Original ArticleSmaller Cerebellar Growth and Poorer Neurodevelopmental Outcomes in Very Preterm Infants Exposed to Neonatal Morphine
Section snippets
Methods
We studied a prospective cohort of 188 infants born very preterm (24-32 weeks gestational age [GA]) admitted to the neonatal intensive care unit at the British Columbia Women's Hospital from April 2006 to September 2010, participating in a study of early brain development. Neonates with adequate quality magnetic resonance imaging (MRI) scans for volumetric analysis and detailed morphine exposure recorded were included in this study (n = 136) (Figure 1; available at www.jpeds.com). Infants
Results
Our cohort of infants was born at a median age of 27.4 weeks postmenstrual age (range 24-32; IQR 25.8-29.8) and had serial imaging at a median age of 32.3 weeks (IQR 30.8-34.0) and at 40.3 weeks (IQR 38.9-42.0). Of the 136 infants, 91 (67%) were exposed to morphine, receiving a median cumulative dose of 1.905 mg/kg. Table I describes the clinical characteristics of our cohort by morphine exposure. Of the 136 infants, 127 (93%) were followed to 18 months CA. Median scores were 96 (IQR 86-98) on
Discussion
Morphine exposure was differentially associated with small cerebellar volumes but not cerebral volumes. Consistent with Steinhorn et al,7 morphine exposure was not related to smaller brain volume; however, higher morphine exposure in very preterm neonates was associated with reduced cerebellar volume at term-equivalent age, even after adjusting for known confounders. This result is consistent with mouse models, suggesting a critical period during development when Purkinje cells of the
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Cited by (0)
Funded by Canadian Institutes of Health Research (MOP79262 [to S.M.] and MOP86489 [to R.G.]). J.Z. was supported by the Canadian Child Health Clinician Scientist Program, Child & Family Research Institute (CFRI), Michael Smith Foundation for Health Research (MSFHR), and NeuroDevNet. S.M. is currently the Bloorview Children's Hospital Chair in Pediatric Neuroscience and was supported by a Tier 2 Canada Research Chair in Neonatal Neuroscience and MSFHR Scholar Award. R.G. and R.B. are supported by CFRI (Senior Scientist Awards) and R.G. holds a Eunice Kennedy Shriver Institute of Child Health and Human Development (RO1 HD039783). C.S.'s research program is supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke (R01 NS061957 and R01 NS055064). The authors declare no conflicts of interest.