In utero exposure to ischemic-hypoxic conditions and attention-deficit/hyperactivity disorder

To examine the association between ischemic-hypoxic conditions (IHCs) and attention-deficit/hyperactivity disorder (ADHD) by gestational age and race/ethnicity.

Nested case-control study using the Kaiser Permanente Southern California (KPSC) medical records. The study cohort included children aged 5 to 11 years who were delivered and cared for in the KPSC between 1995 and 2010 (N = 308,634). Case children had a diagnosis of ADHD and received ≥ 2 prescriptions specific to ADHD during the follow-up period. For each case, 5 control children were matched by age at diagnosis. Exposures were defined by using International Classification of Diseases, Ninth Revision codes. A conditional regression model was used to estimate adjusted odds ratios (ORs).

Among eligible children, 13,613 (4.3%) had a diagnosis of ADHD. Compared with control children, case children were more likely to be male and of white or African American race/ethnicity. Case children were more likely to be exposed to IHCs (OR = 1.16, 95% confidence interval [CI] 1.11-1.21). When stratified by gestational age, cases born at 28 to 33, 34 to 36, and 37 to 42 weeks of gestation, were more likely to be exposed to IHCs (ORs, 1.6 [95% CI 1.2-2.1], 1.2 [95% CI 1.1-1.3], and 1.1 [95% CI 1.0-1.2], respectively) compared with controls. IHC was associated with increased odds of ADHD across all race/ethnicity groups.

These findings suggest that IHCs, especially birth asphyxia, respiratory distress syndrome, and preeclampsia, are independently associated with ADHD. This association was strongest in preterm births.