Royal College of Surgeons in Ireland
Browse

Cord blood haptoglobin, cerebral palsy and death in infants of women at risk for preterm birth: a secondary analysis of a randomised controlled trial

Download (771.17 kB)
journal contribution
posted on 2023-09-14, 16:18 authored by 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 Jr., Susan M. Ramin, Fergal MaloneFergal Malone, Marshall W. Carpenter, Mary J. O'Sullivan, Alan M. Peaceman, George R. Saade, Donald Dudley, Steve N Caritis, Irina A. Buhimschi, Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

Background: Antenatal exposure to intra-uterine inflammation results in precocious Haptoglobin (Hp) expression (switch-on status). We investigated the relationships between foetal Hp expression at birth with newborn and childhood outcomes. 

Methods: We evaluated cord blood samples from 921 newborns of women at imminent risk for preterm delivery randomised to either placebo (n = 471, birth gestational age (GA) median [min-max]: 31 [24–41] weeks) or magnesium sulphate (n = 450, GA 31 [24–42] weeks]). Primary outcome was infant death by 1 year and/or cerebral palsy (CP) ≥ 2 years of corrected age. Adjusted odd ratios (aOR) for neonatal and childhood outcomes were calculated controlling for GA, birth weight, sex, and magnesium exposure. 

Findings: Primary outcome occurred in 2.8% of offspring. Newborns were classified in three pre-defined categorisation groups by cord blood Hp switch status and IL-6 levels: inflammation-nonexposed (Category 1, n = 432, 47%), inflammation-exposed haptoglobinemic (Category 2, n = 449, 49%), and inflammation-exposed anhaptoglobinemic or hypohaptoglobinemic (Category 3, n = 40, 4%). Newborns, found anhaptoglobinemic or hypohaptoglobinemic (Category 3) had increased OR for intraventricular haemorrhage (IVH) and/or death (aOR: 7.0; 95% CI: 1.4–34.6, p = 0.02) and for CP and/or death (aOR: 6.27; 95% CI: 1.7–23.5, p = 0.006) compared with Category 2. Foetal ability to respond to inflammation by haptoglobinemia resulted in aOR similar to inflammation-nonexposed newborns. Hp1-2 or Hp2-2 phenotypes protected against retinopathy of prematurity (aOR = 0.66; 95% CI 0.48–0.91, p = 0.01). 

Interpretation: Foetal ability to switch-on Hp expression in response to inflammation was associated with reduction of IVH and/or death, and CP and/or death. Foetuses unable to mount such a response had an increased risk of adverse outcomes. 

Trial Registration: clinicaltrials.gov Identifier: NCT00014989

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD27869, HD34208, HD34116, HD40544, HD27915,HD34136, HD21414, HD27917, HD27860, HD40560, HD40545,HD40485, HD40500, HD27905, HD27861, HD34122, HD40512,HD53907, HD34210, HD21410, HD36801, HD19897]

MO1-RR-000080

National Institute of Neurological Disorders and Stroke (NINDS)

Centre for Perinatal Research at The Research Institute at Nationwide Children's Hospital

History

Comments

The original article is available at https://www.sciencedirect.com/

Published Citation

Buhimschi CS, et al. 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;9:11-18.

Publication Date

22 March 2019

PubMed ID

31143877

Department/Unit

  • Obstetrics and Gynaecology

Research Area

  • Gynaecology, Obstetrics and Perinatal Health

Publisher

Elsevier BV

Version

  • Published Version (Version of Record)