Lisa Moore
James N. Martin Jr.
A prolonged pregnancy, also commonly called postterm pregnancy, is one that has lasted longer than 42 weeks or 294 days beyond the first day of the last menstrual period (1). Postdatism implies pregnancy lasting beyond the estimated due date at 40 weeks. The term “postmature” is reserved for the pathologic syndrome in which the fetus experiences placental insufficiency and resultant intrauterine growth restriction. Prolonged pregnancies have been recognized since antiquity. Hadrian, emperor of Rome from 117 to 138 A.D., decreed that a child born 11 months after the death of a husband was illegitimate. French law recognizes as legitimate a child born 300 days after the husband's death (2). Postdatism as a risk factor for adverse fetal outcome has been recognized since the early part of the 20th century. Whether prolongation of a low-risk pregnancy results in increased perinatal morbidity and mortality is a matter of debate.
Postdatism occurs in 3% to 12% of all pregnancies (1). The definition of prolonged pregnancy is, however, somewhat arbitrary and was formulated before ultrasound dating of gestation became routine. Divon and colleagues (3) have suggested that the definition should be changed so that pregnancies ≥41 weeks are considered post-term. This recommendation is based on a study of over 180,000 pregnancies at 40 weeks or more in which a significant increase in perinatal mortality was seen after 41 weeks. This same finding was noted by Browne (4), who described perinatal mortality after 41 weeks as 10.5 per 1,000 pregnancies, doubling that at 43 weeks, and tripling that amount at 44 weeks.
Prolonged pregnancies are at risk for macrosomia resulting in shoulder dystocia and fetal injury, oligohydramnios, meconium aspiration, intrapartum fetal distress, and stillbirth. Maternal risks include trauma, hemorrhage, and labor abnormalities (Table 13.1). Interventions for preventing or improving outcomes in low-risk, prolonged pregnancies have proven to be of minimal benefit.
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TABLE 13.1. Complications of prolonged pregnancy |
ETIOLOGY
The most common cause of a prolonged pregnancy is inaccurate dating. Early ultrasound dating of pregnancies has been shown to reduce the number of women who are induced for apparently prolonged pregnancies (5).
The physiology underlying the spontaneous onset of labor remains enigmatic. Several animal models have been studied, and a great deal of information on the process has been gathered. Parturition in the human female, however, is very different from other species. In humans, the role of the fetal hypothalamic–pituitary–adrenal (HPA) axis appears to be permissive rather than essential as in other species (6). Consistent with this, the average gestational age at delivery was 39.6 weeks for a group of anencephalic pregnancies, the same as for normal gestations. This number is questionable because there was a high incidence of extremely preterm (25–30 weeks) and extremely postterm (48–52 weeks) gestations in this series. This seems to demonstrate a loss of precision in timing the onset of labor in anencephalic fetuses.
The synthesis of estrogen and progesterone is controlled differently in humans than nonhumans. In humans the fetal adrenal is deficient in 3β-hydroxysteroid dehydrogenase that converts pregnenolone to progesterone and dehydroepiandrosterone to androstenedione. The placenta is deficient in 17α-hydroxylase and C17-20 lyase but has high sulfatase and aromatase activity. The fetal adrenal secretes dehydroepiandrosterone sulfate (DHEA-S) which the placenta converts to estrogen. Placental sulfatase deficiency is an X-linked disorder that affects male fetuses. The sulfatase-deficient placenta is unable to use DHEA-S and other fetal adrenal precursors to synthesize estrogens (7). These pregnancies are associated with poor response to cervical ripening and induction as well as postdatism.
Postulated maternal risk factors for prolonged pregnancy include primiparity, previous prolonged pregnancy, and young maternal age.
