Approximately 1.5 million nulliparous women deliver annually in the United States,1,2 with more than half having low-risk pregnancies.3,4 Expected management of uncomplicated pregnancies until 42 weeks of gestation is considered a reasonable option5 given the low rate of adverse outcomes among late- and postterm pregnancies.5–10 A randomized trial (the ARRIVE trial) reported that induction of labor at 39 weeks of gestation, compared with expectant management, is associated with several improved outcomes among low-risk nulliparous women. Specifically, the rates of cesarean delivery, hypertensive disorder of pregnancy, and respiratory support for the newborn were significantly lower with planned induction at 39 weeks of gestation.11
However, neither the ARRIVE trial nor a previous randomized trial from the United Kingdom11,12 reported differences in specific major maternal (eg, hysterectomy) or perinatal (eg, seizure) adverse outcomes between women randomized to planned 39-week induction compared with those undergoing planned expectant management. It is uncertain, however, whether this is because there is no actual difference between groups or because the outcomes were so infrequent that the statistical power was insufficient to discern any differences that do exist.7–10
Therefore, the primary objective of this analysis was to compare neonatal and maternal morbidity among a large sample of low-risk nulliparous women who delivered at 39, 40, and 41 weeks of gestation. The primary outcome was composite neonatal morbidity and the secondary outcome was composite maternal morbidity. We hypothesized that among, low-risk nulliparous women, both composite neonatal and maternal morbidity would be significantly higher for those who delivered at 40 and 41 weeks of gestation than for those who delivered at 39 weeks.
This was a population-based cohort study using the Period Linked Birth-Infant Death Data Files of U.S. Vital Statistics Data from 2011 to 2015, assembled by the National Center for Health Statistics and reported annually by the Centers for Disease Control and Prevention. Our study sample was restricted to nulliparous women who delivered between 2011 and 2015, with singleton, nonanomalous gestations, did not have hypertensive disorders, pregestational or gestational diabetes, labored (vaginal delivery or labor with subsequent cesarean delivery) at 39, 40, or 41 weeks of gestation, and had birth data recorded using the 2003 revised birth certificate.
Since 2003, the updated 2003 revision of birth certificates has been incorporated gradually on a statewide basis. Compared with the 1989 birth certificate version, the 2003 version contains more detailed obstetric, medical, and demographic data.13 The revised birth certificate was used by 36 states and Washington, DC in 2011, 38 states and DC in 2012, and 41 states and DC in 2013, 47 states and DC in 2014, and 48 states and DC in 2015, which represented 83%, 86%, 90%, 96%, and 97% of live births in the United States, respectively. Because the data are publicly available and do not contain direct personal identifiers, this study was considered exempt from review by the institutional review board at the McGovern Medical School at University of Texas Health Science Center at Houston.
The 2003 revision of the birth certificate replaced the “clinical estimate of gestation” with the “obstetric estimate of gestation.” Detailed information of the methods for this obstetric estimate of gestation can be found elsewhere.14 The obstetric estimate of gestation is reported in completed weeks (ie, 39 weeks of gestation includes deliveries from 39 0/7 weeks through 39 6/7 weeks).
The main exposure variable for our analysis was gestational age at delivery (ie, 39, 40, 41 weeks of gestation). The primary outcome was composite neonatal morbidity, which included any of the following: Apgar score below 5 at 5 minutes, assisted ventilation longer than 6 hours, neonatal seizure, or neonatal mortality (defined as death within 27 days). The determination of death within 27 days was made by linking birth and death certificates (which has the variable “Age at Death in Days”). The secondary outcome was composite maternal morbidity, which included any of the following: admission to the intensive care unit, maternal blood transfusion, uterine rupture, or unplanned hysterectomy. For determining the frequency of occurrence for both composites, newborns or women with more than one outcome were counted only once.
