Providing sleep tests and evaluating diet and medication intake can help patients sleep better during pregnancy.

 Pregnant women do not sleep normally. This they will tell you. Even before pregnancy is diagnosed, many women experience an overwhelming desire to nap. “I slept all the time,” they say, recalling the early weeks. But as the pregnancy advances, such peaceful slumber becomes a distant memory. Women toss and turn, unable to find a comfortable position in bed. Back pain, fetal movement, and a frequent need to urinate disrupt their sleep. Some women develop restless legs syndrome, some start to snore, and many report vivid dreams.1

Since these problems usually disappear after delivery, there has been little interest in treating them. Obstetricians usually recommend simple sleep hygiene measures. “Pregnancy is a situation where the body is on biologic autopilot and the more we interfere, the more things could go wrong,” explains Meir Kryger, MD, FRCPC, professor of medicine at the University of Manitoba and author of A Woman’s Guide to Sleep Disorders.2

But with increasing awareness of the role of sleep disturbances in many pathologies, both the obstetrical and sleep research communities have been taking a closer look at the sleep of pregnant women. Do polysomnographic changes accompany pregnancy? What causes the typical pregnancy-associated sleep complaints? When are sleep problems linked to serious complications of pregnancy such as prematurity, low birth weight, preeclampsia, or postpartum depression?

In contrast to the insomnia often reported in the third trimester of pregnancy, the first trimester is characterized by a powerful urge to sleep. This symptom has received little previous attention, both because it has seemed largely benign and because it usually diminishes, along with nausea, by the second trimester. For pregnant women, however, it remains a striking phenomenon.

Some common complaints include “I slept every afternoon, 4 or 5 hours. It seemed like I could not stay awake.” “I fell asleep on the subway—three times.” “I fell asleep talking on the phone with a client.” “It was an irresistible feeling. They should find out what causes that and bottle it!”

The Immune System
Recently, researchers investigating changes in the immune system during pregnancy have identified several factors that may promote sleep. One such factor is granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine crucial in establishing pregnancy. Noting that sleep increases markedly in rats in early pregnancy, researchers at Tokyo Medical and Dental University wondered whether GM-CSF could be involved. After first demonstrating that an infusion of GM-CSF increased both REM and non-REM sleep, they next developed an antibody to GM-CSF. Infusing anti-GM-CSF intracerebrally to pregnant rats over 4 nights, they induced a significant drop in both REM and non-REM sleep compared to pregnant animals receiving a control infusion.3

Although sleep disruption has long been believed to begin in late pregnancy, new research is uncovering sleep loss in all three trimesters. Immune factors associated with sleep deprivation in other situations tend to be increased throughout pregnancy as well. At the University of Colorado in Denver, Michele Okun, MA, and Mary Coussons-Read, PhD, studied 34 pregnant women who completed sleep questionnaires (Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index), kept 2-week sleep diaries, and provided blood specimens at 12 to 16 weeks, 22 to 26 weeks, and/or 36/40 weeks gestation. Blood specimens were tested for tumor necrosis factor-alpha (TNF-alpha), interleukin-4, interleukin-6, and interleukin-10.

In the first trimester, an equal number of normal and abnormal sleepers were found, with abnormal sleepers having sleep onset latency (SOL) greater than 15 minutes and wake after sleep onset (WASO) greater than 20 minutes. As pregnancy progressed, the proportion of abnormal sleepers increased, reaching 11:2 in the third trimester. Abnormal sleepers had significantly elevated levels of TNF-alpha, a sleep-promoting cytokine.4 Napping was also significant. “Women who napped longer—and obviously they were compensating for what they were not getting at night—had higher TNF-alpha, which promotes the desire to sleep,” Okun says.

A polysomnographic study conducted by Kathryn Lee, RN, PhD, and colleagues at the University of California, San Francisco examined changes in sleep patterns before, during, and after pregnancy. Initially, a group of 45 women were studied in the follicular and luteal phases of the menstrual cycle; 33 women became pregnant and were studied in each trimester, and 29 were followed at 1 and 3 months postpartum. At each phase, the women received polysomnographic testing at home for two consecutive nights. “By week 10 or 11 of pregnancy, there were already significant changes,” Lee says. “The amount of deep sleep went down and stayed down. It did not really improve until postpartum.” Compared to their prepregnancy levels, the pregnant women experienced a significant increase in total sleep time, but less deep sleep and more awakenings during sleep.5

“The women didn’t say, ‘I had 10% less delta sleep last night,’ but they did complain of feeling fatigued, drowsy, and even depressed. They experienced the sleep loss in a variety of ways,” Lee says.

