Research shows treating sleep disordered breathing in pregnant women may safely reduce the danger of preeclampsia.

My interest in sleep disorders and pregnancy began when, during a monthly meeting, I asked my coworker and fellow sleep technologist Kelsey how her pregnancy was going. “Fine,” she said. “Things are good.” Then someone asked how her sleep was and she started to laugh and said, “What sleep?!?”

Most women notice sleep disturbances very early in pregnancy. Many report an increased desire to sleep during the first trimester,1,2 and, as the gestational course continues, numerous factors contribute to the fragmentation of their sleep. Subjective reports of pregnant women often include complaints of increased restlessness, snoring, fatigue, and sleep fragmentation that result in significantly less total sleep time.2,3 Research dedicated to sleep in pregnant women continues to evolve. Sleep disordered breathing (SDB) problems during pregnancy include snoring, upper-airway flow limitation, and obstructive sleep apnea (OSA)/hypopnea.1,2,4

The true prevalence of OSA in pregnant women is still unknown. A search in the EBSCO (MEDLINE) database results in at least 13,000 entries for the term “sleep apnea.” Adding the term “pregnancy” to the same search elicits only a little more than 100 entries. Most preliminary research indicating the presence of this comorbid condition has been in the form of case reports.5 However, the possibility for adverse maternal and fetal complications from SDB is becoming more apparent as continued research is dedicated to elucidating longitudinal evidence. Recent research indicates the possibility for both snoring and increased upper-airway resistance as being contributing factors to adverse effects and complications during pregnancy.6-8 In addition, researchers have found that SDB in pregnant women may play a contributory role in the development and treatment of more serious conditions that may be present during pregnancy, including preeclampsia.8-10

Snoring, a frequent symptom of OSA, also is common among pregnant women.1,7,8 Although there are few documented cases of OSA in this population, the physiological changes the respiratory system undergoes during pregnancy seem to particularly increase sleep fragmentation during the third trimester. This is also the time when most pregnant women report snoring.6,8 In 2002, Edwards et al6 described these changes as being an increase in ventilatory drive and metabolic rate, a reduced functional capacity and residual volume, increased alveolar-arterial oxygen gradients, and changes in the upper airway. Hormones, such as progesterone, that stimulate the respiratory drive seem to impact these respiratory system changes the most.6,11 Similarly, increased weight, abdominal girth, and pressure on the diaphragm from the developing fetus may all contribute to decreased respiratory ability of the mother, especially while supine.2,8 Edwards et al6 stated that the clinical importance of such changes is indicated by the increase in snoring during pregnancy, which is also likely to be an indication for OSA/hypopnea syndrome and other forms of SDB.

Implications
How then should snoring be identified? Is a complete polysomnogram warranted for all pregnant women who report snoring? How important is snoring to both the maternal and fetal outcomes?

Bliwise et al13 showed that self-reported snoring correlates well with objective findings, such as polysomnography. Compared to the general population, there is significantly more snoring in pregnant women than in similar nonpregnant women.8 Researchers found that 14% of the pregnant versus 4% of nonpregnant women exhibited frequent snoring. Those women in the study who reported frequent snoring during pregnancy did not have significant adverse fetal outcomes. However, this may have been due to the lack of further studies examining such a relationship.8 Similarly, Redline et al14 reported a significant degree of underreporting of snoring and other symptoms of SDB among pregnant women, but found no significant adverse maternal or fetal outcomes.

Yet, when researchers started to look at snoring in pregnant women more empirically, this correlation was associated with significant adverse effects to the fetus. One such study was performed by Franklin et al.7 They sought to identify the relationship between snoring and pregnancy-induced hypertension and growth retardation of the fetus by retrospectively examining medical charts and using questionnaires. Their results showed the snoring frequency to increase quite significantly (P<0.001)7 when the disorders were present. Similarly, apneas were witnessed in 11% of the habitual snorers, as compared to only 2% of the nonhabitual snorers (P<0.001).7 The study revealed that habitual snoring in the mother was independently predictive of hypertension and growth retardation in the fetus, even when the researchers controlled for factors such as weight, age, and smoking.7 Snoring clearly impacts gravidity. Therefore, clinical evidence of sleep fragmentation and/or hypertension—in addition to patient self-reports of snoring—may call for routine polysomnographic testing of these patients.

Other issues
Excessive daytime sleepiness (EDS) is another common sign and symptom of existing sleep pathology. Polysomnographic testing can identify not only forms of sleep apnea, but also the occurrence of other breathing-related sleep disorders, such as the upper-airway resistance syndrome (UARS). Guilleminault et al15 reported that UARS in the general population is associated with abnormal respiratory effort, nasal airflow limitation, absence of OSA, minimal pulse-oxygen fluctuations with oxygen saturations equal or greater than 92%, and frequent nocturnal or reflex brainstem activation. This condition can be manifested with or without snoring, so this research group used a naso-esophageal pressure (PES) catheter to objectively quantify respiratory effort.16-18 A study by Guilleminault et al16 that was published just this year aimed to assess the symptomatic evolution of patients with diagnoses of UARS in the general population. This 41¼2-year longitudinal study used multiple polysomnographic tests to periodically reassess the previously diagnosed UARS condition. The results indicated the importance of treatment.16 Among the study participants, symptoms of insomnia, fatigue, and depressive mood all worsened when left untreated.16

In 2001, Connolly et al4 found that this was also true for pregnant women and there was a very serious additional consequence: preeclampsia or pregnancy-induced high blood pressure. The sample (n=15) of preeclamptic women in the study showed evidence of flow limitations that did not meet standard criteria for hypopnea and therefore went untreated. Treatment for UARS and/or SDB during pregnancy is rarely offered, even though studies are starting to show the usefulness of CPAP on subjects with this type of sleep fragmentation.17

Although snoring and other sleep-related fragmentations are often seen in pregnancy, few women present to hospitals or clinics with these complaints because the links between these problems and more serious conditions, such as preeclampsia, are poorly understood. Studies have reported that preeclampsia is a leading cause of both maternal and fetal morbidity and mortality. It is thought to affect an estimated 7% of all pregnancies,9 and research has shown that SDB may be a possible contributing factor to the preeclampsia.7 There may even be a common link between the onset of severe snoring and preeclampsia.

