Cord Blood Exosomal miRNAs from Small-for-Gestational-Age Newborns: Association with Measures of Postnatal Catch-Up Growth and Insulin Resistance

TL;DR

Cord blood miRNAs in SGA infants differ from AGA infants and are linked to later growth patterns and insulin resistance.

Contribution

Identified exosomal miRNAs at birth that associate with postnatal catch-up growth and metabolic outcomes in SGA infants.

Findings

SGA infants showed distinct exosomal miRNA profiles compared to AGA infants.

Selected miRNAs correlated with changes in BMI, fat mass, and lean mass during infancy.

Target genes of these miRNAs are involved in insulin and metabolic signaling pathways.

Abstract

Small-for-gestational-age (SGA) infants who experience a marked postnatal catch-up, mainly in weight, are at risk for developing metabolic disorders; however, the underlying mechanisms are imprecise. Exosomes and their cargo (including miRNAs) mediate intercellular communication and may contribute to altered crosstalk among tissues. We assessed the miRNA profile in cord blood-derived exosomes from 10 appropriate-for-gestational-age (AGA) and 10 SGA infants by small RNA sequencing; differentially expressed miRNAs with a fold change ≥2.4 were validated by RT-qPCR in 40 AGA and 35 SGA infants and correlated with anthropometric, body composition (DXA) and endocrine–metabolic parameters at 4 and 12 mo. miR-1-3p, miR-133a-3p and miR-206 were down-regulated, whereas miR-372-3p, miR-519d-3p and miR-1299 were up-regulated in SGA infants. The target genes of these miRNAs related to insulin, RAP1, TGF beta and neurotrophin signaling. Receiver operating characteristic analysis disclosed that these miRNAs predicted with accuracy the 0–12 mo changes in body mass index and in total and abdominal fat and lean mass. In conclusion, the exosomal miRNA profile at birth differs between AGA and SGA infants and associates with measures of catch-up growth, insulin resistance and body composition through late infancy. Further follow-up of this population will disclose whether these associations persist into childhood, puberty and adolescence.

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