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

Abstract

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. 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. 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. 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.