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.

Naturally Occurring and Experimentally Induced Rhesus Macaque Models for Polycystic Ovary Syndrome: Translational Gateways to Clinical Application

“…In addition to such evidence for gestational hyperandrogenism contributing to PCOS etiopathogenesis, gestationally diabetic in utero environments [64][65][66][67], as well as poor intrauterine nutrition and fetal growth restriction [67][68][69], contribute developmental, likely epigenetic [37,70,71], programming to women with PCOS. Human placentae readily convey maternal glucose to the fetus engaging a progressively maturing fetal pancreatic beta cell response, but preventing transfer of maternal insulin [72].…”

Associations between prepregnancy body mass index, gestational weight gain and weight catch‐up in small‐for‐gestational‐age children

“…This study demonstrated that prepregnancy underweight (at any GWG level) or appropriate pBMI but with inadequate GWG was associated with the ‘no catch‐up growth’ pattern that was consistent with former studies showing that inadequate GWG was associated with a higher incidence of SGA birth (Goldstein et al, 2017 ; Li et al, 2013 ; Siega‐Riz et al, 2009 ). Children whose weights were less than the 10th percentile from birth to 7 years of age were labelled as the children with the ‘no catch‐up growth’ pattern and were at an increased risk for cerebral palsy, cognitive delay and cardiometabolic diseases (Mas‐Parés et al, 2019 ; Takeuchi et al, 2018 ). Findings in this study were also consistent with previous studies reporting that the offspring of the mothers having lower weight gain during pregnancy had lower body weights at adulthood (Goldstein et al, 2017 ; Gurugubelli Krishna & Vishnu Bhat, 2018 ; Radford et al, 2014 ), and inadequate GWG was associated with a higher risk of stunning at 5 years old (Xie et al, 2016 ).…”

Epigenetics and In Utero Acquired Predisposition to Metabolic Disease

“…These findings are consistent with data reported by Tang et al (2013) who found a significant positive correlation between mRNA expression of PLAG1 and level of IGF2 in placental tissues of fetal growth retardation compared to controls. Moreover, a downregulation of miR-16 and miR-21 in the placenta was significantly related with lower birth weight (Maccani and Marsit, 2011).…”

“…miRNA serum profile in umbilical cord of SGA children with (SGA-CU, n = 18) and without catch-up growth (SGA-nonCU, n = 24) was investigated (Mas-Parés et al, 2018). In particular, 12 miRNA were differentially expressed between SGA-CU and SGA-nonCU (miR-128-3p, miR-222-5p, miR-300, miR-374b-3p, miR-501-3p, miR-548c-5p, miR-628-5p, miR-770-5p, miR-873-5p, miR-876-3p and miR-940).…”