TY - JOUR
T1 - Cord Blood Biomarkers of Placental Maternal Vascular Underperfusion Predict Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension
AU - Mestan, Karen K.
AU - Gotteiner, Nina
AU - Porta, Nicolas
AU - Grobman, William
AU - Su, Emily J.
AU - Ernst, Linda M.
N1 - Funding Information:
Supported by the American Association of Obstetricians and Gynecologists Foundation Bridge Fund (to E.S.), National Heart, Lung, and Blood Institute (R01 HL119846 [to E.S.]), National Heart, Lung, and Blood Institute (K23 HL093302 [to K.M.]), and investigator-initiated research funding from Viacord (to K.M.), and the Comprehensive Metabolic Core at Northwestern University. The authors declare no conflicts of interest.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/6
Y1 - 2017/6
N2 - Objective To assess whether cord blood biomarkers associated with placental maternal vascular underperfusion (MVU) are predictive of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH). Study design Premature infants enrolled in a longitudinal cohort study were randomly sampled from 4 gestational age strata (n = 190, range 23-36 weeks). Fifteen factors from a human angiogenesis panel were measured in cord blood using multiplex immunoassay. Multivariate linear regression was used to compare biomarker levels according to placental histologic MVU, taking into account acute/chronic inflammation and fetal vascular pathology. Biomarkers associated with MVU were further evaluated in the subgroup of extremely low gestational age infants (gestational age ≤ 28 weeks; n = 48), and measured by enzyme-linked immunoassay in an additional 39 infants to determine associations with BPD (defined using the National Institutes of Health workshop criteria) and PH (identified by echocardiogram at 36 weeks of gestation). Results Cord blood placental growth factor (PIGF), granulocyte-colony stimulating factor (G-CSF), and vascular endothelial growth factor-A were decreased with MVU (P <.003), and decreased with BPD-PH (P <.05). The findings were validated for PIGF and G-CSF in 39 additional extremely low gestational age infants. In the combined group (n = 87), PIGF was decreased in infants with BPD-PH (n = 21) versus controls without PH (median 3 pg/mL [IQR 2-7] vs median 15 pg/mL [IQR 6-30], respectively; P <.001). G-CSF was similarly decreased with BPD-PH (median, 55 pg/mL [IQR 38-85] vs median 243 pg/mL [IQR 48-1593], respectively; P =.001). Receiver operator curve analysis revealed that decreased PIGF and G-CSF were predictive of BPD-PH (area under the curve 0.83 and 0.76, respectively). Conclusions Cord blood angiogenic factors that are decreased with placental MVU may serve as predictors of BPD-PH.
AB - Objective To assess whether cord blood biomarkers associated with placental maternal vascular underperfusion (MVU) are predictive of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH). Study design Premature infants enrolled in a longitudinal cohort study were randomly sampled from 4 gestational age strata (n = 190, range 23-36 weeks). Fifteen factors from a human angiogenesis panel were measured in cord blood using multiplex immunoassay. Multivariate linear regression was used to compare biomarker levels according to placental histologic MVU, taking into account acute/chronic inflammation and fetal vascular pathology. Biomarkers associated with MVU were further evaluated in the subgroup of extremely low gestational age infants (gestational age ≤ 28 weeks; n = 48), and measured by enzyme-linked immunoassay in an additional 39 infants to determine associations with BPD (defined using the National Institutes of Health workshop criteria) and PH (identified by echocardiogram at 36 weeks of gestation). Results Cord blood placental growth factor (PIGF), granulocyte-colony stimulating factor (G-CSF), and vascular endothelial growth factor-A were decreased with MVU (P <.003), and decreased with BPD-PH (P <.05). The findings were validated for PIGF and G-CSF in 39 additional extremely low gestational age infants. In the combined group (n = 87), PIGF was decreased in infants with BPD-PH (n = 21) versus controls without PH (median 3 pg/mL [IQR 2-7] vs median 15 pg/mL [IQR 6-30], respectively; P <.001). G-CSF was similarly decreased with BPD-PH (median, 55 pg/mL [IQR 38-85] vs median 243 pg/mL [IQR 48-1593], respectively; P =.001). Receiver operator curve analysis revealed that decreased PIGF and G-CSF were predictive of BPD-PH (area under the curve 0.83 and 0.76, respectively). Conclusions Cord blood angiogenic factors that are decreased with placental MVU may serve as predictors of BPD-PH.
KW - granulocyte colony-stimulating factor
KW - placental growth factor
KW - premature infant
KW - vascular endothelial growth factor
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U2 - 10.1016/j.jpeds.2017.01.015
DO - 10.1016/j.jpeds.2017.01.015
M3 - Article
C2 - 28162769
AN - SCOPUS:85011422724
VL - 185
SP - 33
EP - 41
JO - Journal of Pediatrics
JF - Journal of Pediatrics
SN - 0022-3476
ER -
