The Upper Airway in Pregnancy and Pre-Eclampsia Bilgay Izci, Renata L. Riha, Sascha E. Martin, Marjorie Vennelle, Wang A. Liston, Kirsty C. Dundas, Andrew A. Calder, and Neil J. Douglas Edinburgh Sleep Centre and Department of Reproductive and Developmental Sciences, University of Edinburgh, Edinburgh, Scotland, United Kingdom
Snoring is common in pregnancy, and snoring pregnant women have increased rates of pre-eclampsia. Patients with pre-eclampsia show upper airway narrowing during sleep. The present study aimed to compare upper airway dimensions in pregnant and nonpregnant women and in patients with pre-eclampsia. A total of 50 women in the third trimester of pregnancy and 37 women with pre-eclampsia were recruited consecutively from the antenatal service and matched with 50 nonpregnant women. Upper airway dimensions were measured using acoustic reflection. Comparisons were made by analysis of variance and Student-Newman-Keuls tests. Snoring was reported by 14% of nonpregnant women, 28% of pregnant women, and 75% of pre-eclamptic women (p ⬍ 0.001). When seated, pregnant women had wider upper airways than nonpregnant women (p ⬍ 0.02), but there was no difference when supine. Oropharyngeal junction area in the seated position was less (p ⬍ 0.01) in the women with pre-eclampsia (mean ⫾ SD: 0.9 ⫾ 0.1 cm2) than either nonpregnant (1.1 ⫾ 0.1 cm2) or pregnant women (1.3 ⫾ 0.1 cm2). Supine oropharyngeal junction area was less in the women with pre-eclampsia than in the nonpregnant women (0.8 ⫾ 0.1 versus 1.0 ⫾ 0.1 cm2; p ⫽ 0.01) but similar in women with pre-eclampsia and pregnant women (0.9 ⫾ 0.1 cm2; p ⬎ 0.3). The study showed that women with pre-eclampsia have upper airway narrowing in both upright and supine postures. These changes could contribute to the upper airway resistance episodes during sleep in patients with pre-eclampsia, which may further increase their blood pressure. Keywords: snoring; pre-eclampsia; sleep
Pregnancy is associated with altered breathing during sleep. Snoring is more common in pregnant women, with frequencies of 14–23% compared with around 4% in nonpregnant women of similar age (1, 2). There is some evidence that maternal snoring is a poor prognostic factor for the mothers, who have a greater risk of hypertension and pre-eclampsia, and for the babies, who have lower Apgar scores and fetal growth retardation (2). Conversely, studies in patients with pre-eclampsia have suggested that they have increased upper airway resistance during sleep (3, 4). Sleep apnea can present in pregnancy and early case reports indicated that it might be associated with increased fetal risk (5, 6). The reason for the increased frequency of breathing disorders during sleep in pregnancy has not been established. Snoring results from narrowing of the upper airway during sleep (7), which could result either from sleep-specific changes in upper airway function or from changes in baseline upper airway caliber before sleep. In the population as a whole,
(Received in original form June 21, 2002; accepted in final form October 18, 2002) Supported by the Cunningham Trust. Correspondence and requests for reprints should be addressed to Professor Neil J. Douglas, M.D., Department of Medicine, Royal Infirmary, Edinburgh, EH3 9YW, Scotland, U.K. E-mail:
[email protected] Am J Respir Crit Care Med Vol 167. pp 137–140, 2003 Originally Published in Press as DOI: 10.1164/rccm.200206-590OC on October 31, 2002 Internet address: www.atsjournals.org
snorers tend to have narrower upper airways than nonsnorers even when awake (7). Thus, we have investigated the hypotheses that: (1 ) pregnancy results in upper airway narrowing; (2 ) pre-eclampsia is associated with more marked upper airway narrowing than occurs in normal pregnancy. METHODS Subjects Normal pregnancy. Fifty consecutive women in the third trimester of singleton pregnancies were approached at an antenatal clinic and invited to participate in the study and all agreed. All were healthy with no pre-existing illness. Pre-eclampsia. Thirty-seven consecutive patients with pre-eclampsia and singleton pregnancies admitted to the Simpson Memorial Maternity Pavilion were invited to participate in the study, and all agreed. Preeclampsia was defined as the presence of new hypertension (blood pressure ⬎ 140/90 or ⬎ ⫹30/⫹15 from booking blood pressure) with proteinuria (⬎ 0.3 g/24 hours). None of the women studied had any coexisting illness. Control subjects. Fifty healthy, nonpregnant women aged 18 to 41 years from the hospital staff, naive to the purpose of the study, agreed to be control subjects. All subjects gave written informed consent to the study, which had the approval of the local ethical advisory committee.
