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.

Public Health Relevance

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; 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. In this study we will investigate the potential beneficial effects of delayed umbilical cord clamping on the efficacy and safety of indomethacin in preterm 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 delayed umbilical cord clamping.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
7R01HD070792-02
Application #
8843630
Study Section
Special Emphasis Panel (ZRG1-EMNR-R (55))
Program Officer
Ren, Zhaoxia
Project Start
2013-04-01
Project End
2018-03-31
Budget Start
2014-01-01
Budget End
2014-03-31
Support Year
Fiscal Year
2014
Total Cost
$604,006
Indirect Cost
$159,669
Name
University of Kentucky
Department
Pediatrics
Type
Schools of Medicine
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506