Author information

¹Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

²Department of Gastroenterology and Hepatology, Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland.

³Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.

⁴Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.

⁵Department of Women's Health, Karolinska University Hospital, Stockholm, Sweden.

⁶Division of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

⁷Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.

⁸Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York.

Abstract

Importance: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease worldwide and is increasingly being diagnosed at younger ages, affecting more than one-third of young people with obesity.

Objective: To evaluate associations between perinatal conditions and risk of MASLD and associated progressive liver disease.

Design, setting, and participants: This nationwide, population-based case-control study included all biopsy-confirmed cases of MASLD in Sweden. Individuals aged 25 years or younger (hereafter, young individuals) with biopsy-proven MASLD between January 1, 1992, and December 31, 2016, were matched to up to 5 general population control individuals. Granular data on maternal and perinatal characteristics were retrieved from the Swedish Medical Birth Register. Data were analyzed from June 2023 to June 2024.

Exposures: Birth weight (low [<2500 g], reference [2500 to <4000 g], or high [≥4000 g]), gestational age (GA), and birth weight for GA (small for GA [SGA; <10th percentile], appropriate for GA [10th-90th percentile], or large for GA [LGA; >90th percentile]), compared between patients and matched controls.

Main outcomes and measures: The main outcome was odds of biopsy-proven MASLD and MASLD-associated progressive liver disease (ie, liver fibrosis or cirrhosis) according to birth weight, GA, and birth weight for GA, adjusted for matching factors.

Results: In total, 165 young individuals with biopsy-proven MASLD (median age at diagnosis: 12.0 years [IQR, 4.4-16.9 years]; 100 [60.6%] male) were matched with 717 controls. There was an association between low birth weight and future development of MASLD (adjusted odds ratio [AOR], 4.05; 95% CI, 1.85-8.88) but no association between high birth weight and odds of MASLD (AOR, 0.64; 95% CI, 0.38-1.08) compared with the reference birth weight. An association was seen for SGA (AOR, 3.36; 95% CI, 2.00-5.64) compared with appropriate size for GA (reference category) but not for LGA (AOR, 0.57; 95% CI, 0.27-1.20). Progressive liver disease was more common in individuals born with low birth weight (AOR, 6.03; 95% CI, 1.66-21.87) or SGA (AOR, 4.90; 95% CI, 2.15-11.14).

Conclusions and relevance: In this nationwide study of young individuals with biopsy-proven MASLD, low birth weight and SGA were associated with development of MASLD and progressive liver disease, suggesting a need for structured screening measures to diagnose these conditions early in high-risk individuals.