Oxytocin regimen used for induction of labor and pregnancy outcomes

Background: Following the results of the A Randomized Trial of Induction Versus Expectant Management trial, which demonstrated a reduction in cesarean delivery with no increase in adverse perinatal outcomes after elective induction of labor in low-risk nulliparous patients at 39 weeks of gestation compared with expectant management, the use of induction of labor has increased. Current evidence is insufficient to recommend mid- to high-dose regimens over low-dose regimens for routine induction of labor.

Objective: This study aimed to evaluate the association between oxytocin regimen and cesarean delivery and an adverse perinatal composite outcome in low-risk nulliparous patients undergoing induction of labor at ≥39 weeks of gestation.

Study design: This was a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network's A Randomized Trial of Induction Versus Expectant Management randomized trial. Patients who received a mid- to high-dose oxytocin regimen (starting or incremental increase >2 mU/min) were compared with those who received a low-dose oxytocin regimen (starting and incremental increase ≤2 mU/min). The co-primary outcomes for this secondary analysis were (1) cesarean delivery and (2) composite of perinatal death or severe neonatal complications. Multivariate Poisson regression was used to estimate adjusted relative risks and 97.5% confidence intervals for the co-primary endpoints and 95% confidence intervals for binomial outcomes, and multinomial logistic regression was used to estimate adjusted odds ratios and 95% adjusted relative risks for multinomial outcomes.

Results: Of 6106 participants enrolled in the primary trial, 2933 underwent induction of labor with oxytocin: 861 in the mid- to high-dose group and 2072 in the low-dose group. The lower frequency of cesarean delivery in the mid- to high-dose group than in the low-dose group (20.3% vs 25.2%, respectively; relative risk, 0.81; 95% confidence interval, 0.69-0.94) was not significant after adjustment (adjusted relative risk, 0.90; 97.5% confidence interval, 0.76-1.07). The composite of perinatal death or severe neonatal complications was more frequent in the mid- to high-dose group than in the low-dose group (6.7% vs 4.3%, respectively; relative risk, 1.55; 95% confidence interval, 1.13-2.14) and remained significant after adjustment (adjusted relative risk, 1.61; 97.5% confidence interval, 1.11-2.35). Most cases in the composite were from the respiratory support (5.2% in the mid- to high-dose group vs 3.1% in the low-dose group) component, with an increase in transient tachypnea in newborns (3.8% in the mid- to high-dose group vs 2.5% in the low-dose group; adjusted relative risk, 1.63; 95% confidence interval, 1.04-2.54). The duration of neonatal respiratory support for 1 day was significantly longer in the mid- to high-dose group than in the low-dose group (3.5% vs 1.4%, respectively; adjusted relative risk, 2.59; 95% confidence interval, 1.52-4.39). However, support beyond 1 day was not different between the 2 groups. Compared with the low-dose group, the mid- to high-dose group had a higher operative vaginal delivery rate (10.0% vs 7.0%, respectively; adjusted relative risk, 1.54; 95% confidence interval, 1.18-2.00) and shorter duration of time from start of oxytocin to delivery (crude median: 12 hours [interquartile range, 8-17] vs 13 hours [interquartile range 9-19], respectively; adjusted median difference: -2 [95% CI, -2 to -1]; P<.001).

Conclusion: The use of mid-to high-dose oxytocin regimens for induction of labor in nulliparas at ≥39 weeks of gestation was not associated with a lower cesarean delivery rate or improved neonatal outcomes compared with the use of low-dose oxytocin regimens. Although the use of mid- to high-dose oxytocin regimens was associated with a shorter duration of labor, there was an increase in self-limited neonatal respiratory support and no difference in cesarean delivery rates. More evidences are needed to define the magnitude of potential maternal and neonatal benefits and risks associated with oxytocin regimens.