title: Five-year follow-up of effects of neonatal intensive care and morphine infusion during mechanical ventilation on diurnal cortisol rhythm.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Compared 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. Electronic address: Jookdegraaf@hotmail.com.
authors.forename: Joke
authors.initials: J
authors.lastname: de Graaf
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Erica L T
authors.initials: EL
authors.lastname: van den Akker
authors.affiliation: Princess Amalia Department of Pediatrics, Department of Neonatology, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Richard A
authors.initials: RA
authors.lastname: van Lingen
authors.affiliation: Princess Amalia Department of Pediatrics, Department of Neonatology, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Liesbeth J M
authors.initials: LJ
authors.lastname: Groot Jebbink
authors.affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Grunau
authors.affiliation: Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: van Dijk
authors.affiliation: Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002675:Child, Preschool; D002940:Circadian Rhythm; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D015931:Intensive Care, Neonatal; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D012121:Respiration, Artificial; D012463:Saliva / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D006854:Hydrocortisone