Doxapram Exposure Was Not Associated With Adverse Neurodevelopmental Outcomes in Very Low Birth Weight Infants: A Monocentric Retrospective Cohort Study

ABSTRACT Aim Doxapram is used as an additional therapy for apnea of prematurity when standard treatments such as caffeine or continuous positive airway pressure are insufficient, but its impact on long‐term neurodevelopment remains uncertain. This study evaluated the association between Doxapram exposure and neurodevelopmental outcomes in very low birth weight infants (VLBWI), with a focus on potential dose‐dependent effects. Methods In this monocentric retrospective cohort study, VLBWI with gestational age ≤ 32 weeks were included. Infants treated with Doxapram ( n = 140) were compared to untreated controls ( n = 280) matched by year of birth. Exposure was stratified by cumulative dose. The primary outcome was neurodevelopment at 24 months corrected age assessed by the mental development index or global development quotient (MDI/GDQ). Secondary outcomes included mortality, growth parameters and neurological outcomes. Multivariable logistic regression adjusted for confounders. Results Neurodevelopment did not differ between groups (MDI/GDQ: 94.2 ± 21.2 vs. 97.7 ± 14.8; p = 0.1), nor did mortality (5.0% vs. 6.8%; p = 0.53). No dose‐dependent associations were observed. Secondary outcomes were comparable. Conclusions Doxapram exposure was not associated with adverse neurodevelopmental outcomes in VLBWI within the investigated dosage range, although definitive conclusions on drug safety cannot be drawn from medium‐sized cohorts and confirmation in prospective randomised studies is required.