Prenatal exposure to maternal asthma and asthma medication and neurodevelopmental outcomes: a population cohort study of 179,024 children.

BACKGROUND

Asthma exacerbations during pregnancy can adversely affect maternal and foetal health. However, prenatal exposure to asthma medication may itself impact child outcomes. This study aims to determine whether prenatal exposure to asthma medication was associated with a range of neurodevelopmental outcomes.

METHODS

A birth cohort was constructed using linked health and education records of children liveborn in Wales from 2009 to 2016, with up to 12 years follow-up. Generalized estimating equations with a binomial distribution and logit link function were employed to evaluate special educational need (SEN) and its causes, including autism spectrum disorder (ASD), communication problems, behavioural, emotional, and social difficulties, learning difficulties, physical and medical difficulties, and sensory impairment. Cox proportional hazard models were used to investigate attention deficit hyperactivity disorder (ADHD).

RESULTS

Of the 179,024 offspring, 11,991 (6.7%) had mothers with treated asthma, 4927 (2.8%) had mothers with untreated asthma, and 5265 (2.9%) had mothers who took asthma medication without a record of asthma. SEN was recorded in 50,955 (28.5%) children. Risk of overall SEN and ADHD was higher following prenatal exposure to short-acting beta-agonists (SABA) and inhaled corticosteroids (ICS) but also higher in the offspring of mothers with untreated asthma (SEN aOR 1.14, 95% CI 1.07-1.23; ADHD aHR 1.70, 95% CI 1.42-2.05). ASD was associated with treated, but not untreated, asthma and the association with prenatal medication was specific to SABA as mono- or polytherapy (aOR 1.20, 95% CI 1.05-1.37). However, a direct comparison of treated with untreated asthma was not statistically significant.

CONCLUSIONS

The non-specific associations with overall SEN and ADHD are likely to reflect their associations with asthma and confounding by indication/severity. The associations with ASD may reflect a treatment effect of SABA or confounding by severity. Further studies are needed to confirm or refute the former, to support evidence-based asthma management during pregnancy.