Protocol All subjects completed our in-house sleep questionnaire, which was supplemented to include information on the number of nights per week on which snoring was currently reported and weight prior to pregnancy. All had neck and waist circumferences, height, weight, and blood pressure measured and recorded. Upper airway caliber was measured in each subject using our previously described acoustic reflection technique (8–10). Measurements were made in the seated, supine, and left lateral recumbent positions. At least five satisfactory measurements were recorded in each subject in each position, and all traces recorded were stored on the computer. The traces were then made anonymous, randomized, and scored by a single individual blind to case status. This individual decided which of the traces were technically satisfactory, and then averaged the results. From the traces, measurements were made of oropharyngeal junction area (OPJ) (see Figure 1), mean pharyngeal area and mean pharyngeal volume as previously described (8–10). Percentage narrowing in airway caliber from the seated to supine posture was derived from the mean measurements.
Statistics
Comparisons were performed using analysis of variance, followed when appropriate by between group comparisons using the Student-Neuman-Keuls multiple comparison test. Results are presented as mean with SD or SEM. p Values of 0.05 or less were taken as significant.
RESULTS Subject Characteristics
The mean duration of pregnancy was 36 weeks (SD 3.5 weeks) in the pregnant group, and 36 weeks (SD 3.3 weeks) in the pre-eclampsia group. The pregnant women, women with preeclampsia, and control women did not differ in terms of age,
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tended (p ⫽ 0.06) to be narrower in the women with preeclampsia than in the pregnant women (Table 2). Lateral: There were no differences between groups in airway size when lying in the left lateral position. Percentage upper airway narrowing from the seated to supine posture: The upper airways of pregnant women narrowed more markedly when lying down than did those of either the normal women or women with pre-eclampsia (Table 2). Relationship of snoring to airway size and blood pressure: Across all groups snoring was associated with narrower mean supine OPJ areas (snorers 0.8, SE 0.04 cm2, nonsnorers 0.98, SE 0.04 cm2; p ⫽ 0.005) and supine mean pharyngeal areas (snorers 1.2, SE 0.05 cm2, nonsnorers 1.4, SE 0.05 cm2; p ⬍ 0.03). Snorers had higher systolic (snorers 128, SE 3 mm Hg, nonsnorers 114, SE 2 mm Hg; p ⫽ 0.001) and diastolic (snorers 82, SE 2 mm Hg, nonsnorers 74, SE 1.4 mm Hg; p ⫽ 0.002) blood pressures. Figure 1. Sample trace of upper airway using acoustic reflectance.
DISCUSSION The Upper Airway in Pre-eclampsia
The patients with pre-eclampsia had significantly narrower upper airways when seated than the nonpregnant women or those with normal pregnancies.When supine, patients with pre-eclampsia had significantly narrower upper airways than the nonpregnant women, with a trend toward also having narrower airways than the pregnant women (p ⬍ 0.06). These data were probably the result of difference in soft tissue deposition in the neck, as the women with pre-eclampsia had larger neck circumferences than both the nonpregnant women and those with normal pregnancies. This is most likely due to tissue edema, as most of the women with pre-eclampsia had significant edema. However, differential fat deposition could be a factor. Clarification of this question will require the use of different imaging techniques, and determination of whether this difference pre-existed or occurred during pregnancy will require prospective study. The narrower upper airway observed in women with preeclampsia is compatible with the observation of increased airflow limitation during sleep in pre-eclampsia (3, 4). These episodes may be associated with arousals and with surges in blood pressure (3, 11) in an already compromised circulatory system. Continuous positive airway pressure can reduce mean 24-hour blood pressure in patients with the obstructive sleep apnea/hypopnea syndrome (12, 13) where upper airway narrowing during sleep causes blood pressure surges. Preliminary reports indicate that in patients with pre-eclampsia, continuous positive airway pressure may improve both sleep and blood pressure control (3, 4). However, the role of continuous positive airway pressure in the management of pre-eclampsia requires further study.
