High- vs low-dose oxytocin protocols for labor induction: a systematic review and meta-analysis

Objective: This systematic review aimed to synthesize available literature reporting maternal and neonatal outcomes of induction of labor using high- vs low-dose oxytocin protocols. Data Sources: PubMed, Embase, Scopus, CINAHL, and Cochrane databases, and ClinicalTrials.gov were searched from inception to January 17, 2023. Study Eligibility Criteria: Studies with the following criteria were included: randomized or observational studies conducted with pregnant individuals, published in English, that compared low-dose (starting dose 0.5–2 milliunits/min increased by 1–2 milliunits/min every 15–40 minutes) vs high-dose (≥4 milliunits/min increased by 3–6 milliunits/min every 15–40 minutes) oxytocin infusion protocols for induction of labor. Studies of individuals with fetal death were excluded. Study Appraisal and Synthesis Methods: Two reviewers independently extracted data and appraised study quality following the PRISMA guidelines and using the Cochrane risk of bias assessment tools. The primary outcome was cesarean delivery. Secondary outcomes included spontaneous vaginal delivery, operative vaginal delivery, duration of labor induction, uterine tachysystole, and maternal and neonatal morbidity outcomes. Pooled relative risks (RR) with 95% confidence intervals (CI) were calculated using random-effects models. Heterogeneity was assessed statistically using the Higgins’ I² test and visually using a funnel plot. Results: Six studies (two randomized controlled trials, four observational studies) were included, encompassing 7850 deliveries (3957 in the high-dose group and 3893 in the low-dose group). Overall, there was no difference in the risk of cesarean delivery following induction of labor with a high-dose oxytocin protocol compared with a low-dose protocol (26.0% vs 28.4%, pooled RR 1.02, 95% CI 0.85–1.21). There were also no differences in the likelihood of cesarean delivery for nonreassuring fetal status or neonatal morbidity, or in the duration of labor. Induction with high-dose oxytocin was associated with a lower frequency of postpartum hemorrhage, compared with a low-dose protocol (7.6% vs 9.9%, RR 0.78, 95% CI 0.66–0.92). Details of high- and low-dose protocols varied widely between studies, which all were at medium or high risk of bias. There was moderate heterogeneity (I²=45.5%), and no evidence of publication bias (Harbord test, P=.74). Conclusions: A synthesis of the existing literature demonstrates no difference in the frequency of cesarean delivery following induction of labor using a high- vs low-dose oxytocin protocol. However, this review highlights the methodological limitations of the few available published studies and the need for high-quality trials to guide optimal oxytocin dosing for labor induction.