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

Abstract

Background

Hyperemesis gravidarum (HG), characterized 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 live births in New South Wales, Australia from 2002 to 2010. Maternal HG was classified using hospital admissions and emergency department presentations during pregnancy. The outcomes included standardized educational testing at year 3 (age 7–9 years), disability service utilization for neurodevelopmental disorders, and age-specific hospitalizations up to 7 years of age. Robust Poisson models with generalized estimating equations were used to estimate the risk of lower educational performance and hospitalizations. Cox proportional hazards models with a robust sandwich estimator were used to assess the time to first neurodevelopmental disorder–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 live births 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 (adjusted risk ratio 1.19, 95% confidence interval [CI] 1.09–1.29), spelling (adjusted risk ratio 1.24, 95% CI 1.14–1.34), grammar (adjusted risk ratio 1.12, 95% CI 1.03–1.22), and numeracy (adjusted risk ratio 1.14, 95% CI 1.03–1.23), as well as utilization of neurodevelopmental disorder–related disability services (adjusted hazard ratio 1.44, 95% 1.27–1.63) and age-specific hospitalizations (<1 year, adjusted risk ratio 1.35, 95% CI 1.30–1.39; 1–4 years, adjusted risk ratio 1.24, 95% CI 1.21–1.27; 5–7 years, adjusted risk ratio 1.25, 95% CI 1.20–1.29). However, for most outcomes these associations were nullified in the sibling cohort.

Conclusion

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.