171 - Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in preterm infants: a network meta-analysis

Poster Number: 171
Publication Number: 171.233

Souvik Mitra, Dalhousie University & IWK Health, Halifax, NS, Canada; Abigale MacLellan, Dalhousie University Faculty of Medicine, Halifax, NS, Canada; Courtney Gardner, Isaak Walton Killam (IWK) Health Centre, Halifax, NS, Canada; Timothy Disher, EVERSANA, West Porters Lake, NS, Canada; Danielle M. Styranko, Dalhousie University Faculty of Medicine, Halifax, NS, Canada; MARSHA CAMPBELL-YEO, Dalhousie University School of Nursing, Faculty of Health, Halifax, NS, Canada; Stefan Kuhle, Dalhousie University, Halifax, NS, Canada; Bradley Johnston, Dalhousie, Halifax, NS, Canada; Jon Dorling, University Hospital Southampton, Southampton, England, United Kingdom

Background: Prophylactic cyclooxygenase inhibitor (COX-I) drugs may prevent morbidity and mortality in preterm infants. Controversy exists on which COX-I drug is the most effective and has the best safety profile.

Objective: To determine the comparative effectiveness and safety of prophylactic COX-I drugs in preterm infants using a Bayesian network meta-analysis (NMA).

Design/Methods: We included RCTs that enrolled preterm/low birth weight infants, within the first 72h of birth without prior clinical/echocardiographic diagnosis of PDA and compared prophylactic indomethacin or ibuprofen or acetaminophen vs each other, placebo or no treatment. We used the standard methods of Cochrane Neonatal (updated December 9, 2021) and used the GRADE NMA approach to assess the certainty of evidence.

Results: We included 28 RCTs (n=3999). 19 RCTs (n=2877) compared indomethacin vs placebo, 7 RCTs (n=914) compared ibuprofen vs placebo and 2 RCTs (n=208) compared acetaminophen vs placebo. 9 RCTs had high risk of bias in one or more domains. Bayesian random-effects NMA showed prophylactic indomethacin probably led to a small reduction in severe IVH (network RR 0.66, 95% Credible Intervals [CrI] 0.49 to 0.87; median rank 2, 95% CrI 1-3; moderate-certainty), a moderate reduction in mortality (network RR 0.85, 95% CrI 0.64 to 1.1; median rank 2, 95% CrI 1-4; moderate-certainty) and surgical PDA closure (network RR 0.40, 95%CrI 0.14 to 0.66; median rank 2, 95%CrI 1-2; moderate-certainty) compared to placebo. Prophylactic ibuprofen probably led to a small reduction in severe IVH (network RR 0.69, 95% CrI 0.41 to 1.14; median rank 2, 95% CrI 1-4; moderate-certainty) and a moderate reduction in surgical PDA closure (network RR 0.24, 95% CrI 0.06 to 0.64; median rank 1, 95% CrI 1-2; moderate-certainty) compared to placebo. The evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH (network RR 1.17, 95% CrI 0.04 to 55.2; median rank 4, 95% CrI 1-4; very low-certainty) or mortality (network RR 0.49, 95% CrI 0.16 to 1.4; median rank 1, 95% CrI 1-4; very low-certainty). The GRADE summary of NMA findings is presented in Table 1.Conclusion(s): Prophylactic indomethacin probably results in a small reduction in severe IVH and moderate reduction in mortality and surgical PDA closure (moderate certainty). Prophylactic ibuprofen probably results in a small reduction in severe IVH and moderate reduction in surgical PDA closure (moderate certainty). The evidence is very uncertain about the effect of acetaminophen on any of the clinically relevant outcomes.

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