title: Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth.
abstract: BACKGROUND
  The most well known reproductive consequence of residence at high altitude (HA >2700 m) is reduction in fetal growth. Reduced fetoplacental oxygenation is an underlying cause of pregnancy pathologies, including intrauterine growth restriction and preeclampsia, which are more common at HA. Therefore, altitude is a natural experimental model to study the etiology of pregnancy pathophysiologies. We have shown that the proximate cause of decreased fetal growth is not reduced oxygen availability, delivery, or consumption. We therefore asked whether glucose, the primary substrate for fetal growth, might be decreased and/or whether altered fetoplacental glucose metabolism might account for reduced fetal growth at HA.
  
  
  METHODS
  Doppler and ultrasound were used to measure maternal uterine and fetal umbilical blood flows in 69 and 58 residents of 400 vs 3600 m. Arterial and venous blood samples from mother and fetus were collected at elective cesarean delivery and analyzed for glucose, lactate and insulin. Maternal delivery and fetal uptakes for oxygen and glucose were calculated.
  
  
  RESULTS
  The maternal arterial - venous glucose concentration difference was greater at HA. However, umbilical venous and arterial glucose concentrations were markedly decreased, resulting in lower glucose delivery at 3600 m. Fetal glucose consumption was reduced by >28%, but strongly correlated with glucose delivery, highlighting the relevance of glucose concentration to fetal uptake. At altitude, fetal lactate levels were increased, insulin concentrations decreased, and the expression of GLUT1 glucose transporter protein in the placental basal membrane was reduced.
  
  
  CONCLUSIONS
  Our results support that preferential anaerobic consumption of glucose by the placenta at high altitude spares oxygen for fetal use, but limits glucose availability for fetal growth. Thus reduced fetal growth at high altitude is associated with fetal hypoglycemia, hypoinsulinemia and a trend towards lactacidemia. Our data support that placentally-mediated reduction in glucose transport is an initiating factor for reduced fetal growth under conditions of chronic hypoxemia.
authors.affiliation: Department of Preventive Medicine and Community Health, University of Medicine and Dentistry-New Jersey, Newark, New Jersey, United States of America. Stacy.Zamudio@gmail.com
authors.forename: Stacy
authors.initials: S
authors.lastname: Zamudio
authors.forename: Tatiana
authors.initials: T
authors.lastname: Torricos
authors.forename: Ewa
authors.initials: E
authors.lastname: Fik
authors.forename: Maria
authors.initials: M
authors.lastname: Oyala
authors.forename: Lourdes
authors.initials: L
authors.lastname: Echalar
authors.forename: Janet
authors.initials: J
authors.lastname: Pullockaran
authors.forename: Emily
authors.initials: E
authors.lastname: Tutino
authors.forename: Brittney
authors.initials: B
authors.lastname: Martin
authors.forename: Sonia
authors.initials: S
authors.lastname: Belliappa
authors.forename: Elfride
authors.initials: E
authors.lastname: Balanza
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Illsley
mesh_terms: D000328:Adult; D005260:Female; D047109:Fetal Development; D005947:Glucose / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012039:Regional Blood Flow; D018608:Ultrasonography, Doppler
chemical_list: D005947:Glucose