P1.192: Assessing the Efficacy of Prophylactic Indomethacin for Prevention of Intraventricular Hemorrhage in Extremely Preterm Neonates: A Comparative Analysis

Background: Intraventricular hemorrhage (IVH) is a severe complication in extremely preterm neonates, resulting from the vulnerability of blood vessels in the germinal matrix. Indomethacin has been suggested to prevent IVH by stabilizing blood pressure and cerebral blood flow and promoting microvascular maturation of the germinal matrix. Earlier studies showed that prophylactic indomethacin reduced the incidence of severe IVH. However, recent studies showed no significant reduction in IVH within the first week of life. This study aims to determine whether prophylactic indomethacin reduces the incidence of IVH at day of life (DOL) 7 to 10 and/or at DOL 30. Additional aims of this study include looking at the short-term effects of renal dysfunction, in addition to comorbidities such as necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD), spontaneous intestinal perforation (SIP), and periventricular leukomalacia (PVL).

Methods: This is a retrospective study comparing the effects of prophylactic indomethacin in preterm infants (≤ 28 weeks gestation or with birth weights ≤ 1000 grams) at two delivery hospitals within the NYU Langone hospital system between 2019 to 2024. The primary outcome was the incidence of IVH (grades 1-4) by DOL 10, with secondary outcomes including NEC, PDA, BPD, SIP, PVL, and mortality. Statistical analysis was performed using t-tests and Fisher’s exact tests; p-value < 0.05 considered statistically significant.

Results: A total of 155 patients were included, with 68 in the prophylactic indomethacin group and 87 in the control (no indomethacin) group. Although there were significant differences for certain baseline characteristics, the significance did not consistently favor one group; i.e., indomethacin group had more males and lower birthweight infants, but the control group had lower APGAR scores at 1 and 5 minutes (Figure 1). There were no significant differences for the incidence of any IVH or severe IVH (grades III/IV) by DOL 10 or severe IVH by DOL 30. However, the total IVH incidence by DOL 30 was significantly higher in the indomethacin group (37.7% vs. 21.3%, p=0.049) due to a higher incidence of grades I/II IVH in the indomethacin group (32.3% vs 16.1%, p = 0.022) (Figure 2a). Secondary outcomes showed significantly higher serum creatinine on DOL 7 in the indomethacin group (0.82 vs 0.73, p=0.013) (Figure 2b). No significant differences were found for BPD, hemodynamically significant PDA, surgically treated PDA, NEC, PVL, and mortality (Figure 2c).

Conclusion: Prophylactic indomethacin did not significantly reduce the incidence of severe IVH. However, there was a significant increase in grade I/II IVH by DOL 30 for infants who received indomethacin prophylaxis. To our knowledge, this is the first study to report head ultrasound findings on DOL 30. Our study suggests that indomethacin may not be necessary for IVH prevention and align with recent studies questioning its utility.