Elective induction at 39 weeks: A reasonable option

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The cornerstone of obstetrics is the determination of when it is better for the mother and her fetus to effect delivery. Much attention over the past decade has been focused on avoiding truly elective deliveries prior to 39 weeks because of the risks of iatrogenic prematurity. Conversely, given the increase in perinatal mortality attendant post-term gestations, it has been the longstanding policy of the American College of Obstetricians and Gynecologists (ACOG) to consider induction of labor (IOL) between 41 0/7 and 41 6/7 weeks’ gestation and to recommend IOL after 42 0/7 weeks.¹

However, between 39 and 42 weeks, there are multiple risks to mother and fetus associated with continuing the pregnancy. Perinatal mortality rates nadir at 39 weeks as neonatal risks from prematurity fade and rates of stillbirth grow.²Beyond 39 weeks, pregnancies are at increased risk of placental insufficiency, preeclampsia, and macrosomia, all of which are associated with increased cesarean delivery rates, not to mention increased maternal, perinatal, and neonatal mortality and/or morbidity. These findings all suggest that elective IOL at 39 weeks could reduce adverse pregnancy outcomes and lower cesarean delivery rates compared to expectant management. While older literature did not support this thesis, recent studies suggest that this is indeed the case.

Older studies were flawed

Prior observational studies of the benefits of elective IOL were faulty because they used “spontaneous labor” as the control group. By excluding patients with subsequent post-dates and medically indicated inductions, they biased results toward lower stillbirth and cesarean delivery rates in “control” groups. Because the actual clinical choice is not between elective IOL versus spontaneous labor, but rather between elective IOL compared with expectant management, these older studies did not mirror clinical decision-making. In 2009, Caughey and associates conducted a systematic review of nine randomized clinical trials of elective IOL at either < 41 or ≥ 41 weeks compared with expectant management and noted that overall, the latter was associated with an increased cesarean delivery rate (OR 1.22; 95% CI: 1.07-1.39) but among women < 41 weeks, no significant differences were noted.³However, the authors reported that the two studies conducted at < 41 weeks were of poor quality and not generalizable to current practice. Stock and associates conducted a large retrospective cohort study among 1.27 million Scottish women delivering between 1981 to 2007 with singleton gestations ≥ 37 weeks to compare cesarean delivery rates, perinatal mortality, and neonatal and maternal outcomes for those with elective IOL vs. expectant management.⁴They noted that at 39 weeks, elective IOL was associated with decreased perinatal mortality (0.06% versus 0.18%, P< 0.001; adj OR of 0.28; 99% CI: 0.12-0.67), with a minimal increase in cesarean delivery rates 9.3 versus 8.4% (adj OR: 1.08, 1.00-1.16). However, the problems with these older studies include non-standardized definitions of successful induction, variable induction methods, and heterogenous populations.

Recent studies

In 2016, Walker and colleagues reported on their small clinical trial among 618 nulliparous woman ≥ 35 years with singleton pregnancies randomized to elective IOL at 39 weeks versus expectant management until spontaneous labor or medically or obstetrically indicated delivery.⁵They observed no differences in cesarean rates (RR 0.99; 95%CI: 0.87-1.14) and no differences in operative vaginal delivery, infant deaths, or women’s experience of childbirth. The chief problem with this study was its lack of power, given the rarity of many of these adverse outcomes. 

To address the issue of sample size and rare outcomes, Sinkey and associates conducted a comparative effectiveness study using a sophisticated Monte Carlo micro-simulation model to compare elective IOL at 39 weeks with expectant management including delivery for standard medical or obstetrical indications, or at 41 weeks if undelivered.⁶They based their decision support probabilities of potential maternal and perinatal outcomes on an exhaustive review of the literature and data derived from the Consortium on Safe Labor. They also conducted sensitivity analyses based on maternal preferences for optimizing maternal versus infant health using weighted utilities. The primary objective was to determine which management strategy posed less maternal and neonatal risk. Secondary outcomes were rates of cesarean deliveries, maternal morbidity and mortality, stillbirth, neonatal morbidity and mortality, and preferences regarding the importance of maternal and perinatal health. 

