Sex differences between parental pregnancy characteristics and nonalcoholic fatty liver disease in adolescents

Nonalcoholic fatty liver disease (NAFLD) is a complex chronic liver disorder. Examination of parental pregnancy-related characteristics may provide insights into the origins of risk of NAFLD in offspring. We examined relationships between parental pregnancy-related characteristics and NAFLD in 1170 adolescent offspring aged 17-years participating in the Western Australian Pregnancy (Raine) Cohort Study. Fatty liver was diagnosed using liver ultrasound. NAFLD was diagnosed in 15.2% of the adolescents at age 17 years. In univariate analysis, maternal factors associated with NAFLD in female offspring were younger maternal age (p=0.02), higher maternal pre-pregnancy BMI (p<0.001), higher maternal weight gain by 18 weeks gestation (p<0.001) and maternal smoking during pregnancy (p=0.04). Paternal age or BMI were not associated with NAFLD in female offspring. In contrast, higher paternal BMI (p<0.001), maternal pre-pregnancy BMI (p<0.001) and lower family socio-economic status at time of birth (p=0.001), but not parental age nor maternal gestational weight gain, were associated with NAFLD in male offspring. Using multivariate logistic regression, factors independently associated with NAFLD after adjusting for obesity in adolescent females included maternal obesity (OR 3.46, 95% CI 1.49-8.05, p=0.004) and maternal weight gain ≥ 6.0kg by the 18th week of gestation (OR 1.10, 95% CI 1.04-1.15, p <0.001). In adolescent males, family socio-economic status at the time of birth (OR 9.07, 95% CI 1.54-53.29, p=0.02) remained significantly associated with NAFLD after multivariate modeling adjusted for adolescent obesity.

CONCLUSION: Early life contributors to NAFLD show considerable sexual dimorphism. Maternal obesity and higher early-mid gestational weight gain were associated with NAFLD in female offspring, while lower family socio-economic status at birth was associated with NAFLD in male offspring independent of adolescent obesity. This article is protected by copyright. All rights reserved.