title: Follow-up at the corrected age of 24 months of preterm newborns receiving continuous infusion of fentanyl for pain control during mechanical ventilation.
abstract: The neurodevelopmental impact of fentanyl given to preterm newborns for pain control is still unknown. The aim of this study was to assess the neurodevelopmental impact of 2 regimens of fentanyl administration by a prospective follow-up evaluation. In our previous multicenter, double-blind, randomized controlled trial, 131 mechanically ventilated newborns (gestational age ≤32 weeks) were randomized to fentanyl (continuous infusion of fentanyl + open label boluses of fentanyl) or placebo (continuous infusion of placebo + open label boluses of fentanyl). Infant development was evaluated using Griffiths Mental Developmental Scales (Griffiths, 1996) until 24 months of corrected age by trained psychologists who were not aware of the group allocation. 106/131 infants survived at discharge; 3 died after discharge, 25 were lost to follow-up (12 in the fentanyl and 13 in the placebo group). Seventy-eight patients were evaluated at 2 years of corrected age. Children in the fentanyl group, compared with those in the placebo group, obtained significantly lower Griffiths general developmental quotient (mean [SD]: 89.95 [13.64] vs 97.18 [12.72], P = 0.024) together with the scores on the eye-hand coordination (mean [SD]: 89.09 [12.13] vs 99.19 [13.19], P = 0.002) and performance skills (mean [SD]: 79.71 [15.80] vs 90.09 [15.28], P = 0.009) scales. After adjustment for clinical confounders (gestational age, CRIB score, and sex) only eye-hand co-ordination was associated with fentanyl infusion. This study demonstrates that continuous infusion of fentanyl in very preterm infants, given at 1 mcg·kg·h during mechanical ventilation, is associated with a significant decrease in eye and hand co-ordination skills. Longer follow-up is needed to evaluate the impact on future motor, cognitive, and behavioral functions.
authors.affiliation: Neonatology and Neonatal Intensive Care Unit, Dipartimento Materno-Infantile, Azienda Sanitaria Locale Romagna, Ospedale Rimini, Rimini, Italy.
authors.forename: Gina
authors.initials: G
authors.lastname: Ancora
authors.affiliation: Neonatal Intensive Care Unit, Dipartimento di Salute della Donna e del Bambino, Azienda Ospedaliera Universitaria di Padova, Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Lago
authors.affiliation: Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria di Modena, Modena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Garetti
authors.affiliation: Neonatal Intensive Care and Neonatology, Fondazione MBBM, Azienda Ospedaliera San Gerardo, Monza, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pirelli
authors.affiliation: Neonatal Intensive Care Unit and Neonatology, Azienda Ospedaliera Ospedale Sant'Anna, Como, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Merazzi
authors.affiliation: Neonatal Intensive Care Unit and Neonatology, Ospedale Sant'Orsola-Malpighi, Bologna, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Pierantoni
authors.affiliation: Neonatal Intensive Care Unit, Azienda Ospedaliera Universitaria di Modena, Modena, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ferrari
authors.affiliation: Neonatal Intensive Care Unit and Neonatology, Ospedale Sant'Orsola-Malpighi, Bologna, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Faldella
mesh_terms: D018686:Anesthetics, Intravenous / Q000009:adverse effects*; D002653:Child Behavior Disorders / Q000139:chemically induced; D002675:Child, Preschool; D003072:Cognition Disorders / Q000139:chemically induced; D002658:Developmental Disabilities / Q000139:chemically induced*; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl / Q000009:adverse effects*; D006801:Humans; D007558:Italy; D008137:Longitudinal Studies; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D047928:Premature Birth / Q000628:therapy; D011596:Psychomotor Disorders; D012121:Respiration, Artificial / Q000009:adverse effects*; D012131:Respiratory Insufficiency / Q000209:etiology / Q000628:therapy*; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D018686:Anesthetics, Intravenous; D005283:Fentanyl