Placental microRNAs associate with early childhood growth characteristics

ABSTRACT Poor placental function is a common cause of intrauterine growth restriction, which in turn is associated with increased risks of perinatal morbidity, mortality and long-term adverse health outcomes. Our prior work suggests that birthweight and childhood obesity-associated genetic variants functionally impact placental function and that placental microRNA are associated with birthweight. To address the influence of the placenta beyond birth, we assessed the relationship between placental microRNAs and early childhood growth. Using the SITAR package, we generated two parameters that describe individual weight trajectories of children (0-5 years) in the New Hampshire Birth Cohort Study (NHBCS). Using negative binomial generalized linear models, we identified placental microRNAs that associate with growth parameters (FDR<0.05), while accounting for sex, gestational age at birth, and maternal parity. Genes targeted by the six growth trajectory-associated microRNAs are enriched (FDR<0.02) in growth factor signaling (TGF/beta: miR-1290; EGF/R: miR-155, Let-7c; FGF/R: miR-155; IGF/R: Let-7c, miR-155, miR-1290), cyclic AMP signaling (miR-1246), calmodulin signaling (miR-216a, miR-1246), and NOTCH signaling (miR-629). These pathways function in placental proliferation, differentiation and function. Our results support the hypothesis that fetal environment, specifically placental cellular dynamics and function guided by microRNA expression, can have impacts beyond birth, into early childhood.