The effects of labor induction at 39 weeks in low-risk nulliparous women

January 26, 2019


Grobman WA, Rice MM, Reddy UM, et al. Labor Induction versus Expectant Management in Low-Risk Nulliparous Women. N Engl J Med 2018; 379(6):513-523. PMID 30089070.


Brian C. King, MD
Joseph Hagan, ScD
Gautham Suresh, MD
Texas Children’s Hospital, Baylor College of Medicine


Intervention and Prognosis


In low-risk, nulliparous women, does induction of labor at 39 weeks lead to an increased risk of perinatal complications and maternal Cesarean delivery when compared to expectant-management?


  • Design: Multicenter randomized controlled trial
  • Allocation: Simple Urn Randomization. Allocation was not concealed, due to the nature of the intervention.
  • Blinding: Partially blinded – Initial staff members that reviewed charts were not clearly blinded. Secondary reviewers were blinded, and confirmed each primary outcome event.
  • Setting: Maternal-Fetal Medicine Units Network of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (12 centers)
  • Patients:
    • Inclusion Criteria:
      1. Nulliparous
      2. Singleton gestation
      3. Gestational age at randomization between 38 weeks 0 days and 38 weeks 6 days
      4. Gestational age determined by a sure LMP concordant with findings on a first ultrasound prior to 21 weeks 0 days, or if LMP was unsure, a first dating ultrasound done before 14 weeks 0 days.
    • Exclusion Criteria: At time of recruitment, and again at 38 weeks 0 days to 38 weeks 6 days
      1. Prior plan for C-section or a contraindication to labor
      2. Signs of labor
      3. Breech presentation
      4. Fetal demise or known fetal anomaly
      5. Heparin or low molecular weight heparin use during pregnancy
      6. Placenta previa or accreta; or vasa previa
      7. Ruptured membranes or active vaginal bleeding
      8. Cerclage in current pregnancy
      9. Oligohydramnios
      10. Fetal growth restriction
      11. Known HIV positivity
      12. Major maternal illnesses (including diabetes mellitus, lupus, cardiac disease, renal insufficiency, hypertensive disorders)
      13. Refusal of blood products
      14. Participation in another study that influences management
      15. Delivery planned at a non-network site
    • Intervention:
      • Induction Group: Induction of labor at 39 weeks 0 days to 39 weeks 4 days. No specific induction protocol was mandated.
      • Expectant-Management Group: Elective delivery delayed until after 40 weeks 5 days, but not delayed beyond 42 weeks 2 days. [Women delivered before 42 weeks 2 days either after spontaneous labor, or by elective delivery after 40 weeks 5 days]
    • Outcomes:
      • Primary outcome: Composite of perinatal death and 9 severe neonatal complications (see Table 1)
      • Secondary outcomes:
        1. Neonatal Outcomes
          • Birth weight
          • Duration of respiratory support
          • Cephalohematoma
          • Shoulder dystocia
          • Transfusion of blood products
          • Hyperbilirubinemia requiring phototherapy or exchange transfusion
          • Hypoglycemia requiring intravenous therapy
          • Admission to the neonatal intermediate or intensive care unit
          • Length of hospitalization
        2. Maternal Outcomes
          • Cesarean delivery
          • Hypertensive disorders of pregnancy
          • Indication for cesarean delivery
          • Operative vaginal delivery
          • Indication for operative vaginal delivery
          • Uterine incisional extensions during cesarean delivery
          • Chorioamnionitis
          • Third-degree or fourth-degree perineal laceration
          • Postpartum hemorrhage
          • Postpartum infection
          • Venous thrombo-embolism
          • Number of hours in the labor and delivery unit
          • Length of postpartum hospital stay
          • Admission to the intensive care unit
          • Maternal death
  • Follow-up period:
    • For mothers – 4 to 8 weeks after delivery
    • For infants – Discharge from primary hospitalization
  • Analysis and Sample Size:
    • Using an expected rate of the primary outcome in the expectant-management group of 3.5%, it was estimated that enrollment of 6000 women would provide a power of at least 85% to detect a 40% relative lower rate of the primary outcome in the induction group, with a two-sided type 1 error rate of 5%.
    • Due to a pre-planned interim analysis, their cutoff for significance for their primary outcome was p <0.046
    • The power analysis included an assumption that 7.5% of women would receive management that was inconsistent with the protocol in their assigned strategy.
    • 6,106 women were recruited, with 3062 assigned to the induction group and 3044 in the expectant-management group. Analyses were performed according to the intention-to-treat principle.
    • Prespecified subgroups for the primary perinatal outcome and for the secondary outcome of cesarean delivery were:
      1. Maternal race or ethnic group
      2. Age (>35 years vs < 35 years)
      3. Body-mass index (>30 vs <30)
      4. Modified Bishop Score (<5 vs. >5 or higher)
      5. Specialty of the admiting provider (OBGYN, MFM, FP, Midwifery)
  • Patient follow-up:
    • Three women in the induction group and 7 in the expectant-management group were lost to follow-up or withdrew consent (0.2% of study population).
    • 184 women in the induction group (6.0% of group) and 140 in the expectant-management group (4.6% of group) received management that was not consistent with the protocol for their assigned strategy.


