Parental obesity triples risk of early liver disease in children, new study finds
Parents' BMI before pregnancy linked to greater odds of MASLD by age 24
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People whose biological parents were overweight or obese at the time of their conception face a greater risk of early liver disease, according to a new study by U.S. researchers that found such children are more than three times as likely to develop metabolic dysfunction-associated steatotic liver disease (MASLD) by age 24.
The scientists say these findings could lay the groundwork for efforts to reduce the risk of liver disease in future generations. MASLD, characterized by steatosis, or an abnormal buildup of liver fat, is one of the most common liver disorders worldwide.
“This changes how we think about obesity and obesity-related disease,” Yin Cao, the study’s senior author at Washington University School of Medicine in St. Louis (WashU Medicine), said in a university news story detailing the study’s findings.
“We often oversimplify this topic by talking only about a patient’s current [body weight] as the driving factor for disease, but here we are showing the risk factors for this liver disease may actually emerge years earlier, from the parents,” Cao said. “This indicates a need to better define obesity’s intergenerational impact and to concentrate more of our prevention and education efforts to earlier in life, including preconception, pregnancy and childhood.”
Specifically, the team found that obesity in a child’s mother prepregnancy was linked to a nearly three times greater risk of MASLD, while paternal obesity was tied to nearly twofold higher odds.
The study, “Parental obesity and risk of metabolic dysfunction associated steatotic liver disease in adult offspring: UK birth cohort study,” was published in the journal Gut. The work was funded by the National Institutes of Health, among others, and conducted by researchers at WashU Medicine.
MASLD is marked by steatosis in people who typically have cardiometabolic risk factors such as high blood pressure, obesity, or diabetes. In serious cases, it can progress to cause liver inflammation and scarring, known as fibrosis, setting the stage for life-threatening complications like liver failure.
Most people with MASLD don’t know they have it, because symptoms typically don’t appear until the disease is already advanced.
“It’s not uncommon for young adults who come in to see us to have a fair amount of scarring of their liver already that had been smoldering for quite some time,” said Stefani Tica, MD, the study’s first author and an assistant professor of pediatrics, gastroenterology, hepatology, and nutrition at WashU Medicine.
Ongoing efforts aim to ID those at high risk for liver disease
Given such evidence, there are ongoing efforts to better screen for MASLD at early stages, and to identify individuals with a greater risk of developing the disease. An emerging body of data suggests that parental metabolic factors, particularly the mother’s, can strongly influence the odds of MASLD for children.
“While observational studies have also demonstrated independent associations between paternal obesity and offspring obesity, how paternal obesity influences offspring susceptibility to MASLD is less understood,” the researchers wrote.
In this study, Cao, Tica, and colleagues investigated the potential link between prepregnancy maternal and paternal body mass index — known as BMI, it’s a ratio of weight to height, measured in kilograms per square meter (kg/m2) — and the likelihood that a couple’s offspring would develop MALSD.
The team used data from a U.K. study that followed children born in the early 1990s through age 24. The analysis involved data from nearly 2,000 participants; about 1 in 10 had MASLD by age 24.
Statistical analyses showed a direct association between parental BMI before pregnancy and MASLD risk for the child by that age.
Specifically, maternal obesity was significantly linked to a nearly three times higher risk of offspring MALSD, with every 1 kg/m2 increase in BMI for the mother being significantly associated with a 10% increase in MASLD risk for the child.
For the biological father, being obese was significantly linked to a 1.7 times higher risk of MASLD for their child, with each 1 kg/m2 increase in BMI being significantly associated with a 9% increase in risk of offspring MASLD.
Child with 2 overweight parents 3.5 times more likely to develop MASLD
The findings also showed that if both biological parents had a BMI of 25 kg/m2 or higher — a cutoff commonly used to delineate overweight or obesity — the child was more than 3.5 times more likely to have MASLD at age 24 than when both parents had BMI scores within normal ranges.
“The odds of offspring MASLD development more than tripled when both parents had overweight or obesity before pregnancy compared with offspring of parents with a normal BMI,” the researchers wrote, adding that these findings “highlight [obesity in both parents] as an emerging developmental risk factor for MASLD in offspring.”
In further statistical analyses, the researchers found that the associations between parental BMI and MASLD risk were largely mediated by excessive body fat among the children in their youth. Called childhood adiposity, this condition affects nearly 1 in 5 children in the U.S.
In other words, these data indicated that children whose biological parents were heavier tended to put on more fat during early childhood, and this largely explained the difference in MASLD risk.
The odds of offspring MASLD development more than tripled when both parents had overweight or obesity before pregnancy compared with offspring of parents with a normal BMI.
The researchers noted that the mechanisms behind these associations are not entirely clear. Environmental and lifestyle habits likely play a role, but so might other factors such as gut bacteria and epigenetics — changes in DNA packaging that can affect gene activity and be passed down to biological children.
Nonetheless, these findings suggest that efforts to limit obesity may help reduce MASLD risk not just for individuals, but also for future generations, according to the researchers.
“Our findings highlight the potential of life course interventions aimed at reducing the risk of MASLD later in life and for future generations,” the team concluded.
Still, the scientists noted that “a deeper understanding of the influence of behavioural and social factors, as well as their interplay with genetic, epigenetic and [gut bacteria changes] mechanisms, is critically needed for the design of feasible and scalable interventions.”
