Browsing by Autor "Julian, Colleen G"

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Corrigendum: Noninvasive Maternal-Fetal Hemodynamic Monitoring as A Predictor of Severe Preeclampsia in Low-Resource Settings: A Case Report.
(2025) Toledo-Jaldin, Lilian; Gomez, Richard; Lazo-Vega, Litzi; Larrea, Alison; Vásquez, Adolfo; Ormachea-Orellana, Wilson; Miranda-Garrido, Valquiria; Julian, Colleen G
[This corrects the article DOI: 10.1055/a-2689-2550.].
Dysregulated Fatty Acid Metabolism in Preeclampsia Among Highland Andeans: Insights Into Adaptive and Maladaptive Placental Metabolic Phenotypes.
(2025) O'Brien, Katie A; Toledo-Jaldin, Lilian; Gu, Wanjun; Houck, Julie A; Lazo-Vega, Litzi; Miranda-Garrido, Valquiria; Yung, Hong W; Yasini, Hussna; Moore, Lorna G; Reisz, Julie A; Simonson, Tatum S; Shortt, Jonathan; Stalker, Margaret; D'Alessandro, Angelo; Julian, Colleen G
High-altitude pregnancy presents the complex physiological challenge of fulfilling maternal, placental, and fetal metabolic demands under chronic ambient hypoxia. Highland Andeans exhibit signs of adaptation to high-altitude hypoxia, showing relative protection against altitude-associated fetal growth restriction (FGR) and the positive selection of metabolic genes linked to placental mitochondrial capacity. Not all infants are protected, with both FGR and preeclampsia occurring among highland-resident Andeans. In Andeans, placental metabolic dysfunction is evident. By integrating metabolomic studies of maternal-placental-fetal triads with adaptive genetic signals in the fetal genome, we sought to identify adaptive and maladaptive placental metabolic phenotypes in highland Andeans (La Paz, Bolivia; 3850 m), including normotensive and preeclamptic pregnancies. Widespread differences in metabolite abundance were evident between normotensive and preeclamptic pregnancy across maternal, placental, and fetal compartments. Preeclampsia was characterized by a pronounced accumulation of fatty acid derivatives, specifically medium and long-chain acylcarnitines; these were also associated with low birth weight. Genotype-phenotype association analyses revealed novel links between putatively adaptive fetal haplotypes and placental metabolite abundance. Carriers of specific adaptive fetal haplotypes comprising genes linked to lipid metabolism had a greater abundance of placental short-chain acetyl-carnitine alongside decreased levels of linolenic acid (CPT2/LRP8), lower levels of the medium-chain octanoylcarnitine (EXOC4), and greater abundance of free carnitine (LIPG). Collectively, our study reveals a distinct metabolic phenotype in Andean preeclampsia characterized by incomplete fatty acid oxidation and highlights novel links between putatively adaptive fetal haplotypes and healthy placental metabolic phenotypes.
Noninvasive Maternal-Fetal Hemodynamic Monitoring as A Predictor of Severe Preeclampsia in Low-Resource Settings: A Case Report.
(2025) Toledo-Jaldin, Lilian; Gomez, Richard; Lazo-Vega, Litzi; Larrea, Alison; Vásquez, Adolfo; Ormachea-Orellana, Wilson; Miranda-Girrado, Valquiria; Julian, Colleen G
Preeclampsia is a multiorgan vascular disease complicating approximately 8.5 million pregnancies worldwide annually and is a leading cause of maternal and neonatal mortality. The impact is especially severe in Latin America, where maternal deaths attributable to preeclampsia are 2.5 times higher than in any other region. Bolivia is particularly affected due to economic and environmental challenges, including high altitude, which increases the risk of fetal growth restriction and hypertensive disorders of pregnancy. Early and accessible diagnostic tools are required to maximize patient care and improve reproductive outcomes in limited-resource settings. This report details a case from Bolivia of rapid-onset severe preeclampsia with liver rupture in the third trimester; the patient required multiple surgical interventions for recurrent liver bleeding and extended hospitalization in the intensive care unit (ICU). She delivered a preterm, growth-restricted infant with signs of acute hypoxia by emergency cesarean section. Notably, 2 weeks before ICU admission, abnormal uterine artery and maternal hemodynamic measurements were detected, without other signs of preeclampsia. The patient had previously been healthy and was considered low risk. Both mother and newborn survived. This case underscores the value of combining uterine artery Doppler with maternal hemodynamics to identify high-risk pregnancies early and prevent life-threatening complications.
