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Low birthweight increases severe steatosis risk in pediatric NAFLD

Children with nonalcoholic fatty liver disease who were small for gestational age at birth have an increased risk for severe steatosis, independent and in addition to risk factors such as insulin-resistance and the I148M variant of the PNPLA3 gene.

“We had previously shown the association of pediatric NAFLD with [small for gestational age (SGA)],” Elisabetta Bugianesi, MD, PhD, from the University of Turin, Italy, and colleagues wrote. “However, the current study further extends our knowledge pointing out that, in children with NAFLD, SGA is also a risk factor for a more severe fat accumulation early in life that could eventually translate in a higher rate of hepatic and extrahepatic complications during adulthood.”

To examine the impact of birthweight on liver damage, the researchers enrolled 288 children with NAFLD between June 2001 and December 2015. Thirty-five of the pediatric patients were born SGA, 181 were born appropriate for gestational age (AGA) and 72 were born large for gestational age (LGA).

The SGA patients had a higher prevalence of severe steatosis compared with the AGA (P = .021) and LGA groups (P = .002). Significant fibrosis was more common among AGA patients (P < .001). Lobular inflammation and ballooning were similar in all groups.

On univariate analysis, severe steatosis (66% or greater) was associated with SGA birthweight (OR = 0.99; 95% CI, 0.98-0.99), raised alanine aminotransferase (OR = 1.1; 95% CI, 1.06-1.14) and aspartate aminotransferase (OR = 1.05; 95% CI, 1.03-1.07), increased glucose (OR = 1.04; 95% CI, 1.02-1.06) and insulin levels (OR = 1.1; 95% CI, 1.06-1.13), higher homeostasis model of assessment-insulin resistance index (OR = 1.66; 95% CI, 1.42-1.95) and lower prevalence of the PNPLA3-CC genotype (OR = 0.34; 95% CI, 0.21-0.56).

SGA birthweight significantly increased the risk for severe steatosis after a multivariable analysis (OR = 4; 95% CI, 1.43-10.9), independent of higher homeostasis model of assessment-insulin resistance index and PNPLA3 genotype. After a multivariable analysis of NAFLD activity score, SGA birthweight increased the likelihood of a NAFLD activity score of 5 or greater independent of insulin resistance and PNPLA3 genotype. This was likely due to PNPLA3’s impact on steatosis, according to the researchers.

“In our study cohort, the young age reduces the likelihood of fibrosis, which takes decades to develop, but it is conceivable that an increased liver fat in NAFLD subjects born SGA could be translated into an increased risk of disease progression later in life,” the researchers concluded. “Careful monitoring of SGA children with NAFLD may be considered to avoid hepatic and extrahepatic complications during adulthood.” – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.