Maternal sleep apnea may cause autism-like changes in males

A new animal study suggests that maternal sleep apnea during pregnancy may increase the risk of male children developing brain and behavioral changes associated with autism.

Amanda Vanderplow and colleagues note, “Sleep apnea is characterized by recurrent partial or complete cessation of breathing during sleep, often hundreds of times each night. The resulting swings in blood oxygen levels (intermittent hypoxia) induce profound inflammation, which causes most of the morbidities associated with sleep apnea.” The researchers note that by the third trimester, sleep apnea occurs in about 15 percent of uncomplicated pregnancies and more than 60 percent of high-risk pregnancies.

To determine if maternal sleep apnea might affect the development of children, the researchers subjected pregnant rats to intermittent low oxygen levels at times of rest during the second half of pregnancy. As expected, the intervention led to hypoxia in the mothers, but not in the fetuses.

The researchers report that the offspring of rats exposed to intermittent hypoxia exhibited an increased incidence of cognitive and executive function impairment. (Executive function refers to higher-level brain functions such as planning and impulse control.) In addition, the affected offspring exhibited abnormal juvenile communicative vocalizations, altered social behavior, and increased grooming behavior (a form of repetitive behavior). With the exception of abnormal vocalizations, behavioral alterations occurred solely in male and not female offspring.

As well as behavioral changes, the affected offspring exhibited significant abnormalities in the density and structure of dendritic spines, which are the protrusions on neurons that receive and integrate signals from other neurons. While adolescent rats of both sexes showed an elevated density of dendritic spines, the increase was much more marked in males. This increase, the researchers say, was due primarily to a lack of spine “pruning,” which is critical for normal brain development.

In addition, the researchers found that affected offspring exhibited excess activity of a cell signaling pathway called the mTOR pathway. Studies have shown that this pathway is altered in autism. Administration of rapamycin, an mTOR inhibitor, partially mitigated the behavioral effects of maternal hypoxia.

Study co-author Michael Cahill says, “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.”

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“A feature of maternal sleep apnea during gestation causes autism-relevant neuronal and behavioral phenotypes in offspring,” Amanda M. Vanderplow, Bailey A. Kermath, Cassandra R. Bernhardt, Kimberly T. Gums, Erin N. Seablom, Abigail B. Radcliff, Andrea C. Ewald, Mathew V. Jones, Tracy L. Baker, Jyoti J. Watters, and Michael E. Cahill, PLOS Biology, February 2, 2022 (free online). Address: Michael Cahill, Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, Wisconsin 53706 michael.cahill@wisc.edu.

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“Mothers’ sleep apnea may increase risk of autism-like changes in their male offspring,” news release, Public Library of Science, February 3, 2022

This article originally appeared in Autism Research Review International, Vol. 36, No. 1, 2022