Circulating growth-and-differentiation factor-15 in early life: relation to prenatal and postnatal growth and adiposity measurements.

Background: Growth-and-differentiation-factor-15 (GDF15) is a regulator of energy homeostasis. To determine the relationship between circulating GDF15 and parameters of metabolic health, we assessed longitudinally GDF15 concentrations in infants born either appropriate- (AGA) or small-for-gestational-age (SGA), the latter population known to be at risk for metabolic alterations, particularly after a rapid postnatal catch-up in weight.

Methods: The study cohort consisted of 103 infants (70 AGA and 33 SGA). Assessments included body length, weight, and ponderal index (PI); fasting glucose, insulin, IGF-I, high-molecular-weight adiponectin, GDF15; and body composition (by absorptiometry) at birth, and at age 4, 12 and 24 months.

Results: GDF15 levels at birth were significantly higher than those at each subsequent time point and were similar in AGA and SGA subjects. GDF15 concentrations dropped at age 4 months, more substantially in SGA infants, and continued to decline in both subgroups reaching adult concentrations by age 24 months. GDF15 levels correlated inversely with the changes in PI, IGF-I and body fat throughout follow-up.

Conclusions: Early life is associated with supra-adult concentrations of GDF15. The lower levels of GDF15 in SGA subjects may be an adaptive mechanism to promote catch-up in weight and might increase the risk for obesity later in life.