125 - Prophylactic effects of cyclooxygenase inhibitor on intraventricular hemorrhage: effect modification by risk of intraventricular hemorrhage.

Poster Number: 125
Publication Number: 125.427

Kenichi Suga, Tokushima University Hospital, Tokushima, Tokushima, Japan; Tetsuya Isayama, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan; Katsuaki Toyoshima, Kanagawa Children's Medical Center, Yokohama, Kanagawa, Japan

Background: Prophylactic cyclooxygenase-inhibitors (COX-Is) to prevent intraventricular hemorrhage (IVH) in preterm infants remains controversial. Although prophylactic COX-Is can reduce the risk of severe IVH, their use may expose infants to potentially severe adverse effects. In addition, the incidence of IVH in preterm infants varies depending on prematurity and hospitalization facility. Thus, clinicians need guidance regarding the risks vs. benefits of prophylactic COX-Is.

Objective: We performed meta-regression analyses using existing data from randomized control trials (RCTs) to examine how the effects of prophylactic COX-Is on the incidence of IVH vary by patient population.

Design/Methods: We primarily used RCT data from the most recent Cochrane systematic review of this topic (Mitra 2022, and searched for additional trials in the Ovid MEDLINE updates since 2021 and the Japanese medical database Igaku Chuo Zasshi (https://www.jamas.or.jp/english/, accessed 20 December 2022). We included trials that compared the efficacy of prophylactic COX-I (indomethacin or ibuprofen) vs. placebo or control for severe or all-grade IVH in preterm infants. Trials assessing prophylactic paracetamol were excluded because data on paracetamol are still scarce. The relationships between the risk difference (RD) for severe or all-grade IVH and the rate of severe or all-grade IVH in controls were assessed by weighted meta-regression analyses in the Stata software. A 5% reduction in RD was considered the clinical threshold.

Results: Twenty-four RCTs were retrieved and analyzed, comprising 23 from the Cochrane systematic review, one from the Japanese medical database, and none from the Ovid MEDLINE updates. A significant negative relationship was observed between the RD for severe IVH and the rate of severe IVH in controls (Fig. 1). The regression line crossed the 5% reduction line at a rate of about 14%. A significant negative relationship was also observed between the RD for all-grade IVH and the rate of all-grade IVH in controls (Fig. 2). The regression line crossed the 5% risk reduction line at a rate of about 30%.

 

Conclusion(s): Significant negative relationships were found between the risk reduction of IVH by prophylactic COX-Is and the incidence of IVH in controls. Our data suggest that prophylactic COX-Is are meaningful only for populations in which more than 14% of patients are expected to experience severe IVH or 30% are expected to experience all-grade IVH, based on gestational age group (often corresponding to < 28 weeks) or other factors.
 

 
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