The authors found that elective IOL at 39 weeks resulted in lower cesarean delivery rates (13.9% versus 35.9%, P< 0.01) even among women with unfavorable cervices (8.0% versus 26.1%, P < 0.01). Conversely, there was an increase in maternal morbidity in the expectant management group (21.2% versus 16.5%, P< 0.01) as well as more stillbirths (0.13% versus 0%, P< 0.0003), neonatal deaths (0.25% versus 0.12%, P < 0.03), and neonatal morbidity (12.1% versus 9.4%, P< 0.01). These findings persisted after adjustment for maternal preferences. This decision model simulated a far larger population (> 100,000 women) than any clinical trial could hope to enroll. 

Even more recently, Grobman and colleagues conducted a large prospective multicenter trial among low-risk nulliparous women with a vertex presentation who in their 38^thweek were randomized to either elective IOL (n=3062) at 39 0/7 to 39 4/7 weeks or expectant management (n=3044).⁷No specific induction protocol was mandated. A composite of perinatal death or severe neonatal morbidity was the primary endpoint and cesarean delivery was the secondary outcome. Composite perinatal morbidity was less common in the elective IOL group than in the expectant management group (4.3% versus 5.4%; RR of 0.80; 95% CI: 0.64-1.00). In addition, cesarean delivery rates were lower in the elective IOL group (18.6% versus 22.2%; RR of 0.84; 95% CI: 0.76-0.93) as were rates of hypertension (9.1% versus 14.1%) (RR of 0.64; 95%CI: 0.56-0.74). Conversely, median labor pain scores were higher and average lengths of stay longer in the expectant management group. Subgroup analysis found no differences in results based on maternal race, age, or body mass index nor any effect from initial Bishop score. The results of the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management) add further evidence to the value of elective IOL at 39 weeks. 

Take-home message 

I don’t think we should be surprised by these recent studies. Term stillbirths are frequently related to placental insufficiency and cord accidents, which explains why stillbirths and neonatal morbidity stochastically increase with advancing gestational age. Simply not being in utero would reduce such risks. As for the lower cesarean delivery rates accompanying elective IOL, this may reflect a combination of: (1) fewer cesarean deliveries for non-reassuring fetal testing again due to lower rates of placental insufficiency and cord compression; and (2) smaller infants, as fetal weight progressively increases with increasing gestational age. Macrosomia should also be less common among patients undergoing elective IOL at 39 weeks, reducing the risk of shoulder dystocia and its related morbidity. 

In response to the ARRIVE study, ACOG has opined that “it is reasonable for obstetricians and health-care facilities to offer elective induction of labor to low-risk nulliparous women at 39 weeks gestation.”⁸The ACOG advisory prudently notes that the obstetrician should consider a woman’s preference, available resources and ensure an adequate trial of labor is provided. From my perspective, the decision to be electively delivered at 39 weeks is an intensely personal one for mothers, and their desires should be of paramount importance. However, if a low-risk nulliparous patient whose fetus is in a vertex presentation asks me “when is the safest time for me and my fetus to deliver”, I would feel obligated to describe the outcomes of these studies. 

References:

• Practice bulletin no. 146: Management of late-term and postterm pregnancies. Obstet Gynecol. 2014;124(2 Pt 1):390-396.
• MacDorman MF, Gregory EC. Fetal and Perinatal Mortality: United States, 2013. Natl Vital Stat Rep. 2015 Jul 23;64(8):1-24. 
• Caughey AB, Sundaram V, Kaimal AJ, Gienger A, Cheng YW, McDonald KM, et al. Systematic review: elective induction of labor versus expectant management of pregnancy. Ann Intern Med. 2009 Aug 18;151(4):252-63, W53-63.
• 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 May 10;344:e2838. 
• Walker KF, Bugg GJ, Macpherson M, McCormick C, Grace N, Wildsmith C, et al; 35/39 Trial Group. Randomized trial of labor induction in women 35 years of age or older. N Engl J Med. 2016 Mar 3;374(9):813-22.
• Sinkey RG, Lacevic J, Reljic T, Hozo I, Gibson KS, Odibo AO, et al. Elective induction of labor at 39 weeks among nulliparous women: The impact on maternal and neonatal risk. PLoS One. 2018 Apr 25;13(4):e0193169. 
• Grobman WA, Rice MM, Reddy UM, Tita ATN, Silver RM, Mallett G, et al. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med. 2018 Aug 9;379(6):513-523.
• American College of Obstetricians and Gynecologists. Practice Advisory: Clinical guidance for integration of the findings of The ARRIVE Trial: Labor Induction versus Expectant Management in Low-Risk Nulliparous Women. Available at: https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Advisories/Practice-Advisory-Clinical-guidance-for-integration-of-the-findings-of-The-ARRIVE-Trial Accessed Sept