Indomethacin and delayed umbilical cord clamp for preterm infant IVH

描述（由申请人提供）：新生儿期的脑室内出血（IVH）在早产儿中很常见，是公认的脑损伤和日后相关残疾的主要原因。患有严重IVH的婴儿有很大的发育障碍风险，包括脑瘫和/或严重的认知障碍。尽管其流行，长期的后果，以及巨大的医疗和社会成本，IVH的机制和最佳的策略，以防止或治疗其发生的定义很差。只有一种治疗方法，即在出生后前3天预防性使用吲哚美辛，一直被证明可以预防或降低早产儿IVH的严重程度，但其使用受到药物毒副作用及其长期疗效争议的严重限制。吲哚美辛的副作用很严重，包括胃肠道穿孔、肾毒性和相关器官衰竭，以及已确定的颅内出血事件的实际延长。最近的研究表明，延迟脐带夹紧（DCC）可能会降低IVH的发生率。然而，至少在最大规模的研究中，所有的婴儿都接受了预防性的吲哚美辛沿着延迟的脐带钳夹。与单独使用消炎痛预防性治疗相比，这两种方式联合使用可能在疗效或安全性方面具有优势。我们的目的是：1）比较DCC脐带钳与非DCC脐带钳预防性应用吲哚美辛对早产儿（胎龄<30周）IVH发生率和严重程度的影响，2）研究DCC和吲哚美辛在VLBW婴儿中的相互作用机制。本项目可能会提高安全性和使用消炎痛预防性和进一步确定DCC的医疗价值，潜在的机制，和最佳的实施策略。

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.