Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth

Stacy Zamudio, Tatiana Torricos, Ewa Fik, Maria Oyala, Lourdes Echalar, Janet Pullockaran, Emily Tutino, Brittney Martin, Sonia Belliappa, Elfride Balanza, Nicholas P. Illsley

Research output: Contribution to journalArticle

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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. Principal Findings: 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. Conclusion/Significance: 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.

Original languageEnglish (US)
Article numbere8551
JournalPLoS One
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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hypoglycemia
fetal development
Fetal Development
Hypoglycemia
hypoxia
Glucose
glucose
umbilicus
Umbilicus
Mothers
Oxygen
oxygen
Hypoxia
lactates
Lactic Acid
Blood
insulin
Availability
pregnancy
Insulin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Zamudio, S., Torricos, T., Fik, E., Oyala, M., Echalar, L., Pullockaran, J., ... Illsley, N. P. (2010). Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth. PLoS One, 5(1), [e8551]. https://doi.org/10.1371/journal.pone.0008551

Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth. / Zamudio, Stacy; Torricos, Tatiana; Fik, Ewa; Oyala, Maria; Echalar, Lourdes; Pullockaran, Janet; Tutino, Emily; Martin, Brittney; Belliappa, Sonia; Balanza, Elfride; Illsley, Nicholas P.

In: PLoS One, Vol. 5, No. 1, e8551, 01.01.2010.

Research output: Contribution to journalArticle

Zamudio, S, Torricos, T, Fik, E, Oyala, M, Echalar, L, Pullockaran, J, Tutino, E, Martin, B, Belliappa, S, Balanza, E & Illsley, NP 2010, 'Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth', PLoS One, vol. 5, no. 1, e8551. https://doi.org/10.1371/journal.pone.0008551
Zamudio S, Torricos T, Fik E, Oyala M, Echalar L, Pullockaran J et al. Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth. PLoS One. 2010 Jan 1;5(1). e8551. https://doi.org/10.1371/journal.pone.0008551
Zamudio, Stacy ; Torricos, Tatiana ; Fik, Ewa ; Oyala, Maria ; Echalar, Lourdes ; Pullockaran, Janet ; Tutino, Emily ; Martin, Brittney ; Belliappa, Sonia ; Balanza, Elfride ; Illsley, Nicholas P. / Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth. In: PLoS One. 2010 ; Vol. 5, No. 1.
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AU - Tutino, Emily

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AB - 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. Principal Findings: 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. Conclusion/Significance: 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.

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