• Joke de Graaf, Erica L T van den Akker, Richard A van Lingen, Liesbeth J M Groot Jebbink, Frank H de Jong, Ruth E Grunau, Monique van Dijk, and Dick Tibboel.
• Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. Electronic address: Jookdegraaf@hotmail.com.
• J. Pediatr. 2014 Sep 1;165(3):459-463.e2.

ObjectiveTo test the hypothesis that the diurnal cortisol secretion rhythm of children who as neonates had been hospitalized differs from that of children without a history of neonatal hospital admission and that this rhythm differs between these hospitalized children treated with either continuous morphine infusion or placebo.Study DesignA follow-up cohort study was performed with 5-year-old children who as neonates participated in a randomized controlled trial of continuous morphine infusion (born 24-42 weeks' gestation), and a control group of healthy term born (≥ 37 weeks' gestation) children. Five saliva samples over a school day were assayed for cortisol concentrations. The diurnal cortisol rhythm was analyzed with random regression analysis for repeated measurements.ResultsCompared with the healthy controls, the trial participants had greater cortisol levels (P = .002) after adjustment for sex and socioeconomic status. The administration of morphine did not affect the cortisol concentrations (P = .66) after adjustment for sex, socioeconomic status, and gestational age at birth.ConclusionsThe finding that former trial participants had greater cortisol levels at 5 years of age supports the concept of long-lasting programming of the hypothalamic-pituitary-adrenal axis. Morphine infusion in the neonatal period did not alter cortisol secretion at 5 years of age.Copyright © 2014 Elsevier Inc. All rights reserved.

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