Differences in the maternal characteristics stratified by gestational age at delivery were examined using χ2 tests for categorical variables. The rates of composite neonatal and maternal morbidity, along with the individual components of these composite measures, were reported as the number of cases per 1,000 live births. We used multivariable Poisson regression models with robust error variance to examine the association between gestational age at delivery (using 39 weeks of gestation as the reference) and the risks of composite and individual maternal and neonatal morbidity while adjusting for maternal age (younger than 20, 20–34, 35 years or older), maternal race and ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, non-Hispanic other, unknown), maternal education (less than high school, high school, more than high school, unknown), marital status (married, not married), prepregnancy body mass index [BMI, calculated as weight in kilograms divided by height in meters squared] (underweight, normal weight, overweight, obese, unknown), prenatal care (yes, no, unknown), smoking during pregnancy (yes, no, unknown), neonatal sex (male, female), and delivery year (2011, 2012, 2013). The results are presented as adjusted relative risk (aRR) with 95% CI. Those missing data for maternal race and ethnicity, maternal education, prepregnancy BMI, prenatal care, and smoking during pregnancy were categorized and analyzed as an “unknown” group.
We did three sensitivity analyses to ascertain whether the associations of adverse outcomes with gestational age persists in different clinical scenarios: composite maternal morbidity without transfusion; deliveries of newborns only in the cephalic presentation (excluding those in breech, other or unknown presentations); and, adjusting for maternal obesity class I (BMI 30.0–34.9), II (BMI of 35.0–39.9) and III (BMI of at least 40). All statistical analyses were conducted using SAS 9.4 and STATA 14.
From 2011 to 2015, there were 19,863,745 live births in the United States recorded into the national database, of which 18,245,869 (91.9%) used the 2003 revised birth certificate. After exclusion criteria were applied, 3,300,899 women remained for our analysis, of whom 43.5% (n=1,435,245) delivered at 39 weeks of gestation, 41.4% (n=1,367,534) at 40 weeks, and 15.1% (n=498,120) at 41 weeks (Fig. 1).
Table 1 presents the maternal characteristics among the study population by gestational age at delivery (39, 40, 41 weeks of gestation). Women who delivered at 39 weeks of gestation were more likely to be younger (younger than 35 years of age), of minority race, and have lower education, but they were less likely to be married, or overweight or obese. The overall rate of cesarean delivery was 16.9% (n=242,146) at 39 weeks of gestation, 20.5% (n=280,251) at 40 weeks, and 28.0% (n=139,339) at 41 weeks (P<.001).
The overall rate of composite neonatal morbidity was 8.80 per 1,000 live births (28,939/3,289,481). At 39 weeks of gestation, composite neonatal morbidity was 7.52/1,000 live births (10,754/1,430,610); at 40 weeks, 9.11/1,000 live births (12,413/1,362,557); and at 41 weeks, 11.63/1,000 live births (5,772/496,314). The missing data ranged 0–0.27% (n=8,901) for individual morbidity components, and 0.35% (n=11,418) for composite neonatal morbidity. There was no meaningful difference in the proportion of missing data between 39, 40, and 41 weeks of gestation. The multivariable adjusted analysis showed that the risk of composite neonatal morbidity was higher at 40 (aRR 1.22, 95% CI 1.19–1.25) and 41 weeks of gestation (aRR 1.53, 95% CI 1.49–1.58) than at 39 weeks. The risk for each component of composite neonatal morbidity also were significantly higher at 40 and 41 weeks of gestation than at 39 weeks (Table 2).
The overall rate of composite maternal morbidity was 2.76 per 1,000 live births (9,103/3,297,304). At 39 weeks of gestation, the overall rate was 2.39/1,000 live births (3,423/1,433,863); at 40 weeks, 2.82/1,000 live births (3,852/1,365,967); and at 41 weeks, 3.67/1,000 live births (1,828/497,474). The proportion of missing data was 0.11% (n=3,595) for all individual morbidity components and 0.11% (n=3,595) for composite maternal morbidity. There was no meaningful difference in the proportion of missing data between 39, 40, and 41 weeks of gestation. The multivariable adjusted analysis showed that the risk of composite maternal morbidity was higher at 40 (aRR 1.19; 95% CI 1.14–1.25) and 41 weeks of gestation (aRR 1.56; 95% CI 1.47–1.65) as compared with that at 39 weeks. The risk of three individual maternal morbidities—admission to the intensive care unit, blood transfusion, or unplanned hysterectomy—also were significantly higher at 40 and 41 weeks of gestation than at 39 weeks (Table 3).