height, or in pre-pregnancy weight or body mass index (Table 1). There was also no difference between the pregnant women and the control subjects in measured neck circumference on the day that upper airway dimensions were measured. However, the women with pre-eclampsia had significantly larger neck circumferences than the normal pregnant women (Table 1). Ten control women, ten pregnant women, and six patients with pre-eclampsia reported they did not know if they snored. Of those who reported whether or not they snored, 14% of control women, 28% of pregnant women, and 75% of the patients with pre-eclampsia reported that they snored on at least one night per week at the time of study. Upper Airway Dimensions
Analysis of variance showed significant differences in many upper airway dimensions between groups (Table 2). Subsequent comparison tests showed: Seated: The pregnant women had wider upper airways compared with the nonpregnant women (Table 2) as assessed by the OPJ, mean pharyngeal area and mean pharyngeal volume. Patients with pre-eclampsia had narrower pharynxes at the OPJ compared with both nonpregnant and pregnant women (Table 2) and smaller mean pharyngeal areas and volumes compared with the pregnant women. Supine: There there was no difference in upper airway caliber between pregnant and nonpregnant women in the supine posture. Women with pre-eclampsia had narrower OPJs and mean pharyngeal areas than the nonpregnant women. The OPJ also
TABLE 1. CHARACTERISTICS OF SUBJECTS STUDIED WITH STUDENT-NEUMAN-KEULS MULTIPLE COMPARISON TEST FOR MEASUREMENTS WHERE THERE WAS A SIGNIFICANT DIFFERENCE IN ANALYSIS OF VARIANCE
Nonpregnant (n ⫽ 50) Age, yr Height, m Weight prepregnancy, kg BMI prepregnancy, kg/m2 Neck circumference, cm
29 1.63 64 24 33
(6) (0.1) (10) (3) (2)
Pregnant (n ⫽ 50) 30 1.64 64 24 34
(6) (0.1) (16) (6) (2)
Pre-eclampsia (n ⫽ 37) 29 1.63 65 24 35
p Value
p Value
p Value
Nonpregnant versus Pregnant
Pregnant versus Pre-eclampsia
Nonpregnant versus Pre-eclampsia
p Value for ANOVA
— — — — 0.1
— — — — ⬍ 0.05
— — — — ⬍ 0.05
0.58 0.82 0.87 0.88 0.0001
(5) (0.1) (12) (4) (2)
Definition of abbreviations: ANOVA ⫽ analysis of variance; BMI ⫽ body mass index. Values presented are means ⫾ SD.
Izci, Riha, Martin, et al.: Upper Airway in Pregnancy
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TABLE 2. AIRWAY CALIBRE MEASURES WITH RESULTS OF THE STUDENT-NEUMAN-KEULS MULTIPLE COMPARISON TEST FOR MEASUREMENTS WHERE THERE WAS A SIGNIFICANT DIFFERENCE IN ANALYSIS OF VARIANCE
Upper airway: seated OPJ, cm2 Ap. Mean, cm2 Vp, cm3 Upper airway: supine OPJ, cm2 Ap mean, cm2 Vp, cm3 Upper airway: Lateral OPJ, cm2 Ap. mean, cm2 Vp, cm3 Change from the seated to supine posture OPJ (%) Ap mean (%) Vp (%)
Nonpregnant (n ⫽ 50)
Pregnant (n ⫽ 50)
Pre-eclampsia (n ⫽ 37)
1.1 (0.1) 1.6 (0.1) 15 (1)
1.3 (0.1) 1.8 (0.1) 19 (1)
0.9 (0.1) 1.4 (0.1) 13 (1)
1 (0.1) 1.4 (0.04) 14 (0.7)
0.9 (0.1) 1.3 (0.1) 13 (0.8)
0.8 (0.1) 1.2 (0.1) 12 (0.7)
1.1 (0.04) 1.5 (0.04) 14 (0.6)
1.0 (0.1) 1.5 (0.1) 15 (1.1)
1.0 (0.1) 1.4 (0.1) 14 (0.8)
4 (6) 5 (4) ⫺2 (6)
27 (3) 24 (3) 22 (5)
7 (5) 8 (4) 6 (6)
p Value
p Value
p Value
Nonpregnant versus Pregnant
Pregnant versus Pre-eclampsia
Nonpregnant versus Pre-eclampsia
p Value for ANOVA
0.01 0.01 0.01
0.01 0.08 0.23
0.0001 0.001 0.001
0.058 ⬎ 0.1
0.01 0.01
0.02 0.01 0.07
0.02 0.02 0.01 0.3 ⬎ 0.1
0.8 0.8 0.5 0.01 0.01 0.01
0.01 0.01 0.056
0.6 0.6 0.6
0.001 0.001 0.01
Definition of abbreviations: ANOVA ⫽ analysis of variance; Ap. mean ⫽ mean pharyngeal cross sectional area; OPJ ⫽ oropharyngeal junction; Vp ⫽ pharyngeal volume. Values presented are means ⫾ SE.
