Fentanyl Exposure Is Associated with Adverse Respiratory Outcomes in Ventilated Preterm Neonates: A Retrospective Matched Cohort Study
In brief
Fentanyl exposure raises bronchopulmonary dysplasia risk fivefold in preterm ventilated infants
In a matched cohort of 142 infants born before 34 weeks, continuous fentanyl infusion during mechanical ventilation was linked to a five times higher odds of bronchopulmonary dysplasia and more than double the duration of invasive ventilation, after adjusting for gestational age and fetal distress. An exploratory analysis suggested the risk may climb sharply after about three days of infusion, but this threshold remains uncertain and needs prospective validation.
- Journal
- Journal of clinical medicine (Q1)
- Published
- 20 August 2026
- Study design
- Retrospective cohort
- Evidence level
- Level 3, Low (CEBM 3b)
- Authors
- Maria Di Chiara, Gianluigi Laccetta, Maria Chiara De Nardo, Lucia Dito, Gianluca Terrin
- PMID
- 42652860
- DOI
- 10.3390/jcm15166457
Why clinicians should know about it
- Picked for Neonatology (paper of the day, 31 August 2026): Matched cohort, fentanyl exposure linked to BPD and ventilation
Abstract
Background/Objectives: Fentanyl is widely used in ventilated preterm neonates, but respiratory safety evidence is limited. We assessed the association between fentanyl exposure during mechanical ventilation and respiratory outcomes in preterm neonates <34 weeks and explored a candidate exposure-duration threshold, defined as the duration of continuous fentanyl infusion beyond which the risk of adverse respiratory outcomes rises sharply. Methods: Single-centre retrospective cohort study at Policlinico Umberto I, Sapienza University, Rome (2015-2022). Fentanyl-exposed neonates were 1:2 matched to unexposed neonates on gestational age and birth-weight z-score. Primary outcome: bronchopulmonary dysplasia at 36 weeks postmenstrual age (multivariable logistic regression); secondary outcome: duration of invasive ventilation. A composite outcome (bronchopulmonary dysplasia or invasive ventilation ≥ 7 days) was used for threshold analysis with restricted cubic splines, maximally selected Wald χ2, and segmented logistic regression. Results: Of 315 eligible neonates, 50 fentanyl-exposed neonates were matched with 92 unexposed neonates (n = 142). Fentanyl exposure was associated, after adjustment for gestational age and fetal distress, with bronchopulmonary dysplasia (adjusted odds ratio 5.49, 95% CI 1.72-17.54) and longer invasive ventilation (adjusted exp(β) 2.25, 95% CI 1.54-3.29). Three complementary threshold methods were consistent with an exploratory signal around 3 days of continuous infusion, beyond which composite-outcome odds rose, although the breakpoint estimate was imprecise. Conclusions: Fentanyl exposure during mechanical ventilation was associated, after adjustment for gestational age and fetal distress, with bronchopulmonary dysplasia and longer invasive ventilation in preterm neonates <34 weeks. A possible signal around 3 days of continuous infusion is proposed as a hypothesis-generating stewardship prompt, not as a decision rule.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.