The first sensitivity analysis noted that composite maternal morbidity without transfusion also was higher at 40 and 41 weeks of gestation than at 39 weeks (Table 4). The second sensitivity analysis of women with deliveries of only cephalic neonates showed that both composite neonatal and maternal morbidities (Tables 5 and 6, respectively) were significantly higher at 40 and 41 weeks of gestation than at 39 weeks. Lastly, when adjusted for obesity class I, II, and III, composite neonatal and maternal morbidity increased between 40 and 41 weeks of gestation compared with 39 weeks (Table 7).
The results of this population-based study show that, among low-risk nulliparous women who delivered from 39 through 41 weeks of gestation, more than half (56.5%) delivered at 40 or 41 weeks. Both overall composite neonatal and maternal morbidity, as well as most individual components of the composite outcomes, are significantly higher at 40 and 41 weeks of gestation than at 39 weeks. As expected among low-risk women, the absolute rate of adverse outcomes was low (less than 1%). The sensitivity analysis is supportive of the association of increasing neonatal and maternal morbidity with advancing gestational age from 39 to 41 weeks of gestation in low-risk nulliparous women.
Composite neonatal morbidity in our study (8.8/1,000 live births) was lower than that in the ARRIVE trial11 (55.6/1,000 births). Not only were the inclusion criteria between the studies different, but composite neonatal morbidity in our study differed from that in ARRIVE as well. In our analysis, although we chose outcomes that were thought to be clinically important, we were unable to determine the frequency of some clinically relevant morbidities given that the data are not available in the birth certificate.
Prior publications also have reported increasing frequency of adverse outcomes as term pregnancies progress from 39 to 41 weeks of gestation. Examples of adverse maternal morbidities that increase with advancing gestational age include chorioamnionitis, postpartum hemorrhage, and anal sphincter injury15–18; examples of adverse neonatal outcomes that increase include admission to the neonatal intensive care unit, meconium aspiration syndrome, and sepsis.7,19,20 Using population-based data from Scotland, Stock et al17 report an increasing rate of perinatal mortality as gestational age progressed at term. Our report extends these findings to the present day in the United States, and our sample size provides us with sufficient power to discern differences in uncommon outcomes such as hysterectomy, neonatal seizure, and death.
Even if the rate of actual morbidity is low among uncomplicated nulliparous women, it is clinically important. The number of low-risk nulliparous women who deliver annually in the United States is upwards of 800,000,1–4 and thus this low frequency will still result in a substantial number of individuals affected by a significantly morbid condition. As the results of ARRIVE trial11 and observational studies3,17,20 suggest, the chance of these adverse outcomes is modifiable.
The strengths of the present study include its population-based design with a large sample of live births over 5 years, which account for 83% to 97% of live births in the United States between 2011 and 2015. The data, which are recent, provide contemporary determination of the rates of composite maternal and neonatal morbidities among low-risk nulliparous women.
We acknowledge several limitations. First, because our study used data from the U.S. vital statistics datasets, a variety of clinical information (eg, postpartum hemorrhage), was unavailable for analysis. Second, these data are stratified by gestational age, but are not an actual comparison of outcomes related to specific management strategies. Such a comparison was not performed, given that the coding of “induction” on the birth certificate is reportedly inaccurate.21 Third, our results may not be applicable to low-risk parous women or to high-risk pregnancies. Thus, the rate of composite maternal and neonatal morbidity described here should not be generalized to the national rate of adverse outcomes. Fourth, we excluded women with hypertensive diseases, which may develop after 39 weeks of gestation,11 to make the groups maximally comparable. However, this decision should bias toward the null; had we included women with hypertensive disorders after 39 weeks of gestation, the adverse outcomes at these later gestational ages would be expected to be worse.
In conclusion, among low-risk nulliparous women who delivered between 39 and 41 weeks of gestation, the risk of neonatal and maternal morbidity, although uncommon, increases as gestational age advances. Guidelines for discussion about induction for low-risk women at 39 weeks of gestation emphasize the importance of shared decision-making,22 and these results can be used to provide information during those discussions.12
1. Ventura SJ, Martin JA, Curtin SC, Mathews TJ. Births: final data for 1997. Nat Vital Stat Rep 1999;47:1–96.
2. Martin JA, Hamilton BE, Osterman MJK, Driscoll AK, Drake P. Births: final data for 2016. Nat Vital Stat Rep 2018;67:1–55.
