/AIDS epidemic is maturing in the United States. As a result, increasing numbers of women with HIV are reaching menopause. However, data on menopause in women with HIV are very limited. Menopause in the general US population occurs at a median age of 51.4 years; a few studies have found that menopause occurs 2-3 years earlier in women with HIV. Menopause has also been found to occur earlier among African-American women, cigarette smokers, and drug users; and each of these groups is overrepresented among women with HIV.

    A prospective study of the natural history of menopause among 302 women with HIV and 269 high-risk women without HIV found an average age of menopause of 46 and 47 years, respectively. In addition, this study found that HIV infection, use of cocaine or opioids, and physical inactivity were independently associated with age-adjusted onset of menopause. [51]

    The degree to which a women with HIV experiences menopausal symptoms may relate to her immune status. [52] While hormone replacement therapy (HRT) has been studied extensively among the general population, it has not been studied in women with HIV.

    Women’s Interagency HIV Study (WIHS). Available at https://statepiaps.jhsph.edu/wihs/index.htm. Accessed: June 29, 2011.

    The HERS Investigators’ Executive Committee. The HIV Epidemiology Research Study (HERS) of U.S. Women. Int Conf AIDS. 1994 Aug 7-12. 10:46 (abstract no. 156C).

    American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins–Gynecology. Practice Bulletin No. 167: Gynecologic Care for Women and Adolescents With Human Immunodeficiency Virus. Obstet Gynecol. 2016 Oct. 128 (4):e89-e110. [Medline].

    Centers for Disease Control and Prevention (CDC). HIV Among Women. Available at https://www.cdc.gov/hiv/group/gender/women/index.html. March 9, 2018; Accessed: March 23, 2018.

    Tillerson K. Explaining racial disparities in HIV/AIDS incidence among women in the U.S.: a systematic review. Stat Med. 2008 Sep 10. 27(20):4132-43. [Medline].

    The Foundation for AIDS Research (amfAR). Statistics: Women and HIV/AIDS. Available at http://www.amfar.org/about-hiv-and-aids/facts-and-stats/statistics–women-and-hiv-aids/. August 2017; Accessed: March 23, 2018.

    Levine RS, Briggs NC, Kilbourne BS, King WD, Fry-Johnson Y, Baltrus PT. Black-White mortality from HIV in the United States before and after introduction of highly active antiretroviral therapy in 1996. Am J Public Health. 2007 Oct. 97(10):1884-92. [Medline].

    Centers for Disease Control and Prevention. Leading Causes of Death (LCOD) in Females United States, 2014 (current listing). Available at https://www.cdc.gov/women/lcod/2014/index.htm. January 13, 2017; Accessed: March 23, 2018.

    Lemly DC, Shepherd BE, Hulgan T, Rebeiro P, Stinnette S, Blackwell RB. Race and sex differences in antiretroviral therapy use and mortality among HIV-infected persons in care. J Infect Dis. 2009 Apr 1. 199(7):991-8. [Medline].

    Pence BW, Ostermann J, Kumar V, Whetten K, Thielman N, Mugavero MJ. The influence of psychosocial characteristics and race/ethnicity on the use, duration, and success of antiretroviral therapy. J Acquir Immune Defic Syndr. 2008 Feb 1. 47(2):194-201. [Medline].

    Harlow SD, Schuman P, Cohen M, Ohmit SE, Cu-Uvin S, Lin X. Effect of HIV infection on menstrual cycle length. J Acquir Immune Defic Syndr. 2000 May 1. 24(1):68-75. [Medline].

    Cu-Uvin S, Hogan JW, Warren D, Klein RS, Peipert J, Schuman P. Prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive and high-risk HIV-seronegative women. HIV Epidemiology Research Study Group. Clin Infect Dis. 1999 Nov. 29(5):1145-50. [Medline].

    Cu-Uvin S, Ko H, Jamieson DJ, Hogan JW, Schuman P, Anderson J. Prevalence, incidence, and persistence or recurrence of trichomoniasis among human immunodeficiency virus (HIV)-positive women and among HIV-negative women at high risk for HIV infection. Clin Infect Dis. 2002 May 15. 34(10):1406-11. [Medline].

    Anderson BL, Cu-Uvin S. Determinants of HIV Shedding in the Lower Genital Tract of Women. Curr Infect Dis Rep. 2008 Nov. 10(6):505-11. [Medline].

    [Guideline] Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006 Aug 4. 55:1-94. [Medline].

    [Guideline] Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009 Apr 10. 58:1-207; quiz CE1-4. [Medline].

    McClelland RS, Wang CC, Overbaugh J, Richardson BA, Corey L, Ashley RL, et al. Association between cervical shedding of herpes simplex virus and HIV-1. AIDS. 2002 Dec 6. 16(18):2425-30. [Medline].

    Sobel JD. Treatment of vaginal Candida infections. Expert Opin Pharmacother. 2002 Aug. 3(8):1059-65. [Medline].

    Ohmit SE, Sobel JD, Schuman P, Duerr A, Mayer K, Rompalo A. Longitudinal study of mucosal Candida species colonization and candidiasis among human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women. J Infect Dis. 2003 Jul 1. 188(1):118-27. [Medline].

    Duerr A, Heilig CM, Meikle SF, Cu-Uvin S, Klein RS, Rompalo A. Incident and persistent vulvovaginal candidiasis among human immunodeficiency virus-infected women: Risk factors and severity. Obstet Gynecol. 2003 Mar. 101(3):548-56. [Medline].

    Duerr A, Sierra MF, Feldman J, Clarke LM, Ehrlich I, DeHovitz J. Immune compromise and prevalence of Candida vulvovaginitis in human immunodeficiency virus-infected women. Obstet Gynecol. 1997 Aug. 90(2):252-6. [Medline].

    Jamieson DJ, Duerr A, Klein RS, Paramsothy P, Brown W, Cu-Uvin S. Longitudinal analysis of bacterial vaginosis: findings from the HIV epidemiology research study. Obstet Gynecol. 2001 Oct. 98(4):656-63. [Medline].

    Warren D, Klein RS, Sobel J, Kieke B Jr, Brown W, Schuman P, et al. A multicenter study of bacterial vaginosis in women with or at risk for human immunodeficiency virus infection. Infect Dis Obstet Gynecol. 2001. 9(3):133-41. [Medline].

    Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998 Feb 12. 338(7):423-8. [Medline].

    Koshiol JE, Schroeder JC, Jamieson DJ, Marshall SW, Duerr A, Heilig CM. Time to clearance of human papillomavirus infection by type and human immunodeficiency virus serostatus. Int J Cancer. 2006 Oct 1. 119(7):1623-9. [Medline].

    Massad LS, Seaberg EC, Wright RL, Darragh T, Lee YC, Colie C. Squamous cervical lesions in women with human immunodeficiency virus: long-term follow-up. Obstet Gynecol. 2008 Jun. 111(6):1388-93. [Medline].

    Massad LS, Seaberg EC, Watts DH, Minkoff H, Levine AM, Henry D. Long-term incidence of cervical cancer in women with human immunodeficiency virus. Cancer. 2009 Feb 1. 115(3):524-30. [Medline].

    Leitao MM Jr, White P, Cracchiolo B. Cervical cancer in patients infected with the human immunodeficiency virus. Cancer. 2008 Jun 15. 112(12):2683-9. [Medline].

    Paramsothy P, Jamieson DJ, Heilig CM, Schuman PC, Klein RS, Shah KV. The effect of highly active antiretroviral therapy on human papillomavirus clearance and cervical cytology. Obstet Gynecol. 2009 Jan. 113(1):26-31. [Medline].

    Branson BM, Handsfield HH, Lampe MA, Janssen RS, Taylor AW, Lyss SB. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006 Sep 22. 55(RR-14):1-17; quiz CE1-4. [Medline].

    American Congress of Obstetricians and Gynecologists Committee on Gynecologic Practice. ACOG Committee Opinion no 596: Committee on Gynecologic Practice: Routine human immunodeficiency virus screening. Obstet Gynecol. 2014 May. 123(5):1137-9. [Medline].

    [Guideline] Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec 17. 59:1-110. [Medline]. [Full Text].

    Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol. 2007 Oct. 197(4):346-55. [Medline].

    Paramsothy P, Duerr A, Heilig CM, Cu-Uvin S, Anderson JR, Schuman P. Abnormal vaginal cytology in HIV-infected and at-risk women after hysterectomy. J Acquir Immune Defic Syndr. 2004 Apr 15. 35(5):484-91. [Medline].

    Jamieson DJ, Paramsothy P, Cu-Uvin S, Duerr A, HIV Epidemiology Research Study Group. Vulvar, vaginal, and perianal intraepithelial neoplasia in women with or at risk for human immunodeficiency virus. Obstet Gynecol. 2006 May. 107(5):1023-8. [Medline].

    American Congress of Obstetricians and Gynecologists Committee on Gynecologic Practice. ACOG Committee Opinion no 595: Committee on Gynecologic Practice: Preexposure prophylaxis for the prevention of human immunodeficiency virus. Obstet Gynecol. 2014 May. 123(5):1133-6. [Medline].

    Aaron EZ, Criniti SM. Preconception health care for HIV-infected women. Top HIV Med. 2007 Aug-Sep. 15(4):137-41. [Medline].

    Steiner RJ, Dariotis JK, Anderson JR, Finocchario-Kessler S. Preconception care for people living with HIV: recommendations for advancing implementation. AIDS. 2013 Oct. 27 Suppl 1:S113-9. [Medline].

    Millery M, Vazquez S, Walther V, Humphrey N, Schlecht J, Van Devanter N. Pregnancies in perinatally HIV-infected young women and implications for care and service programs. J Assoc Nurses AIDS Care. 2012 Jan-Feb. 23(1):41-51. [Medline].

    Nanda K, Amaral E, Hays M, Viscola MA, Mehta N, Bahamondes L. Pharmacokinetic interactions between depot medroxyprogesterone acetate and combination antiretroviral therapy. Fertil Steril. 2008 Oct. 90(4):965-71. [Medline].

    Watts DH, Park JG, Cohn SE, Yu S, Hitti J, Stek A. Safety and tolerability of depot medroxyprogesterone acetate among HIV-infected women on antiretroviral therapy: ACTG A5093. Contraception. 2008 Feb. 77(2):84-90. [Medline].

    El-Ibiary SY, Cocohoba JM. Effects of HIV antiretrovirals on the pharmacokinetics of hormonal contraceptives. Eur J Contracept Reprod Health Care. 2008 Jun. 13(2):123-32. [Medline].

    World Health Organization. Medical eligibility for contraceptive use, 2008 update. Geneva, Switzerland.

    Morrison CS, Sekadde-Kigondu C, Sinei SK, Weiner DH, Kwok C, Kokonya D. Is the intrauterine device appropriate contraception for HIV-1-infected women?. BJOG. 2001 Aug. 108(8):784-90. [Medline].

    Wilson TE, Gore ME, Greenblatt R, Cohen M, Minkoff H, Silver S. Changes in sexual behavior among HIV-infected women after initiation of HAART. Am J Public Health. 2004 Jul. 94(7):1141-6. [Medline].

    Heard I, Potard V, Costagliola D, Kazatchkine MD. Contraceptive use in HIV-positive women. J Acquir Immune Defic Syndr. 2004 Jun 1. 36(2):714-20. [Medline].

    Sewell CA, Derr R, Anderson J. Operative complications in HIV-infected women undergoing gynecologic surgery. J Reprod Med. 2001 Mar. 46(3):199-204. [Medline].

    Franz J, Jamieson DJ, Randall H, Spann C. Outcomes of hysterectomy in HIV-seropositive women compared to seronegative women. Infect Dis Obstet Gynecol. 2005 Sep. 13(3):167-9. [Medline].

    Grubert TA, Reindell D, Kästner R, Belohradsky BH, Gürtler L, Stauber M. Rates of postoperative complications among human immunodeficiency virus-infected women who have undergone obstetric and gynecologic surgical procedures. Clin Infect Dis. 2002 Mar 15. 34(6):822-30. [Medline].

    Coleman JS, Green I, Scheib S, Sewell C, Lee JM, Anderson J. Surgical site infections after hysterectomy among HIV-infected women in the HAART era: a single institution’s experience from 1999-2012. Am J Obstet Gynecol. 2014 Feb. 210(2):117.e1-7. [Medline].

    Schoenbaum EE, Hartel D, Lo Y, Howard AA, Floris-Moore M, Arnsten JH. HIV infection, drug use, and onset of natural menopause. Clin Infect Dis. 2005 Nov 15. 41(10):1517-24. [Medline].

    Fantry LE, Zhan M, Taylor GH, Sill AM, Flaws JA. Age of menopause and menopausal symptoms in HIV-infected women. AIDS Patient Care STDS. 2005 Nov. 19(11):703-11. [Medline].

