According to research conducted on rats by Amanda Vanderplow, Michael Cahill, and colleagues at the University of Wisconsin-Madison and published on February 3 in the open-access journal PLOS Biology, sleep apnea during pregnancy may increase the risk for brain and behavioral changes linked to autism, especially in males.
The results reveal a potential mechanism to explain the relationship between sleep apnea and neurodevelopmental problems that has been shown to exist in individuals. Breathing is partially or fully stopped during bouts of sleep apnea, frequently hundreds of times per night, which results in intermittent hypoxia, or decreased blood oxygenation.
In accordance with the obesity epidemic, the prevalence of sleep apnea during pregnancy is rising; by the third trimester, it affects more than 60% of high-risk pregnancies and roughly 15% of pregnancies without complications.
Although the effects of sleep apnea during pregnancy are recognized to be harmful for the baby, the effects on neurodevelopment have not been thoroughly researched. The scientists used pregnant rats in the second half of their gestation to study the effects of periodic low oxygen levels during periods of rest.
Although it was expected, the medication did not cause hypoxia in the fetuses, just in the moms. Beginning soon after birth, behavioral anomalies in the offspring were noticed, including altered distress vocalization patterns in both males and females.
In male but not female kids, maternal hypoxia also reduced cognitive and social function, which both remained into adulthood. Working memory and longer-term memory storage were affected, and interest in socially new settings was also decreased.
To our knowledge, this is the first direct demonstration of the effects of maternal intermittent hypoxia during gestation on the cognitive and behavioral phenotypes of offspring. Our data provide clear evidence that maternal sleep apnea may be an important risk factor for the development of neurodevelopmental disorders, particularly in male offspring.
Michael Cahill
The density and form of dendritic spines, the growths on neurons that receive and integrate messages from other neurons, were significantly aberrant with these behavioral changes.
The density of dendritic spines was higher in adolescents of both sexes, but significantly higher in males, compared to age-matched control animals. This increase was primarily caused by a lack of spine “pruning,” or reduction, a process that starts in childhood and is essential for normal brain development. It is yet unknown how maternal hypoxia affected fetuses that were not experiencing hypoxia on their own.
The authors discovered that treatment with rapamycin, a mTOR inhibitor, partially attenuated the behavioral effects of maternal hypoxia in the offspring and that affected offspring had excessive activity of a cell signaling pathway known as the mTOR pathway, a feature identified in the cortex of humans with autism.
“To our knowledge, this is the first direct demonstration of the effects of maternal intermittent hypoxia during gestation on the cognitive and behavioral phenotypes of offspring,” Cahill says.
“Our data provide clear evidence that maternal sleep apnea may be an important risk factor for the development of neurodevelopmental disorders, particularly in male offspring.” Cahill adds,
“Based on clinical correlations, maternal sleep apnea during pregnancy has been theorized to potentially increase risk for autism diagnosis in her offspring; however, functional studies are lacking. Here we show that sleep apnea during gestation produces neuronal and behavioral phenotypes in rodent offspring that closely resemble autism, and demonstrate the efficacy of a pharmacological approach in fully reversing the observed behavioral impairments.”
