Associations of pregnancy complications and neonatal characteristics with bipolar disorder in the offspring: Nationwide cohort and sibling-controlled studies

Abstract

Objectives: To investigate associations of neonatal characteristics and pregnancy complications with bipolar disorder (BPD) in offspring. Methods: We conducted a nationwide cohort study among 2,059,578 non-malformed singleton live-births in Sweden born 1983–2004. Using national registries with prospectively recorded information, we followed participants for a BPD diagnosis from 13 up to 34 years of age. We compared BPD risks between exposure categories using hazard ratios (HR) with 95% confidence intervals (CI) from adjusted Cox models. We also conducted sibling-controlled analyses among 1,467,819 full siblings. Results: There were 14,998 BPD diagnoses. Risk of BPD was 0.74% through 25 years of age. Very/extremely preterm birth (22 to 31 weeks) was related to increased BPD HRs in sibling-controlled analyses; compared with a gestational age of 37 weeks, adjusted HR (95% CI) for 31, 28, and 22 weeks were, respectively, 1.31 (0.99, 1.74), 2.09 (1.15, 3.79), and 5.74 (1.15, 28.63). Spontaneous but not medically indicated very/extremely preterm birth was associated with increased risk. Compared with vaginal birth, caesarean section birth was associated with 1.20 (1.08, 1.33) and 1.58 (1.06, 2.36) times higher BPD risk in general and sibling cohorts, respectively. Small-for-gestational age (SGA) birth was related to increased BPD HRs in general cohort and sibling analyses (HRs [95% CI] were 1.22 [1.06, 1.39] and 1.68 [1.13, 2.50], respectively); only term SGA was associated with increased risk. Head circumference-for-gestational age, gestational diabetes, preeclampsia, and placental abruption were not associated with BPD. Conclusions: Very/extremely preterm birth, caesarean birth, and SGA are related to BPD incidence.