Postterm Pregnancy

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Postterm Pregnancy

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Postterm pregnancy is defined as a pregnancy that extends to 42 0/7 weeks and beyond. [1] The reported frequency of postterm pregnancy is approximately 3-12%. [1, 2] However, the actual biologic variation is likely less since the most frequent cause of a postterm pregnancy diagnosis is inaccurate dating. [3, 4, 5, 6] Risk factors for actual postterm pregnancy include primiparity, prior postterm pregnancy, male gender of the fetus, and genetic factors. [7, 8, 9, 2, 1, 10]

Laursen et al studied monozygotic and dizygotic twins and their subsequent development of prolonged pregnancies. They found that maternal but not paternal genetic factors influenced the rate of postterm pregnancies and accounted for the etiology in as many as 30% of these pregnancies. [11] A more recently described risk factor is obesity, which appears to increase the risk of pregnancies progressing beyond 41 or 42 weeks of gestation. [12, 13, 14]

Although the last menstrual period (LMP) has been traditionally used to calculate the estimated due date (EDD), many inaccuracies exist using this method in women who have irregular cycles, have been on recent hormonal birth control, or who have first trimester bleeding. In particular, women are more likely to be oligo-ovulatory than polyovulatory, so cycles longer than 28 days are not uncommonly seen. [4] If such a cycle is 35 days instead of 28 days, a second trimester ultrasound will not be powerful enough to redate the pregnancy. Thus, not only the LMP date, but the regularity and length of cycles must be taken into account when estimating gestational age.

Ultrasonographic dating early in pregnancy can improve the reliability of the EDD; however, it is necessary to understand the margin of error reported at various times during each trimester. A calculated gestational age by composite biometry from a sonogram must be considered an estimate and must take into account the range of possibilities.

Estimation range varies. For example, crown-rump length (CRL) is 3-5 days, ultrasonography performed at 12-20 weeks of gestation is 7-10 days, at 20-30 weeks is 2 weeks, and after 30 weeks is 3 weeks. Thus, a pregnancy that is 35 weeks by a 31-week ultrasound could actually be anywhere from 32 weeks to 38 weeks (35 wk +/-3 wk). If the calculated ultrasonographic gestational age varies from the LMP more than the respective range of error, it is used instead to establish the final EDD. The importance of determining by what method a pregnancy is dated cannot be overemphasized because this may have significant consequences if the physician delivers a so-called term pregnancy that is not or observes a so-called term pregnancy that is very postterm.

When determining a management plan for an impending postterm pregnancy (>40 wk of gestation but < 42 wk), the 3 options are (1) elective induction of labor, (2) expectant management of the pregnancy, or (3) antenatal testing. Each of these 3 options may be used at any particular time during this 2-week period.

Note that if the pregnancy is at risk for an adverse outcome from an underlying condition, either maternal or fetal, inducing labor may proceed without documented lung maturity. Also, an elective induction of labor may proceed at or after 39 weeks of gestation in the absence of documented lung maturity provided that 36 weeks have elapsed since documentation of a positive human chorionic gonadotropin (+hCG) test finding, 20 weeks of fetal heart tones have been established by a fetoscope or 30 weeks by a Doppler examination, or 39 weeks’ gestation have been established by a CRL or by an ultrasound performed before 20 weeks of gestation consistent with dates by the patient’s LMP.

Recent studies have shown that the risks to the fetus [15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27] and to the mother [24, 28, 29, 30, 31, 32, 33, 34] of continuing the pregnancy beyond the estimated date of delivery is greater than originally appreciated.

Risks have traditionally been underestimated for 2 reasons. First, earlier studies were published before the routine use of obstetric ultrasonography and, as a result, likely included many pregnancies that were not truly postterm. As noted above, such a misclassification bias would artificially lower the complication rates of pregnancies designated postterm and increase the complication rates in those designated term, resulting in a diminution in the difference between term and postterm pregnancies.

The second issue relates to the definition of stillbirth rates. Traditionally, stillbirth rates were calculated using all pregnancies delivered at a given gestational age as the denominator. However, once a fetus is delivered, it is no longer at risk of intrauterine fetal demise, and use of this denominator has traditionally underestimated the risk of stillbirth. The appropriate denominator is not all deliveries at a given gestational age, but ongoing (undelivered) pregnancies. [19, 20, 34] In one retrospective study of more than 170,000 singleton births, for example, Hilder et al demonstrated that the stillbirth rate increased 6-fold (from 0.35-2.12 per 1,000 pregnancies) when the denominator was changed from all deliveries to ongoing (undelivered) pregnancies. [17]

Antepartum stillbirths account for more perinatal deaths than either complications of prematurity or sudden infant death syndrome. [18] Perinatal mortality (defined as stillbirths plus early neonatal deaths) at 42 weeks of gestation is twice that at 40 weeks (4-7 vs 2-3 per 1,000 deliveries, respectively) and increases 4-fold at 43 weeks and 5- to 7-fold at 44 weeks. [16, 17, 18] These data also demonstrate that, when calculated per 1000 ongoing pregnancies, fetal and neonatal mortality rates increase sharply after 40 weeks. [17]

Cotzias et al calculated the risk of stillbirth in ongoing pregnancies for each gestational age from 35-43 weeks. [18] The risk of stillbirth was 1 in 926 ongoing pregnancies at 40 weeks’ gestation, 1 in 826 at 41 weeks, 1 in 769 at 42 weeks, and 1 in 633 at 43 weeks. Uteroplacental insufficiency, asphyxia (with and without meconium), intrauterine infection, and anencephaly all contribute to excess perinatal deaths, although postterm anencephaly is essentially nonexistent with modern obstetrical care. [35]

A number of key morbidities are greater in infants born to postterm pregnancies as well as pregnancies that progress to and beyond 41 0/7 weeks gestation including meconium and meconium aspiration, neonatal acidemia, low Apgar scores, macrosomia, and, in turn, birth injury. For example, since postterm infants are larger than term infants, with a higher incidence of fetal macrosomia (defined as estimated fetal weight ≥ 4,500 g) [36] , they are, in turn, at greater risk for other complications. [37, 38] Such complications associated with fetal macrosomia include prolonged labor, cephalopelvic disproportion, and shoulder dystocia with resultant risks of orthopedic or neurologic injury.

Approximately 20% of postterm fetuses have fetal dysmaturity (postmaturity) syndrome, which describes infants with characteristics of chronic intrauterine growth restriction from uteroplacental insufficiency. [39] These pregnancies are at increased risk of umbilical cord compression from oligohydramnios, nonreassuring fetal antepartum or intrapartum assessment, intrauterine passage of meconium, and short-term neonatal complications (such as hypoglycemia, seizures, and respiratory insufficiency).

Meconium aspiration syndrome refers to respiratory compromise with tachypnea, cyanosis, and reduced pulmonary compliance in newborns exposed to meconium in utero and is seen in higher rates in postterm neonates. [40] Indeed, the 4-fold decrease in the incidence of the meconium aspiration syndrome in the United States from 1990-1998 has been attributed primarily to a reduction in the postterm delivery rate [22] with very little contribution from conventional interventions designed to protect the lungs from the chemical pneumonitis caused by chronic meconium exposure, such as amnioinfusion [41, 42] or routine nasopharyngeal suctioning of meconium-stained neonates. [43]

Postterm pregnancy is also an independent risk factor for neonatal encephalopathy [44] and for death in the first year of life. [17, 18]

While much of the work above has been conducted in postterm pregnancies. Some of the fetal risks such as presence of meconium, increased risk of neonatal acidemia, and even stillbirth have been described as being greater at 41 weeks of gestation and even at 40 weeks of gestation as compared with 39 weeks’ gestation. [23, 24] For example, in one study, the rates of meconium and neonatal acidemia both increased throughout term pregnancies beyond 38 weeks of gestation. In addition to stillbirth being increased prior to 42 weeks of gestation, one study found that the risk of neonatal mortality also increases beyond 41 weeks of gestation. [45] Thus, 42 weeks does not represent a threshold below which risk is uniformly distributed. Indeed, neonatal morbidity (including meconium aspiration syndrome, birth injury, and neonatal acidemia) appears to be the lowest at around 38 weeks and increase in a continuous fashion thereafter. [46]

While preterm delivery is a well-established risk factor for cerebral palsy, a recent study suggested that delivery at 42 weeks or later is also associated with increased risk (RR 1.4, 95% CI, 1.2-1.6 when compared with delivery at 40 weeks’ gestation). [47]

The maternal risks of postterm pregnancy are often underappreciated. These include an increase in labor dystocia (9-12% vs 2-7% at term), an increase in severe perineal injury (3rd and 4th degree perineal lacerations) related to macrosomia (3.3% vs 2.6% at term) and operative vaginal delivery, and a doubling in the rate of cesarean delivery (14% vs 7% at term). [19, 28, 29, 30] The latter is associated with higher risks of complications such as endometritis, hemorrhage, and thromboembolic disease. [29, 48]

In addition to the medical risks, the emotional impact (anxiety and frustration) of carrying a pregnancy 1-2 weeks beyond the estimated due date should not be underestimated. In a randomized, controlled trial of women at 41 weeks of gestation, women who were induced would desire the same management 74% of the time, whereas women with serial antenatal monitoring only desired the same management 38% of the time. [49]

Similar to neonatal outcomes, maternal morbidity also increases in term pregnancies prior to 42 weeks of gestation. Such complications as chorioamnionitis, severe perineal lacerations, cesarean delivery rates, postpartum hemorrhage, and endomyometritis all increase progressively after 39 weeks of gestation. [24, 31, 32, 33, 22]

The first decision that must be made when managing an impending postterm pregnancy is whether to deliver. In certain cases (eg, nonreassuring surveillance, oligohydramnios, growth restriction, certain maternal diseases), the decision is straightforward. In these high-risk situations, the time at which the risks of remaining pregnant begin to outweigh the risks of delivery may come at an earlier gestational age (eg, 39 weeks of gestation). However, frequently several options can be considered when determining a course of action in the low-risk pregnancy. The certainty of gestational age, cervical examination findings, estimated fetal weight, patient preference, and past obstetric history must all be considered when mapping a course of action.

The main argument against a policy of routine induction of labor at 41 0/7 to 41 6/7 weeks has been that induction increases the rate of cesarean delivery without decreasing maternal and/or neonatal morbidity. Some of the studies that failed to show a reduction in fetal/neonatal morbidity were diluted by poorly dated pregnancies that were not necessarily postterm. In addition, the potential for increasing the risk for cesarean delivery with a failed induction is far less likely in the era of safe and effective cervical ripening agents.

To date, more than 10 studies have been published of elective induction of labor, many of them at 41 weeks of gestation. [50, 35, 51, 52, 53, 54] The preponderance of the evidence from these studies, including meta-analyses, find that not only is rate of cesarean delivery not increased in women who were randomized to routine induction of labor, but also more cesarean deliveries were performed in the noninduction groups, and the most frequent indication was fetal distress. Even with multiple studies, very few neonatal differences have been demonstrated. However, the reduction in meconium is statistically significant and the rate of neonatal mortality is lower.

In summary, routine induction at 41 weeks of gestation does not increase the cesarean delivery rate and may decrease it without negatively affecting perinatal morbidity or mortality. In fact, both the woman and the neonate benefit from a policy of routine induction of labor in well-dated, low-risk pregnancies at 41 weeks’ gestation. Because it is associated with a lower rate of adverse outcomes, including shoulder dystocia and meconium aspiration syndrome, this policy may also prove to be more cost-effective. [55]

A policy of routine induction at 40 weeks’ has few benefits, and there are multiple reasons not to allow a pregnancy to progress beyond 42 weeks.

Prior to 41 weeks of gestation, the evidence becomes more scant with only 3 small, non-US, randomized, controlled trials comparing elective induction of labor to expectant management of pregnancy. [53] However, elective induction of labor is increasingly being used as a management strategy. [56, 57] While this management may be reasonable in a practice that allows 48 hours or more for the management of the latent phase and the first stage of labor overall, in a setting where induction of labor is called a failure after 18-24 hours, it will likely further increase the cesarean delivery rate.

As noted above, the most decisive way to prevent postterm pregnancy is induction of labor prior to 42 weeks’ gestation. However, since complications rise during 40 and 41 weeks’ gestation and both clinicians and patients are concerned about the risks of induction of labor, it is perceivably better for women to go into spontaneous labor at 39 weeks of gestation on their own. Several minimally invasive interventions have been recommended to encourage the onset of labor at term and prevent postterm pregnancy, including membrane stripping, unprotected coitus, and acupuncture.

Stripping or sweeping of the fetal membranes refers to digital separation of the membranes from the wall of the cervix and lower uterine segment. This technique, which likely acts by releasing endogenous prostaglandins from the cervix, requires the cervix to be sufficiently dilated to admit the practitioner’s finger. Although stripping of the membranes may be able to reduce the interval to spontaneous onset of labor, a reduction in operative vaginal delivery, cesarean delivery rates, or maternal or neonatal morbidity has not been consistently proven. [58, 59, 60]

Unprotected sexual intercourse causes uterine contractions through the action of prostaglandins in semen and potentially release of endogenous prostaglandins similar to stripping of the membranes. Indeed, prostaglandins were originally isolated from extract of prostate and seminal vesicle glands, hence their name. Despite some conflicting data, it appears that unprotected coitus may lead to the earlier onset of labor, reduction in postterm pregnancy rates, and less induction of labor. [61, 62, 63]

In a small randomized trial that attempted to address this question, women were randomized to a group advised to have coitus versus a control group that was not. In this study, the women advised to have coitus did so more often (60% vs 40%), the difference in the rate of spontaneous labor was not measurable in this underpowered study. [64] Similarly, the efficacy of acupuncture for induction of labor cannot be definitively assessed because of the paucity of trial data; this requires further examination. [65, 66]

Once the decision to deliver a patient has been made, the management of the labor induction depends on the clinical setting, and a brief review of cervical ripening agents and potential complications of induction of labor is appropriate. A comprehensive review of all available methods for cervical ripening, indications, contraindications, and dosing is beyond the scope of this article.

As many as 80% of patients who reach 42 weeks’ gestation have an unfavorable cervical examination (ie, Bishop Score < 7). Many options are available for cervical ripening. The different preparations, indications, contraindications, and multiple dosing regimes of each require practitioners to familiarize themselves with several of the preparations.

Prostaglandin E2 gel and suppositories for vaginal application were used extensively until the late 1990s when many pharmacies stopped manufacturing them because of the advent of commercially available and less labor-intensive preparations. Currently available chemical preparations include prostaglandin E1 tablets for oral or vaginal use (misoprostol), prostaglandin E2 gel for intracervical application (dinoprostone cervical [Prepidil]), and a prostaglandin E2 vaginal insert (dinoprostone [Cervidil]). Cervidil contains 10 mg of dinoprostone and has a lower constant release of medication than Prepidil. [67] In addition, this vaginal insert device allows for easier removal in the event of uterine hyperstimulation.

Many studies have compared the efficacy and risks of various prostaglandin cervical ripening agents. Rozenburg et al performed a randomized trial comparing intravaginal misoprostol and dinoprostone vaginal insert in pregnancies at high risk of fetal distress. They found that both methods were equally safe for the induction of labor and misoprostol was actually more effective. [68]

Another method for ripening the cervix is by mechanical dilation. These devices may act by a combination of mechanical forces and by causing release of endogenous prostaglandins. Foley balloon catheters placed in the cervix, extra-amniotic saline infusions, and laminaria have all been studied and have been shown to be effective.

Regardless of what method is chosen for cervical ripening, the practitioner must be aware of the potential hazards surrounding the use of these agents in the patient with a scarred uterus. In addition, the potential for uterine tachysystole and subsequent fetal distress requires that care be taken to avoid using too high a dose or too short a dosing interval in an attempt to get a patient delivered rapidly. Care should also be taken when using combinations of mechanical and pharmacologic methods of cervical ripening.

Once an induction of labor has begun, watch for the major potential complications associated with inductions beyond 41 weeks’ gestation and have a plan for dealing with each. Complications include the presence of meconium, macrosomia, and fetal intolerance to labor.

The further the pregnancy progresses beyond 40 weeks, the more likely it is that significant amounts of meconium will be present. This is due to increased uteroplacental insufficiency, which leads to hypoxia in labor and activation of the vagal system. In addition, the presence of a smaller amount of amniotic fluid increases the relative concentration of meconium in utero.

Traditionally, saline amnioinfusion and aggressive nasopharyngeal and oropharyngeal suctioning at the perineum were used to decrease the risk of meconium aspiration syndrome. Recent studies contradict this standard practice. Fraser et al performed a prospective, randomized, multicenter study evaluating the risks and benefits of amnioinfusion for the prevention of meconium aspiration syndrome. [42] They concluded that in clinical settings, which have peripartum surveillance, amnioinfusion of thick meconium-stained amniotic fluid did not decrease the risk of moderate-to-severe meconium aspiration syndrome, perinatal death, or other serious neonatal disorders compared with expectant management. In addition, other recent studies have shown that deep suctioning of the airway at the perineum does not effectively prevent meconium aspiration syndrome, contrary to popular belief.