Research in this area is increasing, as is treatment of pregnant women with nasal CPAP.9-12 Franklin et al7 found that 23% of pregnant women in their study sample (n= 502) reported severe snoring with an onset given by the last trimester; and another 25% reported snoring “seldom” or “sometimes” by the last trimester. Furthermore, Sibai et al18 studied a sample (n=2,947) of healthy single-fetus pregnancies and reported four risk factors that were predictive of preeclampsia. In order of importance, these were: systolic blood pressure at entry, obesity, number of previous abortions or miscarriages, and smoking.18

Another study by Pien et al12 found that women with higher baseline body mass indexes and greater neck circumferences during pregnancy reported higher scores on the Multivariable Apnea Prediction Index18 and had an increase in EDS compared to others in the study. The authors suggested that some women may therefore develop clinically significant OSA during the course of pregnancy.18

Lewis et al reported a case of sleep apnea during pregnancy that resulted in pulmonary hypertension.19 When the patient’s OSA was successfully controlled with nasal CPAP, she also experienced a significant diuresis of 104 pounds.19 Although this does not prove that the OSA seen in this patient’s pregnancy was linked to her pulmonary hypertension, it is consistent with other such cases and clinical histories.19

A more recent study performed at Stanford University has shown longitudinal evidence of the usefulness of CPAP on a sample of 12 pregnant women.17 Of the 12 subjects, seven had a previous diagnosis of SDB prior to pregnancy and the others were diagnosed in the first trimester. All underwent subsequent polysomnography with the addition of nasal CPAP to properly titrate the pressure needed to correct any sleep disordered breathing. Clinical follow-up was performed at 3 to 4 weeks and follow-up polysomnography was recorded at around 6 months gestation and at 8 months gestation utilizing ambulatory monitoring.17 The deliveries of these women occurred between 38 and 40.5 weeks gestation and all the infants were healthy, meaning that they had Apgar scores above 8. This longitudinal study showed evidence of the usefulness of CPAP therapy for OSA in pregnant women.17

Three studies out of the Sydney, Australia-based David Reed Laboratory have investigated the effects of CPAP on preeclampsia. These studies dating from 2000 to 2004 showed significant reduction in the hemodynamic and cardiac output of these patients when they started CPAP therapy.9-11 The authors of the studies concluded that reduced cardiac output during sleep may have an adverse impact on fetal development, but this can be minimized with nasal CPAP treatment.9

Treatment
The most recent analysis of the current literature on sleep and pregnancy (2004) presents useful criteria to follow for the treatment of sleep disordered breathing in pregnancy.1 Research has shown that sleep fragmentation caused by SDB in pregnancy—specifically snoring and UARS—is common.7,10 Therefore, the authors suggested giving those women with clinical symptoms of SDB routine polysomnography testing.1 They also found that during pregnancy it may be necessary to lower the threshold of the apnea-hypopnea index (AHI) normally used to diagnose SDB, and address clinical symptoms as an indication of SDB. Those women whose record shows an AHI between 5 and 30, clinical reports of SDB, and SaO2 that drops lower than 90% should be treated with nasal CPAP to ensure both mother and fetus grow/develop properly.1 However, the authors caution against the treatment of preeclampsia with nasal CPAP unless specific polysomnographic data also shows existing SDB.1

One important aspect of the data is that, although results are preliminary in nature, CPAP has been well tolerated in numerous studies of pregnant women, and sleep laboratory technologists should be familiar with working with obese patients and those who do not sleep on their backs, as few pregnant women do.1,2,19 Among patients on nasal CPAP, treatment compliance is, of course, key to realizing the therapeutic effects of CPAP. Guilleminault et al17 noted the need to periodically adjust the pressure settings as required to treat the SDB symptoms and ensure compliance. Use of newer CPAP instruments that record nightly pressures may be a necessary precaution when treating pregnant women with nasal CPAP.

Sleep is a crucial time for the body to develop neurohormones, such as growth hormone, during pregnancy. Blyton et al9 reported their belief that the period of maternal sleep, when fetal blood delivery may peak, could provide a crucial time for the delivery of such hormones essential for fetal growth and well-being.9 They also hypothesized that long-term treatment with nasal CPAP may help increase fetal growth.9 No adverse effects of nasal CPAP therapy have been reported to date, thus it opens up the possibility for a safe treatment of both SBD and preeclampsia in pregnant women.

Christopher P. Herrera, RPSGT, is a candidate to receive his master in arts in psychology this summer from the University of Houston-Clear Lake. He is currently working as a sleep technologist at the Methodist Hospital Sleep Disorders Center in Houston. Special congratulations to Kelsey for delivering a beautiful, healthy baby girl, Lila.

References
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