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Sleeping for Two

Poor slumber during pregnancy may have consequences beyond gestation.

There’s an old wives’ tale that the sleep problems that often beset pregnant women naturally prepare the mother for the extreme sleep disruption that arrives with the baby. Part of this appears to be true: sleep issues—whether it’s waking up in the night, being unable to fall asleep, or more serious conditions such as sleep apnea—are indeed common complaints of expectant moms, especially as heartburn, back pain, and frequent trips to the toilet set in. But recent research is challenging the assumption that sleep woes represent an advantageous mechanism to gear up for subsequent sleepless nights.

David Gozal, who studies pediatric sleep disorders at the University of Chicago, says he was inspired to look into the effects of sleep disturbances in expectant women about a decade ago, when reports began to appear that pregnancy is accompanied by an increased risk for developing sleep perturbations. “People started talking about whether this could have effects on blood pressure and preeclampsia, things related to the pregnancy itself, but not to the fetus,” says Gozal. “I’m a pediatrician, so I’m interested in what comes out of the pregnancy.”

Yet no one had studied the consequences of a mom’s sleep apnea—which involves microarousals that occur many times each hour because of snoring or other interruptions in normal breathing—for the baby, beyond immediate birth outcomes such as weight and mode of delivery. And for good reason: to do rigorous studies on children’s long-term health and development is incredibly time-intensive, expensive, and logistically difficult. So Gozal turned to mice.

In one experiment, his team subjected rodents during the last third of pregnancy to something akin to sleep apnea—they were in a cage that shook every two minutes during the period when mice sleep. The mice slept just as much as control mice, but their sleep was fragmented, similar to that experienced by women with apnea. To isolate the effects of disturbed sleep per se, the researchers did not induce hypoxia, the low blood oxygen that is another important component of sleep apnea.

At first, Gozal and his team didn’t notice anything different between pups born to mothers with fragmented sleep and those whose mothers slept normally. But after a couple of months, the offspring of the sleep-disrupted mice started eating more and gaining weight (Diabetes, 63:3230-41, 2014). “At 24 weeks. . . these mice were insulin resistant and had features of metabolic syndrome,” says Gozal.

The mechanistic connection between sleep apnea in moms and metabolic changes in pups is still speculative. Gozal suggests a number of possibilities, including changes in the body’s sensitivity to the satiety-related hormone leptin, which is altered during sleep loss. Or there may be changes in other maternal hormones, in the mother’s microbiome, or in inflammation. In a subsequent study, the team compared methylation profiles in the DNA of visceral fat cells between control animals and mice born to sleep-fragmented mothers. The researchers found more than 2,000 differentially methylated regions, some of which are implicated in obesity and metabolic syndrome (International Journal of Obesity, 39:1135-42, 2015). The significance of these epigenetic changes is not yet clear, but they raise the possibility of long-term repercussions of sleep disorders during pregnancy.

“Certainly, it’s very plausible,” says Louise O’Brien, who studies sleep during pregnancy at the University of Michigan (she trained with Gozal as a postdoc, but was not involved in his work on the mice). “It’s been known for decades that what happens in utero can affect the long-term health of the baby.” Observations of Dutch women who were pregnant during the food rationing of World War II and their children demonstrated that the mother’s well-being, in this case her nutrition, could affect offspring over a lifetime. Sons born to women who experienced famine during the first half of pregnancy were more likely to become obese later in life, for instance (NEJM, 295:349-353, 1976). “Do we know that in terms of sleep apnea? We don’t, but it’s a very plausible mechanism,” says O’Brien.

Other problems with sleep are linked with untoward pregnancy outcomes in women. O’Brien and her colleagues have shown that snoring brought on by pregnancy is tied to a greater likelihood of emergency cesarean sections, and babies whose moms snored before and during pregnancy were smaller than babies of nonsnoring moms (Sleep, 36:1625-32, 2013). O’Brien is now looking through those babies’ growth charts to see whether maternal snoring is linked with long-lasting effects on the children, and whether their genomes also display different methylation patterns.

“Snoring is not just an annoying problem,” says BilgayIzci-Balsarak, who studies pregnancy and sleep at the University of Illinois Chicago College of Nursing. “The consequences of sleep disturbance during pregnancy can be very serious.” She cites a study reporting that women who slept just six hours a night during late pregnancy underwent four times as many C-sections as women who slept longer. Sleep disturbances also correlate with gestational diabetes, and even sleep position may make a difference. O’Brien and colleagues, in addition to two other independent teams working different parts of the world, have found that women who reported sleeping on their backs during pregnancy were much more likely to have a small or stillborn baby (International Journal of Gynecology & Obstetrics, 121:261-65, 2013).

Izci-Balsarak says a number of factors predispose pregnant women to sleep disturbances. Body temperature is increased, “which isn’t good for sleep quality,” she says, and estrogen levels rise, which can cause nasal congestion and snoring. Iron deficiency—common as women’s bodies ramp up their blood volume to supply the developing fetus with oxygen—may lead to restless legs syndrome.

Despite these warning signs, few clinicians screen pregnant women with sleep troubles, says O’Brien. “I think historically health-care providers said, ‘Oh, it’s preparing you for the baby.’ Is this really what [sleep problems are] doing? I think we have to be very careful about pooh-poohing it and saying, ‘Oh, it’s normal.’”

 

 

Source: The Scientist
“Sleeping for Two” by Kerry Grens

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