Which Infants Should Receive Indomethacin Prophylaxis: Moving Closer to Individualized Medicine in the Neonatal Intensive Care Unit

Medicine is moving toward individualized interventions to provide the safest and most effective care for patients, and neonates are no exception. According to two recent articles1Qureshi M. Shah P.S. Abdelgadir D. Ye X.Y. Afifi J. Yuen R. et al.Gestational age-dependent variations in effects of prophylactic indomethacin on brain injury and intestinal injury.J Pediatr. 2021; 235: 26-33.e2Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar,2Kandraju H. Kanungo J. Lee K.S. Daspal S. Adie M.A. Dorling J. et al.Association if co-exposure of antenatal steroid and prophylactic indomethacin with spontaneous intestinal perforation.J Pediatr. 2021; 235: 34-41.e1Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar published by the Canadian Neonatal Network, prophylactic indomethacin might be one such intervention that could be individualized for particular infants. Qureshi et al found that gestational age may affect the association between indomethacin prophylaxis and risk for spontaneous intestinal perforation (SIP) and neurologic injury.1Qureshi M. Shah P.S. Abdelgadir D. Ye X.Y. Afifi J. Yuen R. et al.Gestational age-dependent variations in effects of prophylactic indomethacin on brain injury and intestinal injury.J Pediatr. 2021; 235: 26-33.e2Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Infants <25 weeks of gestation were more likely to receive indomethacin (P < .0001) and experience neurologic benefits as compared with infants ≥25 weeks of gestation, who did not have neurologic benefit and experienced increased risk of SIP. Infants in both the prophylactic indomethacin and the non-prophylactic indomethacin groups received antenatal steroids at comparable rates (P = .31). Kandraju et al found that infants who received prophylactic indomethacin and antenatal corticosteroids within 7 days of birth had an increased risk for SIP compared with infants who received antenatal corticosteroids >7 days before birth.2Kandraju H. Kanungo J. Lee K.S. Daspal S. Adie M.A. Dorling J. et al.Association if co-exposure of antenatal steroid and prophylactic indomethacin with spontaneous intestinal perforation.J Pediatr. 2021; 235: 34-41.e1Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar These findings lead us to wonder: if Qureshi et al further stratified infants by timing of antenatal steroids, would their findings change? Over the years, the use of indomethacin prophylaxis has decreased. After the Trial of Indomethacin Prophylaxis in Preterm Infants3Schmidt B. Asztalos E.V. Roberts R.S. Robertson C.M. Sauve R.S. Whitfield M.F. Trial of Indomethacin Prophylaxis in Preterms (TIPP) Investigators. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms.JAMA. 2003; 289: 1124-1129Crossref PubMed Scopus (480) Google Scholar was published in 2001 showing that indomethacin prophylaxis did not prevent death or neurosensory impairment, our center briefly stopped using indomethacin prophylaxis. However, within a few months, we observed several infants with severe intraventricular and pulmonary hemorrhages, which prompted our center to resume the practice for infants <27 weeks of gestation or <750 g birth weight. We read with interest these newest studies from the Canadian Neonatal Network and are hopeful that outlining specific algorithms based on objective risk factors, such as gestational age and antenatal steroid exposure, may help provide individualized medical care at the start of life. Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal InjuryThe Journal of PediatricsVol. 235PreviewTo evaluate the impact of prophylactic indomethacin on early death (<10 days after birth) or severe neurologic injury and on early death or spontaneous intestinal perforation by completed weeks of gestational age in neonates born <29 weeks of gestation. Full-Text PDF ReplyThe Journal of PediatricsVol. 237PreviewWe thank Curtis et al for their insightful comments and appreciate the opportunity to respond. Curtis et al observed that Kandraju et al found an association between timing of antenatal steroids and spontaneous intestinal perforation, which was not explored by Qureshi et al. They ask whether an individualized approach or tool could be developed to maximize benefits of prophylactic indomethacin while minimizing risks. We agree that expecting similar responses from a heterogeneous group of neonates seems holistically inappropriate and that individualized treatment is a reasonable goal. Full-Text PDF