Pediatric Research Update | Maternal and Perinatal Risk Factors for Pediatric Nonalcoholic Fatty Liver Disease

Article Summary

Metabolic dysfunction–associated steatotic liver disease (MASLD) represents the leading form of chronic liver illness worldwide, particularly tied to obesity and insulin dysregulation, and its incidence is steadily climbing among the pediatric population. Influential factors from early life, including a mother’s weight before pregnancy, gestational diabetes status, and infant feeding practices, are emerging as key components in shaping a child’s risk for MASLD. These findings underscore the urgency for expanded research and proactive strategies aimed at prevention.

Article Review

Previously recognized as nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction–associated steatotic liver disease (MASLD) is now the predominant chronic hepatic condition globally, impacting about a quarter of the population. It is defined by excessive lipid buildup within liver cells and may progress to more dangerous forms, such as metabolic associated steatohepatitis (MASH), liver scarring, and ultimately cirrhosis. This disease is commonly linked with obesity and insulin resistance, and it independently heightens the likelihood of cardiovascular events. In children, MASLD stands as the most frequently diagnosed liver disorder, with prevalence significantly higher among those with excess weight—highlighting its complex etiology, shaped by both inherited and environmental influences.

The theory known as the “developmental origins of health and disease” suggests that exposures in the womb and in early life can have profound and lasting impacts on one’s susceptibility to metabolic diseases later in life. Factors like a high maternal body mass index (BMI), diabetes during pregnancy, and being born small for gestational age (SGA) or prematurely are linked to heightened risks of developing chronic metabolic issues. Conversely, breastfeeding has been identified as potentially offering a defense against illnesses like MASLD. However, the biological pathways that connect these early influences with liver disease remain largely unclear.

To explore this relationship further, a systematic review was conducted to evaluate whether different prenatal and perinatal factors contribute to the development of MASLD in individuals between birth and 25 years of age. The review analyzed 33 studies spanning various global regions, incorporating diverse diagnostic tools for MASLD such as magnetic resonance imaging (MRI) with liver fat assessment and ultrasound paired with elastography.

Key insights from the review include:

• Maternal BMI prior to pregnancy, especially when exceeding 25 or 30 depending on the study criteria, was strongly and consistently linked to a higher likelihood of MASLD in their children. Specifically, adolescents aged 12–17 born to women with overweight or obesity had a roughly 2.45 times greater chance of developing the condition.
• The association between maternal diabetes (both pre-existing and developed during pregnancy) and MASLD was less definitive. While several studies suggested a correlation, others found no significant link.
• Breastfeeding, particularly when continued for six months or longer, was observed to offer some degree of protection. Although the general trend was not statistically robust, there was a significant finding: children with MASLD who were breastfed were markedly less likely to progress to MASH. The odds of having MASH were dramatically lower in breastfed children (OR 0.04 and 0.37, p < 0.05), suggesting that while breastfeeding might not prevent MASLD outright, it could slow or prevent the disease from worsening.
• The role of birth characteristics such as being born early or with low birth weight (SGA) in influencing MASLD risk remains uncertain. Some evidence pointed to an increased risk when rapid growth follows an SGA birth, but overall, the conclusions were muddied by inconsistent methodologies, limited study numbers, and variable diagnostic criteria.

These observations make it clear that more rigorous investigation is needed to determine exactly how early life exposures shape MASLD risk. Nonetheless, the evidence already supports advocating for healthier maternal weight before conception and encouraging breastfeeding as potentially valuable interventions to lower the likelihood of pediatric MASLD.