Maternal characteristics at baseline were similar between groups at time of randomization (including age, race or ethnicity, gestational age, method of conception, substance use, BMI and Modified Bishop score), except for an increased incidence of prior pregnancy loss in the induction group compared to the expectant-management group (22.8% vs. 25.6%, p = 0.01). They had excellent follow-up, and there was a relatively small number of women who received management that was not consistent with their intended protocol (324, 5.3%), which was less than the number they accounted for in their power analysis.

Table 1: Neonatal Outcomes

Outcome Induction Group (%) Expectant-Management Group (%) Relative Risk (95% CI)1 P Value
Primary Composite Outcome 132 (4.3) 164 (5.4) 0.80 (0.64 – 1.00) 0.0492
     Perinatal Death 2 (0.1) 3 (0.1) 0.66 (0.12 – 3.33)  
     Respiratory Support 91 (3.0) 127 (4.2) 0.71 (0.55 – 0.93)  
     Apgar score <3 at 5 min 12 (0.4) 18 (0.6) 0.66 (0.32 – 1.37)  
     Hypoxic Ischemic Encephalopathy 14 (0.5) 20 (0.7) 0.70 (0.35 – 1.37)  
     Seizure 11 (0.4) 4 (0.1) 2.74 (0.91 – 8.12)  
     Infection 9 (0.3) 12 (0.4) 0.74 (0.31 – 1.76)  
     Meconium Aspiration Syndrome 17 (0.6) 26 (0.9) 0.65 (0.35 – 1.19)  
     Birth trauma 14 (0.5) 18 (0.6) 0.77 (0.38 – 1.55)  
     Intracranial or Subgaleal


9 (0.3) 7 (0.2) 1.28 (0.48 – 3.42)  
     Hypotension requiring vasopressor


2 (0.1) 5 (0.2) 0.40 (0.06 – 1.79)  
Secondary Outcomes  
     Transfusion of blood products 4 (0.1) 5 (0.2) 0.79 (0.20 – 2.74) 0.75

(requiring treatment)

145 (4.7) 142 (4.7) 1.01 (0.81 – 1.27) 0.91

(requiring treatment)

37 (1.2) 35 (1.2) 1.05 (0.66 – 1.66) 0.84
     Admission to NICU 358 (11.7) 394 (13.0) 0.90 (0.79 – 1.03) 0.13
     Cephalohematoma 83 (2.7) 90 (3.0) 0.92 (0.68 – 1.23) 0.56
     Shoulder dystocia 59 (1.9) 65 (2.1) 0.90 (0.64 – 1.28) 0.56

1Confidence intervals are not adjusted for multiple outcomes

2One interim analysis was performed and as a result a two-tailed P value of <0.046 was considered to indicate statistical significance

  • Primary Outcome: There was no difference in the primary composite perinatal outcome between groups (RR 0.80, 95% CI 0.64-1.00, p= 0.049).
  • Secondary Outcomes:
    • Maternal: Compared to women in the expectantly-managed group, women in the labor induction group had a lower frequency of Cesarean delivery (18.6% vs. 22.2%, RR 0.84, 95% CI 0.76 to 0.93; p <0.001), a decreased incidence of hypertensive disorders of pregnancy, and shorter postpartum hospital stay. They also reported less pain and greater perceived “control during childbirth” using the Labor Agentry Scale.
    • Neonatal: Compared to women in the expectantly-managed group, women in the labor induction group had neonates who had a shorter duration of respiratory support, and a shorter length of hospital stay. There were no differences in other neonatal secondary outcomes, including hyperbilirubinemia requiring treatment, hypoglycemia requiring treatment and admission to neonatal intermediate or intensive care units.
  • Subgroup Analyses: Subgroup analysis by race, modified Bishop score, BMI, age and maternal provider type did not have a significant effect on the relationship between early induction and the primary neonatal composite outcome or incidence of Cesarean delivery


In low-risk nulliparous pregnant women at 39 weeks gestation, compared to expectant management, induction of labor did not result in a statistically significant difference in the incidence of a composite adverse perinatal outcome, but did result in a statistically significant decrease in the frequency of Cesarean delivery, shorter length of stay, as well as improvements in other maternal outcomes. The findings of this study support the conclusion that labor induction is probably not associated with a higher risk of adverse maternal outcomes than expectant management, and may be associated with as much as a 36% lower risk of adverse neonatal outcomes than expectant management.


This trial attempts to address the practice of elective induction starting only at 41 weeks, a practice recommended by ACOG yet based on low quality evidence (1). The authors randomized low-risk nulliparous women to either induction at 39 weeks, or expectant-management with delivery prior to 42 weeks 2 days. A smaller trial based in the UK among women age 35 years and older compared similar groups, and found no significant effects on either the maternal or infant outcomes for elective induction at 39 weeks (2).

For this trial, a composite outcome of perinatal death and 9 “serious neonatal complications” was used for the primary outcome. A strength of this study was the prespecified definition of this composite outcome and the reporting of individual components. While the use of a composite outcome increases statistical power, it also limits interpretation because the included complications are not all of equal importance. There was a 20% relative reduction in this outcome in the early induction group (p = 0.049), with no difference between groups in the most serious outcome – perinatal death. The authors concluded that this p value did not reach statistical significance because they had a priori determined that only a p-value of less than 0.046 would indicate statistical significance due to a pre-planned interim analysis. The authors are to be commended for their intellectual honesty and rigor in interpreting their results.

How should clinicians interpret these results and use them in practice? This trial was conducted in University and Community Hospitals, included all types of maternal providers, and did not stipulate a method for induction which all favors generalizability. However, 16,000 eligible women declined to participate, which could indicate sampling bias. Also, blinding or masking was not possible due to the nature of the intervention, which could have led to performance and ascertainment bias. With those caveats, the implications for practice are as follows: First, this trial provides reassurance that induction of labor at 39 weeks in a select population of low-risk nulliparous women is likely not harmful to women, and may be beneficial. Second, it provides reassurance that induction at 39 weeks in a select population of low-risk women is unlikely to cause neonatal harm (based on the upper limit of the confidence interval at 1), and may potentially be associated with up to a 36% decrease in adverse neonatal outcomes. Ultimately, providers must consider whether their patients fall within that select population.

If these results are extrapolated to the estimated 1,282,544 low-risk, first-time deliveries in the US in 2016 (3), the absolute risk reduction of 1.1% in the primary outcome, while appearing small, would translate into over 10,000 fewer women with perinatal complications annually. The 3.6% absolute risk reduction in Cesarean delivery would translate into 46,000 fewer Cesarean deliveries annually, and along with a reduction in the length of stay, may carry significant cost savings and a reduction in the pain and complications that ensue from such deliveries.


  1. ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 107: Induction of labor. Obstet Gynecol. 2009 August; 114: 386-397. Available from:
  2. 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.
  3. Martin JA, Hamilton BE, Osterman MJK, Driscoll AK, Drake, P. National Vital Statistics Reports. National Center for Health Stastistics 2018; 67: 1-55. Available from: