Pre-pregnancy maternal steatotic liver disease and offspring neurodevelopmental disorders: a nationwide cohort study

Background/Purpose: Maternal metabolic health before pregnancy is increasingly linked to offspring neurodevelopment, but metabolic dysfunction-associated steatotic liver disease (MASLD), the most common chronic liver disease worldwide, has not been examined in this context. We investigated whether maternal steatotic liver disease (SLD) phenotypes identified before pregnancy are associated with offspring neurodevelopmental disorders. Methods: In this nationwide Korean cohort of 778,401 mother-child pairs linked to a pre-pregnancy health examination, mothers were classified as having no SLD, MASLD, or alcohol-involved SLD using the fatty liver index, cardiometabolic criteria, alcohol intake, and diagnostic codes. Offspring intellectual disability, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) were followed through 2022. Cox regression estimated hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for maternal metabolic, socioeconomic, lifestyle, and obstetric factors. Results: Of 778,401 offspring, 94.5% were born to mothers with no SLD, 4.9% to mothers with MASLD, and 0.5% to mothers with alcohol-involved SLD. In fully adjusted models, MASLD was not associated with intellectual disability (HR 1.05, 95% CI 0.89-1.24) or ASD (1.18, 0.98-1.44), but showed a modest association with ADHD (1.09, 1.01-1.17) that attenuated under a stricter ADHD definition requiring at least two separate claims (1.06, 0.98-1.15). Alcohol-involved SLD showed no statistically significant associations with any outcome. Conclusion: Maternal MASLD showed a modest, attenuating association with offspring ADHD but no clear association with intellectual disability or ASD. These hypothesis-generating findings clarify the boundaries of the association between a common maternal hepatic-metabolic phenotype and offspring neurodevelopment, and warrant confirmation with pregnancy-specific exposure assessment and sibling-comparison designs.