Low and High Birth Weights Are Risk Factors for Nonalcoholic Fatty Liver Disease in Children

Abstract

Objective To examine the distribution of birth weight in children with NAFLD compared with the general U.S. population and the relationship between birth weight and severity of NAFLD. Study design A multi-center, cross-sectional study of children with biopsy-proven NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network Database. Birth weights were categorized as low birth weight (LBW), normal birth weight (NBW), or high birth weight (HBW) and compared with distribution of birth weights in the general US population. The severity of liver histology was assessed by birth weight category. Results Children with NAFLD (n=538) had overrepresentation of both LBW and HBW compared with the general US population (LBW 9.3%, NBW 75.8%, HBW 14.9% vs. LBW 6.1%, NBW 83.5%, HBW 10.5%; p<0.0001). Children with HBW had significantly greater odds of having more severe steatosis (OR 1.82, 95% CI 1.15–2.88) and NASH (OR 2.03, 95% CI 1.21–3.40) than children with NBW. Additionally, children with NAFLD and LBW had significantly greater odds of having advanced fibrosis (OR 2.23; 95% CI 1.08–4.62). Conclusion Birth weight involves maternal and in utero factors which may have long-lasting consequences. Children with both LBW and HBW may be at increased risk for developing NAFLD. Among children with NAFLD, those with LBW or HBW appear to be at increased risk for more severe disease.

Perspectives on youth‐onset nonalcoholic fatty liver disease

“…Children with low and high birth weights are more likely to progress to more severe stages of fibrosis and steatosis later in adolescence, suggesting a very early influence of nutritional status on future disease progression. 16 In one study, breastfeeding exclusively for at least 6 months decreased the odds of developing NAFLD during adolescence. 11 In addition, animal studies have shown that early postnatal exposure to a high-fat diet increased the susceptibility to NAFLD through the upregulation of hepatic lipogenesis.…”

Parental metabolic syndrome epigenetically reprograms offspring hepatic lipid metabolism in mice

“…Because altered birth weights are risk factors for the development of NAFLD in children (16), we began by analyzing the body weight trajectories of the offspring. Consistent with our previous observation (10), offspring from insulin-resistant parents at postnatal day 5 presented transient increased body weights compared with controls ( Figure 1A).…”

Pyrroloquinoline quinone prevents developmental programming of microbial dysbiosis and macrophage polarization to attenuate liver fibrosis in offspring of obese mice

“…NAFLD affects ∼34% of obese children in North America, up to half of whom have progressed to nonalcoholic steatohepatitis (NASH; characterized by inflammation and cellular damage in addition to steatosis) at the time of diagnosis . Children with NASH are more likely to have advanced fibrosis, even after adjusting for obesity . Both NAFLD and NASH may progress to hepatocellular carcinoma, and fatty liver disease is rapidly becoming a leading cause for liver transplant in the United States .…”