ArticleEBioMedicine2019
Morphine biotransformation genes and neonatal clinical factors predicted behaviour problems in very preterm children at 18 months.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 31 citations in OpenAlex.
- Quantifying the Pharmacodynamics of Morphine in the Treatment of Postoperative Pain in Preverbal Children.Journal of clinical pharmacology · 2022Trial
- Peroxisome, neuropeptide, and inflammation signaling pathways uniquely impacted by opioid exposure in the hypothalamus of males and females.Molecular and cellular neurosciences · 2025Article
- Neurodevelopmental outcomes at five years in children born very preterm (24-31 weeks) exposed to opioids with or without midazolam: results from the French nationwide EPIPAGE-2 cohort study.The Lancet regional health. Europe · 2025Article
- Brain health in preterm infants: importance of early-life pain and analgesia exposure.Pediatric research · 2024Review
- Association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury: a propensity score-matched cohort study.EClinicalMedicine · 2023Article
- Early-life exposure to analgesia and 18-month neurodevelopmental outcomes in very preterm infants.Pediatric research · 2023Article
- CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor.BMC psychiatry · 2023Article
- Association between morphine exposure and impaired brain development on term-equivalent age brain magnetic resonance imaging in very preterm infants.Scientific reports · 2022Article
- The Behavioral Problems in 2.5-5 Years Old Children Linked with Former Neonatal/Infantile Surgical Parameters.Children (Basel, Switzerland) · 2021Article
- Practical approaches to sedation and analgesia in the newborn.Journal of perinatology : official journal of the California Perinatal Association · 2021Review
- Long-term impact of systematic pain and sedation management on cognitive, motor, and behavioral outcomes of extremely preterm infants at preschool age.Pediatric research · 2021Observational
- The influence of pain, agitation, and their management on the immature brain.Pediatric research · 2020Review
- Genetic and epigenetic factors and early life inflammation as predictors of neurodevelopmental outcomes.Seminars in fetal & neonatal medicine · 2020Review
- Personal perspectives: Infant pain-A multidisciplinary journey.Paediatric & neonatal pain · 2020Review
- Towards personalized medicine in preterm newborns: Morphine analgesia predicted by genotype.EBioMedicine · 2019Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBehaviour problems are prevalent among children born very preterm (≤ 32 weeks gestation), and have been associated with morphine exposure. Morphine accumulation in the brain is determined by genetic variations related to morphine biotransformation. The objective of the study was to investigate whether morphine-biotransformation genotypes contribute to individual differences in long-term effects of morphine on behaviour at 18 months corrected age (CA).
methods198 children born very preterm (24-32 weeks gestation) were followed from birth and seen at 18 months CA. Relationships between child behavior (Internalizing, Externalizing on the Child Behavior Checklist), morphine exposure, neonatal clinical variables, and morphine biotransformation gene variants in ABCB1, UGT1A9, UGT 2B7*2, ABCC2, ABCC3, SLCO1B1, CYP3A4, COMT were examined.
findingsNeonatal clinical predictors and genotypes accounted for 39% of the overall variance in behaviour. In children with the minor allele of UGT1A9 rs17863783 (marker of UGT1A6*4, UDP-glucuronosyltransferase), greater morphine exposure (p = ·0011) was associated with more Internalizing behaviour. More Externalizing behaviour was predicted by greater morphine exposure in children with the COMT rs4680 Met/Met genotype (p = ·0006).
interpretationGenetic variations that affect relative accumulation of morphine in the brain, together with neonatal clinical factors, are differentially related to anxiety and depressive symptoms (internalizing) and to acting out (externalizing) behaviours at 18 months CA in children born very preterm. FUND: NIH/NICHD HD039783 (REG); CIHR MOP86489 (REG), MOP68898 (SPM), MOP79262 (SPM, REG).
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