Impaired Antioxidant Defence Status Is Associated With Metabolic-Inflammatory Risk Factors in Preterm Children With Extrauterine Growth Restriction: The BIORICA Cohort Study.

María Dolores Ordóñez-Díaz,María Dolores Mesa,Juan Luis Pérez-Navero,María José De La Torre-Aguilar,Mercedes Gil-Campos,Katherine Flores-Rojas,Ángel Gil,María Carmen Muñoz-Villanueva

doi:10.3389/fnut.2021.793862

Abstract

Introduction: An impaired antioxidant status has been described during foetal growth restriction (FGR). Similarly, the antioxidant defence system can be compromised in preterm children with extrauterine growth restriction (EUGR). The aim of this prospective study was to evaluate the antioxidant status in prepubertal children with a history of prematurity without FGR, with and without EUGR, compared to a healthy group.Methods: In total, 211 children were recruited and classified into three groups: 38 with a history of prematurity and EUGR; 50 with a history of prematurity and adequate extrauterine growth (AEUG); and 123 control children born at term. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities were assessed in lysed erythrocytes with spectrophotometric methods. Plasma levels of the antioxidants α-tocopherol, retinol and β-carotene were determined through solvent extraction and ultra-high-pressure liquid chromatography coupled to mass spectrometry.Results: Children with the antecedent of EUGR and prematurity had lower CAT activity than the other two groups and lower GPx activity than the control children. Lower SOD, GPx and GR activities were observed in the AEUG group compared to the controls. However, higher concentrations of α-tocopherol and β-carotene were found in the EUGR group compared to the other groups; retinol levels were also higher in EUGR than in AEUG children. In EUGR and AEUG children, enzymatic antioxidant activities and plasma antioxidants were associated with metabolic syndrome components and pro-inflammatory biomarkers.Conclusions: This study reveals, for the first time, that the EUGR condition and prematurity appear to be linked to an impairment of the antioxidant defence status, which might condition an increased risk of adverse metabolic outcomes later in life.

Highlights

An impaired antioxidant status has been described during foetal growth restriction (FGR)
Preterm infants may be susceptible to oxidative stress (OxS) damage due to immaturity of the antioxidant defence systems, which are mainly represented by endogenous cellular antioxidant enzymes, e.g., catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and superoxide dismutase (SOD), and exogenous/dietary non-enzymatic antioxidants [8, 9]
The first group, identified as the extrauterine growth restriction (EUGR) group, included prepubertal children with the following criteria: a history of prematurity: ≤32 weeks gestational age (GA); a weight above P10 for GA at birth and without the diagnosis of FGR following the international consensus of the Ultrasound Obstetrics and Gynaecology [22]; the development of postnatal growth restriction or “a true EUGR,” according to the definitions proposed in the literature [18]

Summary

Introduction

An impaired antioxidant status has been described during foetal growth restriction (FGR). Preterm infants may be susceptible to OxS damage due to immaturity of the antioxidant defence systems, which are mainly represented by endogenous cellular antioxidant enzymes, e.g., catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and superoxide dismutase (SOD), and exogenous/dietary non-enzymatic antioxidants (e.g., retinol, β-carotene, and α-tocopherol) [8, 9] The consequences of this higher OxS condition include a higher risk of developing neonatal pathologies (called “free-radical-related diseases of the newborn”), such as necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, patent ductus arteriosus, and an increased risk of brain damage and neurodevelopmental impairment [10], as well as long-term morbidities and increased mortality [9]. Adverse early life environments such as cumulative exposure to perinatal complications [15] and malnutrition [16], have independently been associated with an impaired antioxidant system and higher levels of lipid peroxidation in children and adolescents [17]

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Discussion

Conclusion