Effects of Pregnancy on the Upper Airway
This study shows that the upper airway in the third trimester of pregnancy is wider in the seated position but of similar caliber in the supine posture when compared with nonpregnant women. The pregnant women had a much larger decrease in airway caliber upon lying down. It is unclear how these results relate to the increased prevalence of snoring in pregnant women (1, 2). A similar supine upper airways caliber but larger percentage narrowing upon lying down has also been found in men compared with nonpregnant women (10), and men have a higher prevalence of snoring than women. The results reported in this study were obtained during wakefulness; during sleep, the loss of upper airway defense by dilating muscle activity could result in further airway narrowing in pregnant women, but this will need to be tested. The small increase in upper airway caliber in seated pregnant women could be due to hormonal changes or to increased activity of upper airway dilating muscles and will require further investigation Why did the pregnant women show greater upper airway narrowing upon lying down? As the neck diameters were not different with pregnancy, it seems unlikely that there was differential local mass loading directly on the upper airway. Functional residual capacity is decreased by 15–25% in pregnancy (14, 15) due to increased abdominal mass raising the diaphragm. In turn, the decreased functional residual capacity and tracheal shortening can produce upper airway narrowing (16–18), and this seems the most likely explanation. The limitations of this study include its cross-sectional design and potential selection biases between the groups of subjects. A cross-sectional study cannot prove cause and effect, but merely suggest causation if other known influences are excluded. Factors that may affect upper airway size include sex (10, 19, 20), age (10), obesity (10), familial factors (21), and sleep state (22, 23). The three groups were not different in terms of age or obesity before pregnancy. All groups were 98% white and drawn from the same Edinburgh population; thus, there is no reason to suggest any difference in familial factors. The control group was drawn from a staff rather than patient population. This is unlikely to have resulted in any significant bias, especially as the control subjects were kept naive to the hypothesis being tested until after
their measurements had been completed. Another limitation is the fact that the acoustic reflection technique can only measure upper airway size via the oral route and thus misses the retropalatal airway, which is often the site of the critical airway narrowing during sleep, at least in sleep apnea (24, 25). Nevertheless, the technique has been previously shown to be a useful tool to discriminate changes in upper airway size with sleep apnea (7, 26), snoring (7), obesity (10), age (10), and posture (10, 27). Furthermore, the measurements can only be performed in awake subjects; thus, care must be taken in extrapolating the results to differences, which may exist during sleep. There were also many comparisons done in the course of the statistical analysis: 108 in the main results (Table 2). However, the statistical approach used was conservative and the main findings showed a high degree of consistency within subjects between independently measured dimensions. Thus, we believe the main results reported are valid. This study shows airway narrowing in patients with preeclampsia, which may explain why such patients have increases in upper airways resistance with consequent rises in blood pressure during sleep periods. References 1. Loube DI, Poceta JS, Morales MC, Peacock MD, Mitler MM. Selfreported snoring in pregnancy association with fetal outcome. Chest 1996;109:885–889. 2. Franklin KA, Holmgren PA, Jonsson F, Poromaa N, Stenlund H, Svanborg E. Snoring, pregnancy-induced hypertension, and growth retardation of the fetus. Chest 2000;117:137–141. 3. Edwards N, Blyton DM, Kirjavainen T, Kesby GJ, Sullivan CE. Nasal continuous positive airway pressure reduces sleep-induced blood pressure increments in pre-eclampsia. Am J Respir Crit Care Med 2000;162: 252–257. 4. Connolly G, Razak AR, Hayanga A, Russell A, McKenna P, McNicholas WT. Inspiratory flow limitation during sleep in pre-eclampsia: comparison with normal pregnant and nonpregnant women. Eur Respir J 2001; 18:672–676. 5. Kowall J, Clark G, Nino-Murcia G, Powell N. Precipitation of obstructive sleep apnea during pregnancy. Obstet Gynecol 1989;74:453–455. 6. Joel-Cohen SJ, Schoenfeld A. Fetal response to periodic sleep apnea: a new syndrome in obstetrics. Eur J Obstet Gynecol Reprod Biol 1978; 8:77–81.
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