Understanding Intergenerational Risk Factors for MASLD, With Stefani Tica, MD, MPH

As rates of metabolic dysfunction-associated steatotic liver disease (MASLD) continue to rise, experts are increasingly examining how risk for metabolic disease may develop earlier in life than previously recognized, with emerging evidence suggesting that factors shaping MASLD risk may extend beyond an individual’s current metabolic health to include early-life exposures and parental health.

A new analysis of data from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) offers additional insight into how risk for MASLD may begin far earlier in life than previously recognized, potentially even before a child is born. In an interview discussing the study, study author Stefani Tica, MD, MPH, an assistant professor of pediatrics in the Division of Gastroenterology, Hepatology, and Nutrition at Washington University School of Medicine in St Louis, explained that the work was motivated by the complex and multifactorial nature of metabolic disease.

“One of the things that I always counsel my MASLD patients about is that usually problems with our metabolism are really complex, and there's no one single thing that has gone awry,” Tica said. “One of the inspirations for this project was really kind of leaning into these complex interactions with not only what we're eating or how we're using these energy stores, but also our genetics, our environment, stress, kind of the realities of our life.”

The study approached MASLD through a population health lens, aiming to better understand how early-life and family-level factors might shape long-term risk. Rising MASLD incidence across both pediatric and adult populations prompted the team to look beyond individual health markers at the time of diagnosis and instead consider a broader life-course perspective.

In pediatric populations, recent research examining National Health and Nutrition Examination Survey (NHANES) 2011-2020 data estimated the overall prevalence of suspected MASLD in the adolescent population was 11.3%.

In the present study, investigators included 1933 offspring from the ALSPAC to assess the associations between parental pre-pregnancy BMI and odds of offspring MASLD at age 24 years, with MASLD defined as hepatic steatosis on transient elastography and ≥1 cardiometabolic risk factors.

Results showed that at age 24 years, 10.4% of offspring had MASLD. Pre-pregnancy maternal and paternal obesity were independently associated with an increased odds of offspring MASLD, with each 1 kg/m2 increase in maternal BMI increasing the odds of MASLD by 10% (odds ratio [OR], 1.10; 95% CI, 1.06 to 1.14), while each 1 kg/m2 increase in paternal BMI raised the odds by 9% (OR, 1.09; 95% CI, 1.04 to 1.13).

Further analysis revealed biparental overweight or obesity was associated with 3.73 times the odds of offspring MASLD (OR, 3.73; 95% CI, 2.43 to 5.73) compared with parents with a normal BMI, with 67% of this association mediated by cumulative excess childhood BMI.

For clinicians, particularly pediatric hepatologists and pediatric providers, these findings underscore the importance of earlier conversations about metabolic risk. Tica noted that framing these discussions around family health and long-term outcomes may help engage both children and parents in preventive efforts.

“I think this is quite interesting in the sense that it's not necessarily the person who we're seeing right then and there and what their BMI is and what their other metabolic health markers are looking like, but that sort of risk for disease might develop much earlier on,” Tica explained. “I think having this more longitudinal life course perspective on it reinvigorates efforts from a public health standpoint to intervene earlier on in life and potentially have a much bigger impact if you can successfully do that.”

She also noted that the research raises several important unanswered questions. As an observational study, it cannot establish the biological mechanisms underlying these associations. However, emerging preclinical evidence suggests potential roles for epigenetic changes and alterations in the gut microbiome, particularly in infants exposed to maternal obesity or dietary differences during early development.

According to Tica, further mechanistic research will be essential to determine whether interventions, such as parental weight loss or metabolic improvements, can meaningfully alter MASLD risk in future generations.

Editor’s note: Tica reports no relevant disclosures.

References

1. Tica S, Luo C, Ren D, et al. Parental obesity and risk of metabolic dysfunction associated steatotic liver disease in adult offspring: UK birth cohort study. Gut. Published online February 24, 2026. doi:10.1136/gutjnl-2025-336165

2. Brooks A. Up to 11% of US Adolescents Have Suspected MASLD, Study Finds. HCPLive. February 17, 2025. Accessed March 5, 2026. https://www.hcplive.com/view/an-estimated-11-us-adolescents-have-suspected-masld-study-finds