Cord Blood Biomarkers of Placental Maternal Vascular Underperfusion Predict Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension

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 P P 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.