Opioid exposure on the preterm brain: qualitative and quantitative MRI analysis

Abstract

AIM: To explore whether opioid exposure (morphine or fentanyl) in the neonatal intensive care unit is associated with altered neurodevelopmental outcome in preterm infants, and whether this association is modified by qualitative (brain lesions) or quantitative (volumetric) brain MRI measures obtained around 30 weeks postmenstrual age (PMA). METHOD: This retrospective cohort study included 280 infants born ≤ 30 weeks of gestation (2008-2016), scanned at 1.5T before 33 weeks PMA. Brain injury was scored by paediatric (neuro)radiologists; brain volumes were obtained via automated segmentation (dHCP-pipeline). Neurodevelopmental outcome was assessed at age 2 (Bayley-III) and age 5 (WPPSI-III, M-ABC-2). Associations between opioid exposure, brain measures, and outcome were examined using multivariable regression and interaction models. RESULTS: Opioid exposure was associated with lower cognitive scores at age 2, but not with IQ at age 5. Motor scores at age 5 were lower in children exposed to opioids. Opioid administration was associated with increased risk of intraventricular haemorrhage and post haemorrhagic ventricular dilatation, but not with brain volumes. No significant interaction between opioid administration and brain injury or volume on outcome was demonstrated. INTERPRETATION: Opioid exposure in preterm neonates is associated with poorer neurodevelopmental outcome in early childhood, but not with early brain injury or structural volumetrics on MRI after birth. Long-term follow up and longitudinal brain imaging may provide greater insight in the association between opioid administration and poor neurodevelopmental outcome. Thus far, quantitative or qualitative brain metrics around 30 weeks PMA have not been proven useful. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s44253-025-00105-1.