Browsing by Autor "Moore, Lorna G"

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Andean compared with european women are protected from altitude-associated intrauterine growth restriction (IUGR)
(Facultad de Medicina, Enfermería, Nutrición y Tecnología Médica, 2003) Moore, Lorna G
Abstract. Babies born at high altitude to long-term high-altitude residents weigh more than those of recent migrants from low altitude. Objective: We asked whether a gradient exists such that persons of Andean ancestry are protected relative to those of mestizo (“mixed”) and, in turn, European or other lowland ancestry. Methods: Medical records were examined from 3565 consecutive deliveries to women with 2+ prenatal visits at public or private hospitals in Santa Cruz (300 m, low), Cochabamba (2500 m, medium), and La Paz or Oruro (3600–3800 m, high). Population ancestry was judged by parental surnames. Persons of Bolivian nationality were assumed to have been born at their altitude of residence and non-Bolivians to have immigrated there as adults. IUGR was defined as birth weights, <10th percentile for gestational age and sex using sea-level criteria …
Andean women have greater uterine artery (UTA) enlargement during pregnancy than european residents of 3600 m.
(Facultad de Medicina, Enfermería, Nutrición y Tecnología Médica, 2003) Moore, Lorna G
Abstract. Babies weigh less at high altitude but multi-generational high-altitude residents are protected from this birth weight decline (Moore HAMB 2001). Objective: We asked if higher arterial oxygenation and/or blood flow raised uteroplacental O2 delivery in multigenerational Andean vs. shorter duration European high-altitude residents. Methods: Subjects were 45 women of Andean (n = 50, And) or European (n = 11, Eur) ancestry who had resided in La Paz, Bolivia since birth (And) or the past 4 years (Eur). Ancestry was confirmed by genetic markers. Studies were performed at weeks 20, 30, 36 of pregnancy and again 4 mo postpartum as an index of the non-pregnant state. Arterial O2 saturation (SaO2) was measured by oximetry, hemoglobin concentration by spectrophotometry, and UtA blood flow calculated from vessel diameter and flow velocity obtained by Doppler ultrasound (ATL 3000 and an investigational Doppler) …
Comparative aspects of high-altitude adaptation in human populations
(Facultad de Medicina, Enfermería, Nutrición y Tecnología Médica, 2000) Moore, Lorna G
Abstract. The conditions and duration of high-altitude residence differ among high-altitude populations. The Tibetan Plateau is larger, more geographically remote, and appears to have been occupied for a longer period of time than the Andean Altiplano and, certainly, the Rocky Mountain region as judged by archaeological, linguistic, genetic and historical data. In addition, the Tibetan gene pool is less likely to have been constricted by small numbers of initial migrants and/or severe population decline, and to have been less subject to genetic admixture with lowland groups. Comparing Tibetans to other high-altitude residents demonstrates that Tibetans have less intrauterine growth retardation better neonatal oxygenation higher ventilation and hypoxic ventilatory response lower pulmonary arterial pressure and resistance lower hemoglobin concentrations and less susceptibility to CMS These findings are consistent with the conclusion that "adaptation" to high altitude increases with time, considering time in generations of high-altitude exposure. Future research is needed to compare the extent of IUGR and neonatal oxygenation in South American high-altitude residents of Andean vs. European ancestry, controlling for gestational age and other characteristics. Another fruitful line of inquiry is likely to be determining whether persons with CMS or other altitude-associated problems experienced exaggerated hypoxia during prenatal or neonatal life. Finally, the comparison of high-altitude populations with respect to the frequencies of genes involved in oxygen sensing and physiologic response to hypoxia will be useful, once candidate genes have been identified.
Does chronic mountain sickness (CMS) have perinatal origins?
(Facultad de Medicina, Enfermería, Nutrición y Tecnología Médica, 2007) Moore, Lorna G
Abstract. Chronic mountain sickness (CMS) occurs in 10% of male high-altitude residents. It is characterized by hypoventilation and hypoxemia but its underlying cause remains unknown. We hypothesized that CMS' origins reside in exaggerated perinatal hypoxia that server, in turn, to impair the development of pulmonary structure and/or respiratory control. As a preliminary test, we asked if birth weights were low and other signs of perinatal hypoxia were present in 12 young men with excessive erythrocytosis (EE, Hb> 18.3 g/dL), a condition thought to be a preclinical phase of CMS. Their birth weights were uniformly low (2571+-243g) and all but one demonstrated perinatl hypoxia as manifested either by being small for their gestational age (SGA, 8%), preterm (67%), born to a preeclamptic (PE) mother (50%), or diagnosed with neonatal hypoxia (83%). Impaired growth in utero has been shown to raise susceptibility to adult disease; these are the first data to demonstrate a possible influence of reduced fetal growth and/or exaggerated perinatal hypoxia on increasing the susceptibility to CMS. future studies, with more detailed testing in larger samples of control as well as EE subjects, with longitudinal follow-up, are required to determine the role of perinatal hypoxiain the development of CMS.
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.
Maternal adaptation to high-altitude pregnancy : an experiment of nature-a review
(Facultad de Medicina, Enfermería, Nutrición y Tecnología Médica, 2004) Moore, Lorna G
A long and productive history of studies at high altitude has demonstrated that chronic hypoxia plays a key role in the aetiology of intrauterine growth restriction (IUGR) and pre-eclampsia. Susceptibility to altitude-associated IUGR varies among high-altitude populations in relation to their duration of altitude exposure, with multigenerational residents demonstrating one-third the birth weight fall present in shorter-resident groups. Higher uteroplacental blood flow during pregnancy in multigenerational high-altitude residents suggests that such population differences are due, at least in part, to differences in maternal vascular responses to pregnancy. We hypothesize that natural selection acting on hypoxia-inducible factor (HIF)-targeted or -regulatory genes has enabled maternal vascular adaptation to pregnancy in long-resident high-altitude groups. Preliminary evidence in support of this hypothesis demonstrates that the potent HIF-targeted vasoconstrictor, endothelin-1 (ET-1), is differentially regulated by pregnancy and chronic hypoxia in Andean vs European residents of high altitude. Andeans show the normal, pregnancy-associated fall in ET-1 levels previously reported at low altitude, whereas Europeans have higher ET-1 levels and little pregnancy-associated change, like pre-eclamptic women. Single nucleotide polymorphisms (SNPs) in the ET-1 gene also differ in Andeans compared with low-altitude populations. We conclude that high altitude serves as an experiment of nature for elucidating genetic factors underlying susceptibility to complications of pregnancy and fetal life. Such studies may be important for identifying persons at risk for these complications at any altitude.
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.