Effect of maternal chronic intermittent hypoxia during gestation on offspring growth in the rat

Am J Obstet Gynecol. 2013 Dec;209(6):564.e1-9. doi: 10.1016/j.ajog.2013.08.027. Epub 2013 Aug 24.


Objective: Obstructive sleep apnea, a breathing disorder caused by the repetitive collapse of the upper airway during sleep, results in a state of chronic intermittent hypoxia (CIH). Although the etiology and consequences of CIH are extensively investigated in the adult, the developmental ramifications of this disease process are unknown.

Design: This study was done to investigate the effect of CIH during gestation on offspring development. Pregnant female Spraque-Dawley rats were exposed to daily CIH throughout the gestational period.

Results: Postnatal day-1 offspring from CIH mothers were asymmetrically growth restricted, with decreased body weights and elevated brain-weight:liver-weight ratios. Furthermore, CIH newborns had elevated heart- and brain-weight:body weight ratios, and decreased liver-weight:body weight ratios. By adulthood, body weights of growth restricted offspring were significantly greater, as were the liver-weight:body weight ratios. CIH offspring also had greater body fat deposition, were hyperglycemic and had elevated plasma levels of insulin during development into adults.

Conclusion: These data suggest that alteration of the maternal intrauterine environment by gestational CIH effects the long-term development of the offspring and increases the risk of the offspring to metabolic diseases in adulthood.

Keywords: chronic intermittent hypoxia; diabetes; fetal programming; intrauterine growth restriction; liver metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn / growth & development*
  • Blood Glucose / analysis*
  • Body Weight / physiology*
  • Disease Models, Animal
  • Female
  • Fetal Growth Retardation / etiology
  • Fetal Growth Retardation / physiopathology*
  • Hypoxia / complications
  • Hypoxia / physiopathology*
  • Insulin / blood*
  • Male
  • Organ Size
  • Pregnancy
  • Pregnancy Complications / physiopathology*
  • Rats
  • Rats, Sprague-Dawley


  • Blood Glucose
  • Insulin