AMNIOTIC FLUID
Reduced amniotic fluid (i.e., oligohydramnios) is a frequent finding in prolonged pregnancies. It presents a problem because it can be a marker for fetal compromise and because it puts the fetus at risk for cord accidents. Oligohydramnios has been attributed to placental insufficiency causing the fetus to redistribute blood flow to protect the brain. This, in turn, is considered to cause renal hypoperfusion with reduced glomerular filtration and urine production leading to decreased amniotic fluid. However, a study of 57 women at gestations greater than 41 weeks in which the resistance index of the fetal middle cerebral, renal, and umbilical arteries was evaluated, found no evidence that oligohydramnios was associated with redistribution of blood flow (8).
It is commonly accepted that amniotic fluid volume decreases as gestational age advances beyond term. In at least one study, this was not found to be the case. Among 511 women at 41 weeks or more, only 11.5% had oligohydramnios defined as a four-quadrant amniotic fluid index (AFI) of 5 or less. The average AFI at 41 weeks was 12.4 cm ± 4.2 cm (9).
The best method to accurately estimate the amount of amniotic fluid is also a matter of debate. Commonly used ultrasound techniques include the four-quadrant AFI and the largest vertical pocket. In a study of 190 women at 40 weeks or more in which four ultrasound methodologies were studied for amniotic fluid volume estimation (the four-quadrant AFI, the largest vertical pocket, the largest transverse pocket, and the sums of all pockets), the only technique which demonstrated diagnostic value was use of the largest vertical pocket. A cutoff of 2.7 cm correlated well with favorable outcomes (10). The traditional cutoff of 2 cm in largest vertical diameter was also found to be an indicator of favorable outcome, but the authors thought that sensitivity could be increased by raising the cutoff to 2.7 cm.
ANTENATAL TESTING
Any pregnancy at risk for uteroplacental insufficiency is a candidate for antenatal fetal monitoring. It is most likely that the morbidity and mortality associated with prolonged gestation is due to placental insufficiency in which fetal requirements for oxygen and nutrients can no longer be met. The goal of antenatal testing is to identify those fetuses that should be delivered. It is useful to remember that no form of antenatal testing will predict random unfortunate events such as sudden significant umbilical cord compression.
Some form of antenatal testing is usually initiated between 41 and 42 weeks in otherwise healthy pregnancies. The frequency and the type of antenatal testing is based mostly on physician preference and experience since no testing modality has been shown to improve outcomes in uncomplicated post-term pregnancies whether initiated before or after 42 weeks (1).
Grubb and colleagues (11) reviewed 8,038 postterm gestations that were followed with twice-weekly nonstress tests (NSTs) and determination of the AFI. Prior to 42 weeks patients received one assessment. There were 9 antepartum deaths giving a stillbirth rate of 1.12 per 1,000. Two of those deaths occurred before 42 weeks. Using twice-weekly biophysical profiles (BPPs), an older study reported a stillbirth rate of 0.44 per 1,000.
Ratios of the middle cerebral artery (MCA) blood flow to the umbilical artery (UA) blood flow have been studied as indicators of fetal compromise. Two common ratios are the UA/MCA pulsatility index ratio and the MCA/UA systolic/diastolic (S/D) ratio. Normally, the UA should have low impedance flow with a relatively low S/D ratio and low pulsatility index. The MCA should have high impedance flow with a high S/D ratio and a high pulsatility index. With brain-sparing redistribution of blood flow, we would expect impedance in the UA to increase resulting in decreased or absent end-diastolic flow. Impedance in the MCA should decrease, with lowering of the S/D ratio and the pulsatility index and an increase in the peak velocity of the blood flow. With redistribution of blood flow, the MCA/UA S/D ratio should be low as the values approach each other. A study of women at 41 weeks or more, by Devine and colleagues (12) found that an MCA/UA S/D ratio less than 1.05 had an 80% sensitivity and 95% specificity with 80% positive predictive value of an adverse perinatal outcome.
