To Örebro University

Background & Aims: Maternal obesity has been linked to the development of cardiovascular disease and diabetes in offspring, but its relationship to non-alcoholic fatty liver disease (NAFLD) is unclear.

Methods: Through the nationwide ESPRESSO cohort study we identified all individuals <= 25 years of age in Sweden with biopsy verified NAFLD diagnosed between 1992 and 2016 (n = 165). These were matched by age, sex, and calendar year with up to 5 controls (n = 717). Through linkage with the nationwide Swedish Medical Birth Register (MBR) we retrieved data on maternal early-pregnancy BMI, and possible confounders, in order to calculate adjusted odds ratios (aORs) for NAFLD in offspring.

Results: Maternal BMI was associated with NAFLD in offspring: underweight (aOR 0.84; 95% CI 0.14-5.15), normal weight (reference, aOR 1), overweight (aOR 1.51; 0.95-2.40), and obese (aOR 3.26; 1.72-6.19) women. Severe NAFLD (biopsy-proven fibrosis or cirrhosis) was also more common in offspring of overweight (aOR 1.94; 95% CI 0.96-3.90) and obese (aOR 3.67; 95% CI 1.61-8.38) mothers. Associations were similar after adjusting for maternal pre-eclampsia and gestational diabetes. Socio-economic parameters (smoking, mother born outside the Nordic countries and less than 10 years of basic education) were also associated with NAFLD in offspring but did not materially alter the effect size of maternal BMI in a multivariable model.

Conclusions: This nationwide study found a strong association between maternal overweight/obesity and future NAFLD in offspring. Adjusting for socio-economic and metabolic parameters in the mother did not affect this finding, suggesting that maternal obesity is an independent risk factor for NAFLD in offspring.

Lay summary: In a study of all young persons in Sweden with a liver biopsy consistent with fatty liver, the authors found that compared to matched controls, the risk of fatty liver was much higher in those with obese mothers. This was independent of available confounders and suggests that the high prevalence of obesity in younger persons might lead to a higher risk of fatty liver in their offspring.