Franklin Andrew, Yallapragada Sushmita, Birkett Robert, Grobman William, Ernst Linda M, Mestan Karen
Department of Pediatrics, NorthShore University HealthSystem, Evanston, IL, USA.
Department of Pediatrics, University of Texas Southwestern, Dallas, TX, USA.
Pulm Circ. 2020 Mar 9;10(1):2045894020910674. doi: 10.1177/2045894020910674. eCollection 2020 Jan-Mar.
Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) may either be concordant or discordant between multiple gestation births. Abnormal placental development, particularly maternal vascular malperfusion, may account for discordance in BPD-PH through fetal programming mechanisms. Maternal vascular malperfusion is a placental histologic lesion associated with intrauterine growth restriction and BPD-PH. We conducted a retrospective longitudinal cohort study of infants born <29 weeks gestation with available placental histology at Prentice Women's Hospital in Chicago from 2005-2012. The primary outcome was discordant BPD-PH associated with placental maternal vascular malperfusion. We secondarily assessed whether the risk of BPD-PH and placental lesions was different among infants of multiple (compared to singleton) gestations. The cohort consisted of 135 multiple gestation infants and 355 singletons. In a separate cohort of 39 singletons and 35 multiples, associations between 12 cytokines and angiogenic growth factors in cord blood plasma for biomarker discordance, maternal vascular malperfusion, and bronchopulmonary dysplasia were explored. Among multiples, discordant maternal vascular malperfusion was not associated with BPD-PH (OR = 1.9 (0.52, 6.9); = 0.33) in infants exposed to placental maternal vascular malperfusion. However, singleton infants were more likely to develop BPD-PH (compared to multiples) after adjusting for mode of delivery, chorioamnionitis, chronic hypertension, placental abruption, small-for-gestational age birth weight, and gestational age (aOR = 2.7 (1.2, 5.8); = 0.038). Singletons were more likely to be small-for-gestational age (11% vs 4%, = 0.025) and have placental lesions compared to their multiple-gestation counterparts (96% vs 81%, < 0.001), principally severe maternal vascular malperfusion (17% vs 4%, < 0.001) and chronic inflammation (32% vs 11%, < 0.001). Increased risk of BPD-PH in singleton pregnancies <29 weeks gestation compared to multiples may be related to increased frequency of these histologic lesions. Placental pathology in singleton and multiple gestation pregnancies may serve as an early biomarker to predict BPD-PH.
支气管肺发育不良相关的肺动脉高压（BPD-PH）在多胎妊娠分娩中可能一致或不一致。胎盘发育异常，尤其是母体血管灌注不良，可能通过胎儿编程机制导致BPD-PH不一致。母体血管灌注不良是一种与宫内生长受限和BPD-PH相关的胎盘组织学病变。我们对2005年至2012年在芝加哥普伦蒂斯妇女医院出生孕周<29周且有可用胎盘组织学资料的婴儿进行了一项回顾性纵向队列研究。主要结局是与胎盘母体血管灌注不良相关的不一致性BPD-PH。我们还评估了多胎（与单胎相比）妊娠婴儿中BPD-PH和胎盘病变的风险是否不同。该队列包括135例多胎妊娠婴儿和355名单胎妊娠婴儿。在一个由39名单胎妊娠婴儿和35例多胎妊娠婴儿组成的单独队列中，探索了脐带血血浆中12种细胞因子和血管生成生长因子与生物标志物不一致、母体血管灌注不良和支气管肺发育不良之间的关联。在多胎妊娠中，暴露于胎盘母体血管灌注不良的婴儿中，不一致的母体血管灌注不良与BPD-PH无关（OR = 1.9（0.52，6.9）；P = 0.33）。然而，在调整分娩方式、绒毛膜羊膜炎、慢性高血压、胎盘早剥、小于胎龄出生体重和孕周后，单胎妊娠婴儿比多胎妊娠婴儿更易发生BPD-PH（校正后OR = 2.7（1.2，5.8）；P = 0.038）。与多胎妊娠婴儿相比，单胎妊娠婴儿更易小于胎龄（11%对4%，P = 0.025）且有胎盘病变（96%对81%，P < 0.001），主要是严重母体血管灌注不良（17%对4%，P < 0.001）和慢性炎症（32%对11%，P < 0.001）。与多胎妊娠相比，孕周<29周的单胎妊娠中BPD-PH风险增加可能与这些组织学病变频率增加有关。单胎和多胎妊娠的胎盘病理学可能作为预测BPD-PH的早期生物标志物。
