title: Early life intervention with glucocorticoids has negative effects on motor development and neuropsychological function in 14-17 year-old adolescents.
abstract: OBJECTIVE
  To reduce the risk of bronchopulmonary dysplasia, preterm infants receive neonatal treatment with glucocorticoids, mostly dexamethasone (DEX). Compared to current protocols, treatment regimens of the late 1980s - early 1990s prescribed high doses of DEX for an extensive period up to 6 weeks. Worldwide at least one million children have been treated with this dose regimen. Previous studies have shown adverse effects of neonatal treatment with the glucocorticoid dexamethasone (DEX) on outcome in children aged 7-10 years. On the other hand, treatment with another glucocorticoid, hydrocortisone (HC), was not related to adverse effects in childhood. In the current study we determined the consequences of early life intervention with DEX or HC in adolescents (age 14-17 years). Besides motor function and intellectual capacities, we also examined fundamental neuropsychological functions which have so far received little attention.
  
  
  METHODS
  In an observational cohort study we compared 14-17 year-old adolescents who received DEX (.5 mg/kg/day tapering off to .1 mg/kg/day over 21 days, n=63), or HC (5 mg/kg/day tapering off to 1 mg/kg/day over 22 days, n=67), or did not receive neonatal glucocorticoids (untreated, n=71) after premature birth (gestational age<32 weeks). Because gestational age was shorter and duration of ventilation was longer in the DEX-treated group, all analyses were corrected for these potential confounders. Motor function, IQ, and neuropsychological functions were assessed.
  
  
  RESULTS
  DEX-treated group participants scored lower on gross motor skill tasks than their HC-treated and untreated counterparts. A higher proportion of DEX-treated girls needed special education compared to the other groups. DEX-treated adolescents performed poorer on neuropsychological tasks measuring alertness, visuomotor coordination, and emotion recognition. The HC-treated group did not differ from the untreated group.
  
  
  CONCLUSIONS
  Even after 14-17 years, neonatal treatment with .5 mg/kg/day DEX was associated with adverse effects on motor function, school level, and neuropsychological functions, whereas treatment with the clinically equally effective dose of 5 mg/kg/day HC was not. Potential physiological mechanisms underlying the differences in dexamethasone and hydrocortisone effects are discussed. Based on the current findings, we recommend early identification of neuropsychological deficits after DEX treatment in order to specify extra educational needs.
authors.affiliation: Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maike
authors.initials: M
authors.lastname: ter Wolbeek
authors.forename: Leo M J
authors.initials: LM
authors.lastname: de Sonneville
authors.forename: Willem B
authors.initials: WB
authors.lastname: de Vries
authors.forename: Annemieke
authors.initials: A
authors.lastname: Kavelaars
authors.forename: Sylvia
authors.initials: S
authors.lastname: Veen
authors.forename: René F
authors.initials: RF
authors.lastname: Kornelisse
authors.forename: Mirjam
authors.initials: M
authors.lastname: van Weissenbruch
authors.forename: Wim
authors.initials: W
authors.lastname: Baerts
authors.forename: Kian D
authors.initials: KD
authors.lastname: Liem
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
mesh_terms: D000293:Adolescent; D001288:Attention / Q000187:drug effects; D001997:Bronchopulmonary Dysplasia / Q000188:drug therapy*; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D004522:Educational Status; D056344:Executive Function / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D009048:Motor Skills / Q000187:drug effects*; D009483:Neuropsychological Tests
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone