Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth: A Secondary Analysis of a Randomised Controlled Trial
Year: 2019
Type: article
Abstract: 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: : clinicaltrials.gov Identifier: NCT00014989.
Source: EClinicalMedicine
Authors: 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
Institutions: The Ohio State University, George Washington University, University of Alabama at Birmingham, University of Utah, National Institutes of Health, Eunice Kennedy Shriver Center, Eunice Kennedy Shriver National Institute of Child Health and Human Development, MetroHealth Medical Center, Case Western Reserve University, The University of Texas Southwestern Medical Center, Thomas Jefferson University, Drexel University, Wayne State University, University of North Carolina at Chapel Hill, The University of Texas Health Science Center at Houston, Columbia University, Brown University, University of Miami, Northwestern University, The University of Texas Medical Branch at Galveston, The University of Texas at San Antonio, University of Pittsburgh, Nationwide Children's Hospital, Abigail Wexner Research Institute
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,500
Awards: G1092124974, G1216570417, G161141704, G1873590977, G1882602020, G2254024324, G2594613454, G284963502, G2925552923, G29782494, G3579211174, G3681478966, G3786447104, G3875946430, G4027080872, G4189700973, Data Coord Ctr-NICHD Cooperative Multicenter Maternal Medicine Units Research Net, G4657398957, G50908112, Maternal Fetal Medicine Units Network, G5425254544, G6657596466, G673807916, UofU Maternal-Fetal Medicine Units (MFMU) Network: Clinical Centers, Case Western Reserve University Center of the NICHD MFMU Network, Columbia University Maternal-Fetal Medicine Units Network Clinical Center, NICHD maternal fetal medicine units network, G922324195
OpenAlex ID: W2923314962