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Birth Weight, Gestational Age, and Risk of Pediatric-Onset MASLD
Fahim Ebrahimi1,2, Jialu Yao1, Hannes Hagström3,4
1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Insights
Low birth weight and being small for gestational age (SGA) are linked to developing metabolic dysfunction-associated steatotic liver disease (MASLD) and its progression in young individuals. Early screening is recommended for those at higher risk.
Area of Science:
- Hepatology
- Pediatric Gastroenterology
- Public Health
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health concern, increasingly affecting younger populations.
- Early-onset MASLD in individuals with obesity highlights the need to understand developmental risk factors.
Purpose of the Study:
- To investigate the association between perinatal conditions and the risk of developing MASLD in young individuals.
- To examine the link between birth characteristics and the progression to advanced liver disease (fibrosis or cirrhosis) in pediatric MASLD patients.
Main Methods:
- A nationwide population-based case-control study in Sweden, including biopsy-confirmed pediatric MASLD cases (age ≤25) and matched controls.
- Data on birth weight, gestational age, and birth weight for gestational age (SGA, appropriate, LGA) were analyzed from the Swedish Medical Birth Register.
Main Results:
- Low birth weight (<2500g) and being small for gestational age (SGA) were significantly associated with an increased risk of MASLD in young individuals.
- Individuals born with low birth weight or SGA also showed a higher likelihood of developing progressive liver disease, including fibrosis and cirrhosis.
Conclusions:
- Perinatal factors such as low birth weight and SGA are critical risk factors for the development and progression of MASLD in youth.
- Implementing structured screening protocols for MASLD in high-risk individuals identified through perinatal assessments is crucial for early diagnosis and intervention.
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.
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