Prolonged postnatal adaptation and enhanced prevalence of congenital heart diseases due to altitude may contribute to newborn mortality in Bolivia.
(2025) Heath, Alexandra; von Alvensleben, Inge; Spielvogel, Jesús Ardiles; Freudenthal, Pablo; Trapp, Johannes; Noya, Ivanna; Gálvez, Miguel; Mendizábal, Fanny; Gonzales, Mariana; Apaza, Ceylan; Sanga, Leibniz; Mc Cann, Erin; Julian, Colleen G
Highland populations suffer from significant infant mortality due to chronic ambient hypoxia, which increases the risk of congenital heart disease (CHD) and neonatal pulmonary hypertension. Neither the prevalence of these conditions nor the effectiveness of neonatal cardiac screening to identify CHD or pulmonary hypertension among neonates born at altitudes >4000 m in Bolivia has been reported. In a study of 1033 newborns in El Alto, Bolivia (4150 m), we determined the prevalence of CHD and prolonged postnatal adaptation. We also tested the accuracy of a neonatal cardiac screening tool in identifying infants with/without these conditions. Finally, diagnoses were contrasted between offspring born to parents of lowland versus highland origin. CHD was found in 54 neonates (5.2%), with the most common diagnoses being patent ductus arteriosus and atrial septal defect. Pulmonary hypertension without CHD was observed in 64 neonates (6.8%), with seven cases of persistent pulmonary hypertension of the newborn (PPHN). The neonatal cardiac screening tool showed a sensitivity of 45% and specificity of 99% for CHD, and 35% sensitivity and 92% specificity for prolonged pulmonary adaptation. Offspring of highland-origin women tended to have increased CHD risk, while those from lower altitudes were predisposed to prolonged postnatal adaptation and PPHN; paternal altitude of origin had no statistic significance but showed same tendency. The high prevalence of relevant CHD and prolonged pulmonary adaptation in neonates born >4000 m in Bolivia likely contributes to the high infant mortality rates observed. The poor sensitivity of the pilot neonatal cardiac screening instrument underscores the need to develop evidence-based tools optimized for use in low-resource, high-altitude settings.
Surviving birth at high altitude.
(2024) Heath-Freudenthal, Alexandra; Estrada, Alejandra; von Alvensleben, Inge; Julian, Colleen G
This Symposium Review examines challenges to surviving birth and infancy at high altitudes. Chronic exposure to the environmental hypoxia of high altitudes increases the incidence of maternal vascular disorders of pregnancy characterized by placental insufficiency, restricted fetal growth and preterm delivery, and impairs pulmonary vascular health during infancy. While each condition independently contributes to excess morbidity and mortality in early life, evidence indicates vascular disorders of pregnancy and infantile pulmonary vascular dysfunction are intertwined. By integrating our recent scientific and clinical observations in Bolivia with existing literature, we propose potential avenues to reduce the infant mortality burden at high altitudes and reduce pulmonary vascular disease in highland neonates, and emphasize the need for further research to address unresolved questions.
Vascular Disorders of Pregnancy Increase Susceptibility to Neonatal Pulmonary Hypertension in High-Altitude Populations.
(2022) Heath-Freudenthal, Alexandra; Toledo-Jaldin, Lilian; von Alvensleben, Inge; Lazo-Vega, Litzi; Mizutani, Rodrigo; Stalker, Margaret; Yasini, Hussna; Mendizabal, Fanny; Dorado Madera, Jesus; 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
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.