    Centers for Disease Control and Prevention (CDC). HIV/AIDS Surveillance Report, 2005. Vol. 17. Rev ed. Atlanta: US Department of Health and Human Services, CDC: 2007: 1-46. Available at http://www.cdc.gov/hiv/topics/surveillance/resources/reports/2005report/pdf/2005surveillancereport.pdf. Accessed: March 17, 2010.

    ACOG Committee Opinion. Routine human immunodeficiency virus screening. Obstet Gynecol. 2008 Aug. 112(2 Pt 1):401-3. [Medline].

    Delany-Moretlwe S, Lingappa JR, Celum C. New Insights on Interactions Between HIV-1 and HSV-2. Curr Infect Dis Rep. 2009 Mar. 11(2):135-42. [Medline].

    Strick LB, Wald A, Celum C. Management of herpes simplex virus type 2 infection in HIV type 1-infected persons. Clin Infect Dis. 2006 Aug 1. 43(3):347-56. [Medline].

    World Health Organization. Medical eligibility for contraceptive use, 3rd edition 2004. Geneva, Switzerland.

    D’Nyce L Williams, MD, MPA, MPH, FACOG Clinical Associate Professor, Department of Obstetrics and Gynecology, Morehouse School of Medicine; Medical Officer, CONRAD/Centers for Disease Control and Prevention, Division of Reproductive Health, Women’s Health and Fertility Branch USHIR Team

    D’Nyce L Williams, MD, MPA, MPH, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Public Health Association

    Disclosure: Nothing to disclose.

    Denise J Jamieson, MD, MPH Clinical Professor of Gynecology and Obstetrics, Emory University School of Medicine; Team Leader, Unintended Pregnancy, STD, HIV Intervention Research Team Leader (USHIR), Women’s Health and Fertility Branch, Division of Reproductive Health, Centers for Disease Control and Prevention

    Denise J Jamieson, MD, MPH is a member of the following medical societies: American College of Obstetricians and Gynecologists

    Disclosure: Nothing to disclose.

    Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

    Disclosure: Received salary from Medscape for employment. for: Medscape.

    Christine Isaacs, MD Associate Professor, Department of Obstetrics and Gynecology, Division Head, General Obstetrics and Gynecology, Medical Director of Midwifery Services, Virginia Commonwealth University School of Medicine

    Christine Isaacs, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists

    Disclosure: Nothing to disclose.

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    Genital Herpes in Pregnancy

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    Infection with genital herpes simplex virus (HSV) (see the image below) remains a common viral sexually transmitted disease, often subclinical, and a major worldwide problem in women of reproductive age.

    See Herpes Simplex Viruses: Test Your Knowledge, a Critical Images slideshow, for more information on clinical, histologic, and radiographic imaging findings in HSV-1 and HSV-2.

    Women newly diagnosed with genital herpes will often experience psychological distress and worry about future sexual relationships and childbearing.

    In the United States, approximately 45 million individuals aged 12 years or older (1 in 5) have been infected with genital herpes. Each year, 1.5 million new cases are diagnosed. Five percent of all women of childbearing age report a history of genital herpes, and up to 30% have antibodies to herpes simplex virus 2 (HSV-2).  Approximately 22% of pregnant women are infected with HSV-2 and 2% of women acquire genital herpes in pregnancy. 

    Approximately 1500-2000 new cases of neonatal HSV infection are diagnosed each year. The incidence of neonatal herpes varies considerably in international studies (about 1:3,200 births in the US and 1:60,000 in the UK). Approximately 80% of infected infants are born to mothers with no reported history of HSV infection. [1]  Untreated neonatal HSV infection is associated with a mortality rate of 60%, and even with early and appropriate treatment, survivors experience considerable disability. [2]

    Pregnant women with untreated genital herpes during the first or second trimester appear to have a greater than two-fold risk of preterm delivery compared with women not exposed to herpes, particularly in relation to premature rupture of membrane and early preterm delivery (≤ 35 wk of gestation). [3] Pregnant women who receive antiherpes treatment have a lower risk of preterm delivery than untreated women, and their preterm delivery risk is similar to that seen in unexposed women.

    This article reviews (1) the types of genital HSV infections, (2) the risks and sequelae of neonatal HSV infection, and (3) the strategies to reduce perinatal transmission of HSV.

    HSV is a DNA virus. HSV has 2 subtypes: herpes simplex virus 1 (HSV-1) and HSV-2. The two types are differentiated by glycoproteins on the lipid bilayer envelope. Glycoprotein G1 is associated with HSV-1 and glycoprotein G2 is associated with HSV-2. Although each is a distinct virus, they share some antigenic components, such that antibodies that react to one type may “neutralize” the other. Most individuals who are infected with HSV are unaware that they have contracted the virus with only approximately 10-15% of infected individuals reporting recognition of their infection. [1]  Another factor in the underestimation of the prevalence of genital herpes is because HSV-1 can also cause the genital disease.

    Risk factors for HSV infection include female gender, duration of sexual activity, minority ethnicity, previous genital infection, socioeconomic status and number of sexual partners. 

    HSV-1 infections were traditionally associated with the oral area causing herpes labialis (fever blisters), gingivostomatitis and keratoconjunctivitis, whereas HSV-2 infections occurred in the genital region. However, because of increasing oral-genital contact, either HSV type may be found in either location. Currently, approximately 15% of genital HSV infections are caused by HSV-1, however, HSV-1 is increasingly recognized as the etiologic agent of genital herpes infection with a large proportion of new genital infections being caused by HSV-1 in young women. 

    Herpes simplex virus is transmitted from person to person through direct contact.  Virus contacting mucosa or disrupted skin initiates the infection. Incubation is approximately 2-12 days where the HSV virus replicates in the dermis and epidermis. This results in cellular destruction and inflammation. The virus then becomes latent in the  sensory ganglia and reactivate periodically with either asymptomatic shedding or recurrent ulcerative lesions. Recurrences and subclinical shedding are much more frequent for genital HSV-2 infection than for genital HSV-1 infection.  

    The following 4 designations are given for genital HSV infections:

    Primary

    Nonprimary first-episode

    Recurrent

    Asymptomatic viral shedding

    In a primary infection, no type-specific immunoglobulin G (IgG) antibodies to either HSV-1 or HSV-2 exist at the time of the outbreak. This indicates that the patient had no prior exposure to HSV.  In pregnancy, the incidence of new HSV-1 of HSV-2 infection is approximately 2%. [1] Timing of infection throughout the trimesters is evenly distributed with approximately one third of women becoming infected per trimester. Primary HSV has a rate of transmission of 50%. [4]

    Typically, lesions appear 2-12 days after exposure. Without antiviral therapy, the lesions usually last for 20 days. Viral shedding usually lasts 12 days, with the highest rates of shedding during the prodrome and the first half of the outbreak. Viral shedding usually ceases before complete resolution of the lesion.

    Antibody response occurs 3-4 weeks after the infection and is lifelong. However, unlike protective antibodies to other viruses, antibodies to HSV do not prevent local recurrences. The symptoms associated with local recurrences tend to be milder than those occurring with primary disease.

    The lesions of a primary infection begin as tender vesicles bilaterally, which may rupture and become ulcers. The vaginal mucosa is commonly inflamed and edematous. The cervix is involved in 70-90% of patients.

    Symptoms associated with primary infections may be both local and constitutional. Local symptoms include intense pain, dysuria, itching, vaginal discharge, and lymphadenopathy. Constitutional symptoms are due to viremia and include fever, headache, nausea, malaise, and myalgia.

    Importantly, more than 75% of patients with primary genital HSV infection are asymptomatic. Asymptomatic primary HSV infections in gravidas at term are responsible for most neonatal HSV infections.

    A nonprimary first-episode infection is a first genital HSV outbreak in a woman who has heterologous HSV antibodies. For example, if a woman develops a nonprimary first-episode HSV-2 infection on the labia, she would have antibodies against HSV-1 prior to and at the time of her genital outbreak. Because of the partial protection of the preexisting antibodies, systemic symptoms during these outbreaks tend to be fewer and shorter in duration. The duration of lesions is also shorter (averaging 15 days), and shedding lasts for only approximately 7 days.

    Distinguishing primary infections from nonprimary first-episode infections by clinical presentation is difficult. Instead, the diagnosis is based on type-specific culture and type-specific serology. The absence of any HSV antibodies at the time of the outbreak confirms a primary infection, whereas antibody to the heterologous HSV type confirms a nonprimary first-episode infection.

    A recurrent infection is defined as a genital HSV outbreak in a woman with homologous IgG antibodies to the HSV type. Recurrent infections occur most frequently during the first 3 months after a primary infection, especially with HSV-2. These lesions are classically unilateral on the labia.  Approximately 14% of all pregnant women with a history of genital HSV infection experience recurrent lesions or prodromal symptoms at delivery. However, among women with recurrent lesion at the time of delivery, only 3% of neonates will be infected. Recurrent HSV outbreaks may be symptomatic or asymptomatic. When present, most symptoms are localized (eg, pain, itching, vaginal discharge).  

    Lesions typically last for 9 days, and shedding lasts for approximately 4 days. The viral load tends to be lower in recurrent outbreaks than with primary lesions, and shedding tends to occur during the prodrome and early stage of the clinical outbreak. Shedding is usually completed before the lesions resolve.

    Asymptomatic viral shedding is episodic and brief, usually lasting 24-48 hours. One to 2% of pregnant women with a history of recurrent HSV infection have asymptomatic shedding at the time of delivery. Coinfection with HIV may increase asymptomatic shedding of HSV in women. [5]

    Type-specific HSV serologic assays have been approved by the US Food and Drug Administration (FDA) for commercial use. These assays distinguish HSV-1 from HSV-2 antibodies on the basis of differences in the surface glycoprotein G between the two HSV subtypes. The Centers for Disease Control and Prevention (CDC) now recommends the use of glycoprotein G–based assays for all HSV type-specific serologic testing. Immunoglobulin M (IgM)-specific serology is generally not useful because this test may be positive during recurrent genital or oral episodes. Use of type-specific serology in conjunction with HSV culture makes it possible to determine the type of genital infection.

    Hensleigh and colleagues evaluated 23 pregnant women with severe first-episode infections that were presumed to be primary by the clinician. All had HSV cultures and type-specific serology at the time of presentation. Of the 23 women, 1 (4%) had primary HSV-1, 3 (13%) had nonprimary first-episode infections (all HSV-2), and 19 (83%) had recurrent infection (14 with HSV-2). [6] This study demonstrated both the utility of HSV serology in determining the type of infection and the overdiagnosis of primary infections during pregnancy.

    Unfortunately, in a proficiency test administered by the American College of Pathology to 172 participating laboratories, more than 50% reported the presence of HSV-2 antibodies from a sample that contained only HSV-1 antibodies. All of the labs using a glycoprotein G–based assay correctly identified only HSV-1 antibodies. [7] These test results underscore the importance for clinicians to know the type of assays used by their laboratory when ordering type-specific serology to distinguish the type of genital HSV infection. If the assay is not a glycoprotein G–based test, the accuracy of the typing should be challenged.

    HSV can be vertically transmitted to the infant before, during, or after delivery, although intrapartum transmission accounts for most cases. Maternal age of less than 21 years is a risk factor for vertical transmission. [8]

    Approximately 5% of all cases of neonatal HSV infection result from in utero transmission. With primary infection, transient viremia occurs. HSV has the potential for hematogenous spread to the placenta and to the fetus. Hematogenous spread can produce a spectrum of findings similar to other TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus, and herpes simplex) infections, such as microcephaly, microphthalmia, intracranial calcifications, and chorioretinitis.

    Intrapartum transmission accounts for most neonatal infections and occurs with passage of the infant through an infected birth canal. The use of a fetal-scalp electrode increases the risk for intrapartum transmission. [8] From 75% to 90% of infants with neonatal HSV are born to infected asymptomatic mothers who have no known history of genital HSV.

    Postnatal transmission of HSV can occur through contact with infected parents or health care workers.

    Intrapartum transmission rates depend on the type of clinical HSV infection. Lower rates are noted in the presence of protective maternal antibodies that cross the placenta. See the following:

    Primary HSV infection – Transmission rate of 50%

    Nonprimary first-episode infection – Transmission rate of 33%

    Recurrent infection or asymptomatic shedding – Transmission rate of 0-4%

    The overall chance of neonatal infection from asymptomatic shedding in a woman with a history of genital HSV infection is estimated to be less than 4 in 10,000 (ie, 1% risk of asymptomatic shedding multiplied by the [up to] 4% risk of transmission).

    To determine the frequency and sequelae of HSV shedding at the time of delivery, Brown and colleagues obtained HSV cultures (from both cervix and external genitalia) within 48 hours of delivery in 40,023 women. [9] HSV was isolated in 202 women (0.5%), of whom approximately one half had no prior history of genital HSV. Serology was also available in 177 of the 202 cases (see image below). Based on the serology of these 177 women, 26 (15%) had first-episode disease, and 151 (85%) had recurrent infection.

    Of the 26 first-episode viral shedders, 3 had primary HSV-1, 6 had primary HSV-2, 1 had nonprimary HSV-1 and 16 had nonprimary HSV-2. Among those with recurrent infections, 11 had HSV-1 and 140 had HSV-2.

    A total of 18 infants developed neonatal HSV during the study period, for a rate of 1 per 3200 of all deliveries and 5% (10 in 202) of all mothers shedding HSV at delivery.

    The rates of perinatal transmission from women who had cultures positive for HSV at delivery were as follows:

    Primary HSV-1 – 100% (3 in 3)

    Primary HSV-2 – 17% (1 in 6)

    Nonprimary first-episode HSV-2 – 25% (4 in 16)

    Recurrent HSV-1 – 18% (2 of 11)

    Recurrent HSV-2 – 0% (0 in 140)

    Although the presence of heterologous antibody did not appear protective, numerous factors significantly influenced perinatal transmission rates. These factors included the following:

    Cesarean delivery – Odds ratio (OR) 0.14; 95% confidence interval (CI) 0.02-1.08

    Lack of homologous antibodies – OR 33.1; 95% CI 6.5-168

    HSV-1 subtype – OR 16.5; 95% CI 4.1-65

    Use of scalp electrode during labor – OR 6.8; 95% CI 1.4-32

    This important observational study demonstrated the following:

    Neonatal transmission is highest in women who are seronegative, confirming the importance of maternal antibodies in preventing neonatal transmission.

    The presence of HSV-2 antibodies appears to reduce not only neonatal HSV-2 infections (no neonatal HSV infections from 140 recurrent shedders) but also maternal HSV-1 infections (ie, no cases of nonprimary HSV-1 infections).

    Rates of neonatal HSV infection, both primary and recurrent, are greater with HSV-1 than with HSV-2.

    Cesarean delivery is protective against neonatal infection, confirming a long-standing practice that had never previously been scientifically validated.

    The significance of neonatal HSV infection varies and depends on the extent of the infection (see Table 1). Localized infections are the most common and benign type. However, serious infections can occur and can lead to death or long-term CNS morbidity.  Neonatal HSV infections can be classified as disseminated disease (25%); central nervous system disease (30%); and disease limited to the skin, eyes or mouth (45%). Mortality has decreased to 30% for disseminated disease and 4% for central nervous system disease over the past two decades.  Approximately 20% of affected neonates will have long term neurologic sequelae.  

    A study by Kimberlin et al suggests that neonatal suppression therapy with acyclovir in infants with HSV may improve neurodevelopmental outcomes. [10]

    Table 1. Types and Sequelae of Neonatal HSV Infection (Open Table in a new window)

    Disease Type

    Incidence, %

    Mortality, %

    Long-term Morbidity, %*

    Localized disease of

    skin, eye, mouth

    45

    0

    5

    CNS

    35

    15

    65

    Disseminated

    20

    60-80

    40

    *Morbidity includes mental retardation, chorioretinitis, seizures, and other CNS effects.

    HSV culture has long been the criterion standard for diagnosis of HSV infection, with a sensitivity of 70% and a specificity of nearly 100%. A final culture report may take up to 7 days. The sensitivity of HSV culture is related to the HSV type and the location from which the culture is taken. The culture yield is highest during the prodrome and lowest during the second half of the outbreak, especially with recurrent lesions. Sensitivity of HSV viral culture is lower for HSV-2 than for HSV-1. In asymptomatic women, the yield is greatest when cultures are taken from the cervix and the site of recurrence, even if no lesion is visualized. When obtaining HSV cultures, request that the lab type the specimens for both HSV-1 and HSV-2 strains so that the results can be compared with type-specific serology to determine the type of clinical infection.

    The Tzank smear is an older test that is no longer used because of the large number of both false-positive and false-negative results. The Tzank smear was taken in a manner similar to that of a Papanicolaou test (Pap smear), with unroofing and scraping of the base of a lesion. After spraying with a fixative and staining, light microscopy was used to look for the presence of multinucleated giant cells. The Tzank smear is now of historical interest only.

    Polymerase chain reaction (PCR) is a molecular test that is being increasingly used and that may ultimately replace HSV culture as the criterion standard. [11, 12, 13] Like the viral culture, PCR can distinguish HSV-1 from HSV-2. The test takes approximately 1 day for results to be returned and has the potential for a higher detection rate than HSV culture. In one study, 9% of women in labor who had culture-negative results for HSV had PCR-positive results. [12] Additionally, increased levels of HSV DNA may be associated with an increased risk of neonatal transmission. Unfortunately, PCR does not differentiate actively replicating HSV from latent HSV DNA.

    Acyclovir, a nucleoside analogue, was the first antiviral therapy approved for the treatment and prevention of HSV infection. Acyclovir selectively inhibits viral DNA replication of HSV, while having little effect on normal cells. Acyclovir is selective for HSV-infected cells because it requires phosphorylation by a viral enzyme (thymidine kinase) to acyclovir monophosphate. Phosphorylation does not occur in uninfected cells, where it remains virtually undetectable. After its conversion to acyclovir monophosphate in infected cells, other cellular enzymes convert it to acyclovir triphosphate, which acts to inhibit HSV-specific DNA polymerase, resulting in termination of the DNA transcript.

    With primary HSV infection in nonpregnant women, acyclovir reduces the duration of local pain, dysuria, and viral shedding, and it shortens the time to crusting and healing of lesions. [14] With daily usage, acyclovir also reduces symptomatic recurrences and subclinical viral shedding.

    During pregnancy, acyclovir crosses the placenta and concentrates in the amniotic fluid. Postpartum, acyclovir concentrates in breast milk. Fetal serum concentrations are equivalent to maternal serum concentrations. A potential drawback of acyclovir therapy is delayed and decreased antibody response to a primary HSV infection. Whether this is due to a decreased viral load or to immune suppression is unknown. Acyclovir has been labeled a category B drug (no teratogenic effects were found in animal studies, but no or limited human studies are available).

    Since the introduction of acyclovir, newer second-generation antivirals have been introduced (eg, valacyclovir, famciclovir). Valacyclovir is identical to acyclovir except for the addition of an ester side chain that increases bioavailability. Once absorbed, it is converted to acyclovir in vivo. This allows for higher serum levels with a less-frequent dosing schedule. Famciclovir is a nucleotide analogue that has a longer intracellular half-life.

    As with acyclovir, these second-generation agents have been used for treatment of symptomatic primary and recurrent lesions as well as for daily suppression. Both valacyclovir and famciclovir have been labeled category B drugs.

    The recommended dosages of the 3 antiviral agents are as follows:

    Table 2. Recommended Dosages of the Antiviral Agents for Genital Herpes Infection (Open Table in a new window)

    Indication

    Acyclovir

    Valacyclovir

    Famciclovir

    First episode

    400 mg tid OR 200 mg 5 times/d (for 7-10 d)

    1000 mg bid (for 7-10 d)

    250 mg tid (for 7-10 d)

    Recurrent

    400 mg tid (for 3-5 d) OR 800 mg PO tid (for 2 d)

    500 mg bid (for 3 d)

    1000 mg bid (for 1 d)

    Daily suppression

    400 mg bid

    500 mg qd

    or

    1000 mg qd

    (if >9 recurrences/y)

    250 mg bid

     

    Table 3. Recommended Dosages of the Antiviral Agents for Genital Herpes Infection for the Pregnant Patient (Open Table in a new window)

     

     

    In 1984, the manufacturer of acyclovir, in conjunction with the CDC, established a registry monitoring the safety of the drug. The registry was closed in 1999. In that time, 1129 acyclovir-exposed pregnancies were reported to the registry; 712 of these occurred in the first trimester. Additionally, 56 valacyclovir-exposed pregnancies were reported; 14 of these occurred in the first trimester.

    No increase in the number of malformations occurred with acyclovir, and no pattern of birth defects emerged. Too few cases of valacyclovir-exposed pregnancies precluded the drawing of any meaningful conclusions. Thus, acyclovir appears to be relatively safe to use during pregnancy and should be prescribed as medically indicated. The acyclovir registry can be accessed at the GlaxoSmithKline Web site.

    A recent Danish study that assessed more than 800,000 pregnancies suggests that exposure to acyclovir or valacyclovir in the first trimester is not associated with an increased risk of major birth defects. [15]

    Historical Approach: Weekly cervical cultures of asymptomatic women with history of genital HSV infection

    In the early 1980s, weekly cervical cultures starting at 34 weeks were the standard in pregnant women with a history of genital HSV. If the last culture prior to labor was positive for HSV, a cesarean delivery was recommended. However, later studies demonstrated that most women with asymptomatic antepartum shedding were culture-negative during labor. Additionally, those women with positive intrapartum cultures were often negative during the antepartum period.

    In 1988, the Infectious Disease Society for Obstetrics and Gynecology developed a position statement that recommended the following practices [16] :

    Abandon weekly cervical cultures.

    In the absence of active lesions or prodromal symptoms, vaginal delivery should be allowed.

    At the time of delivery, consider obtaining a herpes culture from the mother or the neonate for the benefit of the pediatricians.

    Herpes cultures, when obtained, should be obtained from the cervix and the site of recurrence.

    If there is an active herpetic lesion, cesarean delivery should be performed, preferably within 4-6 hours of membrane rupture.

    If there is a recent infection near term, check cervical cultures every 3-5 days until results are negative.

    Current strategies to prevent vertical transmission with antiviral therapy have focused on 3 approaches, as follows:

    Antiviral suppression for gravidas with first-episode infections during pregnancy

    Routine antiviral suppression for gravidas with a history of genital HSV

    Identification of seronegative gravidas at risk for primary and nonprimary first-episode genital HSV infections

    Recognizing that recurrent infections occur more frequently within the first year after a primary infection, Scott et al randomized 46 gravidas with first genital outbreak during pregnancy to either acyclovir (400 mg tid) or placebo beginning at 36 weeks’ gestation. [17] Patients receiving acyclovir experienced a significant reduction in the percentage of HSV recurrences at delivery (36% vs 0%) and cesarean deliveries for HSV (36% vs 0%). However, the reduction in the total number of cesarean deliveries in enrolled women was not statistically significant (40% vs 19%).

    No patients in this study had asymptomatic shedding at the time of delivery, and no infant developed neonatal HSV infection or had complications from acyclovir. No attempt was made to distinguish between primary infections, nonprimary first-episode infections, or first-recognized recurrent infections. This study was, however, the first to demonstrate the utility of antiviral suppression in reducing the number of recurrences at the time of delivery.

    In 1998, Brocklehurst and colleagues performed a double-blind placebo-controlled trial that involved 63 women with a history of recurrent HSV infection. [18] These women were randomized to either acyclovir (200 mg qid) or placebo, both beginning at 36 weeks’ gestation. Nonsignificant reductions were found in recurrent HSV outbreaks at delivery, cesarean deliveries for HSV, and total cesareans in the acyclovir group. No infant in either group developed neonatal HSV, and no gravida experienced toxicity from acyclovir. The authors concluded that the sample size was too small to demonstrate a significant benefit from acyclovir and recommended that acyclovir be used only in clinical trials.

    Since that time, additional randomized clinical studies have been performed, each demonstrating nonsignificant reductions in cesarean deliveries for recurrent HSV outbreaks and no differences in neonatal outcomes.

    A 2003 meta-analysis pooled the results of five randomized clinical trials evaluating the use of antenatal suppressive acyclovir in 799 gravidas. [19] The results of the meta-analysis are shown in Table 3.

    Table 3. Antiviral Trial Results (Open Table in a new window)

    Outcome

    Acyclovir, %

    Placebo, %

    OR (95% CI)

    Recurrent HSV infection at delivery

    3.5

    15.5

    .25 (.15-.40)

    Cesarean deliveries for HSV

    4.0

    14.7

    .30 (.13-.67)

    Total cesarean deliveries

    16.7

    25.9

    .61 (.43-.86)

    Asymptomatic HSV shedding at delivery

    0

    3.1

    .09 (.02-.39)

     

    All of the observed outcomes were significantly reduced with suppressive use of acyclovir (no 95% confidence interval included the value of 1). No cases of neonatal herpes were reported in any of the 799 infants in all 5 studies, whether in the acyclovir or placebo group. Due to the rarity of neonatal HSV infections, far larger numbers of subjects are required to demonstrate a significant difference in this important outcome.

    Recommended regimen for suppressive therapy for pregnant women with recurrent genital herpes

    ·      Acyclovir 400mg orally three times per day

    ·      Valacyclovir 500mg orally twice a day

    This approach is the most ambitious of all strategies to prevent vertical transmission. Its logic is based on the observation that most neonatal HSV transmission occurs not in gravidas with a history of genital HSV, but rather in women who have primary or nonprimary first-episode genital infections at the time of labor. If routine serologic screening revealed that a woman was at risk for primary HSV (no antibodies) or nonprimary first-episode infection (either HSV-1 or HSV-2 only), she could be counseled to avoid genital-genital or oral-genital contact in order to prevent new genital infections during the third trimester of pregnancy and, hence, reduce neonatal HSV infections.

    An alternative strategy would be to check the serologic status of the sexual partner, as well, and to recommend sexual abstinence only if the woman was at risk and the couple was serologically discordant, which occurs in 15-25% of couples. For example, if a woman was seronegative for HSV-2, and her partner was seropositive for HSV-2, the woman’s risk of acquiring HSV-2 during pregnancy would be as high as 20%. Such a couple would, thus, be advised to abstain from sexual activity during pregnancy.

    Despite the theoretical appeal of such an approach, no clinical trials have been published that show this approach resulting in a reduced rate of neonatal HSV infection. Three cost-benefit analyses have yielded conflicting results.

    In 2000, Rouse and Stringer performed a decision analysis model to test the value of routine screening of couples for HSV serology during pregnancy. [20] Of 1 million hypothetical women screened, the rate of neonatal HSV-1 transmission would be marginally reduced from 126 to 99, and the rate of neonatal HSV-2 infection would be reduced from 157 to 124. The cost per serious case of neonatal HSV averted would be $891,000. The authors concluded that HSV serology was not a cost-effective strategy to prevent neonatal HSV, predominantly through failure of counseling to prevent horizontal transmission.

    Similarly, Thung and Grobman performed a decision analysis comparing 1) current routine care (no serology testing), 2) couple screening for susceptible gravidas with counseling for discordant couples, and 3) counseling for discordant couples plus acyclovir prophylaxis for seropositive women to prevent symptomatic and asymptomatic shedding in labor. [21] Out of 100,000 hypothetical women, serology screening would prevent 2 and 3.8 neonatal deaths or neurologic sequelae for strategies 2 and 3, respectively, with respective costs of 5.8 and 4 million dollars for each adverse sequela prevented.

    In contrast, the decision analysis of HSV-2 screening by Baker and colleagues compared 1) no routine serology screening; 2) routine screening, counseling for HSV-negative gravidas about safe sex, and offering acyclovir prophylaxis to HSV-positive women at 36 weeks; and 3) testing the partners of HSV-negative women and offering suppressive therapy for HSV-positive men starting at 15 weeks. [22] These researchers found that the cost of each case of neonatal herpes prevented with strategy 2 was $194,000, while the additional cost of partner screening and suppressive therapy was nearly 5 million dollars for each case of neonatal herpes prevented. They concluded that routine maternal serology screening with acyclovir suppression in seropositive gravidas was cost-effective, while partner screening and suppression was not.

    Currently, routine maternal serologic screening is not widespread. Reasons for this include cost considerations; the unproven value of abstinence counseling in susceptible women; and the psychosocial ramifications of discovering a positive serology, as HSV-2 is predominantly a sexually-transmitted disease. At this time, the American College of Obstetricians and Gynecologists has not endorsed routine maternal HSV serology screening. [1]

    PPROM and HSV infection

    An increased risk of transmission occurs with rupture of membranes.  For pregnant patients with recurrent HSV infection and PPROM, risk associated with prematurity must be balanced with risk for in utero infection on a case by case basis.  If delay of delivery is appropriate, IV acyclovir 5mg/kg every 8 hours is recommended to shorten duration of active lesions.  For pregnant patients with a primary or first episode in genital HSV infection and PPROM, no data is available for the risk of fetal infection for expectant management. [1]

    Procedures and HSV in pregnancy

    Transcervical procedures such as cerclage placement are avoided while an active lesion is present to prevent transmission. Transabdominal procedures are not contraindicated in women with history of recurrent HSV infections such as amniocentesis and percutaneous umbilical cord sampling. These abdominal procedures may even be performed with an active lesion if necessary. Invasive monitoring such as fetal scalp electrodes is a risk factor for transmission, increasing the neonatal infection risk by 6 fold. However, if there are indications for the invasive monitoring, it is reasonable to use if there is no active lesion.

    In 2007, the American College of Obstetricians and Gynecologists (ACOG) published a practice bulletin regarding HSV in pregnancy. [1] Their conclusions were as follows:

    See the list below:

    Women with active recurrent genital herpes should be offered suppressive viral therapy at or beyond 36 weeks of gestation.

    Cesarean delivery is indicated in women with active genital lesions or prodromal symptoms (eg, vulvar pain or burning) at the time of delivery, because these symptoms may indicate an impending outbreak.

    See the list below:

    In women with premature rupture of membranes, there is no consensus on the gestational age at which the risks of prematurity outweigh the risks of HSV infection.

    Cesarean delivery is not recommended for women with a history of HSV infection but no active genital disease during labor.

    Routine antepartum genital HSV cultures in asymptomatic patients with recurrent disease are not recommended.

    Routine HSV screening of pregnant women is not recommended.

    In 2013, the American Academy of Pediatrics (AAP) Committees on Infectious Diseases and on Fetus and Newborn developed an algorithm for the management of asymptomatic neonates born vaginally or by cesarean delivery to women with active genital HSV lesions. [23] Clinicians should determine primary versus recurrent infection and obtain HSV DNA results from genital swabs taken from women in labor to identify symptomatic or asymptomatic shedding.

    If the mother has a history of prepregnancy genital HSV infection, the following are included in the AAP algorithm [23] :

    At about 24 hours post delivery, if the neonate is asymptomatic, obtain neonatal skin and mucosal cultures as well as neonatal blood for HSV DNA PCR assay. If the neonate is asymptomatic, do not administer acyclovir.

    If the neonatal surface cultures as well as the blood and surface PCRs are negative for 48 hours and there are no clinical conditions indicating otherwise, the infant may be discharged, with close monitoring for signs/symptoms of neonatal HSV. A full diagnostic evaluation and initiation of intravenous (IV) acyclovir are necessary if signs/symptoms of neonatal HSV develop.

    If the neonatal surface cultures or the blood or surface PCRs are positive, perform a full diagnostic evaluation (eg, obtain cerebrospinal fluid [CSF] analyses and HSV DNA PCR assay, serum chemistries, including alanine transaminase [ALT] levels) and initiate IV acyclovir.

    If the mother does not have a history of prepregnancy genital HSV infection, the AAP algorithm includes the following [23] :

    If available, obtain maternal type specific serology for HSV-1 and HSV-2 antibodies.

    At about 24 hours post delivery, if the neonate is asymptomatic, obtain neonatal skin and mucosal cultures and neonatal blood for HSV DNA PCR assay. In addition, obtain CSF analyses and HSV DNA PCR assay, serum chemistries, including ALT levels, and initiate IV acyclovir.

    Once the maternal disease classification is determined (eg, first episode primary/nonprimary, recurrent), further management options include further diagnostic workup and/or neonatal empiric IV acyclovir or IV acyclovir for treatment of surface, CNS, or disseminated disease.

    For full details of the 2013 AAP algorithm, see Kimberlin DW, Baley J, for the Committee on Infectious Diseases and Committee on Fetus and Newborn. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013 Feb;131(2):383-6. PMID: 23378604. [23]

    Currently, recurrent HSV infections account for only a small proportion of neonatal HSV infections. However, routine HSV suppression with antiviral agents, especially in pregnant women with a history of frequent recurrences, may suppress clinical recurrences during labor and may reduce the need for cesarean deliveries in these women.

    In order to truly reduce the incidence of neonatal HSV infection, physicians and researchers must focus on the prevention and recognition of asymptomatic primary genital HSV infections. In the future, this might require a combination of PCR analysis for faster diagnosis, as well as type-specific serology to identify pregnancies at risk for primary HSV infections.

    [Guideline] American College of Obstetricians and Gynecologists. ACOG practice bulletin. Management of herpes in pregnancy. 2007 Jun. 10 (ACOG practice bulletin; no. 82). Available at http://guideline.gov/content.aspx?id=11430. Accessed: December 10, 2016.

    Corey L, Wald A. Maternal and neonatal herpes simplex virus infections. N Engl J Med. 2009 Oct 1. 361(14):1376-85. [Medline]. [Full Text].

    Li DK, Raebel MA, Cheetham TC, et al. Genital herpes and its treatment in relation to preterm delivery. Am J Epidemiol. 2014 Dec 1. 180(11):1109-17. [Medline].

    Centers for Disease Control and Prevention. Genital HSV Infection. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/std/tg2015/herpes.htm. Accessed: November 10, 2016.

    Nasoodi A, Quah S, Dinsmore WW. Neonatal herpes in herpes simplex virus type 2 and HIV-seropositive pregnant patients; the role of preventive measures in the absence of clinical disease of herpes. Int J STD AIDS. 2007 Dec. 18(12):863-6. [Medline].

    Hensleigh PA, Andrews WW, Brown Z, et al. Genital herpes during pregnancy: inability to distinguish primary and recurrent infections clinically. Obstet Gynecol. 1997 Jun. 89(6):891-5. [Medline].

    Morrow RA, Brown ZA. Common use of inaccurate antibody assays to identify infection status with herpes simplex virus type 2. Am J Obstet Gynecol. 2005 Aug. 193(2):361-2. [Medline].

    Baker DA. Consequences of herpes simplex virus in pregnancy and their prevention. Curr Opin Infect Dis. 2007 Feb. 20(1):73-6. [Medline].

    Brown ZA, Wald A, Morrow RA, et al. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA. 2003 Jan 8. 289(2):203-9. [Medline].

    Kimberlin DW, Whitley RJ, Wan W, et al. Oral acyclovir suppression and neurodevelopment after neonatal herpes. N Engl J Med. 2011 Oct 6. 365(14):1284-92. [Medline].

    Boggess KA, Watts DH, Hobson AC, et al. Herpes simplex virus type 2 detection by culture and polymerase chain reaction and relationship to genital symptoms and cervical antibody status during the third trimester of pregnancy. Am J Obstet Gynecol. 1997 Feb. 176(2):443-51. [Medline].

    Cone RW, Hobson AC, Brown Z, et al. Frequent detection of genital herpes simplex virus DNA by polymerase chain reaction among pregnant women. JAMA. 1994 Sep 14. 272(10):792-6. [Medline].

    Wald A, Huang ML, Carrell D, et al. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J Infect Dis. 2003 Nov 1. 188(9):1345-51. [Medline].

    Mertz GJ, Critchlow CW, Benedetti J, et al. Double-blind placebo-controlled trial of oral acyclovir in first- episode genital herpes simplex virus infection. JAMA. 1984 Sep 7. 252(9):1147-51. [Medline].

    Pasternak B, Hviid A. Use of acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk of birth defects. JAMA. 2010 Aug 25. 304(8):859-66. [Medline].

    Gibbs RS, Amstey MS, Sweet RL, et al. Management of genital herpes infection in pregnancy. Obstet Gynecol. 1988 May. 71(5):779-80. [Medline].

    Scott LL, Sanchez PJ, Jackson GL, et al. Acyclovir suppression to prevent cesarean delivery after first-episode genital herpes. Obstet Gynecol. 1996 Jan. 87(1):69-73. [Medline].

    Brocklehurst P, Kinghorn G, Carney O, et al. A randomised placebo controlled trial of suppressive acyclovir in late pregnancy in women with recurrent genital herpes infection. Br J Obstet Gynaecol. 1998 Mar. 105(3):275-80. [Medline].

    Sheffield JS, Hollier LM, Hill JB. Acyclovir prophylaxis to prevent herpes simplex virus recurrence at delivery: a systematic review. Obstet Gynecol. 2003 Dec. 102(6):1396-403. [Medline].

    Rouse DJ, Stringer JS. An appraisal of screening for maternal type-specific herpes simplex virus antibodies to prevent neonatal herpes. Am J Obstet Gynecol. 2000 Aug. 183(2):400-6. [Medline].

    Thung SF, Grobman WA. The cost-effectiveness of routine antenatal screening for maternal herpes simplex virus-1 and -2 antibodies. Am J Obstet Gynecol. 2005 Feb. 192(2):483-8. [Medline].

    Baker D, Brown Z, Hollier LM, et al. Cost-effectiveness of herpes simplex virus type 2 serologic testing and antiviral therapy in pregnancy. Am J Obstet Gynecol. 2004 Dec. 191(6):2074-84. [Medline].

    Kimberlin DW, Baley J, for the Committee on Infectious Diseases and the Committee on Fetus and Newborn. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013 Feb. 131(2):383-6. [Medline].

    Centers for Disease Control and Prevention. QuickStats: Percentage of Adults Aged 20–29 Years with Genital Herpes* Infection, by Race/Ethnicity† — National Health and Nutrition Examination Survey, United States, 1988–1994, 1999–2002, and 2003–2006. CDC. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5807a6.htm?s_cid=mm5807a6_e. Accessed: November 11, 2016.

    Randolph AG, Hartshorn RM, Washington AE. Acyclovir prophylaxis in late pregnancy to prevent neonatal herpes: a cost-effectiveness analysis. Obstet Gynecol. 1996 Oct. 88(4 Pt 1):603-10. [Medline].

    Disease Type

    Incidence, %

    Mortality, %

    Long-term Morbidity, %*

    Localized disease of

    skin, eye, mouth

    45

    0

    5

    CNS

    35

    15

    65

    Disseminated

    20

    60-80

    40

    *Morbidity includes mental retardation, chorioretinitis, seizures, and other CNS effects.

    Indication

    Acyclovir

    Valacyclovir

    Famciclovir

    First episode

    400 mg tid OR 200 mg 5 times/d (for 7-10 d)

    1000 mg bid (for 7-10 d)

    250 mg tid (for 7-10 d)

    Recurrent

    400 mg tid (for 3-5 d) OR 800 mg PO tid (for 2 d)

    500 mg bid (for 3 d)

    1000 mg bid (for 1 d)

    Daily suppression

    400 mg bid

    500 mg qd

    or

    1000 mg qd

    (if >9 recurrences/y)

    250 mg bid

    Outcome

    Acyclovir, %

    Placebo, %

    OR (95% CI)

    Recurrent HSV infection at delivery

    3.5

    15.5

    .25 (.15-.40)

    Cesarean deliveries for HSV

    4.0

    14.7

    .30 (.13-.67)

    Total cesarean deliveries

    16.7

    25.9

    .61 (.43-.86)

    Asymptomatic HSV shedding at delivery

    0

    3.1

    .09 (.02-.39)

    Marie K Grove, MD Resident Physician, Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine

    Marie K Grove, MD is a member of the following medical societies: Alpha Omega Alpha, American Congress of Obstetricians and Gynecologists, American Medical Association, Medical Society of Virginia

    Disclosure: Nothing to disclose.

    Nan G O’Connell, MD Assistant Professor, Department of Obstetrics and Gynecology, VCU Medical Center, Virginia Commonwealth University School of Medicine; Medical Director, Obstetrics and Gynecology Services, VCU Medical Center at Stony Point

    Nan G O’Connell, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of Professors of Gynecology and Obstetrics

    Disclosure: Nothing to disclose.

    Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

    Disclosure: Received salary from Medscape for employment. for: Medscape.

    Richard S Legro, MD Professor, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Pennsylvania State University College of Medicine; Consulting Staff, Milton S Hershey Medical Center

    Richard S Legro, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Society of Reproductive Surgeons, American Society for Reproductive Medicine, Endocrine Society, Phi Beta Kappa

    Disclosure: Received honoraria from Korea National Institute of Health and National Institute of Health (Bethesda, MD) for speaking and teaching; Received honoraria from Greater Toronto Area Reproductive Medicine Society (Toronto, ON, CA) for speaking and teaching; Received honoraria from American College of Obstetrics and Gynecologists (Washington, DC) for speaking and teaching; Received honoraria from National Institute of Child Health and Human Development Pediatric and Adolescent Gynecology Research Thi.

    Ronald M Ramus, MD Professor of Obstetrics and Gynecology, Director, Division of Maternal-Fetal Medicine, Virginia Commonwealth University School of Medicine

    Ronald M Ramus, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Medical Society of Virginia, Society for Maternal-Fetal Medicine

    Disclosure: Nothing to disclose.

    Serdar H Ural, MD Associate Professor of Obstetrics and Gynecology and Radiology, Director, Division of Maternal-Fetal Medicine, Medical Director, Labor and Delivery Suite, Pennsylvania State University College of Medicine

    Serdar H Ural, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Medical Association, Association of Professors of Gynecology and Obstetrics, AAGL, Society for Maternal-Fetal Medicine

    Disclosure: Received honoraria from GSK for speaking and teaching; Received honoraria from J&J for speaking and teaching.

    Genital Herpes in Pregnancy

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    Cervicitis Organism-Specific Therapy 

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    Cervicitis Organism-Specific Therapy 

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    Organism-specific therapeutic regimens for cervicitis are provided below, including those for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium and Trichomonas vaginalis. [1, 2, 3, 4, 5, 6]

    Recommendations are as follows:

    Ceftriaxone 250 mg IM in a single dose plus

    Azithromycin 1 g PO in a single dose

    If ceftriaxone is not available:

    Cefixime 400 mg PO in a single dose plus

    Azithromycin 1 g PO in a single dose

    If patient has severe cephalosporin allergy:

    Azithromycin 2 g PO in a single dose plus

    Gemifloxacin 320 mg PO in a single dose or

    Gentamicin 240 mg IM in a single dose

    Test-of-cure in 1 week

    Treatment failure should be considered in persons whose symptoms do not resolve within 3–5 days after appropriate treatment and persons with a positive test-of-cure, when no sexual contact is reported during the post-treatment follow-up period. Before retreatment, relevant clinical specimens should be obtained for culture and antimicrobial susceptibility testing if N. gonorrhoeae is isolated

    Recommendations are as follows:

    Azithromycin 1 g PO in a single dose or

    Doxycycline 100 mg PO BID for 7 days

    Alternative regimens:

    Erythromycin base 500 mg PO QID for 7 days or

    Erythromycin ethylsuccinate 800 mg PO QID for 7 days or

    Ofloxacin 300 mg PO BID for 7 days or

    Levofloxacin 500 mg PO once daily for 7 days

    Recommendations are as follows:

    Azithromycin 1 g PO in a single dose or

    Moxifloxacin 400 mg PO daily for 7 days

    Recommendations are as follows:

    Metronidazole 2 g orally in a single dose or

    Tinidazole 2 g orally in a single dose

    Alternative regimen

    Metronidazole 500 mg orally twice a day for 7 days*

    * Patients should be advised to avoid consuming alcohol during treatment with metronidazole or tinidazole. Abstinence from alcohol use should continue for 24 hours after completion of metronidazole or 72 hours after completion of tinidazole.

    Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR: Recommendations and Reports. June 5, 2015. 64(3):[Full Text].

    Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR 2006. 55 (No. RR-11):

    Centers for Disease Control and Prevention. Update to CDC’s sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for the treatment of gonococcal infections. MMWR 2007 Apr 13. 56(14):332-336.

    Ollendorf AT. Cervicitis. Medscape Drugs & Diseases from WebMD. Available at http://emedicine.medscape.com/article/253402-overview. Updated: February 9, 2017; Accessed: February 13, 2017.

    Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR 2010. 59 (No. RR-12):

    CDC. Update to CDC’s Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012 Aug 10. 61(31):590-4. [Medline].

    Thomas E Herchline, MD Professor of Medicine, Wright State University, Boonshoft School of Medicine; Medical Consultant, Public Health, Dayton and Montgomery County (Ohio) Tuberculosis Clinic

    Thomas E Herchline, MD is a member of the following medical societies: Alpha Omega Alpha, Infectious Diseases Society of America, Infectious Diseases Society of Ohio

    Disclosure: Nothing to disclose.

    Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

    Disclosure: Received salary from Medscape for employment. for: Medscape.

    Nicole W Karjane, MD Associate Professor, Department of Obstetrics and Gynecology, Virginia Commonwealth University Medical Center

    Nicole W Karjane, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of Professors of Gynecology and Obstetrics, North American Society for Pediatric and Adolescent Gynecology

    Disclosure: Received income in an amount equal to or greater than $250 from: Merck<br/>Served as Nexplanon trainer for: Merck.

    Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

    Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

    Disclosure: Nothing to disclose.

    Cervicitis Organism-Specific Therapy 

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    Cervicitis Empiric Therapy 

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    Cervicitis Empiric Therapy 

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    Empiric therapeutic regimens for cervicitis are outlined below, including presumptive treatment, treatment for recurrent and persistent cervicitis, and treatment for pregnant patients with nongonococcal cervicitis. [1, 2, 3, 4, 5, 6, 7, 8]

    See the list below:

    Azithromycin 1 g PO in a single dose or

    Doxycycline 100 mg PO BID for 7d (contraindicated during pregnancy)

    Consider the addition of concurrent treatment for gonococcal infection if prevalence of gonorrhea is high in the patient population under assessment:

    Ceftriaxone 250 mg IM in a single dose (strongly preferred) or

    Ceftizoxime 500 mg IM in a single dose or

    Cefotaxime 500 mg IM in a single dose or

    Cefoxitin 2 g IM plus probenecid 1 g PO in a single dose

    Fluoroquinolones should not be used as empiric therapy because of increasing resistance of Neisseria gonorrhoeae isolates [2, 4]

    Oral cephalosporins are no longer recommended for gonococcal infections [6]

    See the list below:

    Reevaluate for possible reexposure to a sexually transmitted disease, and reassess patient for potential bacterial vaginosis

    Important to assess, manage, and treat partners

    Management of persistent cervicitis of unknown etiology is undefined

    See the list below:

    Erythromycin base 500 mg PO QID for 7d or

    Erythromycin ethylsuccinate 800 mg PO QID for 7d or

    Amoxicillin 500 mg PO TID for 7d

    Doxycycline and fluoroquinolones are contraindicated during pregnancy

    Workowski KA, Bolan GA, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5. 64 (RR-03):53-55. [Medline].

    Centers for Disease Control and Prevention. Centers for Disease Control and Prevention. Update to CDC’s sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for the treatment of gonococcal infections. MMWR 2007 Apr 13. 56(14):332-336.

    Ollendorf AT. Cervicitis. Medscape Reference. [Full Text].

    [Guideline] Centers for Disease Control and Prevention (CDC). Update to CDC’s sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep. 2007 Apr 13. 56(14):332-6. [Medline]. [Full Text].

    Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec 17. 59:1-110. [Medline].

    Update to CDC’s Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012 Aug 10. 61(31):590-4. [Medline].

    Massad LS, Einstein MH, Huh WK, et al, for the 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol. 2013 Apr. 121(4):829-46. [Medline].

    American College of Obstetricians and Gynecologists. Practice Bulletin No. 140: management of abnormal cervical cancer screening test results and cervical cancer precursors. Obstet Gynecol. 2013 Dec. 122(6):1338-67. [Medline].

    Thomas E Herchline, MD Professor of Medicine, Wright State University, Boonshoft School of Medicine; Medical Consultant, Public Health, Dayton and Montgomery County (Ohio) Tuberculosis Clinic

    Thomas E Herchline, MD is a member of the following medical societies: Alpha Omega Alpha, Infectious Diseases Society of America, Infectious Diseases Society of Ohio

    Disclosure: Nothing to disclose.

    Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

    Disclosure: Received salary from Medscape for employment. for: Medscape.

    Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

    Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

    Disclosure: Nothing to disclose.

    Cervicitis Empiric Therapy 

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    Thromboembolism Prophylaxis in Gynecologic Surgery

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    Thromboembolism Prophylaxis in Gynecologic Surgery

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    Venous thromboembolism (VTE) is a leading cause of disability and death in postoperative hospitalized gynecologic patients. Pulmonary embolism (PE) remains the most common preventable cause of hospital death and is responsible for approximately 150,000-200,000 deaths per year in the United States. [1] In general, VTE occurs in the form of a deep venous thrombosis (DVT) or PE.

    Other chronic conditions may result from acute conditions such as postthrombotic syndrome, venous insufficiency, and pulmonary hypertension. This article provides practical background and evidence-based recommendations for clinical practice.

    Approximately two million patients in the United States are diagnosed with deep venous thrombosis (DVT) each year. Of these patients, nearly 60,000 die and one third develop pulmonary embolism (PE). [2] Overall, PE has a case-fatality rate of approximately 12%, with lower rates in younger patients and higher rates in patients with cancer. [3, 4] First-time–diagnosed venous thromboembolism (VTE) has an incidence of 1-2 per 1,000 individuals per year. [4, 5] Patients at bedrest are 9 times more likely to develop VTE than the general population. [6] The odds ratio of increased VTE risk in hospitalized and surgical patients is 11.1 and 5.9, respectively. [6]

    Without thromboprophylaxis, patients who undergo major gynecologic surgery have a prevalence of DVT in the range of 15%-40%. [7] Asymptomatic DVT is also highly associated with the development of significant PE. [8] Because most PE-associated fatalities occur within 30 minutes of onset, leaving a very narrow window for medical intervention, clinicians must identify those at high risk for VTE and administer effective thromboprophylaxis to minimize the occurrence of this potentially preventable cause of death.

    Traditionally, gynecologic surgical patients have been classified preoperatively into 1 of 4 risk categories; low, medium, high, and highest risk. [9] This classification is used to determine the most appropriate thromboprophylaxis regimen for specific patients. Based on the procedure type and duration, age, and presence of additional risk factors, a risk of venous thromboembolism (VTE) is determined.

    Table 1. Traditional Risk Classification for Gynecologic Surgery* (Open Table in a new window)

    Risk level

    Definition

    Low

    Surgery lasting < 30 minutes in patients < 40 years with no additional risk factors

    Moderate

    Surgery lasting < 30 minutes in patients with additional risk factors; surgery lasting < 30 minutes in patients aged 40-60 years with no additional risk factors; major surgery in patients < 40 years with no additional risk factors

    High

    Surgery lasting < 30 minutes in patients >60 years or with additional risk factors; major surgery in patients >40 years or with additional risk factors

    Highest

    Major surgery in patients >60 years plus prior VTE, cancer, or molecular hypercoagulable state

    *Modified from ACOG Practice Bulletin No. 84: Prevention of deep vein thrombosis and pulmonary embolism. Obstet Gynecol. Aug 2007;110(2 Pt 1):429-40. [PMID: 17666620]. [9]

    In May 2012, the American College of Chest Physicians (ACCP), [10, 11] in their published evidence-based clinical practice guidelines, described several methods for stratifying the risk of VTE in nonorthopedic surgical patients. This classification is broken down into the risk percentage among patients who would have no VTE prophylaxis: very low (< 0.5%), low (approximately 1.5%), moderate (approximately 3%), and high risk (approximately 6%).

    In addition, two methods are described to develop an overall risk score, the Rogers Score and the Caprini Score (see Tables 2 and 3). [1, 11] These scores can then be used to place patients in an ACCP risk class (see Table 4).

    Table 2. Rogers Score for VTE Risk Assessment* (Open Table in a new window)

    Risk Factor

    Risk Score Points

    Operation type

     

    Respiratory and hemic

    9

    Cardiovascular

    7

    Aneurysm

    4

    Mouth, palate

    4

    Stomach, intestines

    4

    Integument

    3

    Hernia

    2

    ASA physical status classification

     

    3, 4, or 5

    2

    2

    1

    Female sex

    1

    RVU

     

    >17

    3

    10-17

    2

    2 points for each condition

    2

    Disseminated cancer

     

    Chemotherapy for malignancy within 30 days of surgery

    2

    Preoperative serum sodium level >145 mmol/L

    2

    Transfusion >4 units of packed RBCs in 72 hours before surgery

    2

    Ventilator-dependent

    2

    1 point for each condition

     

    Wound class (clean/contaminated)

    1

    Preoperative hematocrit level ≤38%

    1

    Preoperative bilirubin level >1 mg/dL

    1

    Dyspnea

    1

    Albumin level < 3.5 mg/dL

    1

    Emergency

    1

    0 points for each condition

     

    ASA physical status class 1

    0

    Work RVU < 10

    0

    Male sex

    0

    *Modified from Rogers SO Jr, Kilaru RK, Hosokawa P, Henderson WG, Zinner MJ, Khuri SF. Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: results from the patient safety in surgery study. J Am Coll Surg. Jun 2007;204(6):1211-21. [PMID: 17544079].

    Abbreviations: ASA, American Society of Anesthesiologists; WVU, Work Relative Value Unit

    Table 3: Caprini Risk Assessment Model* (Open Table in a new window)

    1 Point

    2 Points

    3 Points

    5 Points

    Age 41-60 years

    Age 61-74 years

    Age ≥75 years

    Stroke (1 month)

    Minor surgery

    Arthroscopic surgery

    History of VTE

    Elective arthroplasty

    BMI >25 kg/m2

    Major open surgery (>45 minutes)

    Family history of VTE

    Hip, pelvis, or leg fracture

    Swollen legs

    Laparoscopic surgery (>45 minutes)

    Factor V Leiden

    Acute spinal cord injury (< 1 month)

    Varicose veins

    Malignancy

    Prothrombin 20210A

     

    Pregnancy or postpartum

    Confined to bed (>72 hours)

    Lupus anticoagulant

     

    History of unexplained or recurrent spontaneous abortion

    Immobilizing plaster cast

    Anticardiolipin antibodies

     

    Oral contraceptives or hormone replacement use

    Central venous access

    Elevated serum homocysteine

     

    Sepsis (< 1 month)

     

    Heparin-induced thrombocytopenia

     

    Serious lung disease, including pneumonia (< 1 month)

     

    Other congenital or acquired thrombophilia

     

    Abnormal pulmonary function

     

     

     

    Acute myocardial infarction

     

     

     

    Congestive heart failure

     

     

     

    History of inflammatory bowel disease

     

     

     

    Medical patient at bedrest

     

     

     

    *Modified from Bahl V, Hu HM, Henke PK, Wakefield TW, Campbell DA Jr, Caprini JA. A validation study of a retrospective venous thromboembolism risk scoring method. Ann Surg. Feb 2010;251(2):344-50. [PMID: 19779324].

    Table 4. VTE Risk Scores and Categories for General Surgical Patients [12] * (Open Table in a new window)

    VTE Risk Category

    Rogers Score

    Caprini Score

    Baseline Risk of VTE Without Prophylaxis, %

    Very low

    < 7

    0

    < 0.5

    Low

    7-10

    1-2

    1.5

    Moderate

    >10

    3-4

    3

    High

    N/A

    ≥5

    6

    *Modified from Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. Feb 2012;141(2 Suppl):e195S-226S. [PMID: 22315261].

    Multiple inherited risk factors influence coagulability but do not usually result in venous thromboembolism (VTE) in the absence of a contributing medical event, such as pregnancy, surgery, or exogenous hormone ingestion. [13] The most prevalent genetic mutations found in patients with VTE are factor V Leiden mutation and prothrombin gene mutation G20210A. Patients with either of these conditions during pregnancy or major surgery are at an increased risk of perioperative VTE.

    Factor V Leiden mutation is the most common inherited thrombophilia, affecting 5% of whites. [14, 15] One in 5 patients diagnosed with VTE and 50% of those with thrombophilia are found to have this mutation. Whites are almost the exclusive carrier of the prothrombin G20210A mutation, and it is found in only 6% of patients with VTE. Factor V Leiden causes activated protein C resistance, while the prothrombin G20210A mutation causes an abnormally elevated prothrombin level, resulting in a 3-fold higher VTE rate. [16] Either mutation can be diagnosed via DNA analysis, while factor V Leiden may also be found via an abnormal activated protein C resistance assay result.

    Antithrombin-III (AT-III), protein C, and protein S are uncommon causes of VTE but should be considered in patients who test negative for factor V Leiden and prothrombin mutation but report multiple thrombotic events in their family history. Since AT-III, protein C, and protein S inhibit coagulation, heterozygote carriers have a 10-fold increased risk of VTE, and homozygotes have severe thrombotic events soon after birth. [17] Any of these 3 disorders can be diagnosed via serum assays, but results are unreliable during an acute thrombotic event and during anticoagulation therapy.

    Genetic or acquired elevated homocysteine levels have been linked to VTE. Homozygous carriers of the methylenetetrahydrofolate reductase variant 677T have slightly elevated homocysteine levels and a slightly increase risk of thrombosis and arteriosclerosis. [18] Dietary deficiencies of folate, vitamin B6, and vitamin B12 result in acquired hyperhomocysteinemia. [13] It is unknown whether homocysteine itself is a risk factor or simply a marker, and it is unclear whether lowering homocysteine levels would decrease VTE risk. [19]

    Antiphospholipid syndrome is an acquired thrombophilia associated with both arterial and venous thrombosis. Fifty percent of patients with systemic lupus erythematosus (SLE) test positive for antiphospholipid antibodies. Testing for lupus includes serum assays for both lupus anticoagulant and anticardiolipin antibodies. Lupus anticoagulant is the more significant test since it reveals b2-glycoprotein-1 antibodies, which correlate highly with thromboembolic complications and morbidity during pregnancy. [20] Clinicians should consider testing in patients with VTE, SLE, recurrent pregnancy loss, early and/or severe preeclampsia, and/or thrombocytopenia. [21]

    Graded compression stockings or elastic stockings, intermittent pneumatic compression (IPC) devices, low-dose unfractionated heparin (LDUH), low molecular weight heparin (LMWH), fondaparinux, aspirin, inferior vena cava (IVC) filters, and surveillance with venous compression ultrasonography (VCU) have all been used to prevent venous thromboembolism (VTE). The incidence of VTE in gynecologic oncology patients has been reported to be 1%-6.5%. [22, 23, 24]

    In high-risk patients, a combined regimen of medical and mechanical prophylaxis may improve clinical efficacy, although there is limited evidence in gynecologic patients. Extrapolation from the general surgery literature suggests a significant benefit from a combined regimen. [25, 26]

    Some investigators question the benefits of routine use of VTE prophylaxis in patients who undergo minimally invasive surgery for gynecologic malignancies. [27] In a study that included 419 women who underwent such surgery (at least a simple/radical total laparoscopic hysterectomy or pelvic lymph node dissection), the rate of VTE was 0.57% within 30 postoperative days in the 352 patients (84%) who did not receive any VTE prophylaxis. Of the 62 women who received VTE prophylaxis, no VTEs occurred in the same postoperative time period. [27]

    The American College of Obstetricians and Gynecologists (ACOG) recommends that, until more evidence is accumulated, patients undergoing laparoscopic surgery should be stratified by risk category and should receive prophylaxis similar to that provided to patients undergoing laparotomy. [9] Among members of the Society of Gynecologic Oncology, the preferred method of VTE prevention during laparoscopic surgery for high-risk patients was combination prophylaxis. [28]

    In general, optimal prophylaxis for gynecologic surgery considers the risk of VTE and bleeding complications, as well as the wishes of the individual patient. [29]

    ACOG grades the quality of evidence in the literature according to the method outlined by the U.S. Preventive Services Task Force, as follows:

    I: Evidence obtained from at least one properly designed randomized controlled trial

    II-1: Evidence obtained from well-designed controlled trials without randomization

    II-2: Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group

    II-3: Evidence obtained from multiple time series with or without the intervention; dramatic results in uncontrolled experiments could also be regarded as this type of evidence

    III: Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

    Then, based on the highest level of evidence found in the data, recommendations are provided and graded by ACOG according to the following categories:

    level A: Recommendations are based on good and consistent scientific evidence

    level B: Recommendations are based on limited or inconsistent scientific evidence

    level C: Recommendations are based primarily on consensus and expert opinion

    For the 2012 ACCP guidelines for the prevention of VTE in nonorthopedic surgical patients, the group used the grades of the Recommendations, Assessment, Development, and Evaluation system to assess the quality of evidence and describe the strength of recommendations (see Table 5). [30, 31, 32]

    Table 5. Strength of the Recommendations Grading System [12] * (Open Table in a new window)

    Grade of Recommendation

    Benefit vs Risk and Burdens

    Methodologic Strength of Supporting Evidence

    Implications

    Strong recommendation, high-quality evidence (1A)

    Benefits clearly outweigh risk and burdens or vice versa.

    Consistent evidence from randomized controlled trials without important limitations or exceptionally strong evidence from observational studies.

    Recommendation can apply to most patients in most circumstances. Further research is very unlikely to change our confidence in the estimate of effect.

     

    Strong recommendation, moderate-quality evidence (1B)

    Benefits clearly outweigh risk and burdens or vice versa.

    Evidence from randomized controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise) or very strong evidence from observational studies.

    Recommendation can apply to most patients in most circumstances. Higher-quality research may well have an important impact on our confidence in the estimate of effect and may change the estimate.

     

    Strong recommendation, low- or very-low-quality evidence (1C)

    Benefits clearly outweigh risk and burdens or vice versa.

    Evidence for at least one critical outcome from observational studies, case series, or randomized controlled trials, with serious flaws or indirect evidence.

    Recommendation can apply to most patients in many circumstances. Higher-quality research is likely to have an important impact on our confidence in the estimate of effect and may well change the estimate.

     

    Weak recommendation, high-quality evidence (2A)

    Benefits closely balanced with risks and burden.

    Consistent evidence from randomized controlled trials without important limitations or exceptionally strong evidence from observational studies.

    The best action may differ depending on circumstances or patient or societal values. Further research is very unlikely to change our confidence in the estimate of effect.

     

    Weak recommendation, moderate-quality evidence (2B)

    Benefits closely balanced with risks and burden.

    Evidence from randomized controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise) or very strong evidence from observational studies.

    Best action may differ depending on circumstances or patient or societal values. Higher-quality research may well have an important impact on our confidence in the estimate of effect and may change the estimate.

     

    Weak recommendation, low- or very-low-quality evidence (2C)

    Uncertainty in the estimates of benefits, risks, and burden; benefits, risk, and burden may be closely balanced.

    Evidence for at least one critical outcome from observational studies, case series, or randomized controlled trials, with serious flaws or indirect evidence.

    Other alternatives may be equally reasonable. Higher-quality research is likely to have an important impact on our confidence in the estimate of effect and may well change the estimate.

    *Modified from Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. Feb 2012;141(2 Suppl):e195S-226S. [PMID: 22315261].