3. Gibson KS, Waters TP, Bailit JL. A risk of waiting: the weekly incidence of hypertensive disorders and associated maternal and neonatal morbidity in low-risk term pregnancies. Am J Obstet Gynecol 2016;214:389.e1–12.
4. Chauhan SP, Rice MM, Grobman WA, Bailit J, Reddy UM, Wapner RJ, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Neonatal morbidity of small- and large-for-gestational-age neonates born at term in uncomplicated pregnancies. Obstet Gynecol 2017;130:511–9.
5. Management of late-term and postterm pregnancies. Practice Bulletin No. 146. American College of Obstetricians and Gynecologists. Obstet Gynecol 2014;124:390–6.
6. Chauhan SP, Ananth CV. Induction of labor in the United States: a critical appraisal of appropriateness and reducibility. Semin Perinatol 2012;36:336–43.
7. Alexander JM, McIntire DD, Leveno KJ. Forty weeks and beyond: pregnancy outcomes by week of gestation. Obstet Gynecol 2000;96:291–4.
8. Vrouenraets FP, Roumen FJ, Dehing CJ, van den Akker ES, Aarts MJ, Scheve EJ. Bishop score and risk of cesarean delivery after induction of labor in nulliparous women. Obstet Gynecol 2005;105:690–7.
9. Vahratian A, Zhang J, Troendle JF, Sciscione AC, Hoffman MK. Labor progression and risk of cesarean delivery in electively induced nulliparas. Obstet Gynecol 2005;105:698–704.
10. Davey MA, King J. Caesarean section following induction of labour in uncomplicated first births—a population-based cross-sectional analysis of 42,950 births. BMC Pregnancy Childbirth 2016;16:92.
11. Grobman WA, Rice MM, Reddy UM, Tita ATN, Silver RM, Mallett G, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med 2018;379:513–23.
12. Walker KF, Bugg GJ, Macpherson M, McCormick C, Grace N, Wildsmith C, et al. Randomized trial of labor induction in women 35 years of age or older. N Engl J Med 2016;374:813–22.
13. Osterman MJ, Martin JA, Mathews TJ, Hamilton BE. Expanded data from the new birth certificate, 2008. Natl Vital Stat Rep 2011;59:1–28.
14. National Center for Health Statistics. Guide to completing the facility worksheets for the certificate of live birth and report of fetal death (2003 revision). Available at: https://www.cdc.gov/nchs/data/dvs/GuidetoCompleteFacilityWks.pdf
. Retrieved November 2, 2018.
15. Caughey AB, Musci TJ. Complications of term pregnancies beyond 37 weeks of gestation. Obstet Gynecol 2004;103:57–62.
16. Caughey AB, Bishop JT. Maternal complications of pregnancy increase beyond 40 weeks of gestation in low-risk women. J Perinatol 2006;26:540–5.
17. Stock SJ, Ferguson E, Duffy A, Ford I, Chalmers J, Norman JE. Outcomes of elective induction of labour compared with expectant management: population based study. BMJ 2012;344:e2838.
18. Bailit JL, Grobman W, Zhao Y, Wapner RJ, Reddy UM, Varner MW, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. Nonmedically indicated induction vs expectant treatment in term nulliparous women. Am J Obstet Gynecol 2015;212:103.e1–7.
19. Caughey AB, Washington AE, Laros RK Jr. Neonatal complications of term pregnancy: rates by gestational age increase in a continuous, not threshold, fashion. Am J Obstet Gynecol 2005;192:185–90.
20. 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;207:502.e1–8.
21. Martin JA, Wilson EC, Osterman MJK, Saadi EW, Sutton SR, Hamilton BE. Assessing the quality of medical and health data from the 2003 birth certificate revision: results from two states. Natl Vital Stat Rep 2013;62:1–19.
22. Society for Maternal-Fetal Medicine (SMFM) Publications Committee. SMFM statement on elective induction of labor in low-risk nulliparous women at term: the ARRIVE trial. Am J Obstet Gynecol 2018 Aug 9 [Epub ahead of print].