Alexandra Heath-Freudenthal, Lilian Toledo-Jaldin, Inge von Alvensleben, Litzi Lazo Vega, Rodrigo Mizutani, Margaret Stalker, Hussna Yasini, Fanny Mendizabal, Jesus Dorado Madera, William Mundo, Melany Castro-Monrroy, Julie A. Houck, Any Moreno-Aramayo, Valquiria Miranda-Garrido, Emily J. Su, Dino A. Giussani, Steven H. Abman, Lorna G. Moore, Colleen G. Julian
Kardiozentrum. Hospital Materno-Infantil. University of Colorado. Universidad Mayor de San Andrés. University of Cambridge.
Bolivia, United States and United Kingdom
Hypertension
Hypertension 2022; 79: 1286-1296
DOI: 10.1161/HYPERTENSIONAHA.122.19078
Abstract
Background: Preeclampsia and fetal growth restriction increase cardiopulmonary disease risk for affected offspring and occur more frequently at high-altitude (≥2500 m). Retrospective studies indicate that birth to a preeclampsia woman at high altitude increases the risk of pulmonary hypertension (PH) in later life. This prospective study asked whether preeclampsia with or without fetal growth restriction exaggerated fetal hypoxia and impaired angiogenesis in the fetal lung, leading to neonatal cardiopulmonary circulation abnormalities and neonatal or infantile PH.
Methods and results: We studied 79 maternal-infant pairs (39 preeclampsia, 40 controls) in Bolivia (3600-4100 m). 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 (VEGF [vascular endothelial growth factor]) and antiangiogenic (sFlt1 [soluble fms-like tyrosine kinase]) factors were determined. Postnatal echocardiography (1 week and 6-9 months) assessed pulmonary hemodynamics and PH. Preeclampsia augmented fetal hypoxia and increased the risk of PH in the neonate but not later in infancy. Pulmonary abnormalities were confined to preeclampsia cases with fetal growth restriction. Maternal and fetal plasma sFlt1 levels were higher in preeclampsia than controls and positively associated with PH.
Conclusions: The effect of preeclampsia with fetal growth restriction 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.
Category
Environmental Factors Associated with Pulmonary Vascular Disease
Acquired Patient Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes