Long-term health, neurodevelopmental and educational outcomes of children born to mothers with hyperemesis gravidarum: A population-based sibling-design record linkage cohort study.

Background: Hyperemesis gravidarum (HG), characterised by severe and constant nausea and vomiting in pregnancy, can lead to nutritional deficiencies and other pregnancy complications. In turn, HG has also been linked with adverse long-term health and neurodevelopmental outcomes for the children of women affected by HG. However, previous studies have not accounted for potential confounding due to shared family-level factors.

Objective: This study aimed to determine whether maternal HG was associated with long-term educational, neurodevelopmental, and health outcomes for children, and whether these findings were substantiated when using a sibling-comparison design.

Study Design: This population-based record linkage cohort study featured livebirths in New South Wales, Australia from 2002 to 2010. Maternal HG was classified using hospital admissions and emergency department presentations during pregnancy. Outcomes included standardised educational testing at Year 3 (age 7 to 9 years), disability service utilisation for neurodevelopmental disorders (NDDs), and age-specific hospitalisations up to 7 years of age. Robust Poisson models with generalised estimating equations were used to estimate the risk of lower educational performance and hospitalisations. Cox Proportional Hazards models with a robust sandwich estimator were used to assess the time to first NDD-related disability service. Inverse probability of treatment weighting was used to account for potential confounding. Analyses were also restricted to an exposure-discordant sibling cohort to account for unmeasured genetic and familial factors.

Results: Of the 700,082 livebirths included in our study, 10,282 (1.5%) were born to mothers who had HG during their pregnancy. Maternal HG was associated with a higher risk of their offspring being below the national standard in reading (aRR 1.19, 95% CI 1.09-1.29), spelling (aRR 1.24, 95% CI 1.14-1.34), grammar (aRR 1.12, 95% CI 1.03-1.22) and numeracy (aRR 1.14, 95% CI 1.03-1.23), as well as utilisation of NDD-related disability services (aHR 1.44, 95% 1.27-1.63) and age-specific hospitalisations (<1 year, aRR 1.35, 95% CI 1.30-1.39; 1 to 4 years, aRR 1.24, 95% CI 1.21-1.27; 5 to 7 years, aRR 1.25, 95% CI 1.20-1.29). However, for most outcomes these associations were nullified in the sibling cohort.

Conclusions: We did not find an association between HG exposure and long-term educational, neurodevelopmental, and health outcomes for children when accounting for shared family influences using a sibling-comparison design. The lack of evidence of a direct link between maternal HG and long-term impacts on children is reassuring for mothers who are afflicted with this condition.