How much these sleep changes might have been due to specific immune factors and how much to progesterone is unclear. Progesterone levels in late pregnancy are 10 times the average at the peak of the menstrual cycle. But even as progesterone begins to rise, it produces many secondary effects on sleep. For example, Lee points out that in the first trimester as well as the third, women often wake up with bladder frequency. “That is too early for pressure from the gravid uterus to be pressing on the bladder. But because of hormonal changes in the smooth muscle of the bladder, ureters, and urethra, women in the first trimester have to go [to the bathroom] more frequently,” Lee says.

“Any process that makes sleep unstable will cause a reduction in stage three and four sleep,” Kryger says. He notes that to enter stages three and four, the sleeper must be in a stable state. “If another physiological process keeps waking the sleeper up, or putting her into stage one or two, she is not going to get into long stages of stable sleep,” he says.

Weight Gain and Snoring
Many women also start to snore during pregnancy. With a massive increase in abdominal girth, and the fundus of the uterus pressing on the diaphragm, a pregnant woman who snores might appear to be a prime candidate for OSA. On the contrary, however, apneas and hypopneas during sleep are reduced in both frequency and duration in most pregnant women versus their nonpregnant counterparts.6 This effect has been attributed to progesterone, which stimulates respiration during pregnancy. Because pregnant women have the same impairments of lung function as the morbidly obese, with reduced residual volume and functional residual capacity, as well as reduced cardiac output lying supine, theoretically they would be at risk for oxygen desaturation at night.1 Yet this rarely occurs. Rather, high levels of progesterone increase alveolar ventilation, primarily by increasing tidal volume, thus the fetus is protected from hypoxemia at night.1

Snoring, however, remains an important warning sign. Risks of both hypertension and preeclampsia are twice as high in pregnant women who snore. In one large study, 14% of pregnant snorers developed hypertension and 10% developed preeclampsia compared to 4% of nonsnorers.8 Close links have been found between preeclampsia and OSA. In a case described by Roush and Bell in 2004,8 a woman being evaluated for preeclampsia at 37 weeks gestation was undergoing polysomnography when she experienced a witnessed oxygen desaturation with concurrent fetal heart rate deceleration. She subsequently delivered an infant small for gestational age. The authors wonder whether monitoring for snoring during pregnancy might help to prevent such outcomes.9

If a pregnant woman snores, Kryger recommends that she have her blood pressure and urine protein checked, and potentially be evaluated for OSA. If indicated, she should be placed on nasal CPAP immediately.1 Several current studies show that treatment with CPAP reduces the nocturnal rise in blood pressure seen in preeclampsia and improves cardiac output during sleep. This in turn may reduce the risk of intrauterine growth retardation associated with preeclampsia.10,11

Because many women with OSA during pregnancy gain excessive amounts of weight, the problem should not be expected to go away after delivery. The mother must continue CPAP. This is a matter of safety, Kryger cautions, since without CPAP, a new mother with OSA might become too sleepy to attend to her infant.2

Sleep Testing
Conducting polysomnography on a pregnant woman should be well within the capabilities of an experienced sleep technician. As Kryger points out, sleep technicians are accustomed to dealing with very large individuals with very large abdomens. The only unusual feature is that the woman will almost certainly insist on sleeping on her side. For this reason, the technician should double-check to make sure that the sensors used to record respirations are working properly before beginning the study. A bigger concern for Kryger is the possibility that clinicians might take their time analyzing the results, perhaps because they do not plan to intervene. “Some obstetricians and midwives still believe that CPAP is hazardous in pregnancy,” he says. In his view, the real danger lies in not using CPAP soon enough—in a split night if necessary.

Restless Legs Syndrome
In the second and third trimesters of pregnancy, about 19% of women develop RLS, as compared to about 5% of the general population. The precise prevalence is uncertain since different studies have produced estimates ranging from 12% to 27%, depending in part on the diagnostic criteria used.13 RLS should not be confused with nocturnal leg cramps, also common in pregnancy. Although agreement exists that RLS in pregnancy is triggered by deficiencies in iron and folate, treatment with folate and oral or even intravenous iron does not always succeed in suppressing symptoms once they have begun. Treatment with benzodiazepines, opioids, dopaminergic agents, or antiepileptic drugs sometimes used to quiet restless legs in other settings is contraindicated in pregnancy. Thus, prevention is essential.

