Prematurity With Extrauterine Growth Restriction Increases the Risk of Higher Levels of Glucose, Low-Grade of Inflammation and Hypertension in Prepubertal Children

Maria D Ordóñez-Díaz,Mercedes Gil-Campos,Katherine Flores-Rojas,Maria C Muñoz-Villanueva,Josune Olza-Meneses,Concepción M Aguilera-García,Juan L Pérez-Navero

doi:10.3389/fped.2020.00180

Abstract

Introduction: An adipose tissue programming mechanism could be implicated in the extrauterine growth restriction (EUGR) of very preterm infants with morbidity in the cardiometabolic status later in life, as has been reported in intrauterine growth restriction. The aim of this study was to assess whether children with a history of prematurity and EUGR, but also with an adequate growth, showed alterations in the metabolic and inflammatory status.Methods: This was a case–control study. A total of 88 prepubertal children with prematurity antecedents were selected: 38 with EUGR and 50 with an adequate growth pattern (PREM group). They were compared with 123 healthy children born at term. Anthropometry, metabolic parameters, blood pressure (BP), C-reactive protein, hepatocyte growth factor (HGF), interleukin-6 (IL-6), IL-8, monocyte chemotactic protein type 1 (MCP-1), neural growth factor, tumour necrosis factor-alpha (TNF-α) and plasminogen activator inhibitor type-1 were analysed at the prepubertal age.Results: EUGR children exhibited higher BP levels and a higher prevalence of hypertension (46%) compared with both PREM (10%) and control (2.5%) groups. Moreover, there was a positive relationship between BP levels and values for glucose, insulin and HOMA-IR only in children with a EUGR history. The EUGR group showed higher concentrations of most of the cytokines analysed, markedly higher TNF-α, HGF and MCP-1 levels compared with the other two groups.Conclusion: EUGR status leads to cardiometabolic changes and a low-grade inflammatory status in children with a history of prematurity, and that could be related with cardiovascular risk later in life.

Highlights

An adipose tissue programming mechanism could be implicated in the extrauterine growth restriction (EUGR) of very preterm infants with morbidity in the cardiometabolic status later in life, as has been reported in intrauterine growth restriction
Significant differences were found in age, sex and Z-scores for Body mass index (BMI) at the prepubertal age between the EUGR group and the other two groups
EUGR children showed a higher percentage of weigh-height delays than PREM children, and lower Z-scores for BMI compared with those of the control children

Summary

Introduction

An adipose tissue programming mechanism could be implicated in the extrauterine growth restriction (EUGR) of very preterm infants with morbidity in the cardiometabolic status later in life, as has been reported in intrauterine growth restriction. The growth of very preterm infants during the postconceptional period is likely to be in a similar environment as the condition of intrauterine growth restriction (IUGR), which has been associated with different pathologies such as obesity, diabetes, metabolic syndrome and CVD [3, 15]. A recent review has highlighted that EUGR in preterm infants associates with poor neurodevelopment and lower later anthropometric measures in childhood, and alterations in cardiometabolic risk markers [16]. The effects of this condition may reinforce the approach that the first 1,000 days (from conception to 2 years) is a critical period for human growth and development [17]. The metabolic and inflammatory consequences of this early stunted growth have been scarcely studied [18, 19], and it is not clear if these outcomes could depend on the postnatal growth restriction per se and/or prematurity [20]

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