@article{1a999ebcc8f34cd29818aad5a6839a96,
title = "Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth: A Secondary Analysis of a Randomised Controlled Trial",
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: 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",
keywords = "Cerebral palsy, Haptoglobin, Magnesium, Preterm birth",
author = "{Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network} and Buhimschi, {Catalin S.} and Jablonski, {Kathleen A.} and Rouse, {Dwight J.} and Varner, {Michael W.} and Reddy, {Uma M.} and Mercer, {Brian M.} and Leveno, {Kenneth J.} and Wapner, {Ronald J.} and Yoram Sorokin and Thorp, {John M.} and Ramin, {Susan M.} and Malone, {Fergal D.} and Carpenter, {Marshall W.} and O'Sullivan, {Mary J.} and Peaceman, {Alan M.} and Saade, {George R.} and Donald Dudley and Caritis, {Steve N.} and Buhimschi, {Irina A.}",
note = "Funding Information: Support for this work was provided by grants from the 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; and by the National Institute of Neurological Disorders and Stroke (NINDS). Funds for laboratory analyses uniquely reported in this study were from the Centre for Perinatal Research at The Research Institute at Nationwide Children's Hospital (to I.A.B). Comments and views of the authors do not necessarily represent views of the NIH. Funding Information: Support for this work was provided by grants from the 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; and by the National Institute of Neurological Disorders and Stroke (NINDS). Funds for laboratory analyses uniquely reported in this study were from the Centre for Perinatal Research at The Research Institute at Nationwide Children's Hospital (to I.A.B). Comments and views of the authors do not necessarily represent views of the NIH. Publisher Copyright: {\textcopyright} 2019",
year = "2019",
month = mar,
doi = "10.1016/j.eclinm.2019.03.009",
language = "English (US)",
volume = "9",
pages = "11--18",
journal = "EClinicalMedicine",
issn = "2589-5370",
publisher = "Lancet Publishing Group",
}