Umbilical Cord miRNAs in Small-for-Gestational-Age Children and Association With Catch-Up Growth: A Pilot Study

Abstract

Context: Catch-up growth in infants who are small for gestational age (SGA) is a risk factor for the development of cardiometabolic diseases in adulthood. The basis and mechanisms underpinning catch-up growth in newborns who are SGA are unknown.

Objective: To identify umbilical cord miRNAs associated with catch-up growth in infants who are SGA and study their relationship with offspring's cardiometabolic parameters.

Design: miRNA PCR panels were used to study the miRNA profile in umbilical cord tissue of five infants who were SGA with catch-up (SGA-CU), five without catch-up (SGA-nonCU), and five control infants [appropriate for gestational age (AGA)]. The miRNAs with the smallest nominal P values were validated in 64 infants (22 AGA, 18 SGA-nonCU, and 24 SGA-CU) and correlated with anthropometric parameters at 1 (n = 64) and 6 years of age (n = 30).

Results: miR-501-3p, miR-576-5p, miR-770-5p, and miR-876-3p had nominally significant associations with increased weight, height, weight catch-up, and height catch-up at 1 year, and miR-374b-3p, miR-548c-5p, and miR-576-5p had nominally significant associations with increased weight, height, waist, hip, and renal fat at 6 years. Multivariate analysis suggested miR-576-5p as a predictor of weight catch-up and height catch-up at 1 year, as well as weight, waist, and renal fat at 6 years. In silico studies suggested that miR-576-5p participates in the regulation of inflammatory, growth, and proliferation signaling pathways.

Conclusions: Umbilical cord miRNAs could be novel biomarkers for the early identification of catch-up growth in infants who are SGA. miR-576-5p may contribute to the regulation of postnatal growth and influence the risk for cardiometabolic diseases associated with a mismatch between prenatal and postnatal weight gain.