Fetal Haptoglobin as Potential Biomaker for Increased Risk of Cerebral Palsy

MedicalResearch.com Interview with:

MedicalResearch.com Interview with:Catalin S. Buhimschi MD, MMS, MBAProfessor of Obstetrics and GynecologyDivision of Maternal Fetal MedicineDirector of ObstetricsDepartment of Obstetrics and GynecologyChicago, IL, 60612

Dr. Buhimschi

Catalin S. Buhimschi MD, MMS, MBA
Professor of Obstetrics and Gynecology
Division of Maternal Fetal Medicine
Director of Obstetrics
Department of Obstetrics and Gynecology
Chicago, IL, 60612

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In 2008, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal–Fetal Medicine Units Network published the results of a randomized controlled trial of magnesium sulfate for the prevention of cerebral palsy (CP). The results of this trial suggested that fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate to severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. As such, the search for a biomarker or a therapeutic solution to prevent CP had to continue.

We are grateful to the NICHD for giving us access to the umbilical cord blood samples retrieved at the time of birth for the infants enrolled, who were also followed for 2 years postnatally. We discovered that fetus’s ability to switch-on haptoglobin (Hp) expression in response to inflammation was associated with reduction of intra-ventricular hemorrhage (IVH) and/or death, and cerebral palsy and/or death. Fetuses unable to mount such a response in-utero had an increased risk of adverse outcomes.

 MedicalResearch.com: What should readers take away from your report?

Response: Fetal Hp expression is an important biomarker for exposure to infection before birth. This protein represents a diagnostic biomarker that could one day inform neonatologists on whether to increase supervision of preterm infants. Infants that do not express Hp at birth are at increased risk for complications and they require increased supervision.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Development of rapid tools to determine the presence and level of Hp expression in Labor and Delivery wards will be an important line of research. A second question we are very excited about is whether providing exogenous Hp to neonates unable to mount a normal response will be protective against IVH/death or retinopathy of prematurity.  Animal models of IVH already demonstrated a beneficial effect of Hp when injected into the brain of pups that suffered from such complications.

MedicalResearch.com: Is there anything else you would like to add? 

Response: The original trial and availability of archived cord blood samples offered a unique opportunity to investigate the relationships between fetal Hp expression patterns at birth and neurodevelopmental outcomes in a large population. The future of study design in perinatal medicine depend on our ability as reproductive scientists to design clinical trials that are smaller, economically feasible, targeted, personalized, and translational. Such trials would represent a much-needed departure from the status-quo with potential to positively impact the lives of our patients. 

Citation:

Catalin S. Buhimschi, Kathleen A. Jablonski, Dwight J. Rouse, Michael W. Varner, Uma M. Reddy, Brian M. Mercer, Kenneth J. Leveno, Ronald J. Wapner, Yoram Sorokin, John M. Thorp, Susan M. Ramin, Fergal D. Malone, Marshall W. Carpenter, Mary J. O’Sullivan, Alan M. Peaceman, George R. Saade, Donald Dudley, Steve N. Caritis, Irina A. Buhimschi. Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth: A Secondary Analysis of a Randomised Controlled Trial. EClinicalMedicine, 2019; DOI: 10.1016/j.eclinm.2019.03.009 

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