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

Each month, the OMA Pediatric Committee reviews a pediatric-focused obesity research update to help keep you up to date about the latest findings. This month’s update refers to a systematic review of maternal and perinatal risk factors for pediatric nonalcoholic fatty liver disease.

Article Summary

Metabolic associated liver disease (MASLD) is the most common chronic liver disease globally, linked to obesity and insulin resistance, with a growing prevalence in children. Early life factors such as maternal BMI, gestational diabetes, and breastfeeding play crucial roles in influencing the risk and progression of MASLD, highlighting the need for further research and preventive measures.

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Article Review

Metabolic associated liver disease (MASLD, previously called nonalcoholic fatty liver disease [NAFLD]) is the most common chronic liver disease globally, with a prevalence of approximately 25%. MASLD is marked by excessive fat accumulation in the liver and can progress to more severe conditions like metabolic associated steatohepatitis (MASH), liver fibrosis, and cirrhosis. This disease is closely linked to obesity and insulin resistance, serving as an independent cardiovascular risk factor. In children, MASLD is also the most common liver disease, with a higher prevalence among children with obesity, indicating its multifactorial nature influenced by genetic and environmental factors.

The "developmental origins of health and disease" hypothesis suggests that early life and intrauterine environments significantly impact long-term metabolic health and disease risk. Perinatal stressors such as increased maternal body mass index (BMI), gestational diabetes, and being born small for gestational age (SGA) or preterm have been associated with higher risks of metabolic disorders. Breastfeeding, however, has shown potential protective effects against chronic diseases like MASLD. The specific pathophysiological mechanisms linking early life exposure to metabolic diseases like MASLD remain poorly understood.

This systematic review aimed to assess whether exposure to various perinatal risk factors affects the risk of developing MASLD in individuals aged 0–25 years. The review included 33 studies from diverse geographical regions and used various methods to diagnose MASLD, including MRI with hepatic fat fraction and ultrasound with elastography.

The primary findings include:

• An elevated maternal pre-pregnancy BMI (greater than 25 or greater than 30, depending on the study) is consistently associated with an increased risk of NAFLD in offspring, with an odds ratio of around 2.45 for development of MASLD among 12-17y who were born to women with overweight or obesity.
• The impact of pregestational and gestational diabetes is less clear, with some studies showing associations while others do not.
• Breastfeeding, especially for 6 months or greater, appears to offer some protective effects, although this difference was not statistically significant. Interestingly, MASH was significantly less prevalent in children with MASLD who were breastfed (OR 0.04 and 0.37, p <0.05), showing that even if MASLD is present, the progression to fibrosis/steatohepatitis may be mitigated by breastfeeding.

The study found inconsistencies in the influence of birth anthropometrics like preterm birth and being born SGA on MASLD development. Rapid catch-up growth after being born SGA may correlate with an increased risk. However, the small number of studies, varied methodologies, and differing diagnostic tools for MASLD contributed to heterogeneity in the findings. These results highlight the need for further research into the causal relationships between perinatal factors and MASLD and suggest that interventions such as maintaining a healthy pre-pregnancy BMI and promoting breastfeeding could play a role in reducing the risk of MASLD in children.