RLS is one of the most distressing and least talked about symptoms of pregnancy, according to Lee. In a study she published in 2001, time to sleep onset was significantly delayed and depressed mood was significantly higher in women who complained of RLS. Compared to women without RLS, those with the disorder had low serum ferritin at preconception and at each trimester. But rather than indicators of iron deficiency anemia (serum ferritin, serum iron, and hemoglobin) or pernicious anemia (vitamin B12), it was reduced serum folate levels that were most strongly associated with RLS.14 “Originally, I was looking at hemoglobin and iron as another way of explaining fatigue, other than by lost sleep. The lab values going into pregnancy were all within normal limits. But when we went back and looked at our data, the women who got restless legs in the third trimester were really low on folate and iron storage to begin with, before they even got pregnant. They all dropped in the third trimester, but it was those who had been low but still within normal limits initially who developed restless legs,” Lee says. She believes this may indicate a need to reconsider recommendations about the normal ranges of serum ferritin and serum folate during pregnancy.

 The Importance of Diet
Relative to current recommendations, approximately 30% of women are deficient in iron stores at the start of pregnancy, according to Virginia Hall, MD, associate professor of obstetrics and gynecology at Penn State-Milton S. Hershey Medical Center in Hershey, Pa. “Beginning in the third trimester, 50% of maternal iron goes to the fetus and placenta, increasing to 90% at the end of pregnancy. And it takes 1,200 calories of a normal diet—not vegan or vegetarian—to provide 1 mg of iron,” Hall says.

Kryger is also concerned about the increasing number of women on extreme diets. “There is an assumption that no one is deficient in folate in North America because all cereal products are fortified. But this assumption no longer holds with all the extreme diets we see,” he says. Kryger tries to make absolutely sure that pregnant patients do not take anything to help them sleep. “There are still people who believe that if they buy something in a health food store, or even over the counter, it is safe. In other words, don’t take melatonin, kava, or antihistamines sold over the counter,” he says.

Medication Intake
If a woman has narcolepsy, she must discontinue medications such as methylphenidate, modafinil, or amphetamines before becoming pregnant. Careful planning will be required. “Once she stops her medications, she will need to stop driving. If she already has children, she will now need to have someone with her to help care for them, and if she has a job, she may have to plan to leave that job before she becomes too sleepy,” Kryger says.

Women with preexisting depression may be allowed to take antidepressants, but this is a complex decision to be made by the woman and her physician, according to Barbara Parry, MD, professor of psychiatry and director of research at the Women’s Mood Disorder Clinic at the University of California, San Diego. None of the tricyclic antidepressants or serum serotonin reuptake inhibitors (SSRIs), especially fluoxetine, have been shown to cause major organ malformations or short-term neurological problems in the fetus. “But we don’t know the risks of long-term behavioral effects,” Parry says. “What we do know is that the risks of not treating depression are much higher—because untreated depression in the mother will impair the neurocognitive development of the child.” According to Parry, women with depression are more vulnerable to sleep problems in pregnancy. “You see more changes in REM density in those women,” she says. Depression can also develop for the first time during pregnancy and may be reflected in REM changes as well.

Postpartum Depression
Recently, Parry has been testing selective sleep deprivation as a novel therapy for postpartum depression.15 The idea is counterintuitive, since sleep deprivation in the care of the newborn is generally believed to contribute to postpartum depression. “But when we sleep-deprive someone in our study, it is a consolidated period of no sleep, not just tossing and turning,” Parry says. The approach was discovered by observing patients with bipolar disorder. As they switch from the depressed phase to the manic phase, they don’t sleep. “We think this may reset the circadian clock and shift the sleep cycle into sync with the underlying circadian rhythm,” Parry says. In her present protocol, subjects are kept awake for half a night or 4 hours. Whereas people without depression feel worse after being sleep deprived, people with major depression or depression related to the menstrual cycle feel better. “We are still testing it in pregnancy, but so far it look as though it is more effective in women with postpartum depression,” Parry says.

Interrupted sleep makes the postpartum period a difficult rite of passage for new mothers. Lee’s results on sleep efficiency reveal just how difficult that transition can be. Initially, the women pregnant with their first child were sleeping at 95% efficiency, which declined to 90% in the third trimester. The women who already had a child slept at 90% efficiency throughout all three trimesters.

“But when I looked at the postpartum data, I just about cried,” Lee says. The sleep of the experienced mothers had dropped to 85% efficiency—not an unexpected finding, but the first-time mothers were trying to survive on 75%.16 “They had dropped from 95% to 75%,” Lee says. “It was taking them longer to feed the baby, taking them longer to change the diapers. They were more vigilant during the night, waking up with any little noise the baby made.” By contrast, the experienced mothers were more efficient and more relaxed. Thus, with better understanding of the causes of sleep loss during pregnancy and postpartum, Lee and other researchers hope that strategies can be developed to manage this crucial life transition.

India Smith is a contributing writer for Sleep Review.

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