Long-term risk of epilepsy, cerebral palsy and attention-deficit/hyperactivity disorder in children affected by a threatened abortion in utero

Abstract

Background: The birth of a child affected by a threatened abortion (TAB) in utero is associated with autism spectrum disorder; association with other neurological disorders is unknown. Methods: This nationwide registry-based cohort study included singletons live-born in Denmark (1979-2010), followed through 2016. The outcomes were epilepsy, cerebral palsy (CP) and attention-deficit/hyperactivity disorder (ADHD). We used Cox regression to compute hazard ratios (HRs), adjusted for birth year, birth order, parental age, morbidity, medication use and maternal socio-economic factors. To remove time-invariant family-shared confounding, we applied sibling analyses. Results: The study population included 1 864 221 singletons live-born in 1979-2010. Among the TAB-affected children (N = 59 134) vs TAB-unaffected children, at the end of follow-up, the cumulative incidence was 2.2% vs 1.6% for epilepsy, 0.4% vs 0.2% for CP and 5.5% vs 4.2% for ADHD (for children born in 1995-2010). The adjusted HRs were 1.25 [95% confidence interval (CI) 1.16-1.34] for epilepsy, 1.42 (95% CI 1.20-1.68) for CP and 1.21 (95% CI 1.14-1.29) for ADHD. In the sibling design, the adjusted HRs were unity for epilepsy (full siblings: 0.96, 95% CI 0.82-1.12; maternal: 1.04, 95% CI 0.90-1.20; paternal: 1.08, 95% CI 0.93-1.25) and ADHD (full: 1.08, 95% CI 0.92-1.27; maternal: 1.04, 95% CI 0.90-1.20; paternal: 1.08, 95% CI 0.93-1.25). For CP, HRs shifted away from unity among sibling pairs (full: 2.92, 95% CI 1.33-6.39; maternal: 2.03, 95% CI 1.15-3.57; paternal: 3.28, 95% CI 1.36-7.91). Conclusions: The birth of a child affected by TAB in utero was associated with a greater risk of CP, but not epilepsy or ADHD.