title: Long-term effects of routine morphine infusion in mechanically ventilated neonates on children's functioning: five-year follow-up of a randomized controlled trial.
abstract: Newborns on ventilatory support often receive morphine to induce analgesia. Animal experiments suggest that this may impair subsequent cognitive and behavioral development. There are sparse human data on long-term effects of neonatal morphine. We aimed to investigate the effects of continuous morphine administered in the neonatal period on the child's functioning. We conducted a follow-up study among 5-year-olds who, as mechanically ventilated neonates, had participated in a placebo-controlled trial on effects of morphine administration on pain and neurologic outcome. They were now tested on intelligence, visual motor integration, behavior, chronic pain, and health-related quality of life. Univariate analyses showed significantly lower overall intelligence quotient (IQ) scores for children who earlier had received morphine, that is, mean 94 (SD 14.5) versus 100 (SD 12.9) for those who received placebo (P = 0.049). Other between-group differences in outcomes were not found. The statistical difference disappeared after correction for treatment condition, open-label morphine consumption over the first 28 days, and a propensity score for clinically relevant co-variables in multiple regression analyses. However, scores on one IQ subtest, "visual analysis," were significantly negatively related to having received morphine and to open-label morphine consumption the first 28 days. The finding of a significant effect of morphine on the "visual analysis" IQ subtest calls for follow-up at a later age focusing on the higher-order neurocognitive functions. Morphine received in the neonatal period has negative effects on the child's cognitive functioning at the age of 5 years which warrants follow-up at a later age.
authors.affiliation: Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands Princess Amalia Department of Pediatrics, Department of Neonatology, Isala Clinics, Zwolle, The Netherlands Department of Pediatrics, VUMC, Amsterdam, The Netherlands Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA Departments of Medical Psychology and Psychotherapy, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands Department of Neonatology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands Department of Medical Psychology, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Joke
authors.initials: J
authors.lastname: de Graaf
authors.forename: Richard A
authors.initials: RA
authors.lastname: van Lingen
authors.forename: Sinno H P
authors.initials: SHP
authors.lastname: Simons
authors.forename: Kanwaljeet J S
authors.initials: KJS
authors.lastname: Anand
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Duivenvoorden
authors.forename: Nynke
authors.initials: N
authors.lastname: Weisglas-Kuperus
authors.forename: Daniella W E
authors.initials: DWE
authors.lastname: Roofthooft
authors.forename: Liesbeth J M
authors.initials: LJM
authors.lastname: Groot Jebbink
authors.forename: Ravian R
authors.initials: RR
authors.lastname: Veenstra
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Monique
authors.initials: M
authors.lastname: van Dijk
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002675:Child, Preschool; D002908:Chronic Disease; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007360:Intelligence; D008137:Longitudinal Studies; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects; D009426:Netherlands; D010146:Pain / Q000188:drug therapy*; D011788:Quality of Life; D012044:Regression Analysis; D012121:Respiration, Artificial / Q000009:adverse effects*
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine