Indomethacin and delayed umbilical cord clamp for preterm infant IVH

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DESCRIPTION (provided by applicant): Intraventricular hemorrhage (IVH) during the neonatal period is a common occurrence in preterm infants and is a well-recognized major contributor to brain injury and related disabilities later in life. Infants who develop severe IVH are at significant risk for developmental disabilities, including cerebral palsy and/or major cognitive handicaps. Despite its prevalence, long term consequences, and enormous medical and social costs, mechanisms of IVH and optimal strategies to prevent or treat its occurrence are poorly defined. Only one therapy, prophylactic indomethacin during the first 3 days of life, has consistently been shown to prevent or decrease the severity of IVH in preterm infants but its use is severely limited by the drug's toxic side effects and its controversial efficacy with respect to long-term outcomes. Indomethacin side effects are severe and include gastrointestinal perforation, renal toxicity and related organ failure, and actual extension of an established intra-cranial bleeding episode. Recent studies suggest that delayed umbilical cord-clamping (DCC) may decrease the incidence of IVH. However, at least in the largest study, all the infants received prophylactic indomethacin along with delaying of the cord clamp. These two modalities in combination may have advantages with respect to efficacy or safety when compared to prophylactic indomethacin used alone. Our Aims are 1) Compare efficacy and safety of prophylactic indomethacin with vs. without DCC cord clamp in affecting the incidence and severity of IVH in preterm (gestational age <30wks), and 2) Investigate mechanistic interactions of DCC and indomethacin in VLBW infants. This project may improve the safety and use of prophylactic indomethacin and further define the medical value, potential mechanisms, and optimal implementation strategies for DCC.