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, maternal pre-pregnancy phenotypes (no SLD, MASLD, and alcohol-involved SLD) were defined using the fatty liver index (FLI), cardiometabolic criteria, alcohol intake, and diagnostic codes. Offspring were followed through 2022 for registration-confirmed intellectual disability and autism spectrum disorder (ASD) and for claims-based attention-deficit/hyperactivity disorder (ADHD). Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs), with and without adjustment for body mass index (BMI), diabetes, hypertension, and dyslipidemia in addition to other covariates. RESULTS: Without this adjustment, MASLD was associated with intellectual disability (HR 1.72, 95% CI 1.52-1.96), ASD (1.42, 1.22-1.66), and ADHD (1.22, 1.15-1.30). After this adjustment, HRs were 1.05 (0.89-1.24), 1.18 (0.98-1.44), and 1.09 (1.01-1.17), respectively. The ADHD estimate was smaller when at least two separate claims were required (1.06, 0.98-1.15). Estimates for alcohol-involved SLD were imprecise. CONCLUSION: Pre-pregnancy MASLD was associated with higher risks of offspring neurodevelopmental disorders in analyses without adjustment for maternal BMI and metabolic conditions. These associations were substantially attenuated after adjustment; a modest ADHD association remained only under the least stringent claims-based definition and should be interpreted with caution. These hypothesis-generating findings warrant confirmation with pregnancy-specific exposure assessment and sibling-comparison designs.