title: Long-Term Effects of Neonatal Morphine Infusion on Pain Sensitivity: Follow-Up of a Randomized Controlled Trial.
abstract: Short-term and long-term effects of neonatal pain and its analgesic treatment have been topics of translational research over the years. This study aimed to identify the long-term effects of continuous morphine infusion in the neonatal period on thermal pain sensitivity, the incidence of chronic pain, and neurological functioning. Eighty-nine of the 150 participants of a neonatal randomized controlled trial on continuous morphine infusion versus placebo during mechanical ventilation underwent quantitative sensory testing and neurological examination at the age of 8 or 9 years. Forty-three children from the morphine group and 46 children from the placebo group participated in this follow-up study. Thermal detection and pain thresholds were compared with data from 28 healthy controls. Multivariate analyses revealed no statistically significant differences in thermal detection thresholds and pain thresholds between the morphine and placebo groups. The incidence of chronic pain was comparable between both groups. The neurological examination was normal in 29 (76%) of the children in the morphine group and 25 (61%) of the children in the control group (P = .14). We found that neonatal continuous morphine infusion (10 μg/kg/h) has no adverse effects on thermal detection and pain thresholds, the incidence of chronic pain, or overall neurological functioning 8 to 9 years later. Perspective: This unique long-term follow-up study shows that neonatal continuous morphine infusion (10 μg/kg/h) has no long-term adverse effects on thermal detection and pain thresholds or overall neurological functioning. These findings will help clinicians to find the most adequate and safe analgesic dosing regimens for neonates and infants.
authors.affiliation: Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands. Electronic address: a.valkenburg@erasmusmc.nl.
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Valkenburg
authors.affiliation: Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Gerbrich E
authors.initials: GE
authors.lastname: van den Bosch
authors.affiliation: Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Joke
authors.initials: J
authors.lastname: de Graaf
authors.affiliation: Princess Amalia Department of Pediatrics, Division of Neonatology, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Richard A
authors.initials: RA
authors.lastname: van Lingen
authors.affiliation: Department of Neonatology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Nynke
authors.initials: N
authors.lastname: Weisglas-Kuperus
authors.affiliation: Department of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: van Rosmalen
authors.affiliation: Princess Amalia Department of Pediatrics, Division of Neonatology, Isala Clinics, Zwolle, The Netherlands.
authors.forename: Liesbeth J M
authors.initials: LJ
authors.lastname: Groot Jebbink
authors.affiliation: Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.affiliation: Department of Pediatric Surgery, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands; Department of Neonatology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: van Dijk
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D002648:Child; D002658:Developmental Disabilities / Q000139:chemically induced; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015931:Intensive Care, Neonatal; D008137:Longitudinal Studies; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009483:Neuropsychological Tests; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D012044:Regression Analysis; D012189:Retrospective Studies; D011795:Surveys and Questionnaires
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine
keywords: Morphine; follow-up; neonatal intensive care; quantitative sensory testing; randomized controlled trial