Fetal macrosomia can lead to maternal and fetal birth trauma and to arrest of both first- and second-stage labor. Because the risk of macrosomia increases throughout term and postterm pregnancies, one of the most important parts of the delivery plan is being prepared for shoulder dystocia in the event that this unpredictable, anxiety-provoking, and potentially dangerous condition arises. To prepare such an event, experienced clinicians should be present at the delivery, a stool/step next to the delivery bed should be placed to help with suprapubic pressure, and the maneuvers to reduce the shoulder dystocia should be reviewed.

Finally, intrapartum fetal surveillance in an attempt to document fetal intolerance to labor before it leads to acidosis is critical. Whether continuous fetal monitoring or intermittent auscultation is used, interpretation of the results by a well-trained clinician is of paramount importance. If the fetal heart rate tracing is equivocal, fetal scalp stimulation and/or fetal scalp blood sampling may provide the reassurance necessary to justify continuing the induction of labor. If the practitioner cannot find reassurance that the fetus is tolerating labor, cesarean delivery is recommended.

Antepartum fetal surveillance is suggested in postterm pregnancies when delivery is not performed. Although no randomized prospective trials demonstrate a benefit of fetal monitoring, no proof exists that it negatively affects postterm pregnancies either. Despite a lack of evidence, antepartum fetal surveillance of postterm pregnancies has become an accepted standard of care despite a lack of consensus as to a specific regimen of surveillance to be offered. [1]

The perinatal mortality rate increases gradually throughout pregnancy, with the greatest risk affecting pregnancies continuing past 41 weeks. Therefore, although no evidence can prove that routine monitoring between 40 and 42 weeks improves perinatal outcome, ACOG states that it is reasonable to begin antepartum testing after 41 weeks’ gestation. [1] In one study of this issue, Bochner et al demonstrated that initiating monitoring at 41 weeks of gestation led to lower rates of complications. [69]

No single method of antenatal surveillance has been shown to be superior to any other. Options include a nonstress test, contraction stress test, full biophysical profile, modified biophysical profile (nonstress test and amniotic fluid index), or a combination of these modalities. Evaluation of the amniotic fluid level has been shown to be especially important because of demonstrated increased adverse pregnancy outcomes. Therefore, delivery should be implemented in the event of oligohydramnios with or without other nonreassuring tests. Doppler ultrasonography has been shown to provide no proven advantage for evaluating postdate or postterm pregnancies and should not be routinely used.

A modified biophysical profile has been shown to be as sensitive as a full biophysical profile. Boehm et al demonstrated that twice-weekly testing of patients at risk for fetal distress was superior to weekly testing, decreasing the rate of stillbirth from 6.1 per 1000 live births to 1.9 per 1000.

In summary, the use of a nonstress test and an amniotic fluid index 2 times per week for pregnancies continuing past 41 weeks is reasonable. In addition, if any indication during antepartum surveillance leads the practitioner to question the intrauterine environment, delivery should be expedited.

The management of postterm pregnancies is complicated and fraught with complex issues. The decision of whether to induce labor or to proceed with expectant management with or without antepartum fetal surveillance is not taken lightly. Data support inducing labor at 41 weeks’ gestation in an accurately dated, low-risk pregnancy, regardless of cervical examination findings. This strategy, although not without its critics, averts the need for antepartum fetal surveillance and does not increase the cesarean delivery rate; in fact, it may decrease the cesarean delivery rate.

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Aaron B Caughey, MD, MPH, PhD Department Chair, Department of Obstetrics and Gynecology, Julie Newpert Stott Director of Center for Women’s Health, Oregon Health and Science University School of Medicine

Aaron B Caughey, MD, MPH, PhD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, Society for Medical Decision Making, Society for Reproductive Investigation

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.

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.

Jennifer R Butler, MD Assistant Director, Department of Obstetrics and Gynecology, Divison of General Obstetrics and Gynecology, Carolinas Medical Center

Jennifer R Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Obstetricians and Gynecologists, American Medical Association, Association of Professors of Gynecology and Obstetrics

Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Paul T Wilkes, MD and Henry Galan, MD to the development and writing of this article.

Postterm Pregnancy

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