ExtraUterine Growth Restriction (EUGR) in Preterm Infants: Growth Patterns, Nutrition, and Epigenetic Markers. A Pilot Study

Abstract

Background/Aims: IntraUterine (IUGR) and ExtraUterine Growth Restriction (EUGR) may induce reprogramming mechanisms, finalized to survive before and after birth. Nutritional factors and other environmental signals could regulate gene expression through epigenetic modification, but the molecular mechanisms involved are not yet well understood. Epigenetic mechanisms could be considered as a bridge between environmental stimuli and long lasting phenotype, acquired during the intrauterine life and the first weeks of life. Our aim was to investigate the relationship between growth patterns, nutritional determinants, and epigenetic pathways.Methods: We enrolled 38 newborns admitted to Neonatal Intensive Care Unit (NICU) at University Hospital of Pisa. Gestational age at birth was <34 weeks and post-menstrual age (PMA) was 36–42 weeks at discharge. We excluded infants with malformations or clinical syndromes. EUGR was defined as the reduction in weight z score between birth and discharge >1 SD. We also evaluated DNA methylation of Imprinting Centre 1 (IC1) at birth and at discharge.Results: We observed a decrease in SD of weight and head circumference mainly during the first weeks of life. We found a correlation between EUGR for weight and for head circumference and an increased IC1 methylation (p = 0.018 and p = 0.0028, respectively). We observed a relationship between reduced protein and lipid intake and IC1 hypermethylation (p = 0.009 and p = 0.043, respectively).Conclusion: IC1 hypermethylation could be a reprogramming mechanism to promote a catch-up growth, by means of an increased Insulin-like growth factor 2 (IGF2) expression, that may have potential effects on metabolic homeostasis later in life.

Correlation between the growth and development of extremely preterm infants in intensive care units and the intestinal microecology

“…The high incidence of EUGR reveals the challenging nature of the nutritional status of VLBWIs in China during hospitalization [9]. The lower the gestational age, the lower the birth weight and the higher the incidence of EUGR [10]. In this study, the incidence of EUGR is signi cantly lower, which may be due to the small sample size or better NICU preterm infant management.…”

<p>Clinical and Nutritional Determinants of Extrauterine Growth Restriction Among Very Low Birth Weight Infants</p>

“…19 In a recent report from Italy, EUGR was diagnosed in 71% and 50% of less than 34-week infants based on weight and head circumference at discharge, respectively. 12 One of the main factors for development of EUGR is the inadequate nutritional status at birth. The rate of EUGR among SGA infants included in our study was 97% (70 out of 72) compared with 73% (128 out of 175) in non-SGA.…”

“…These factors include antenatal growth status, postnatal nutritional support, co-morbidities, and genetic and epigenetic factors. 12,13 Studies have shown that the risk of EUGR increases with decreasing birth weight and gestational age and is more obviously seen in the more mature SGA infants. 13 Another factor that affects the risk of EUGR is the duration of initial weight loss in the neonatal period.…”

“…16 In addition, genomic imprinting is one of the major reported genetic mechanisms that has been studied and strongly linked to impaired growth and development. 12 In Jordan and nearby countries in the region, research is limited about the nutritional support in neonatal ICUs, and there have been no studies to evaluate the rate or causes of EUGR. A single-center limited prospective report from Jordan University Hospital reviewed the local nutritional practice among 43 VLBW infants and concluded that utilization of breastmilk and early fortification after reaching full feeds are essential factors in optimizing neonatal nutrition.…”

Challenges in Early Postnatal Care and Growth in Extremely Low Birth Weight Infants: A Multi-Center Study

“…Currently, EUGR is still a serious problem for ≤ 34w preterm infants, and the risk factors leading to EUGR include gestational age, birth weight, BPD, and SGA (7,33) . Previous studies reported that the EUGR incidence of preterm infants with gestational age ≤ 32w was 57%-71% (33)(34)(35)(36) , and Chinese studies reported that the incidence of EUGR in preterm infants with birth weight ≤ 1200 g was 83.8% (37) . In this literature, the overall survival rate of ELBW infants was higher than the domestic level, but approximately 2/3 of ELBW infants suffered from GR, de ned as the decline of Z score more than one.…”