Cognitive, motor, and behavioral outcomes in preterm infants exposed to opioids

Pediatr Res. 2025 Apr 12. doi: 10.1038/s41390-025-04048-3. Online ahead of print.

ABSTRACT

BACKGROUND: Preterm infants undergo multiple painful procedures, which may negatively affect neurodevelopment. Proper pain management, including opioid use, is essential. This study aimed to determine the impact of opioid administration in very and extremely preterm infants on cognitive, motor, and behavioral outcomes at the corrected age of 3 years.

METHODS: This retrospective, single-center study included preterm infants born between 23 and 32 weeks of gestation, admitted to the Medical University of Vienna between 2011 and 2017. Follow-up data were collected at 3 years corrected age. Primary outcomes included behavioral outcomes assessed by the Child Behavior Checklist (CBCL) and cognitive and motor outcomes using the Bayley Scales of Infant Development (BSID).

RESULTS: A total of 333 preterm infants were included, with 214 in the non-opioid group (no exposure to opioids) and 119 in the opioid-group (exposure to opioids). Significant differences in cognitive and motor scores were observed between the groups (92.5 (85.5-98.5) vs 88 (79-94) and 85 (76-96) vs 76 (67-85), both p = 0.001). Behavioral outcomes were within the normal range in both groups, although higher depressive scores were noted in the opioid group.

CONCLUSIONS: Cumulative opioid exposure in neonatal care may negatively impact cognitive and motor development but did not significantly affect overall behavioral outcomes.

IMPACT: Our findings suggest that cumulative opioid exposure in the NICU does not significantly influence overall behavioral problems at the age of 3 years. However, it poses a risk for altered cognitive and motor development. This study highlights the distinct effects of opioid exposure on motor development and cognitive outcomes, while offering a nuanced perspective on behavioral outcomes, filling gaps in understanding the long-term neurodevelopmental consequences in preterm infants. The findings emphasize the need for careful management of opioid administration in NICU settings, balancing pain relief with potential long-term neurodevelopmental risks, while also underscoring the role of confounding factors such as IVH in shaping developmental trajectories.

PMID:40221633 | DOI:10.1038/s41390-025-04048-3