    A wide variety of venous thromboembolism (VTE) prophylactic measures have been shown to reduce deep venous thrombosis (DVT) formation. However, the real desire for VTE prophylaxis is to prevent fatal PE in gynecologic surgery patients. Since pulmonary embolism (PE) is relatively rare, most studies in the literature have not been sufficiently powered to show a reduction in mortality as a result of VTE prophylaxis. Without hard data, it still seems reasonable to assume that the prevention of VTE will reduce the incidence of PE in gynecologic surgery patients.

    The currently available methods include both mechanical and pharmacologic interventions. Mechanical methods promote circulation and reduce venous stasis. Pharmacologic methods prevent clot formation by effects at different points on the clotting cascade. The individual methods and the evidence for using each are discussed below.

    Graduated compression stockings have the advantage of being simple and relatively low cost. Postoperative DVT usually develops within 24 hours after surgery. Graduated compression stockings prevent pooling of blood in the calf veins.

    A recent Cochrane review reported a 65% reduction in DVT formation with the use graduated compression stockings when compared to no prophylaxis. [33]

    The drawbacks of graduated compression stockings include improper fitting, in which the stockings may act as a tourniquet, causing an increase in venous stasis. Because of this, knee-length stockings are recommended. [9] In addition, the use of graduated compression stockings has been associated with an increased risk of skin complications, including ulcers, blisters, and necrosis. [12]

    IPC devices diminish blood stasis by repetitively compressing the calf with a removable pneumatic wrap.

    Several meta-analyses have assessed the effectiveness of IPC versus no prophylaxis in perioperative patients. These analyses report that IPC reduced the risk of both asymptomatic and distal DVT by 60%. Proximal DVT risk was diminished by 50%. [34] Many studies to date have too few a number of patients to properly assess IPC effectiveness in PE prevention or mortality.

    After major gynecologic surgery, IPC devices reduce DVT formation as effectively as LMWH and low-dose heparin. [23, 24, 35] Adherence to ideal IPC use is often suboptimal, but, when used properly, they may increase systemic fibrinolysis, [36, 37] although this was not confirmed in data from a large series analysis. [38, 39] IPC should be worn continuously on the calf until a perioperative patient is fully ambulatory and ready for hospital discharge. [7] One study of intraoperative use of IPC in gynecologic oncology surgical patients showed a 3-fold reduction in VTE. [40]

    One of the most extensively studied thromboprophylaxis methods is low doses (10,000-15,000 units/d) of subcutaneously administered unfractionated heparin. LDUH is not only proven effective in VTE prevention, but it also a low cost to administer.

    Many studies show that effective DVT prevention is best achieved when LDUH is administered 2 hours prior to surgery and continued every 8-12 hours postoperatively. [7] Benign gynecologic surgery patients benefit from LDUH administered preoperatively and again at 12-hour intervals postoperatively. [7] Gynecologic oncology surgical patients require a different approach of 5,000 units of heparin 2 hours preoperatively, repeated every 8 hours postoperatively in order to effectively prevent VTE. [41]

    A published meta-analysis reported that LDUH was associated with an 18% reduction in the odds of death from any cause, a 47% reduction in the odds of fatal PE, and a 41% reduction in the odds of nonfatal PE, along with a 57% increase in the odds of nonfatal major bleeding. [12] Other studies have not shown an increase of intraoperative blood loss with LDUH use but have noted an increase in postoperative wound hematoma formation. [41, 42] When administering LDUH for more than 4 days, patients should be monitored for heparin-induced thrombocytopenia, which is reported in approximately 6% of patients. [41]

    Since original studies dating back to 1985, [43] LMWH has been proven an effective thromboprophylaxis. When compared to LDUH, LMWH has once-daily dosing, a greater bioavailability and longer half-life, and, thus, a more predictable form of pharmacokinetics. [44] Studies show that LMWH and LDUH have similar efficacy rates in VTE prevention. [44] Similar risk reduction to intermittent IPC use was also seen when LMWH was administered preoperative and daily postoperatively. [24] In patients undergoing gynecologic oncology surgery, recent prospective trials showed a 2% incidence of VTE when LMWH prophylaxis was administered preoperatively and postoperatively. [45]

    Original reports proposed that LMWH yielded a decreased incidence of perioperative bleeding and wound hematoma formation owing to its lower antithrombin activity and increased levels of antifactor Xa. Although more expensive than LDUH, LMWH is rarely associated with heparin-induced thrombocytopenia; thus, screening is not recommend with extended use. [9] However, a recent meta-analysis has shown that LMWH may actually double the risk of major perioperative bleeding and wound hematoma formation. [12] These findings were confirmed in another recent study by the British National Collaborating Centre for Acute Care, which studied GI, gynecologic, urological, and thoracic surgery. [12]

    Major risk factors for VTE usually dictate LMWH therapy duration. Noted risk factors include prior VTE, cancer diagnosis, age older than 60 years, extended surgical time, and bedrest. [45] Forty percent of patients with cancer who develop VTE do so more than 3 weeks postoperatively. [45] Four weeks of LMWH administration postoperatively, versus only 1 week of therapy, reduced VTE risk by 60%, with no increase in bleeding or thrombocytopenia. [46]

    The combined use of compression stockings and either LDUH or LMWH has been analyzed in the general surgery literature. A Cochrane review of 19 studies revealed that LDUH in conjunction with graduated compression stockings was 4 times more effective in VTE prevention than LDUH alone. [46] A study of neurosurgical patients also showed a significant VTE reduction with combined LMWH and graduated compression stockings compared with compression stockings alone. [46]

    In a cost-benefit analysis of prophylaxis for postoperative VTE in patients with gynecologic malignancies, Japanese investigators suggested a strategy that combined unfractionated heparin three times daily combined with graduated compression stockings and intermittent pneumatic compression; close monitoring of oxygen saturation; and perioperative bilateral circumference measurements of the thighs and calves. [47]

    There are no randomized trial data in the gynecology literature to prove the benefits of combining mechanical and pharmacologic therapies in VTE prophylaxis. However, if gynecologic patients fall into high-risk VTE categories (ie, >40 years, cancer diagnosis, prior VTE), a dual prophylactic approach may be warranted to reduce both hypercoagulability and venous stasis. [40] Combined therapy is recommended by the Ninth American College of Chest Physicians Consensus Conference for patients at high risk for VTE. [12] A decision analysis in high-risk gynecologic oncology patients found that combined IPC devices and LMWH use is cost-effective. [25]

    The ACOG recommends prophylaxis for women undergoing surgery who have deficiencies of protein C, protein S, or AT-III and for heterozygous carriers of factor V Leiden or prothrombin gene mutation G20210A without a personal history of thrombosis. [9] These patients, by definition, would fall into the “highest risk” category for perioperative VTE.

    Based on current ACOG and ACCP evidence-based guidelines, below are recommendations for venous thromboembolism (VTE) prophylaxis in gynecologic surgical patients.

    Early ambulation (grade 1B)

    IPC (grade 2C) placed before the initiation of surgery and continued until the patient is fully ambulatory

    Patients at moderate risk for venous thromboembolism (approximately 3%) (ACOG high risk and level A evidence) but not at high risk for bleeding complications LMWH (grade 2B) or dalteparin 2,500 antifactor-Xa units or enoxaparin 40 mg administered subcutaneously 12 hours before surgery and once a day postoperatively until discharge

    LDUH (grade 2B) or unfractionated heparin (5,000 units) administered subcutaneously 2 hours before surgery and every 12 hours after surgery until discharge

    IPC (grade 2C) placed before the initiation of surgery and continued until the patient is fully ambulatory

    IPC (grade 2C) placed before the initiation of surgery and continued until the patient is fully ambulatory

    LMWH (grade 2B) or dalteparin 2,500 antifactor-Xa units or enoxaparin 40 mg administered subcutaneously 12 hours before surgery and once a day postoperatively until dischargeLDUH (grade 2B) or unfractionated heparin (5,000 units) administered subcutaneously 2 hours before surgery and every 12 hours after surgery until discharge

    PLUS

    IPC (grade 2C) placed before the initiation of surgery and continued until the patient is fully ambulatory

    LMWH extended for a duration of 4 weeks (grade 1B)

    IPC (grade 2C) placed before the initiation of surgery and continued until the patient is fully ambulatory

    Martino MA, Borges E, Williamson E, Siegfried S, Cantor AB, Lancaster J, et al. Pulmonary embolism after major abdominal surgery in gynecologic oncology. Obstet Gynecol. 2006 Mar. 107(3):666-71. [Medline].

    Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism. A statement for healthcare professionals. Council on Thrombosis (in consultation with the Council on Cardiovascular Radiology), American Heart Association. Circulation 1996;93:2212–45.

    Cushman M, Tsai AW, White RH, Heckbert SR, Rosamond WD, Enright P, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med 2004;117:19–25.

    Anderson FA Jr, Wheeler HB, Goldberg RJ, Hosmer DW, Patwardhan NA, Jovanovic B, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991;151: 933–8.

    Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d’Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost 2000;83:657–60.

    van der Meer FJ, Koster T, Vandenbroucke JP, Briet E, Rosendaal FR. The Leiden Thrombophilia Study (LETS). Thromb Haemost 1997;78:631–5.

    Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(suppl): 338S–400S.

    Ibrahim EH, Iregui M, Prentice D, Sherman G, Kollef MH, Shannon W. Deep vein thrombosis during prolonged mechanical ventilation despite prophylaxis. Crit Care Med 2002;30:771–4.

    ACOG Practice Bulletin No. 84: Prevention of deep vein thrombosis and pulmonary embolism. Obstet Gynecol. 2007 Aug. 110(2 Pt 1):429-40. [Medline].

    ACOG Committee Opinion No 610: Chronic Antithrombotic Therapy and Gynecologic Surgery. Obstet Gynecol. 2014 Oct. 124:856-62.

    Rogers SO Jr , Kilaru RK , Hosokawa P , Henderson WG , Zinner MJ , Khuri SF. Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: results from the patient safety in surgery study . J Am Coll Surg . 2007 ; 204 ( 6 ): 1211 – 1221.

    Susan R. Kahn, MD; Wendy Lim, MD; Andrew S. Dunn, MD; Mary Cushman, MD; Francesco Dentali, MD; Elie A. Akl, MD, MPH, PhD; Deborah J. Cook, MD, MSc(Epi); Alex A. Balekian, MD, MSHS; Russell C. Klein, MD; Hoang Le, MD, FCCP; Sam Schulman, MD; M. Hassan Murad, MD, MPH Prevention of VTE in Nonsurgical PatientsPrevention of VTE in Nonsurgical Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHES…

    Oger E, Lacut K, Le Gal G, Couturaud F, Guenet D, Abalain JH, et al. Hyperhomocysteinemia and low B vitamin levels are independently associated with venous thromboembolism: results from the EDITH study: a hospital-based case-control study. EDITH Collaborative Study Group. J Thromb Haemost 2006;4:793–9.

    Middeldorp S, Henkens CM, Koopman MM, van Pampus EC, Hamulyak K, van der Meer J, et al. The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis. Ann Intern Med 1998;128:15–20.

    Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci U S A 1993;90:1004–8.

    Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995;346:1133–4.

    Rosendaal FR. Venous thrombosis: the role of genes, environment, and behavior. Hematology Am Soc Hematol Educ Program 2005;1–12.

    Kluijtmans LA, den Heijer M, Reitsma PH, Heil SG, Blom HJ, Rosendaal FR. Thermolabile methylenetetrahydrofolate reductase and factor V Leiden in the risk of deep-vein thrombosis. Thromb Haemost 1998;79:254–8.

    Lentz SR. Mechanisms of homocysteine-induced athero-thrombosis. J Thromb Haemost 2005;3:1646–54.

    de Groot PG, Derksen RH. The antiphospholipid syndrome: clinical characteristics, laboratory features and pathogenesis. Curr Opin Infect Dis 2005;18:205–10.

    Bertolaccini ML, Khamashta MA, Hughes GR. Diagnosis of antiphospholipid syndrome. Nat Clin Pract Rheumatol 2005;1:40–6.

    Clarke-Pearson DL, Dodge RK, Synan I, McClelland RC, Maxwell GL. Venous thromboembolism prophylaxis: patients at high risk to fail intermittent pneumatic compression. Obstet Gynecol 2003;101:157–63. (level II-2).

    Clarke-Pearson DL, Synan IS, Dodge R, Soper JT, Berchuck A, Coleman RE. A randomized trial of low-dose heparin and intermittent pneumatic calf compression for the prevention of deep venous thrombosis after gynecologic oncology surgery. Am J Obstet Gynecol 1993;168: 1146–53; discussion 1153–4.

    Maxwell GL, Synan I, Dodge R, Carroll B, Clarke-Pearson DL. Pneumatic compression versus low molecular weight heparin in gynecologic oncology surgery: a randomized trial. Obstet Gynecol 2001;98:989–95.

    Agnelli G, Piovella F, Buoncristiani P, Severi P, Pini M, D’Angelo A, et al. Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 1998;339:80–5.

