Vascular Disorders of Pregnancy Increase Susceptibility to Neonatal Pulmonary Hypertension in High-Altitude Populations.
Vascular Disorders of Pregnancy Increase Susceptibility to Neonatal Pulmonary Hypertension in High-Altitude Populations.
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DOI：
10.1161/hypertensionaha.122.19078
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发表时间：
2022-06
期刊：
影响因子：
8.3
通讯作者：
Julian, Colleen G.
中科院分区：
文献类型：
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作者：
Heath-Freudenthal, Alexandra;Toledo-Jaldin, Lilian;von Alvensleben, Inge;Lazo-Vega, Litzi;Mizutani, Rodrigo;Stalker, Margaret;Yasini, Hussna;Mendizabal, Fanny;Madera, Jesus Dorado;Mundo, William;Castro-Monrroy, Melany;Houck, Julie A.;Moreno-Aramayo, Any;Miranda-Garrido, Valquiria;Su, Emily J.;Giussani, Dino A.;Abman, Steven H.;Moore, Lorna G.;Julian, Colleen G.
先兆子痫（PE）和胎儿生长受限（FGR）增加了受影响后代的心肺疾病风险，并且在高海拔（≥ 2500 m）更常见。回顾性研究表明，在高海拔地区出生的PE妇女在以后的生活中增加肺动脉高压（PH）的风险。这项前瞻性研究询问是否PE与或不FGR加重胎儿缺氧和受损的血管生成在胎儿肺，导致新生儿心肺循环异常和新生儿和/或婴儿PH。我们研究了79对母婴（39 PE，40对照组）在玻利维亚（3,600 - 4,100米）。检测脐血促红细胞生成素、血红蛋白、脐动脉和脐静脉血气作为胎儿缺氧的指标。测定母体和脐带血浆中血管生成因子（血管内皮生长因子[VEGF]）和抗血管生成因子（可溶性fms样酪氨酸激酶[sFlt 1]）的水平。出生后超声心动图（一周和六至九个月）评估肺血流动力学和PH。PE增加胎儿缺氧，增加新生儿PH的风险，但在婴儿期不晚。肺异常仅限于肺栓塞伴FGR的病例。母胎血浆sFlt 1水平在PE高于对照组，并与PH呈正相关。PE与FGR增加胎儿缺氧和sFlt 1水平的影响可能会阻碍高海拔地区肺循环的正常发育，导致不良的新生儿肺血管结局。我们的观察突出了重要的时间窗口，为预防肺血管疾病的婴儿出生的高原居民或那些夸大缺氧在子宫内或新生儿的生活。
Preeclampsia (PE) and fetal growth restriction (FGR) increase cardiopulmonary disease risk for affected offspring and occur more frequently at high-altitude (≥ 2500 m). Retrospective studies indicate that birth to a PE woman at high altitude increases the risk of pulmonary hypertension (PH) in later life. This prospective study asked whether PE with or without FGR exaggerated fetal hypoxia and impaired angiogenesis in the fetal lung, leading to neonatal cardiopulmonary circulation abnormalities and neonatal and/or infantile PH. We studied 79 maternal-infant pairs (39 PE, 40 controls) in Bolivia (3,600 – 4,100m). Cord blood erythropoietin, hemoglobin, and umbilical artery and venous blood gases were measured as indices of fetal hypoxia. Maternal and cord plasma levels of angiogenic (vascular endothelial growth factor [VEGF]) and antiangiogenic (soluble fms-like tyrosine kinase [sFlt1]) factors were determined. Postnatal echocardiography (one-week and six-to-nine months) assessed pulmonary hemodynamics and PH. PE augmented fetal hypoxia and increased the risk of PH in the neonate but not later in infancy. Pulmonary abnormalities were confined to PE cases with FGR. Maternal and fetal plasma sFlt1 levels were higher in PE than controls and positively associated with PH. The effect of PE with FGR to increase fetal hypoxia and sFlt1 levels may impede normal development of the pulmonary circulation at high altitude, leading to adverse neonatal pulmonary vascular outcomes. Our observations highlight important temporal windows for the prevention of pulmonary vascular disease among babies born to highland residents or those with exaggerated hypoxia in utero or newborn life.