MicroRNAs in newborns with low birth weight: relation to birth size and body composition.

Abstract

Children with low birth weight (LBW) have a higher risk of developing endocrine-metabolic disorders later in life. Deregulation of specific microRNAs (miRNAs) could underscore the programming of adult pathologies. We analyzedthe miRNA expression pattern in both umbilical cord serum samples from LBW and appropriate-for-gestational-age (AGA) newborns and maternal serum samples in the 3rd trimester of gestation, and delineated the relationships with fetal growth, body composition, and markers of metabolic risk. Serum samples of 12 selected mother-newborn pairs, including 6 LBW and 6 AGA newborns, were used for assessing miRNA profile by RNA-sequencing. The miRNAs with differential expression were validated in a larger cohort [49 maternal samples and 49 umbilical cord samples (24 LBW, 25 AGA)] by RT-qPCR. Anthropometric, endocrine-metabolic markers and body composition (by DXA) in infants were determined longitudinally over 12 months. LBW newborns presented reduced circulating concentrations of miR-191-3p (P = 0.015). miR-191-3p levels reliably differentiated LBW from AGA individuals (ROC AUC = 0.76) and were positively associated with anthropometric and body composition measures at birth and weight Z-score at 12 months (P < 0.05). miR-191-3p was reliably different in LBW individuals, and could be a new player in the epigenetic mechanisms linking LBW and future endocrine-metabolic adverse outcomes. Children with low birth weight (LBW) have a higher risk of developing endocrine-metabolic disorders. Deregulation of specific microRNAs (miRNAs) could underscore the programming of those pathologies. miR-191-3p is downregulated in serum of LBW newborns, and its concentrations associate positively with neonatal anthropometric measures, with lean mass and bone accretion at age 15 days and with weight Z-score at age 12 months. miR-191-3p was reliably different in individuals with LBW, and could be a new player in the epigenetic mechanisms connecting LBW and future endocrine-metabolic adverse outcomes.