The causal association between maternal depression, anxiety, and infection in pregnancy and neurodevelopmental disorders among 410 461 children: a population study using quasi-negative control cohorts and sibling analysis

• DOI: 10.1017/s0033291723003604
• Publication Date: 2024-01-11T08:59:20Z
• Authors: Holly Hope; Matthias Pierce; Hend Gabr; Maja R. Radojčić; Eleanor Swift; Vicky P. Taxiarchi; Kathryn M. Abel
• Keywords: Depression

Abstract Background To address if the long-standing association between maternal infection, depression/anxiety in pregnancy, and offspring neurodevelopmental disorder (NDD) is causal, we conducted two negative-control studies. Methods Four primary care cohorts of UK children (pregnancy, 1 2 years prior to siblings) born January 1990 31 December 2017 were constructed. NDD included autism/autism spectrum disorder, attention-deficit/hyperactivity intellectual disability, cerebral palsy, epilepsy. Maternal exposures and/or infection. (age, smoking status, comorbidities, body mass index, NDD); child (gender, ethnicity, birth year); area-level (region level deprivation) confounders captured. The incidence rate among (1) exposed during or outside pregnancy (2) siblings discordant for exposure was compared using Cox-regression models, unadjusted adjusted confounders. Results analysis 410 461 297 426 mothers 793 018 person-years follow-up with 8900 cases (incidence = 3.2/1000 person years). After adjustments, depression anxiety consistently associated (pregnancy-adjusted HR 1.58, 95% CI 1.46–1.72; 1-year adj. 1.49, 1.39–1.60; 2-year 1.62, 1.50–1.74); a lesser extent, infection (pregnancy 1.16, 1.10–1.22; 1.20, 1.14–1.27; 1.19, 1.12–1.25). risk did not differ mental illness 0.97, 0.77–1.21 0.99, 0.90–1.08. Conclusions appears be unspecific pregnancy: our study provided no evidence specific, therefore link in-utero common illness, later development NDD.