Late- and Postterm Pregnancy

Definition

The American College of Obstetricians and Gynecologists (ACOG), International Federation of Gynecology and Obstetrics (FIGO), and World Health Organization (WHO) have defined a postterm pregnancy as a gestation that has completed or gone beyond 42 weeks or 294 days from the first day of the last menstrual period (LMP). This gestational age cutoff has been used for several decades and was first suggested based on early studies that reported an increased risk of fetal death at 42 weeks and beyond. However, in view of more recent perinatal mortality data that were derived from accurately dated pregnancies, it would be reasonable to conclude that the gestational age that warrants clinical concern should be 41 weeks.

Many terms have been used in the literature, including postmature, postdates, prolonged , and postterm . These terms have been used with varying definitions, which has led to some confusion regarding proper terminology. Recently ACOG and the Society for Maternal Fetal Medicine (SMFM) have endorsed the use of new terminology recommended by the Defining Term Pregnancy Workgroup not only to decrease confusion among physicians, patients, and researchers but also to designate gestational ages at higher risk. Patients are now considered “early term” if they are at 37 ^0/7 weeks through 38 ^6/7 weeks. Full term is defined as 39 ^0/7 weeks through 40 ^6/7 weeks. Pregnancies are now be designated as “late term” if they are 41 ^0/7 weeks through 41 ^6/7 weeks. Postterm continues to be defined as 42 ^0/7 weeks and beyond.

Incidence

According to the vital statistics reported by the Centers for Disease Control and Prevention, the overall incidence of postterm pregnancies in 2016, as compared with previous years, decreased to 0.35%. This percentage is significantly lower than what had been reported in previous years. It is important to note that the Centers for Disease Control and Prevention have changed their methodology for determining gestational age. In 2014 the National Center for Health Statistics discontinued the use of menstrual age and adopted the obstetric estimate to determine gestational age at the time of delivery.

Other published studies have shown the incidence to vary depending on the population studied. The incidence of prolonged pregnancies in European countries varies widely, with rates as low as 0.4% in Austria and as high as 7% to 8% in Denmark and Sweden. These differences are most likely explained by (1) different approaches for managing pregnancies beyond the estimated date of delivery (EDD) and (2) different criteria for gestational age dating.

Etiology

The etiology of most late- or postterm pregnancies is unknown, but some may be defined as late- or postterm because of an error in dating. It is a common practice to assign an EDD based on the date of the LMP. This practice has been proven by several studies to be unreliable and may have led to the incorrect classification of a pregnancy as late- or postterm.

Understanding the events that lead to parturition in human gestation may help provide clues to the pathophysiology in prolonged pregnancies. Parturition is the result of a complex interplay between the mother, fetus, and placenta. The mechanism of human gestation is unknown but may be similar to that of other mammals. In sheep, the hypothalamic pituitary adrenal (HPA) axis is important in the timing of birth. The release of corticotrophin-releasing hormone from the fetal brain results in the secretion of adrenocorticotropic hormone from the pituitary gland and cortisol from the adrenal gland. The increase in cortisol parallels an increase in the secretion of prostaglandin and estrogens and a fall in progesterone. Decreases in progesterone and increases in prostaglandins are known triggers of the uterine myometrium. Further support for the role of the HPA axis in the initiation of labor is seen in studies with hypophysectomized sheep; in these animals, disruption of the HPA axis results in prolonged pregnancy. More recent studies have proposed a similar involvement of the HPA axis in human gestation, and its dysregulation may play a role in prolonged pregnancies.

Early studies likened anencephaly to the hypophysectomized sheep. It is hypothesized that the absence of the fetal brain in the anencephalic fetus may result in a similar dysfunction of the HPA axis and lead to prolonged gestation. Epidemiologic studies of anencephalic pregnancies have observed prolongation of pregnancy. This finding supports current thinking that the interaction between the fetal brain and placenta plays an important role in triggering labor.

Pregnancies complicated by placental sulfatase deficiency, an X-linked recessive disorder characterized by the absence of the enzyme steroid sulfatase, are marked by abnormally low estriol levels and, in general, fail to go into spontaneous labor. This is an example of a genetic etiology for prolonged pregnancy and lends further support to the important role of the placenta in the initiation of labor.

A number of observational studies have identified risk factors for postterm pregnancy, including primigravidity, prior postterm pregnancy, male fetus, obesity, and a genetic predisposition. A 10-year cohort study of births in Norway failed to find a strong association of risk factors with postterm pregnancy but may have had a bias toward nondetection. Intergenerational studies suggest a genetic predisposition for postterm pregnancy. Mothers who themselves were born postterm also have an increased risk of prolonged pregnancy. A study of 475,429 Swedish birth records demonstrated that sisters were at higher risk of having a postterm birth. Twin studies have found higher rates of concordance for postterm pregnancy among female twins as compared with male twins, implicating a maternal influence on the risk for prolonged pregnancy.

Diagnosis

The diagnosis of truly late- and postterm pregnancy is based on accurate gestational dating. The three most commonly used methods to determine the EDD are (1) knowledge of the date of the LMP, (2) timing of intercourse or embryo transfer, and (3) early ultrasound assessment. Other methods have been described—including the determination of uterine size, quickening, ability to detect fetal heart tones by Doptone, and fundal height measurement—but are rarely used in contemporary practice. In most cases the date of conception is rarely known and, therefore, is infrequently used to determine gestational age. The EDD is most commonly assigned based on the first day of the LMP, but this assumes that conception occurs on the 14th day of the menstrual cycle. This method can be very inaccurate because the timing of ovulation varies between an individual's menstrual cycles and between individuals. Basing gestational age solely on the LMP generally results in an overestimation of gestational age, and may result in a higher frequency of induction of labor for presumed postterm pregnancy.

The use of ultrasound to determine the accuracy of gestational dating based on the LMP is superior to the use of LMP alone. The EDD is most accurately determined if the crown-rump length is measured in the first trimester with an error of plus or minus 5 to 7 days. The EDD is considered suboptimally dated if not confirmed by an ultrasound before 22 weeks. Boyd and colleagues showed that the incidence of pregnancies that exceeded 293 days was 7.5% based on menstrual dating and declined to 2.6% when dates were determined by early sonographic examination. A similar conclusion was reached by Gardosi and colleagues, who evaluated 24,675 spontaneous, normal singleton deliveries and showed a decline in the postterm (>294 days) pregnancy rate from 7.5% when pregnancies were dated by LMP to 1.5% when ultrasound dating was used. These authors also reported that about 72% of routine labor inductions at 42 weeks of gestation were not indicated because, based on ultrasound assessment of gestational age, they were performed before the patients reached 42 weeks. Similarly, Nguyen and colleagues evaluated 14,805 spontaneous deliveries with a reliable LMP and showed that ultrasound dating reduced the proportion of deliveries beyond 294 days of gestation by 39% (from 7.9% to 5.2%). Bennett and colleagues confirmed these findings in a prospective, randomized study of 218 women and found fewer postterm inductions of labor in women dated by a first trimester sonogram as compared with women whose dates were established by second-trimester sonography. A 2015 Cochrane review of 11 trials including 37,505 women reported similar findings, with a decrease in postterm inductions when these women, compared with controls, were offered early ultrasounds.

Perinatal Morbidity and Mortality

Numerous studies have evaluated the risk to the fetus in late- and postterm pregnancies. Early descriptive studies found that pregnancies that continued past their EDD had an increased risk of fetal death. In 1963 McClure found a twofold increase in “fetal distress” at 42 weeks, with an increase in operative deliveries, and surmised that 42 weeks constituted a significant risk to the fetus. Therefore this author proposed intervening with induction of labor or cesarean delivery to avoid the risk of fetal death. Early studies were likely fraught with inaccurate dating and inconsistent definitions of postterm pregnancy. Last, it is important to note that these studies included pregnancies complicated by fetal anomalies, intrauterine growth restriction, and mothers with coexisting medical conditions, all of which increase the risk of fetal demise.

More recent observational studies that have evaluated the risk of perinatal mortality at each gestational week show an increased risk as gestational age advances beyond the EDD. Divon and colleagues evaluated fetal and neonatal mortality rates in 181,524 accurately dated full-, late- and postterm pregnancies. A significant increase in fetal mortality was detected from 41 weeks of gestation onward (odds ratio [OR] of 1.5, 1.8, and 2.9 at 41, 42, and 43 weeks, respectively). Campbell and colleagues performed a multivariate analysis of factors associated with perinatal death among 65,796 singleton postterm births (≥294 days). Three variables were identified as independent predictors of perinatal mortality: (1) birthweight less than the 10th percentile for gestational age had a relative risk (RR) of 5.7 (95% confidence interval [CI], 4.4 to 7.4); (2) maternal age 35 years or greater had a RR of 1.88 (95% CI, 1.2 to 2.9); and (3) birthweight at the 90th percentile for gestational age or above was associated with a modest protective effect for perinatal death (RR, 0.51; 95% CI, 0.26 to 1.0).

Many of these studies have used the perinatal mortality rate, which has been suggested by Yudkin and Smith to be an inappropriate assessment of risk to the fetus. The denominator in the calculation of the perinatal mortality rate is the number of deliveries. As stated by Smith, “estimating the probability of an event requires that the number of events (numerator) be divided by the number of subjects at risk for that event (denominator).” Therefore it seems logical to calculate fetal mortality as fetal deaths per 1000 ongoing pregnancies (rather than per 1000 deliveries). When Hilder and colleagues used ongoing pregnancies in a large retrospective study that included 171,527 births, they found higher rates of stillbirth. There was a nadir at 41 weeks but an eightfold increase in stillbirth at 43 weeks compared with 37 weeks of gestation ( Fig. 29.1 ). Using the Scottish birth registry, Smith also found a significant increase in the risk of stillbirth from 37 weeks (0.4 per 1000) to 43 weeks (11.5 per 1000). A recent study performed using California birth records including 3,820,826 nonanomalous singleton births dated by menstrual age found a similar trend, with an increased risk of stillbirth as pregnancy progressed after 39 weeks, with the highest risk at 42 weeks.

Several studies evaluated the association of perinatal morbidity with postterm pregnancy. Clausson and colleagues evaluated a large Swedish database of term and postterm (defined as ≥ 294 days) singleton, normal neonates and showed that postterm pregnancies were associated with an increased frequency of neonatal convulsions, meconium aspiration syndrome, and Apgar scores of less than 4 at 5 minutes ( Table 29.1 ). Tunon and colleagues compared neonatal intensive care unit (NICU) admission rates among 10,048 term pregnancies and 246 postterm pregnancies (≥296 days by both scan and LMP dates). Postterm pregnancy was associated with a significant increase in NICU admissions (OR, 2.05; 95% CI, 1.35 to 3.12).

Guidetti and colleagues reported an increased incidence of perinatal morbidity at 41 weeks of gestation or greater. Maternal and fetal complications were evaluated in a large ( n = 45,673) retrospective cohort study by Caughey and Musci. These authors documented a significant increase in the rate of intrauterine fetal death beyond 41 weeks. They concluded that risks to both the mother and fetus increase as pregnancy progresses beyond 40 weeks of gestation.