Analgesia and Sedation Increases Bronchopulmonary Dysplasia Risk Without Significant Neurodevelopmental Impairment in Very Preterm Infants

Bowen WengChongbing YanYuanyang ZhangYibo LiuCheng Cai^*

• Department of Neonatology, Shanghai Children’s Hospital, Shanghai, China

Background: The associations between analgesia and/or sedation exposure and adverse outcomes in very preterm infants remain controversial. Evidence linking these medications to moderate-to-severe bronchopulmonary dysplasia (BPD) and long-term neurodevelopmental outcomes is particularly limited in large Chinese preterm cohorts. Objective: The primary aim was to investigate the associations between exposure to analgesia/sedation and the composite outcome of BPD or death. The secondary aim was to assess the association with neurodevelopmental outcomes at 18 months. Methods: This large, retrospective cohort study included preterm infants (gestational age < 32 weeks) admitted to a tertiary NICU in Shanghai, China, from 2018 to 2022. The primary outcomes were two composite measures: (1) moderate-to-severe BPD or death, and (2) any BPD or death, both assessed at 36 weeks postmenstrual age. The secondary outcomes included neurodevelopmental outcomes at 18 months and key neonatal morbidities. Propensity score matching (PSM) followed by multivariable logistic regression was used to adjust for confounders. Results: Of the 713 infants included in the primary analysis, 116 (16.3%) were exposed to analgesia/sedation. In the PSM cohort (n=460), after multivariable adjustment, exposure was associated with a significantly increased risk of moderate-to-severe BPD or death (adjusted OR, 6.00; 95% CI, 3.35–10.74; p < 0.001) and any BPD or death (adjusted OR, 5.32; 95% CI, 3.15–8.98; p < 0.001). Furthermore, the exposure group experienced significantly longer durations of invasive mechanical ventilation (IMV), higher incidences of hypotension requiring intervention and feeding intolerance (all p < 0.05). In a separate analysis of the matched neurodevelopmental subcohort (n=129), no significant associations were found with neurodevelopmental outcomes at 18 months. Conclusions: In this large Chinese preterm cohort, analgesia/sedation exposure was significantly associated with an increased risk of BPD or death. This association was observed alongside a series of neonatal morbidities such as prolonged IMV and hemodynamic instability, though no significant long-term neurodevelopmental harm was detected at 18 months.