Outcomes among participants vs nonparticipants of randomized trials during pregnancy: a systematic review and meta-analysis

OBJECTIVE: This study aimed to evaluate the outcomes among individuals who were eligible and approached for participation in a randomized controlled trial during pregnancy, comparing those who enrolled with those who declined participation. DATA SOURCES: MEDLINE, Scopus, CINAHL, the Cochrane Library, and Ovid were searched from study inception to May 2022. STUDY ELIGIBILITY CRITERIA: This study included all obstetrical randomized controlled trials that reported clinical outcomes for both participants and nonparticipants. METHODS: The primary outcome captured the presence of morbidity. It was a composite of the primary outcome of each study comparing the participant arm with the nonparticipant arm. If a primary outcome was not clearly defined, a surrogate was developed on the basis of the core outcomes for the clinical condition studied. The risk of bias was assessed with the Newcastle-Ottawa Scale. Subgroup analyses for relevant obstetrical and neonatal outcomes were performed. The summary comparisons were reported as odds ratios with 95% confidence intervals computed using random-effects meta-analysis with heterogeneity evaluated using the I2 statistic. A funnel plot was used to examine publication bias, and there was no asymmetry. RESULTS: After reviewing more than 1100 abstracts, 17 obstetrical randomized controlled tri-als (103,610, with 26,293 participants and 77,317 nonparticipants) met our inclusion criteria and were analyzed. Of note, 9 studies were not rated as high quality, primarily for failing to control for confounding factors. Trial interventions were categorized as antepartum (n=11),intrapartum (n=5), or postpartum (n=1). Overall, participants in obstetrical randomized con-trolled trials had no difference in outcomes compared with nonparticipants (n=17: odds ratio, 0.88; 95% confidence interval, 0.52-1.49; I2=90%). Moreover, there was no difference seen when only randomized controlled trials that reported a primary outcome were included (n=12: odds ratio, 0.76; 95% confidence interval, 0.38-0.1.49; I2=93%). In addition, there was no difference noted in the subgroup where the randomized controlled trial intervention was not available to nonparticipants (n=7: odds ratio, 0.91; 95% confidence interval, 0.45 -1.85; I2=68%). CONCLUSION: Pregnant individuals who agreed to participate in randomized controlled trials had no difference in outcomes compared with those who decline participation. Pregnant indi-viduals should be provided with this reassuring information when offered to participate in a randomized controlled trial. Moreover, this information may improve patient recruitment into randomized controlled trials.