A prospective case-control study on miRNA circulating levels in subjects born small for gestational age (SGA) evaluated from childhood into young adulthood.

Objective: microRNAs (miRNAs) associated with metabolic risk have never been extensively investigated in SGA subjects. The aim of the current study was to evaluate miRNAs in SGA and AGA subjects and their relationships with the metabolic status and growth.

Design And Methods: A prospective longitudinal case-control study was performed in 23 SGA with postnatal catch-up growth and 27 AGA subjects evaluated at the age of 9 and 21 years. Circulating levels of miR-122-5p, miR-16-5p, miR-126-3p, and miR-486-5p were assessed by qPCR.

Results: SGA subjects were shorter both at 9 and at 21 years. No significant differences in insulin like growth factors and metabolic profile were found with the exception of basal glycemia at 9 years. miRNA levels did not differ between SGA and AGA subjects, at 9 and 21 years. miR-16-5p and miR-126-3p levels were higher at 9 than at 21 years. In SGA subjects, miR-122-5p at 9 years was inversely related to adiponectin levels at 21 years and miR-486-5p at 9 years was inversely related to whole-body insulin sensitivity at 9 years and directly related to Hb1Ac at 21 years. Regression analyses showed no predictive value of miRNAs for growth parameters in neither SGA nor AGA subjects.

Conclusions: SGA with postnatal catch-up growth did not show any difference in metabolic risk markers or miRNA circulating levels compared to AGA controls in childhood and young adulthood. miR-122-5p during childhood could identify SGA subjects at higher risk of developing insulin resistance and, eventually, type 2 diabetes in adulthood but further studies are needed to confirm it.