Background Hypertensive disorders of pregnancy (HDP) have been linked to adverse neurodevelopmental outcomes, including attention deficit hyperactivity disorder (ADHD). However, limitations of the literature such as residual confounding, and confounding due to shared genetics need to be addressed before more definitive conclusions can be reached. Therefore, the objective of this study was to examine the association between HDP and ADHD, using large Swedish-based registry data, allowing us to control for a wide range of confounding factors including confounding due to shared genetics.

Methods All singleton live births in Sweden from 1990 to 2010 were included in the study. Data on HDP were obtained from the Medical Birth Register, and included three exposures of interest: 1. Preeclampsia 2. Chronic hypertension (both of which were classified according to ICD-9 and ICD-10 coding) 3. Preeclampsia and small for gestational age (SGA) combined, used as a proxy for the recent inclusion of uteroplacental dysfunction in the definition of preeclampsia. Data on ADHD was obtained from the National Patient Register and Prescribed Drug Register. A diagnosis of ADHD was determined in one of two ways: 1. If a diagnosis of ADHD was present in the National Patient Register, using ICD-10 coding. 2. If an individual was in receipt of ADHD medication, classified according to Anatomical Therapeutic Chemical classification system. Multivariate Cox proportional hazards regression analysis was conducted, adjusting for several perinatal and sociodemographic factors, selected a priori from previous literature. Sibling-matched analysis further controlled for shared genetic and familial confounding when an association was present in the adjusted Cox model.

Results The cohort consisted of 2,047,619 children, with 114,934 (5.6%) cases of ADHD. In the adjusted Cox model, preeclampsia was associated with a 15% increase in the likelihood of ADHD (Hazard Ratio (HR): 1.15, 95% CI: 1.12, 1.19) compared to those unexposed to preeclampsia. Result of the sibling-matched analysis did not change materially (HR: 1.13, 95% CI: 1.05, 1.22). The HR for preeclampsia and those born SGA was 1.43 (95% CI: 1.31, 1.55) in the adjusted model, and 1.55 (95% CI: 1.28, 1.88) in the sibling-matched analysis. The HR for chronic hypertension-ADHD was 1.07 (95% CI: 0.97, 1.18) in the adjusted Cox model.

Conclusion Exposure to preeclampsia or preeclampsia/SGA (i.e. SGA baby exposed to preeclampsia) was associated with ADHD, while chronic hypertension was not associated with ADHD. Placental pathology may be a common factor increasing the likelihood of ADHD given the stronger association with preeclampsia/SGA than preeclampsia alone.