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Maternal obesity increases the risk and severity of NAFLD in offspring

Hagström H, Simon T, Roelstraete B, Stephansson O, Söderling J, Ludvigsson J (2021) Journal of Hepatology Jul 10;S0168-8278(21)01899-7 doi: 10.1016/j.jhep.2021.06.045 

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Background and 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 in Sweden with biopsy-verified NAFLD ≤25 years of age diagnosed between 1992 and 2016 (n=165). These were matched on 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 body mass index (BMI), and possible confounders, in order to calculate adjusted odds ratios (aORs) for future offspring NAFLD.

Results: Maternal BMI was associated with offspring NAFLD (underweight women (aOR=0.84; 95%CI=0.14-5.15); normal weight (reference, aOR=1), overweight (aOR=1.51; 0.95-2.40), and obesity (aOR=3.26; 1.72-6.19). Also, severe NAFLD (biopsy-proven fibrosis or cirrhosis) was more common in offspring of overweight (aOR=1.94; 95%CI=0.96-3.90) and obese mothers (aOR=3.67; 95%CI=1.61-8.38). 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 ten years of basic education) were also associated with offspring NAFLD but did not materially affect 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 the offspring. Adjusting for socio-economic and metabolic parameters in the mother did not affect the finding. This suggests that maternal obesity may be an independent risk factor for offspring NAFLD.

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 suggest that the high prevalence of obesity in younger persons might lead to a higher risk of fatty liver in their offspring.


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