The contraction stress test (CST) was the first test used for antepartum fetal monitoring. The underlying premise is that the fetus with uteroplacental insufficiency would experience late decelerations with contractions in response to hypoxia generated by decreased blood flow to the intervillous space. The NST is the first-line screening test at many medical centers. It is quickly and easily performed in an outpatient setting. The NST is based on the knowledge that fetal hypoxia interrupts the pathway between the fetal heart and an intact central nervous system (CNS). The fetus with an intact CNS will have heart rate accelerations with movement or stimulation. The CST has a high false-positive rate and the NST has a false-negative rate of 2.7 per 1,000 in a high-risk population (13). The BPP score predicts the presence or absence of asphyxia. The loss of the components of the BPP reflects sequential adaptive deletions to reduce fetal oxygen requirements. A normal BPP has a false-negative rate of 0.7 to 0.8 per 1,000.
The CST, NST, and BPP were compared in 583 women who had completed 42 weeks gestation (14). There were three protocols:
1. Weekly NST with CST for nonreactive NST.
2. Twice weekly NST with BPP for nonreactive NST with induction for a 4/10 BPP.
3. Twice weekly NST with BPP for nonreactive NST and a weekly determination of the amniotic fluid volume.
Patients were induced for low fluid or decelerations on the NST. In protocol 1, patients were reevaluated in 24 hours for a suspicious CST and induced for a positive CST. Protocol 3 had the highest intervention rate and the least perinatal morbidity. Protocol 1 had no interventions and the highest perinatal morbidity rate. Cesarean delivery was more common in protocols 2 and 3. Of note, the best outcomes were achieved with a low threshold for intervention.
THE FETUS
In 1954 Clifford (15) described the fetal postmaturity syndrome in which the postmature infant was characterized by peeling, parchmentlike skin, wasted appearance and meconium staining of skin, membranes, and the cord. The syndrome progressed in three stages from placental insufficiency with minimal associated morbidity and mortality to chronic insufficiency with an associated anoxic event.
The postmaturity syndrome described by Clifford is seen in only a small percentage of prolonged pregnancies. By far the most common complication is macrosomia resulting in dystocia with associated brachial plexus injuries and fractures.
Seven thousand infants were studied to determine the rate of growth after 39 weeks (16). Mean birth weight increased from 39 to 42 completed weeks. A similar increase was seen in head circumference and crown-to-heel length. In a study of 519 pregnancies beyond 41 weeks, 23% weighed more than 4,000 g and 4% were larger than 4,500 g (17).
To assess the risk to the fetus in a prolonged uncomplicated gestation, 1,408 infants delivered at 41 weeks and 340 delivered at 42 weeks were compared to 5,915 delivered at 39 or 40 weeks (18). Fetal distress and meconium release were twice as common at or after 42 weeks than at term. There was an eight-fold increase in meconium aspiration, which occurred 1 per 455 at term, 1 per 175 at 41 weeks, and 1 per 57 at 42 weeks. There was no increase in the incidence of birth asphyxia measured by the need for mechanical ventilation at birth.
MANAGEMENT
The management of uncomplicated prolonged pregnancies is controversial. An adverse event in a pregnancy that has carried beyond 40 weeks seems especially difficult because it might have been avoided by simply delivering the patient. Although rare, the risk of stillbirth increases as gestational age increases. Nonetheless, available data indicate that induction and expectant management have similar outcomes, and either is suitable for managing the uncomplicated prolonged gestation.
The National Institutes of Health (NIH) (19) sponsored a clinical trial to compare induction at 41 weeks (n = 265) to expectant management (n = 175) consisting of twice weekly NST and AFI. There were no differences in outcome between the two groups. The trial concluded that either approach was acceptable.
Active management of the prolonged pregnancy, defined as induction at 42 weeks was studied in 707 patients (20). Sixty-two percent of the patients labored spontaneously and 38% were induced. Perinatal mortality was 12 per 1,000. All deaths were in the spontaneously laboring group. Cesarean sections and indications for cesarean sections were similar in both groups. Meconium was present in 23% of inductions and 34% of the spontaneously laboring group. The authors concluded that routine induction at 42 weeks was justified to prevent perinatal deaths in this population.
The Parkland Group studied 56,317 pregnancies at 40, 41, and 42 weeks (21). Labor was induced at 42 weeks. Neonatal outcomes were similar in all groups. Sepsis and neonatal intensive care unit admission were more common in the 42-week group. Labor complications increased between 40 and 42 weeks, including length of labor and operative delivery. Their data suggest that routine induction at 41 weeks would increase labor complications with little or no neonatal benefit.
