Background: Current nutritional intervention strategies have not proven effective in improving childhood ponderal and linear growth in underweight and stunted children. Novel markers are needed to classify children who are likely to respond to available interventions and to identify those requiring additional interventions. Fibroblast Growth Factor 21 (FGF21), an endocrine hormone that regulates metabolism and growth during periods of reduced protein intake, may be useful in this context.
Objectives: We aimed to determine the associations between plasma FGF21 concentrations and subsequent growth, and the association between change in FGF21 concentrations and concurrent growth, in children receiving nutritional supplementation.
Methods: A total of 120 children between ages 6 and 13 mo with weight-for-age z score (WAZ) between -3 and -2 were enrolled from an urban slum in Dhaka, Bangladesh. Children received 376-kcal feeding supplements daily for 5 mo and were followed for 5 additional mo. FGF21 was measured in plasma collected at enrollment and month 5. FGF21 values that fell above the 90th percentile of baseline concentrations (1056.5 pg/mL) were considered high. Linear regression was used to examine the association between baseline FGF21 status and 5-mo change in WAZ and length-for-age z score (LAZ), and the association between 5-mo change in FGF21 and concurrent WAZ and LAZ change.
Results: The median baseline FGF21 concentration was 241.4 pg/mL (IQR: 111.7, 451.3 pg/mL). On average, children with high baseline FGF21 gained 0.58 WAZ (95% CI: 0.28, 0.88) and 0.54 LAZ (95% CI: 0.23, 0.84) more during supplementation than those with low values. Change in FGF21 concentration during supplementation was negatively associated with change in WAZ (-0.48; 95% CI: -0.67, -0.29) and LAZ (-0.31; 95% CI: -0.52, -0.11).
Conclusions: FGF21 may be a useful marker of growth faltering and may allow identification of children who are more or less likely to respond to nutritional supplementation. This trial was registered at clinicaltrials.gov as NCT02441426.
Keywords: FGF21; growth hormone resistance; protein deficiency; stunting; supplementation; undernutrition; underweight.