Background
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide with rising incidence in children and young adults. Emerging evidence suggests that developmental and early-life exposures, such as parental obesity, may play a critical role in one’s susceptibility to disease, yet epidemiologic evidence is limited.
Methods
We conducted a prospective case-cohort study leveraging data from the Avon Longitudinal Study of Parents and Children, a birth cohort study enrolling over 14,000 pregnancies between 1990 and 1992 in Avon, UK. Offspring were followed periodically from birth to adulthood, with assessments on lifestyle, clinical measures, and collection of biologic specimens. At age 24, transient elastography (TE) was also performed along with measurement of plasma/serum biomarkers. MASLD was identified based on the recently updated definition, using the presence of at least grade S1 (≥ 11%) steatosis on TE and at least one cardiometabolic risk factor: BMI ≥25 kg/m²or waist circumference >94cm for men, >80cm for women; fasting glucose >100mg/dL, HbA1c ≥5.7%, or known diabetes; blood pressure ≥130/85 or known hypertension; triglycerides >= 150mg/dL or on lipid-lowering medication; and/or HDL ≤40mg/dL for males, ≤50mg/dL for females). Logistic regressions were used to assess the relationships between parent BMI, with adjustment of a range of parental characteristics during pregnancy (parental age, education, pre-pregnancy alcohol consumption, smoking; maternal physical activity, diet, and Townsend Deprivation Index) and early life factors (mode of delivery, birthweight, duration of breastfeeding, early antibiotic exposure, and diet at age 7).
Results
A total of 3668 offspring were included with a MASLD prevalence of 18.4% (n=XX) at age 24. Maternal and parental obesity were independently associated with offspring risk of MASLD. Specifically, maternal obesity (every 5 unit increase in BMI) was associated with 37% (aOR 1.37, 95% CI 1.14 – 1.64) increased risk of offspring MASLD, and paternal obesity (every 5 unit increase in BMI) was associated with 54% (aOR 1.54, 95% CI 1.26 – 1.87) higher risk of MASLD in the offspring. Notably, offspring with parents who were both overweight (BMI≥25 kg/m2) at pregnancy had 2.61-fold risk of MASLD in young adulthood (aOR 2.61, 95% CI 1.73 – 3.95) compared to those with both parents with normal weight.
Conclusion
To our knowledge, this is among the initial studies to demonstrate that obesity in both mothers and fathers is linked to a heightened risk of MASLD in their children, extending into early adulthood. These compelling results underscore the importance of further validation in diverse populations and emphasize the urgency of preventing and managing parental obesity as a way to combat the escalating incidence of MASLD among younger generations.

Phillip Tarr

Washington Univ School of Medicine

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