Maternal obesity increases the risk and severity of NAFLD in offspring

Hannes Hagström; Tracey G Simon; Bjorn Roelstraete; Olof Stephansson; Jonas Söderling; Jonas F Ludvigsson

doi:10.1016/j.jhep.2021.06.045

Maternal obesity increases the risk and severity of NAFLD in offspring

J Hepatol. 2021 Nov;75(5):1042-1048. doi: 10.1016/j.jhep.2021.06.045. Epub 2021 Jul 18.

Authors

Hannes Hagström¹, Tracey G Simon², Bjorn Roelstraete³, Olof Stephansson⁴, Jonas Söderling⁵, Jonas F Ludvigsson⁶

Affiliations

¹ Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. Electronic address: hannes.hagstrom@ki.se.
² Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA.
³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁴ Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Division of Women's Health, Department of Obstetrics, Karolinska University Hospital, Stockholm, Sweden.
⁵ Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Orebro University Hospital, Orebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, UK; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.

PMID: 34289397
DOI: 10.1016/j.jhep.2021.06.045

Abstract

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.

Keywords: children; cirrhosis; fibrosis; obesity; steatosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Body Mass Index
Case-Control Studies
Child
Child, Preschool
Cohort Studies
Female
Humans
Non-alcoholic Fatty Liver Disease / diagnosis*
Non-alcoholic Fatty Liver Disease / epidemiology
Non-alcoholic Fatty Liver Disease / etiology
Obesity, Maternal / complications*
Obesity, Maternal / epidemiology
Pregnancy
Risk Factors
Sweden / epidemiology

Grants and funding

K23 DK122104/DK/NIDDK NIH HHS/United States