Parental Obesity and Risk of Metabolic Dysfunction Associated Steatotic Liver Disease in Adult Offspring: UK Birth Cohort Study

BACKGROUND:Metabolic dysfunction associated steatotic liver disease (MASLD), the most common chronic liver disease globally, may originate early in life. While maternal obesity is linked to offspring MASLD, the roles of paternal obesity and mediation by childhood adiposity remain unclear. OBJECTIVES:This study evaluates prospective associations between pre-pregnancy biparental adiposity and offspring MASLD in adulthood. DESIGN:We included 1933 offspring from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) to assess the associations between parental pre-pregnancy body mass index (BMI) and odds of offspring MASLD at age 24 years. MASLD was defined as hepatic steatosis on transient elastography and ≥1 cardiometabolic risk factors. We evaluated causal mediation by childhood adiposity measures. RESULTS:At age 24 years, 10.4% of offspring had MASLD. Pre-pregnancy maternal and paternal obesity were independently associated with an increased odds of offspring MASLD. Each 1 kg/m2 increase in maternal BMI increased the odds of MASLD by 10% (Odds Ratio [OR] 1.10, 95% CI 1.06 to 1.14), while each 1 kg/m2 increase in paternal BMI raised the odds by 9% (OR 1.09, 95% CI 1.04 to 1.13). Biparental overweight or obesity was associated with 3.73 times the odds of offspring MASLD (OR 3.73, 95% CI 2.43 to 5.73) compared with parents with a normal BMI, with 67% of this association mediated by cumulative excess childhood BMI, a defined area under the curve for BMI Z score >1 for ages 7-17 years. CONCLUSIONS:Excess parental adiposity pre-pregnancy was associated with a higher odds of offspring MASLD, mediated by cumulative excess childhood BMI, highlighting the potential of life course interventions to reduce the risk of MASLD in future generations.