Oxytocin regimen used for induction of labor and pregnancy outcomes.

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

Objective(s): We sought to evaluate the association of oxytocin regimen with cesarean delivery and an adverse perinatal composite outcome in low-risk nulliparous patients undergoing IOL at 39 weeks of gestation or greater.

Study design: This is a secondary analysis of the NICHD Maternal-Fetal Medicine Units Network ARRIVE randomized trial. Patients induced with a mid-to high-dose oxytocin regimen (MHD; starting or incremental increase >2 mU/min) were compared with those receiving a low-dose oxytocin regimen (LD; 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. Multivariable Poisson regression was used to estimate adjusted relative risks (aRR) and 97.5% confidence intervals (CI) for the co-primary endpoints, 95% CI for binomial outcomes and multinomial logistic regression was used to estimate adjusted odds ratios (aOR) and 95% CIs for multinomial outcomes.

Results: Of 6,106 participants enrolled in the primary trial, 2,933 underwent induction with oxytocin: 861 in the MHD group and 2,072 in the LD group. The lower frequency of cesarean delivery in the MHD group compared with the LD group (20.3% vs. 25.2%, RR 0.81, 95%CI (0.69-0.94)) was not significant after adjustment (aRR 0.90, 97.5%CI (0.76-1.07)). The composite of perinatal death or severe neonatal complications was more frequent in the MHD group compared with the LD group (6.7% vs. 4.3%, RR 1.55, 95%CI (1.13-2.14)) and remained significant after adjustment (aRR 1.61, 97.5%CI (1.11-2.35)). The majority of the cases in the composite were from the respiratory support (5.2% vs. 3.1%) component with an increase in transient tachypnea of the newborn (3.8% vs. 2.5%, aRR 1.63, 95% CI (1.04-2.54)). The duration of neonatal respiratory support for one day was significantly higher in the MHD group compared with the LD group (3.5% vs. 1.4%, aRR 2.59, 95%CI (1.52-4.39)); however, support beyond one day was not different between the two groups. The MHD group, when compared with the LD group had a higher operative vaginal delivery rate (10.0% vs. 7.0%, aRR 1.54, 95%CI (1.18-2.00)) and shorter duration of time from start of oxytocin to delivery [crude median (interquartile range) 12 (8-17) vs. 13 (9-19) hours, adjusted median difference -2 (-2 to -1), p<0.001], respectively.

Conclusion(s): Mid-high-dose oxytocin regimen use for IOL in nulliparas at ≥ 39 weeks' gestation was not associated with improved maternal or neonatal outcomes compared with low-dose regimens. Although mid-high-dose oxytocin regimen use was associated with a shorter duration of labor, there was an increase in self-limited neonatal respiratory support and no difference in cesarean rates. More evidence is needed to define the magnitude of potential maternal and neonatal benefits and risks associated with oxytocin regimens.