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      Cortisol and Cortisone in Early Childhood in Very-Low-Birthweight Infants and Term-Born Infants

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          Abstract

          Introduction: Besides programming of the hypothalamic-pituitary-adrenal (HPA) axis, changes in the activity of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) could contribute to the later metabolic and cardiovascular consequences of preterm birth. Objective: We compared serum cortisol, cortisone, and cortisol/cortisone ratio in early childhood in very-low-birthweight (VLBW) infants and term appropriate for gestational age (AGA) born infants. Methods: We included 41 VLBW infants, participating in the randomized controlled Neonatal Insulin Replacement Therapy in Europe trial, and 64 term AGA-born infants. Cortisol and cortisone were measured in blood samples taken at 6 months and 2 years corrected age (VLBW children) and at 3 months and 1 and 2 years (term children). At 2 years of (corrected) age (HDL) cholesterol, triglycerides, glucose, and insulin were also measured. Results: During the first 2 years of life, cortisol/cortisone ratio is higher in VLBW children compared to term children. In the total group of children, cortisol/cortisone ratio is positively related to triglycerides at 2 years of (corrected) age. In VLBW children, over the first 2 years of life both cortisol and cortisone are higher in the early-insulin group compared to the standard care group. Conclusions: In VLBW infants, lower 11β-HSD2 activity probably contributes to the long-term metabolic and cardiovascular risks. In VLBW infants, early insulin treatment could affect programming of the HPA axis, resulting in higher cortisol and cortisone levels during early childhood.

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          Most cited references 36

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          Homeostasis model assessment: insulin resistance and ?-cell function from fasting plasma glucose and insulin concentrations in man

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            The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero.

            Potential mechanisms underlying prenatal programming of hypertension in adult life were investigated using a rat model in which maternal protein intake was restricted to 9% vs. 18% casein (control) during pregnancy. Maternal low protein (MLP) offspring exhibit glucocorticoid-dependent raised systolic blood pressure throughout life (20-30 mm Hg above the control). To determine the molecular mechanisms underlying the role of alterations in glucocorticoid hormone action in the prenatal programming of hypertension in MLP offspring, tissues were analyzed for expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11betaHSD1, 11betaHSD2, and corticosteroid-responsive Na/K-adenosine triphosphatase alpha1 and beta1. GR protein (95 kDa) and messenger RNA (mRNA) expression in kidney, liver, lung, and brain was more than 2-fold greater in MLP vs. control offspring during fetal and neonatal life and was more than 3-fold higher during subsequent juvenile and adult life (P < 0.01). This was associated with increased levels of Na/K-adenosine triphosphatase alpha1- and beta1-subunit mRNA expression. Levels of MR gene expression remained unchanged. Exposure to the MLP diet also resulted in markedly reduced levels of 11betaHSD2 expression in the MLP placenta on days 14 and 20 of gestation (P < 0.001), underpinning similar effects on 11betaHSD2 enzyme activity that we reported previously. Levels were also markedly reduced in the kidney and adrenal of MLP offspring during fetal and postnatal life (P < 0.001). This programmed decline in 11betaHSD2 probably contributes to marked increases in glucocorticoid hormone action in these tissues and potentiates both GR- and MR-mediated induction of raised blood pressure. In contrast, levels of 11betaHSD1 mRNA expression in offspring central and peripheral tissues remained unchanged. In conclusion, we have demonstrated that mild protein restriction during pregnancy programs tissue-specific increases in glucocorticoid hormone action that are mediated by persistently elevated expression of GR and decreased expression of 11betaHSD2 during adult life. As glucocorticoids are potent regulators not only of fetal growth but also of blood pressure, our data suggest important potential molecular mechanisms contributing to the prenatal programming of hypertension by maternal undernutrition in the rat.
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              High blood pressure in 2.5-year-old children born extremely preterm.

              Adolescents and young adults born preterm have elevated blood pressure (BP). The objective of this study was to investigate if BP is elevated at 2.5 years of age after an extremely preterm birth (EXPT). In a regional subset of the national population-based cohort Extremely Preterm Infants in Sweden Study, BP at 2.5 years of age was studied in 68 survivors of EXPT (gestational age: 23.6-26.9 weeks; mean ± SD birth weight: 810 ± 164 g), and 65 matched controls born at term. At follow-up at 2.5 years of corrected age, EXPT children had significantly higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) z scores than controls born at term, according to pediatric BP nomograms by age, gender, and height. The proportion of SBP ≥90th percentile was 44% (30 of 68) in EXPT children and 23% (15 of 65) in controls (P = .01). In logistic regression analyses stratified according to gender, EXPT was associated with an odds ratio for a SBP ≥90th percentile of 3.32 (95% confidence interval: 1.25-8.81) among boys. The corresponding odds ratio among EXPT girls was 2.18 (95% confidence interval: 0.62-7.61). In EXPT children, SBP and DBP z scores were inversely correlated to catch-up growth from 36 weeks' postmenstrual age to follow-up at 2.5 years of age. Children born extremely preterm have elevated office SBP and DBP at a corrected age of 2.5 years. This finding might have implications for their cardiovascular health later in life.
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                Author and article information

                Journal
                HRP
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2020
                March 2021
                03 February 2021
                : 93
                : 7-8
                : 453-459
                Affiliations
                aDepartment of Pediatrics, Albert Schweitzer Hospital, Dordrecht, The Netherlands
                bDepartment of Neonatology, Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
                cDepartment of Clinical Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
                Author notes
                *Mirjam M. van Weissenbruch, Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, PO Box 7057, NL–1007 MB Amsterdam (The Netherlands), m.vanweissenbruch@amsterdamumc.nl
                Article
                512784 Horm Res Paediatr 2020;93:453–459
                10.1159/000512784
                33535224
                © 2021 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Tables: 3, Pages: 7
                Categories
                Research Article

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