Birth Weight, Gestational Age, and Risk of Pediatric-Onset MASLD

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 lt;2500 g, reference 2500 to lt;4000 g, or high ≥4000 g), gestational age (GA), and birth weight for GA (small for GA SGA; lt;10th percentile, appropriate for GA 10th-90th percentile, or large for GA LGA; gt;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.