Rachel Steinhorn1, Christopher McPherson2, Peter J Anderson3, Jeffrey Neil4, Lex W Doyle5, Terrie Inder6. 1. Department of Pediatrics, Washington University in St. Louis, St. Louis, MO. 2. Department of Pharmacy, Brigham and Women's Hospital, Boston, MA; Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA. 3. Department of Pediatrics, Royal Women's Hospital, The University of Melbourne, Carlton, Victoria, Australia; Murdoch Children's Research Institute, Parkville, Victoria, Australia. 4. Department of Neurology, Boston Children's Hospital, Boston, MA. 5. Department of Pediatrics, Royal Women's Hospital, The University of Melbourne, Carlton, Victoria, Australia; Murdoch Children's Research Institute, Parkville, Victoria, Australia; Department of Obstetrics and Gynecology, Royal Women's Hospital, The University of Melbourne, Carlton, Victoria, Australia. 6. Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA. Electronic address: tinder@partners.org.
Abstract
OBJECTIVE: To investigate the association of morphine exposure in very preterm infants with cerebral volumes and neurodevelopmental outcome from birth through middle childhood. STUDY DESIGN: Observational study of very preterm infants in the Victorian Infant Brain Study cohort. A total of 230 infants born <30 weeks' gestational age or <1250 g were recruited from all admissions to the neonatal intensive care unit of the Royal Women's Hospital. Fifty-seven (25%) infants received morphine analgesia during their neonatal intensive care unit stay at the attending physician's discretion. Primary outcomes were regional brain volumes at term and 7 years; neurobehavioral performance at term; and cognitive, motor, emotional, behavioral, communication, and executive function scores at age 2 and 7 years. Linear regressions were used to compare outcomes between participants who did and did not receive morphine. RESULTS: At term, preterm infants who received morphine had similar rates of gray matter injury to no-morphine infants, but a trend toward smaller cortical volumes in the orbitofrontal (Pleft=.002, Pright=.01) and subgenual (Pleft=.01) regions. At 7 years, cortical volumes did not differ between groups. At 2 years, morphine-exposed children were more likely to show behavioral dysregulation (P=.007) than no-morphine children, but at 7 years no detrimental impacts of morphine on neurobehavioral outcome were observed. CONCLUSIONS: Low-dose morphine analgesia received during neonatal intensive care was associated with early alterations in cerebral structure and short-term neurobehavioral problems that did not persist into childhood.
OBJECTIVE: To investigate the association of morphine exposure in very preterm infants with cerebral volumes and neurodevelopmental outcome from birth through middle childhood. STUDY DESIGN: Observational study of very preterm infants in the Victorian Infant Brain Study cohort. A total of 230 infants born <30 weeks' gestational age or <1250 g were recruited from all admissions to the neonatal intensive care unit of the Royal Women's Hospital. Fifty-seven (25%) infants received morphine analgesia during their neonatal intensive care unit stay at the attending physician's discretion. Primary outcomes were regional brain volumes at term and 7 years; neurobehavioral performance at term; and cognitive, motor, emotional, behavioral, communication, and executive function scores at age 2 and 7 years. Linear regressions were used to compare outcomes between participants who did and did not receive morphine. RESULTS: At term, preterm infants who received morphine had similar rates of gray matter injury to no-morphineinfants, but a trend toward smaller cortical volumes in the orbitofrontal (Pleft=.002, Pright=.01) and subgenual (Pleft=.01) regions. At 7 years, cortical volumes did not differ between groups. At 2 years, morphine-exposed children were more likely to show behavioral dysregulation (P=.007) than no-morphinechildren, but at 7 years no detrimental impacts of morphine on neurobehavioral outcome were observed. CONCLUSIONS: Low-dose morphine analgesia received during neonatal intensive care was associated with early alterations in cerebral structure and short-term neurobehavioral problems that did not persist into childhood.
Authors: Susanne Brummelte; Ruth E Grunau; Vann Chau; Kenneth J Poskitt; Rollin Brant; Jillian Vinall; Ayala Gover; Anne R Synnes; Steven P Miller Journal: Ann Neurol Date: 2012-02-28 Impact factor: 10.422
Authors: Gillian C Smith; Jordan Gutovich; Christopher Smyser; Roberta Pineda; Carol Newnham; Tiong H Tjoeng; Claudine Vavasseur; Michael Wallendorf; Jeffrey Neil; Terrie Inder Journal: Ann Neurol Date: 2011-10-04 Impact factor: 10.422
Authors: Joke de Graaf; Richard A van Lingen; Abraham J Valkenburg; Nynke Weisglas-Kuperus; Liesbeth Groot Jebbink; Barbara Wijnberg-Williams; Kanwaljeet J S Anand; Dick Tibboel; Monique van Dijk Journal: Pain Date: 2012-12-20 Impact factor: 6.961
Authors: Rakesh Rao; Jackie S Sampers; Shari S Kronsberg; Josephine V Brown; Nirmala S Desai; K J S Anand Journal: Am J Perinatol Date: 2007-09-28 Impact factor: 1.862
Authors: Sinno H P Simons; Monique van Dijk; Richard A van Lingen; Daniella Roofthooft; Hugo J Duivenvoorden; Niesje Jongeneel; Carin Bunkers; Enna Smink; K J S Anand; John N van den Anker; Dick Tibboel Journal: JAMA Date: 2003-11-12 Impact factor: 56.272
Authors: David F Grabski; Rick D Vavolizza; Sarah Lepore; Daniel Levin; Sara K Rasmussen; Jonathan R Swanson; Eugene D McGahren; Jeffrey W Gander Journal: Pediatrics Date: 2020-11-12 Impact factor: 7.124
Authors: Marine Bouyssi-Kobar; Adré J du Plessis; Robert McCarter; Marie Brossard-Racine; Jonathan Murnick; Laura Tinkleman; Richard L Robertson; Catherine Limperopoulos Journal: Pediatrics Date: 2016-11 Impact factor: 7.124
Authors: Elizabeth Allocco; Marjorie Melker; Florencia Rojas-Miguez; Caitlin Bradley; Kristen A Hahn; Elisha M Wachman Journal: Adv Neonatal Care Date: 2016-10 Impact factor: 1.968
Authors: Jill G Zwicker; Steven P Miller; Ruth E Grunau; Vann Chau; Rollin Brant; Colin Studholme; Mengyuan Liu; Anne Synnes; Kenneth J Poskitt; Mikaela L Stiver; Emily W Y Tam Journal: J Pediatr Date: 2016-01-04 Impact factor: 4.406
Authors: Richard Sindelar; Edward G Shepherd; Johan Ågren; Howard B Panitch; Steven H Abman; Leif D Nelin Journal: Pediatr Res Date: 2021-05-19 Impact factor: 3.756
Authors: Christopher McPherson; Steven P Miller; Mohamed El-Dib; An N Massaro; Terrie E Inder Journal: Pediatr Res Date: 2020-01-02 Impact factor: 3.953
Authors: Mihai Puia-Dumitrescu; Bryan A Comstock; Sijia Li; Patrick J Heagerty; Krystle M Perez; Janessa B Law; Thomas R Wood; Semsa Gogcu; Dennis E Mayock; Sandra E Juul Journal: JAMA Netw Open Date: 2021-07-01