Association between prenatal antimicrobial use and offspring attention deficit hyperactivity disorder.

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.

Early-life gut microbiota and attention deficit hyperactivity disorder in preadolescents.

BACKGROUND: Gut microbiota maturation coincides with nervous system development. Cross-sectional data suggest gut microbiota of individuals with and without attention deficit hyperactivity disorder (ADHD) differs. We hypothesized that infant gut microbiota composition is associated with later ADHD development in our on-going birth cohort study, WHEALS. METHODS: Gut microbiota was profiled using 16S ribosomal RNA and the internal transcribed spacer region 2 (ITS2) sequencing in stool samples from 1 month and 6 months of age. ADHD was defined by parent-reported or medical record doctor diagnosis at age 10. RESULTS: A total of 314 children had gut microbiota and ADHD data; 59 (18.8%) had ADHD. After covariate adjustment, bacterial phylogenetic diversity (p = 0.017) and bacterial composition (unweighted UniFrac p = 0.006, R2 = 0.9%) at age 6 months were associated with development of ADHD. At 1 month of age, 18 bacterial and 3 fungal OTUs were associated with ADHD development. At 6 months of age, 51 bacterial OTUs were associated with ADHD; 14 of the order Lactobacillales. Three fungal OTUs at 6 months of age were associated with ADHD development. CONCLUSIONS: Infant gut microbiota is associated with ADHD development in pre-adolescents. Further studies replicating these findings and evaluating potential mechanisms of the association are needed. IMPACT: Cross-sectional studies suggest that the gut microbiota of individuals with and without ADHD differs. We found evidence that the bacterial gut microbiota of infants at 1 month and 6 months of age is associated with ADHD at age 10 years. We also found novel evidence that the fungal gut microbiota in infancy (ages 1 month and 6 months) is associated with ADHD at age 10 years. This study addresses a gap in the literature in providing longitudinal evidence for an association of the infant gut microbiota with later ADHD development.

Prenatal IgE as a Risk Factor for the Development of Childhood Neurodevelopmental Disorders.

Background: Few studies have examined if maternal allergic disease is associated with an offspring's neurodevelopment. We hypothesized that Th-2 biased maternal immune function assessed as total serum immunoglobulin (Ig) E is associated with attention deficit hyperactivity disorder (ADHD). Methods: Data are from the Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study (WHEALS), a racially and socioeconomically diverse birth cohort in metropolitan Detroit, Michigan. Maternal total IgE was measured prenatally and at 1-month postpartum. Child total IgE was assessed at birth, 6 months, and 2 years of age. ADHD diagnosis was based on the parental report at the 10-12-year study visits or medical chart abstraction. Total IgE was log2 transformed. Poisson regression models with robust error variance were used to calculate the risk ratios (RR). Inverse probability weighting was used to correct for potential bias due to a loss to follow-up and non-response. Results: Of the 636 maternal-child pairs in the analysis, 513 children were neurotypical and 123 had ADHD. Maternal prenatal total IgE was significantly associated with ADHD even after adjustment for potential confounders (RR = 1.08, 95% CI 1.03-1.13). Maternal and child IgE measures were positively and significantly correlated, but child total IgE was not associated with ADHD at any time point. Conclusions: Maternal prenatal IgE may influence neurodevelopment, but additional studies are needed to confirm and expand these findings.

Prenatal pet keeping and caregiver-reported attention deficit hyperactivity disorder through preadolescence in a United States birth cohort.

BACKGROUND: While the keeping of pets has been shown to protect against childhood allergic disease and obesity, less is known regarding potential associations of prenatal pet keeping and attention deficit hyperactivity disorder (ADHD). We sought to examine the associations between prenatal dog or cat keeping with caregiver-reported ADHD in preadolescents in the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) birth cohort (N = 1258). METHODS: At an interview with the caregiver at child age 10-12 years, caregivers reported if the WHEALS child had ever been diagnosed with ADHD. Similarly, during an interview with the mother prenatally, pet keeping (defined as dog or cat kept inside ≥1 h/day) was ascertained. Logistic regression models were fit to examine the association of prenatal pet keeping (dog keeping and cat keeping, separately) with ADHD. RESULTS: A subset of 627 children were included in the analyses: 93 who had ADHD and 534 with neurotypical development. After accounting for confounders and loss to follow-up, maternal prenatal dog exposure was associated with 2.23 times (95% CI: 1.15, 4.31; p = 0.017) greater odds of ADHD among boys. Prenatal dog keeping was not statistically significantly associated with ADHD in girls (odds ratio = 0.27, 95% CI: 0.06, 1.12; p = 0.070). Prenatal cat keeping was not associated with ADHD. CONCLUSIONS: In boys, but not girls, maternal prenatal dog keeping was positively associated with ADHD. Further study to confirm these findings and to identify potential mechanisms of this association (e.g., modification of the gut microbiome, exposure to environmental toxicants or pet-related medications) is needed.