Intrapartum exposure to synthetic oxytocin, maternal BMI, and neurodevelopmental outcomes in children within the ECHO consortium

Background: Synthetic oxytocin (sOT) is frequently administered during parturition. Studies have raised concerns that fetal exposure to sOT may be associated with altered brain development and risk of neurodevelopmental disorders. In a large and diverse sample of children with data about intrapartum sOT exposure and subsequent diagnoses of two prevalent neurodevelopmental disorders, i.e., attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we tested the following hypotheses: (1) Intrapartum sOT exposure is associated with increased odds of child ADHD or ASD; (2) associations differ across sex; (3) associations between intrapartum sOT exposure and ADHD or ASD are accentuated in offspring of mothers with pre-pregnancy obesity.

Methods: The study sample comprised 12,503 participants from 44 cohort sites included in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Mixed-effects logistic regression analyses were used to estimate the association between intrapartum sOT exposure and offspring ADHD or ASD (in separate models). Maternal obesity (pre-pregnancy BMI ≥ 30 kg/m²) and child sex were evaluated for effect modification.

Results: Intrapartum sOT exposure was present in 48% of participants. sOT exposure was not associated with increased odds of ASD (adjusted odds ratio [aOR] 0.86; 95% confidence interval [CI], 0.71-1.03) or ADHD (aOR 0.89; 95% CI, 0.76-1.04). Associations did not differ by child sex. Among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of offspring ADHD (aOR 0.72; 95% CI, 0.55-0.96). No association was found among mothers without obesity (aOR 0.97; 95% CI, 0.80-1.18).

Conclusions: In a large, diverse sample, we found no evidence of an association between intrapartum exposure to sOT and odds of ADHD or ASD in either male or female offspring. Contrary to our hypothesis, among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of child ADHD diagnosis.