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Published on: February 9, 2024
Prematurity, Opioid Exposure and Neonatal Pain: Do They Affect the Developing Brain?
Gerbrich E van den Bosch1, Tonya White, Hanan El Marroun
1Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Insights
Premature infants receiving morphine may have altered brain volumes, but long-term neurocognitive and sensory development appears unaffected. Further research with larger groups is recommended to confirm these findings in preterm children.
Area of Science:
- Neonatal care and developmental neuroscience
- Pediatric neurology and long-term outcomes
Background:
- Historically, morphine was routinely administered to preterm infants, particularly those on mechanical ventilation.
- Neonatal pain and opioid exposure have been linked to adverse long-term effects in animal models.
Purpose of the Study:
- To investigate the potential long-term effects of prematurity, procedural pain, and opioid exposure on neurobiological, neuropsychological, and sensory development in children.
- To examine associations between these factors and outcomes 10 years later.
Main Methods:
- A cohort of 19 children born preterm, previously enrolled in a morphine RCT and follow-up studies, was assessed.
- Evaluations included brain morphology (n=11), neuropsychological functioning (n=19), and thermal sensitivity (n=17).
- Associations with gestational age, painful procedures, and morphine exposure were analyzed.
Main Results:
- Significant correlations were found between gestational age, number of painful procedures, morphine exposure, and brain volumes (coefficients 0.60-0.85).
- No significant correlations were established between these factors and thermal sensitivity.
- Neuropsychological outcomes showed moderate correlations with morphine exposure in only two subtests; overall performance was average.
Conclusions:
- While prematurity, opioid exposure, and neonatal pain correlated with brain volume, major impacts on neuropsychological functioning or thermal sensitivity were not detected.
- Neonatal morphine administration does not appear to affect neurocognitive performance or thermal sensitivity in childhood for preterm infants without early brain damage.
- Larger sample sizes are required for future studies to validate these findings.
Background:
Traditionally, 10 years ago, children born preterm often routinely received morphine, especially during mechanical ventilation. Studies in neonatal rats, whose stage of brain development roughly corresponds to that of children born preterm, found negative long-term effects after pain and opioid exposure.
Objectives:
We studied possible effects of prematurity, procedural pain and opioids in humans 10 years later. We hypothesized that these factors would negatively influence neurobiological, neuropsychological and sensory development later in life.
Methods:
We included 19 children born preterm who as neonates participated in an RCT on the short-term effects of morphine administration and who previously participated in our follow-up studies at ages 5 and 8/9 years. We assessed associations between brain morphology (n = 11), neuropsychological functioning (n = 19) and thermal sensitivity (n = 17) and prematurity, opioid exposure and neonatal pain.
Results:
Significant correlations (coefficients 0.60-0.85) of gestational age, number of painful procedures and morphine exposure with brain volumes were observed. Significant correlations between these factors and thermal sensitivity were not established. Neuropsychological outcome was significantly moderately correlated with morphine exposure in only two subtests, and children performed in general 'average' by Dutch norms.
Conclusions:
Although prematurity, opioid exposure and neonatal pain were significantly associated with brain volume, no major associations with neuropsychological functioning or thermal sensitivity were detected. Our findings suggest that morphine administration during neonatal life does not affect neurocognitive performance or thermal sensitivity during childhood in children born preterm without brain damage during early life. Future studies with larger sample sizes are needed to confirm these findings.
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