BACKGROUND: Fentanyl is commonly used in preterm infants. Relatively little is known regarding the neurodevelopmental outcomes of preterm infants exposed to fentanyl. OBJECTIVE: To investigate the association between cumulative fentanyl dose and brain injury and diameters in a cohort of preterm infants. METHODS: Data on demographics, perinatal course, and neonatal course, including total fentanyl exposure prior to term equivalent age, were retrospectively evaluated for 103 infants born at ≤30 weeks gestational age (mean gestational age 26.9 ± 1.8 weeks) who underwent magnetic resonance imaging at term equivalent age. Magnetic resonance images were evaluated for brain injury and regional brain diameters. Developmental testing was conducted at term equivalent and 2 years of age. RESULTS: Seventy-eight infants (76%) received fentanyl (median cumulative dose 3 µg/kg, interquartile range 1-441 µg/kg). Cumulative fentanyl dose in the first week of life correlated with the incidence of cerebellar hemorrhage after correction for covariates (odds ratio 2.1, 95% confidence interval 1.1-4.1). Cumulative fentanyl dose before term equivalent age correlated with reductions in transverse cerebellar diameter after correction for covariates, including the presence of cerebellar hemorrhage (r = 0.461, P = 0.002). No correlation was detected between cumulative fentanyl dose and development at 2 years of age. CONCLUSIONS: Higher cumulative fentanyl dose in preterm infants correlated with a higher incidence of cerebellar injury and lower cerebellar diameter at term equivalent age. Our findings must be taken with caution, but emphasize the need for future prospective trials examining the risks and benefits of commonly used analgesic agents in preterm infants.
BACKGROUND:Fentanyl is commonly used in preterm infants. Relatively little is known regarding the neurodevelopmental outcomes of preterm infants exposed to fentanyl. OBJECTIVE: To investigate the association between cumulative fentanyl dose and brain injury and diameters in a cohort of preterm infants. METHODS: Data on demographics, perinatal course, and neonatal course, including total fentanyl exposure prior to term equivalent age, were retrospectively evaluated for 103 infants born at ≤30 weeks gestational age (mean gestational age 26.9 ± 1.8 weeks) who underwent magnetic resonance imaging at term equivalent age. Magnetic resonance images were evaluated for brain injury and regional brain diameters. Developmental testing was conducted at term equivalent and 2 years of age. RESULTS: Seventy-eight infants (76%) received fentanyl (median cumulative dose 3 µg/kg, interquartile range 1-441 µg/kg). Cumulative fentanyl dose in the first week of life correlated with the incidence of cerebellar hemorrhage after correction for covariates (odds ratio 2.1, 95% confidence interval 1.1-4.1). Cumulative fentanyl dose before term equivalent age correlated with reductions in transverse cerebellar diameter after correction for covariates, including the presence of cerebellar hemorrhage (r = 0.461, P = 0.002). No correlation was detected between cumulative fentanyl dose and development at 2 years of age. CONCLUSIONS: Higher cumulative fentanyl dose in preterm infants correlated with a higher incidence of cerebellar injury and lower cerebellar diameter at term equivalent age. Our findings must be taken with caution, but emphasize the need for future prospective trials examining the risks and benefits of commonly used analgesic agents in preterm infants.
Authors: Erin M Lammers; Peter N Johnson; Kimberly D Ernst; Tracy M Hagemann; Shelley M Lawrence; Patricia K Williams; Michael P Anderson; Jamie L Miller Journal: Ann Pharmacother Date: 2013-12-05 Impact factor: 3.154
Authors: Deanne K Thompson; Simon K Warfield; John B Carlin; Masa Pavlovic; Hong X Wang; Merilyn Bear; Michael J Kean; Lex W Doyle; Gary F Egan; Terrie E Inder Journal: Brain Date: 2006-09-28 Impact factor: 13.501
Authors: K J S Anand; R Whit Hall; Nirmala Desai; Barbara Shephard; Lena L Bergqvist; Thomas E Young; Elaine M Boyle; Ricardo Carbajal; Vinod K Bhutani; Mary Beth Moore; Shari S Kronsberg; Bruce A Barton Journal: Lancet Date: 2004-05-22 Impact factor: 79.321
Authors: Chandler Rebecca Lee Mongerson; Russell William Jennings; David Zurakowski; Dusica Bajic Journal: Int J Dev Neurosci Date: 2019-09-26 Impact factor: 2.457
Authors: Alan Leviton; Stephen R Hooper; Scott J Hunter; Megan N Scott; Elizabeth N Allred; Robert M Joseph; T Michael O'Shea; Karl Kuban Journal: Pediatr Neurol Date: 2017-12-21 Impact factor: 3.372
Authors: Lillian G Matthews; Brian H Walsh; Clare Knutsen; Jeffrey J Neil; Christopher D Smyser; Cynthia E Rogers; Terrie E Inder Journal: Pediatr Res Date: 2018-02-07 Impact factor: 3.756
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: Giulia Spoto; Greta Amore; Luigi Vetri; Giuseppe Quatrosi; Anna Cafeo; Eloisa Gitto; Antonio Gennaro Nicotera; Gabriella Di Rosa Journal: Front Syst Neurosci Date: 2021-06-10