Exogenous oxytocin administration during labor and autism spectrum disorder.

BACKGROUND: Oxytocin is a neuropeptide hormone that plays a key role in social behavior, stress regulation, and mental health. Synthetic oxytocin administration is a common obstetrical practice, and importantly, previous research has suggested that intrapartum exposure may increase the risk of neurodevelopmental disorders, such as autism spectrum disorder. OBJECTIVE: This study aimed to examine the association between synthetic oxytocin exposure during labor and autism spectrum disorder diagnosis in the child. STUDY DESIGN: This population-based retrospective cohort study compared 2 cohorts of children: (1) all children born in British Columbia, Canada between April 1, 2000 and December 31, 2014 (n=414,336 births), and (2) all children delivered at Soroka University Medical Center in Be'er-Sheva, Israel between January 1, 2011 and December 31, 2019 (n=82,892 births). Nine different exposure groups were examined. Cox proportional hazards models were used to estimate crude and adjusted hazard ratios of autism spectrum disorder in both cohorts on the basis of induction and/or augmentation exposure status. To further control for confounding by indication, we conducted sensitivity analyses among a cohort of healthy, uncomplicated deliveries and among a group that was induced only for postdates. In addition, we stratified our analyses by infant sex to assess for potential sex differences. RESULTS: In the British Columbia cohort, 170,013 of 414,336 deliveries (41.0%) were not induced or augmented, 107,543 (26.0%) were exposed to oxytocin, and 136,780 (33.0%) were induced or augmented but not exposed to oxytocin. In the Israel cohort, 51,790 of 82,892 deliveries (62.5%) were not induced or augmented, 28,852 (34.8%) were exposed to oxytocin, and 2250 (2.7%) were induced or augmented but not exposed to oxytocin. On adjusting for covariates in the main analysis, significant associations were observed in the Israel cohort, including adjusted hazard ratios of 1.51 (95% confidence interval, 1.20-1.90) for oxytocin-augmented births and 2.18 (95% confidence interval, 1.32-3.57) for those induced by means other than oxytocin and not augmented. However, oxytocin induction was not significantly associated with autism spectrum disorder in the Israel cohort. In the Canadian cohort, there were no statistically significant adjusted hazard ratios. Further, no significant sex differences were observed in the fully adjusted models. CONCLUSION: This study supports that induction of labor through oxytocin administration does not increase the risk of autism spectrum disorder in the child. Our international comparison of 2 countries with differences in clinical practice regarding oxytocin administration for induction and/or augmentation suggests that previous studies reporting a significant association were likely confounded by the underlying indication for the induction.

Autism Risk and Perinatal Antibiotic Use.

OBJECTIVES: Antibiotics are commonly administered during labor and delivery, and research has suggested that fetal exposure to antibiotics can increase risk for autism spectrum disorder (ASD). We assessed whether antibiotic exposure during labor and delivery increased the risk of ASD in the offspring. METHODS: This retrospective cohort study included everyone who delivered a live singleton-term infant in British Columbia, Canada, between April 1, 2000, and December 31, 2014. This cohort included 569 953 deliveries. To examine the association among pregnant individuals being treated for the same indication, we studied a subcohort of those who tested positive for group B Streptococcus. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios in both cohorts. A sensitivity analysis was conducted using length of first stage of labor as a proxy measure for dose to assess for a dose-response relationship. RESULTS: In this population-based study, antibiotic use during labor and delivery was not associated with an increased risk of ASD in offspring. The unadjusted and adjusted hazard ratios were 1.29 (95% confidence interval, 1.24-1.35) and 0.99 (0.94-1.04), respectively; and 1.07 (0.90-1.27) and 0.88 (0.74-1.05), respectively, in the group B Streptococcus-positive cohort. We observed no substantial difference in the association between antibiotic exposure and ASD depending on length of the first stage of labor. CONCLUSIONS: Our findings suggest that concern for ASD should not factor into the clinical decision on whether to administer antibiotics during labor and delivery. Future research is needed to examine longer durations of prenatal antibiotic exposure.