Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth

A Secondary Analysis of a Randomised Controlled Trial

Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

Research output: Contribution to journalArticle

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 Identifier: NCT00014989

Original languageEnglish (US)
Pages (from-to)11-18
Number of pages8
JournalEClinicalMedicine
Volume9
DOIs
StatePublished - Mar 1 2019

Fingerprint

Haptoglobins
Premature Birth
Cerebral Palsy
Fetal Blood
Randomized Controlled Trials
Inflammation
Odds Ratio
Newborn Infant
Gestational Age
Parturition
Hemorrhage
Magnesium Sulfate
Retinopathy of Prematurity
Infant Death
Birth Weight
Magnesium
Interleukin-6
Fetus
Placebos
Phenotype

Keywords

  • Cerebral palsy
  • Haptoglobin
  • Magnesium
  • Preterm birth

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network (2019). 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, 9, 11-18. https://doi.org/10.1016/j.eclinm.2019.03.009
Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. / Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth : A Secondary Analysis of a Randomised Controlled Trial. In: EClinicalMedicine. 2019 ; Vol. 9. pp. 11-18.
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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 Identifier: NCT00014989",
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Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network 2019, '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, vol. 9, pp. 11-18. https://doi.org/10.1016/j.eclinm.2019.03.009

Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth : A Secondary Analysis of a Randomised Controlled Trial. / Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

In: EClinicalMedicine, Vol. 9, 01.03.2019, p. 11-18.

Research output: Contribution to journalArticle

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T1 - Cord Blood Haptoglobin, Cerebral Palsy and Death in Infants of Women at Risk for Preterm Birth

T2 - A Secondary Analysis of a Randomised Controlled Trial

AU - Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

AU - Buhimschi, Catalin S.

AU - Jablonski, Kathleen A.

AU - Rouse, Dwight J.

AU - Varner, Michael W.

AU - Reddy, Uma M.

AU - Mercer, Brian M.

AU - Leveno, Kenneth J.

AU - Wapner, Ronald J.

AU - Sorokin, Yoram

AU - Thorp, John M.

AU - Ramin, Susan M.

AU - Malone, Fergal D.

AU - Carpenter, Marshall W.

AU - O'Sullivan, Mary J.

AU - Peaceman, Alan M.

AU - Peaceman, Alan M

AU - Dudley, Donald

AU - Caritis, Steve N.

AU - Buhimschi, Irina A.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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

AB - 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

KW - Cerebral palsy

KW - Haptoglobin

KW - Magnesium

KW - Preterm birth

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Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. 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 Mar 1;9:11-18. https://doi.org/10.1016/j.eclinm.2019.03.009