Associations of preterm birth, small-for-gestational age, preeclampsia and placental abruption with attention-deficit/hyperactivity disorder in the offspring: Nationwide cohort and sibling-controlled studies

Aim The aim of this study was to investigate preterm birth, small-for-gestational age (SGA), preeclampsia and placental abruption in relation to attention-deficit/hyperactivity disorder (ADHD) in offspring. Methods We conducted a population-based cohort study among non-malformed live-born singleton children in Sweden born during 2002-2014. Using national registries with recorded information, we followed 1,212,201 children for an ADHD diagnosis from 3 to 15 years. We compared ADHD rates between exposure categories using adjusted hazard ratios (HR) with 95% confidence intervals (CI) from Cox proportional hazards models. We also conducted sibling-controlled analyses among 751,464 full siblings. Results There were 27,665 ADHD diagnoses in the cohort. Compared with term birth (>= 37 weeks), adjusted HR (95% CI) for ADHD increased with decreasing gestational age: 1.18 (1.11, 1.25), 1.61 (1.37, 1.89) and 2.79 (2.23, 3.49) for 32-36 weeks, 28-31 weeks and 22-27 weeks. Both spontaneous and medically indicated preterm birth were associated with ADHD. SGA was related to 1.62 (1.49, 1.77) times higher ADHD incidence. Preeclampsia, but not placental abruption, was associated with ADHD. Sibling-controlled analyses showed similar results. Preterm birth did not fully explain the associations of SGA or preeclampsia with ADHD. Conclusion Preterm birth, SGA and preeclampsia are related to ADHD incidence in offspring.