Antenatal tocolytic exposure and postnatal patent ductus arteriosus outcomes in preterm infants born at ≤32 weeks: a retrospective cohort study.

OBJECTIVES

The impact of antenatal tocolytic therapy on postnatal patent ductus arteriosus (PDA) outcomes in preterm infants remains unclear. Previous studies have rarely evaluated clinically significant treatment-requiring PDA and treatment resistance as distinct but related outcomes. This study aimed to evaluate the association between antenatal tocolytic exposure and postnatal PDA outcomes in infants born at ≤32 weeks of gestation.

METHODS

In this single-center retrospective cohort study, preterm infants (≤32 weeks) admitted to a tertiary neonatal intensive care unit between January 2018 and August 2025 and undergoing echocardiographic evaluation were included. Infants were classified as exposed or unexposed to antenatal tocolytics and further categorized as receiving indomethacin-containing or indomethacin-free regimens. Primary outcomes were clinically significant treatment-requiring PDA supported by echocardiographic criteria and pharmacological treatment resistance. Multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW) analyses were performed.

RESULTS

Among 236 infants, 53 (22.5%) were exposed to antenatal tocolytics. Clinically significant treatment-requiring PDA was identified in 87 infants (36.9%). Tocolytic exposure was independently associated with a lower likelihood of treatment-requiring PDA in the original adjusted model (aOR 0.377, 95% CI 0.17-0.85; p = 0.018) and in an expanded model including multiple gestation (aOR 0.368, 95% CI 0.15-0.87; p = 0.023). In contrast, among infants who developed treatment-requiring PDA, exposure was associated with treatment resistance (original model: aOR 21.802, 95% CI 2.72-175.02; p = 0.004; IPTW analysis: OR 8.794, 95% CI 1.46-52.96; p = 0.018). Among tocolytic-exposed infants, treatment-requiring PDA was more frequent after indomethacin-containing than indomethacin-free regimens (41.7% vs 13.8%, p = 0.022).

CONCLUSIONS

Antenatal tocolytic exposure was associated with a lower overall likelihood of clinically significant treatment-requiring PDA, whereas treatment resistance among infants who developed treatment-requiring PDA was more frequent, particularly after indomethacin-containing regimens. These observational findings should be interpreted as hypothesis-generating because of potential residual confounding, practice-dependent outcome assessment, and small subgroup sizes.