The Effect on Extubation of Early vs. Late Definitive Closure of the Patent Ductus Arteriosus in Premature Infants: A Target Trial Emulation Using Electronic Health Records

<b>Background/Objectives</b>: Premature infants are often referred for the definitive procedural closure of the patent ductus arteriosus (PDA) with the failure of, or contraindication to, pharmacotherapy and the inability to wean respiratory support. However, once this need is identified, the importance of expedited closure is unclear. The objective of this study was to compare the effect of the timing of definitive closure (i.e., surgical ligation or device occlusion) on early respiratory outcomes in premature infants. <b>Method</b>: We first specify a hypothetical randomized trial (the "target trial") that would estimate the effect on extubation of early (0-4 days from referral) vs. late (5-14 days from referral) definitive PDA closure. We then emulate this target trial using a single-institution registry of premature infants (born <30 weeks or with a birth weight < 1500 g) who underwent the definitive closure of PDA between January 2014 and October 2023. <b>Results</b>: We identify 131 eligible infants. At the end of the follow-up, 70 and 38 infants were adherent to early and late PDA closure strategies, respectively. The cumulative incidence of extubation in the early group was higher than that in the late group until day 40 (maximum risk difference: 22 percentage points at day 13; 95% CI: -11 to 56). Outcomes were similar at the end of the 45-day follow-up period (risk difference: -1 percentage point; 95% CI: -46 to 42). <b>Conclusions</b>: The need for mechanical ventilation was equivalent between early and late PDA closure strategies at the end of a 45-day follow-up period although infants in the early intervention group were extubated sooner.