Association between prenatal antimicrobial use and offspring attention deficit hyperactivity disorder

Abstract

Background Gut-brain cross-talk may play an important role in modulating neurodevelopment. Few studies have examined the association between antimicrobials that influence infant gut microbiota assemblage and attention deficit hyperactivity disorder (ADHD). Objective To examine the association between maternal prenatal antimicrobial use and ADHD in offspring at 10 years of age. Methods Data are from the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study, a racially and socioeconomically diverse birth cohort in metropolitan Detroit, Michigan. Maternal antimicrobial use was extracted from the medical record. ADHD diagnoses were based on parental report at the 10-year study visit. Poisson regression models with robust error variance were used to calculate risk ratios (RR). Cumulative frequency of exposure to antibiotics, and effect modification were also evaluated. Results Among the 555 children included in the analysis, 108 were diagnosed with ADHD. During pregnancy, 54.1% of mothers used antibiotics while 18.7% used antifungals. Overall, there was no evidence of an association between prenatal antibiotic exposure and ADHD (RR [95% CI] = 0.98 [0.75, 1.29]), but there was an increased risk of ADHD among those with mothers using 3+ courses of antibiotics (RR [95%CI] = 1.58 [1.10, 2.29]). Prenatal exposure to antifungals was associated with a 1.6 times higher risk of ADHD (RR [95% CI] = 1.60 [1.19, 2.15]). In examining effect modification by child sex for antifungal use, there was no evidence of an association among females (RR [95% CI] = 0.97 [0.42, 2.23]), but among males, prenatal antifungal use was associated with 1.82 times higher risk of ADHD (RR [95% CI] = 1.82 [1.29, 2.56]). Conclusions Maternal prenatal antifungal use and frequent prenatal antibiotic use are associated with an increased risk of ADHD in offspring at age 10. These findings highlight the importance of the prenatal environment and the need for careful use of antimicrobials.