The Canadian Multicenter Post-term Pregnancy Trial was conducted at 22 hospitals, over a 5-year period (22). Singleton pregnancies at 41 weeks or more were assigned to induction or monitoring. In the monitored group, women were asked to perform kick counts each day. In addition, the fetuses received NSTs three times a week and AFI determinations two or three times weekly. Patients in the monitored group were delivered at 44 weeks or for maternal–fetal indication(s). Perinatal morbidity and mortality were the same for both groups.
PREVENTION
Separation of the membranes from the lower uterine segment (membrane sweeping) is a safe and inexpensive method of inducing labor, although its effectiveness is most likely operator-dependent. Membrane sweeping works by causing prostaglandin release from the chorionic membranes. One hundred eighty women at 38 weeks were randomized to either weekly membrane sweeping or a gentle cervical exam to determine Bishop score. The treatment group had a significant reduction in prolonged gestation, 3.3% compared to 15.6% in the control group (23). In another investigation, women with a Bishop score ≤4 and negative fetal fibronectin at 39 weeks received either membrane sweeping every 3 days or gentle cervical exams. The mean gestational age for onset of labor in the treatment group was 39.9 ± 0.3 compared to 41.5 ± 0.6 in the control group. Eighteen of 32 women in the control group were induced at 42 weeks versus none in the treatment group (24). In summary, membrane sweeping prior to 40 weeks appears to be an effective method for reducing postdate inductions.
INDUCTION OF LABOR
In the presence of a favorable cervix, induction after 41 weeks is reasonable.
Because induction of an unfavorable cervix may be unsuccessful and lead to cesarean delivery, the course of action in an otherwise uncomplicated prolonged gestation with an unfavorable cervix is less clear. Patients at 41 weeks of an uncomplicated gestation with Bishop scores of 4 or less were randomized to daily cervical exams, daily membrane sweeping, or daily prostaglandin gel for 1 week (25). Sixty-nine percent of the control group required induction at 42 weeks compared to only 20% (prostaglandin gel) and 17% (membrane sweeping) in the treatment groups. Wing and colleagues gave women who were at 41 weeks or more with unfavorable cervixes either 200 mg of mifepristone or placebo 24 hours before induction. They found only a modest effect on cervical ripening (26). Sequential application of prostaglandin E2 (PGE2) gel for cervical ripening was tested in 50 women at or beyond 41 weeks. All had Bishop scores less than 9 and received 2 mg of PGE2 gel twice a week as outpatients. PGE2 gel failed to improve cervical ripening over placebo (27). Alexander and colleagues (28) scheduled 1,325 women at 41 weeks for induction at 416/7 weeks. Six hundred eighty-seven women entered spontaneous labor before their scheduled inductions and served as controls. Labor was longer in the women who were induced and there was an increase in cesarean sections for failure to progress in the induced group but not for fetal distress. Associated risk factors for cesarean delivery in this study were undilated cervix, analgesia, and nulliparity.
SUMMARY POINTS
· Solid evidence from several randomized controlled trials indicates that uncomplicated prolonged gestations can be managed expectantly or by induction of labor and that outcomes are similar for either method.
· Accurate dating of the pregnancy is important and an early dating ultrasound can prevent unnecessary interventions.
· Perinatal morbidity and mortality increase significantly beyond 41 weeks gestation.
· Membrane sweeping can help to reduce the number of pregnancies that continue beyond 40 weeks.
· Antenatal testing is initiated to identify the fetus in need of delivery. No testing modality has been shown to improve outcomes in prolonged gestations.
· The uncomplicated post-term pregnancy with an unfavorable cervix can be watched expectantly with twice weekly fetal assessments or labor induction can be undertaken. Induction at 41 weeks reduces the risk of stillbirth.
· It remains unclear which method of induction is most effective for prolonged pregnancy.
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