    Wille-Jorgensen P, Rasmussen MS, Andersen BR, Borly L. Heparins and mechanical methods for thromboprophylaxis in colorectal surgery. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD001217. DOI: 10.1002/14651858.CD001217.

    Bouchard-Fortier G, Geerts WH, Covens A, Vicus D, Kupets R, Gien LT. Is venous thromboprophylaxis necessary in patients undergoing minimally invasive surgery for a gynecologic malignancy?. Gynecol Oncol. 2014 Aug. 134(2):228-32. [Medline].

    Worley MJ Jr, Rauh-Hain JA, Sandberg EM, Muto MG. Venous thromboembolism prophylaxis for laparoscopic surgery: a survey of members of the Society of Gynecologic Oncology. Int J Gynecol Cancer. 2013 Jan. 23(1):208-15. [Medline].

    ACOG Committee Opinion No. 619: Gynecologic surgery in the obese woman. Obstet Gynecol. 2015 Jan. 125:274-8.

    Guyatt GH, Oxman AD, Vist GE; et al. GRADE Working Group GRADE: an emerging consensus on rating quality of evidence and strength of recommendations, BMJ 2008 3367650 924-9266.

    Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ; GRADE Working Group What is “quality of evidence” and why is it important to clinicians?, BMJ 2008 3367651 995-9987.

    Guyatt GH, Oxman AD, Kunz R; et al. GRADE Working Group Going from evidence to recommendations, BMJ 2008 3367652 1049-1051.

    Sachdeva A, Dalton M, Amaragiri SV, Lees T; Elastic compression stockings for prevention of deep vein thrombosis, Cochrane Database Syst Rev 20107 CD001484.

    Dentali F, Douketis JD, Gianni M, Lim W, Crowther MA; Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients, Ann Intern Med 2007 1464 278-288.

    Ginzburg E, Cohn SM, Lopez J, Jackowski J, Brown M, Hameed SM. Randomized clinical trial of intermittent pneumatic compression and low molecular weight heparin in trauma. Miami Deep Vein Thrombosis Study Group. Br J Surg 2003;90:1338–44.

    Kohro S, Yamakage M, Sato K, Sato JI, Namiki A. Intermittent pneumatic foot compression can activate blood fibrinolysis without changes in blood coagulability and platelet activation. Acta Anaesthesiol Scand 2005; 49:660–4.

    Tarnay TJ, Rohr PR, Davidson AG, Stevenson MM, Byars EF, Hopkins GR. Pneumatic calf compression, fibrinolysis, and the prevention of deep venous thrombosis. Surgery 1980;88:489–96.

    Killewich LA, Cahan MA, Hanna DJ, Murakami M, Uchida T, Wiley LA, et al. The effect of external pneumatic compression on regional fibrinolysis in a prospective randomized trial. J Vasc Surg 2002;36:953–8.

    Cahan MA, Hanna DJ, Wiley LA, Cox DK, Killewich LA. External pneumatic compression and fibrinolysis in abdominal surgery. J Vasc Surg 2000;32:537–43.

    Clarke-Pearson DL, Synan IS, Hinshaw WM, Coleman RE, Creasman WT. Prevention of postoperative venous thromboembolism by external pneumatic calf compression in patients with gynecologic malignancy. Obstet Gynecol 1984;63:92–8.

    Clarke-Pearson DL, DeLong E, Synan IS, Soper JT, Creasman WT, Coleman RE. A controlled trial of two low-dose heparin regimens for the prevention of postoperative deep vein thrombosis. Obstet Gynecol 1990;75: 684–9.

    Clagett GP, Reisch JS. Prevention of venous thromboembolism in general surgical patients. Results of meta-analysis. Ann Surg 1988;208:227–40.

    Kakkar VV, Murray WJ. Efficacy and safety of low-molecular-weight heparin (CY216) in preventing postoperative venous thrombo-embolism: a co-operative study. Br J Surg 1985;72:786–91.

    Holzheimer RG. Prophylaxis of thrombosis with low-molecular-weight heparin (LMWH). Eur J Med Res 2004;9:150–70.

    Agnelli G, Bolis G, Capussotti L, Scarpa RM, Tonelli F, Bonizzoni E, et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg 2006;243:89–95.

    Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, Le Moigne-Amrani A, et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. ENOXACAN II Investigators. N Engl J Med 2002;346:975–80.

    Morimoto A, Ueda Y, Yokoi T, Tokizawa Y, Yoshino K, Fujita M, et al. Perioperative venous thromboembolism in patients with gynecological malignancies: a lesson from four years of recent clinical experience. Anticancer Res. 2014 Jul. 34(7):3589-95. [Medline].

    Bahl V, Hu HM, Henke PK, Wakefi eld TW, Campbell DA Jr , Caprini JA . A validation study of a retrospective venous thromboembolism risk scoring method . Ann Surg . 2010 ;251 ( 2 ): 344 – 350.

    Wille-Jorgensen P, Rasmussen MS, Andersen BR, Borly L. Heparins and mechanical methods for thromboprophylaxis in colorectal surgery. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD001217. DOI: 10.1002/14651858.CD001217.

    Risk level

    Definition

    Low

    Surgery lasting < 30 minutes in patients < 40 years with no additional risk factors

    Moderate

    Surgery lasting < 30 minutes in patients with additional risk factors; surgery lasting < 30 minutes in patients aged 40-60 years with no additional risk factors; major surgery in patients < 40 years with no additional risk factors

    High

    Surgery lasting < 30 minutes in patients >60 years or with additional risk factors; major surgery in patients >40 years or with additional risk factors

    Highest

    Major surgery in patients >60 years plus prior VTE, cancer, or molecular hypercoagulable state

    *Modified from ACOG Practice Bulletin No. 84: Prevention of deep vein thrombosis and pulmonary embolism. Obstet Gynecol. Aug 2007;110(2 Pt 1):429-40. [PMID: 17666620]. [9]

    Risk Factor

    Risk Score Points

    Operation type

     

    Respiratory and hemic

    9

    Cardiovascular

    7

    Aneurysm

    4

    Mouth, palate

    4

    Stomach, intestines

    4

    Integument

    3

    Hernia

    2

    ASA physical status classification

     

    3, 4, or 5

    2

    2

    1

    Female sex

    1

    RVU

     

    >17

    3

    10-17

    2

    2 points for each condition

    2

    Disseminated cancer

     

    Chemotherapy for malignancy within 30 days of surgery

    2

    Preoperative serum sodium level >145 mmol/L

    2

    Transfusion >4 units of packed RBCs in 72 hours before surgery

    2

    Ventilator-dependent

    2

    1 point for each condition

     

    Wound class (clean/contaminated)

    1

    Preoperative hematocrit level ≤38%

    1

    Preoperative bilirubin level >1 mg/dL

    1

    Dyspnea

    1

    Albumin level < 3.5 mg/dL

    1

    Emergency

    1

    0 points for each condition

     

    ASA physical status class 1

    0

    Work RVU < 10

    0

    Male sex

    0

    *Modified from Rogers SO Jr, Kilaru RK, Hosokawa P, Henderson WG, Zinner MJ, Khuri SF. Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: results from the patient safety in surgery study. J Am Coll Surg. Jun 2007;204(6):1211-21. [PMID: 17544079].

    Abbreviations: ASA, American Society of Anesthesiologists; WVU, Work Relative Value Unit

    1 Point

    2 Points

    3 Points

    5 Points

    Age 41-60 years

    Age 61-74 years

    Age ≥75 years

    Stroke (1 month)

    Minor surgery

    Arthroscopic surgery

    History of VTE

    Elective arthroplasty

    BMI >25 kg/m2

    Major open surgery (>45 minutes)

    Family history of VTE

    Hip, pelvis, or leg fracture

    Swollen legs

    Laparoscopic surgery (>45 minutes)

    Factor V Leiden

    Acute spinal cord injury (< 1 month)

    Varicose veins

    Malignancy

    Prothrombin 20210A

     

    Pregnancy or postpartum

    Confined to bed (>72 hours)

    Lupus anticoagulant

     

    History of unexplained or recurrent spontaneous abortion

    Immobilizing plaster cast

    Anticardiolipin antibodies

     

    Oral contraceptives or hormone replacement use

    Central venous access

    Elevated serum homocysteine

     

    Sepsis (< 1 month)

     

    Heparin-induced thrombocytopenia

     

    Serious lung disease, including pneumonia (< 1 month)

     

    Other congenital or acquired thrombophilia

     

    Abnormal pulmonary function

     

     

     

    Acute myocardial infarction

     

     

     

    Congestive heart failure

     

     

     

    History of inflammatory bowel disease

     

     

     

    Medical patient at bedrest

     

     

     

    *Modified from Bahl V, Hu HM, Henke PK, Wakefield TW, Campbell DA Jr, Caprini JA. A validation study of a retrospective venous thromboembolism risk scoring method. Ann Surg. Feb 2010;251(2):344-50. [PMID: 19779324].

    VTE Risk Category

    Rogers Score

    Caprini Score

    Baseline Risk of VTE Without Prophylaxis, %

    Very low

    < 7

    0

    < 0.5

    Low

    7-10

    1-2

    1.5

    Moderate

    >10

    3-4

    3

    High

    N/A

    ≥5

    6

    *Modified from Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. Feb 2012;141(2 Suppl):e195S-226S. [PMID: 22315261].

    Grade of Recommendation

    Benefit vs Risk and Burdens

    Methodologic Strength of Supporting Evidence

    Implications

    Strong recommendation, high-quality evidence (1A)

    Benefits clearly outweigh risk and burdens or vice versa.

    Consistent evidence from randomized controlled trials without important limitations or exceptionally strong evidence from observational studies.

    Recommendation can apply to most patients in most circumstances. Further research is very unlikely to change our confidence in the estimate of effect.

     

    Strong recommendation, moderate-quality evidence (1B)

    Benefits clearly outweigh risk and burdens or vice versa.

    Evidence from randomized controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise) or very strong evidence from observational studies.

    Recommendation can apply to most patients in most circumstances. Higher-quality research may well have an important impact on our confidence in the estimate of effect and may change the estimate.

     

    Strong recommendation, low- or very-low-quality evidence (1C)

    Benefits clearly outweigh risk and burdens or vice versa.

    Evidence for at least one critical outcome from observational studies, case series, or randomized controlled trials, with serious flaws or indirect evidence.

    Recommendation can apply to most patients in many circumstances. Higher-quality research is likely to have an important impact on our confidence in the estimate of effect and may well change the estimate.

     

    Weak recommendation, high-quality evidence (2A)

    Benefits closely balanced with risks and burden.

    Consistent evidence from randomized controlled trials without important limitations or exceptionally strong evidence from observational studies.

    The best action may differ depending on circumstances or patient or societal values. Further research is very unlikely to change our confidence in the estimate of effect.

     

    Weak recommendation, moderate-quality evidence (2B)

    Benefits closely balanced with risks and burden.

    Evidence from randomized controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise) or very strong evidence from observational studies.

    Best action may differ depending on circumstances or patient or societal values. Higher-quality research may well have an important impact on our confidence in the estimate of effect and may change the estimate.

     

    Weak recommendation, low- or very-low-quality evidence (2C)

    Uncertainty in the estimates of benefits, risks, and burden; benefits, risk, and burden may be closely balanced.

    Evidence for at least one critical outcome from observational studies, case series, or randomized controlled trials, with serious flaws or indirect evidence.

    Other alternatives may be equally reasonable. Higher-quality research is likely to have an important impact on our confidence in the estimate of effect and may well change the estimate.

    *Modified from Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. Feb 2012;141(2 Suppl):e195S-226S. [PMID: 22315261].

    Howard A Shaw, MD, MBA Clinical Professor of Obstetrics and Gynecology, Yale University School of Medicine; Chief Medical Officer, Medical City Denton

    Howard A Shaw, MD, MBA is a member of the following medical societies: American Association for Physician Leadership, American College of Forensic Examiners Institute, American College of Healthcare Executives, American College of Obstetricians and Gynecologists

    Disclosure: Nothing to disclose.

    Julia A Shaw, MD, MBA, FACOG Assistant Professor and Residency Program Director, Department of Obstetrics and Gynecology, Yale School of Medicine; Medical Director, Yale-New Haven Hospital Women’s Center

    Julia A Shaw, MD, MBA, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Association for Physician Leadership, Connecticut State Medical Society, AAGL, North American Menopause Society

    Disclosure: Nothing to disclose.

    Kris Strohbehn, MD Professor of Obstetrics and Gynecology, Geisel School of Medicine at Dartmouth; Director, Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, Dartmouth-Hitchcock Medical Center

    Kris Strohbehn, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American College of Surgeons, American Urogynecologic Society, Society of Gynecologic Surgeons

    Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: I am on the Board for the Society of Gynecologic Surgeons (SGS). SGS is a non-profit organization whose mission is: “is to promote excellence in gynecologic surgery through acquisition of knowledge and improvement of skills…”.

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