Keywords Body mass index - Epworth Sleepiness Scale - excessive daytime sleepiness - Pitts - restless legs syndrome - the International Restless Legs Syndrome Study Group
Introduction
Restless leg syndrome (RLS), also known as Willis-Ekbom Disease, is a sensorimotor sleep disorder that causes discomfort or a “creepy-crawly” sensation in the legs during rest and is relieved by activity. The clinical course of RLS is variable from mild to severe, but the symptoms tend to fluctuate over time. The disorder could be either primary or secondary. Primary RLS is idiopathic, and 42% of patients have a first-degree relative with this disorder.[1 ],[2 ] Secondary RLS is accompanied by pregnancy or other medical conditions such as renal insufficiency, iron deficiency anemia, Parkinson's disease, and diabetic neuropathy.[3 ]
The pathophysiology of the syndrome is thought to be related to iron deficiency in the brain that affects the dopaminergic pathways.[4 ],[5 ] There are also assumptions that genetics could play a role in the etiology.[2 ] The disease, which could be autosomal, recessive, or dominant, affects the chromosomes 12q, 14q, 9p, 20p, 4q, and 17p2.[2 ],[6 ] The availability of serotonin transporters in the brainstem could also contribute to the disease; the less serotonin transporters there are, the more serotonin transmission there is in the brain, and this exacerbates RLS symptoms.[7 ]
The diagnosis of RLS depends on four well-defined criteria: (i) the urge to move the legs whether it was with or without the abnormal sensation, (ii) worsening of symptoms with rest, (iii) improvement with activity, and (iv) worsening of symptoms at night.[8 ]
The prevalence of restless leg syndrome is variable, and it ranges from 1% to 17%.[9 ],[10 ],[11 ],[12 ],[13 ],[14 ],[15 ],[16 ],[17 ],[18 ],[19 ] A local study among Saudi participants suggests that the prevalence of RLS in adult Saudis attending healthcare is 5.2%, while it is 8.4% among middle-age school employees and 14.7% among the general population.[18 ],[20 ],[21 ]
The prevalence of RLS in pregnancy is reported to range from 11 to 30%.[10 ],[19 ],[22 ],[23 ],[24 ],[25 ],[26 ],[27 ],[28 ],[29 ],[30 ] RLS is most common in the third trimester of pregnancy, and it usually improves after delivery.[28 ],[31 ] However, this condition has not been described in the pregnant Saudi population. This will be the first study of its kind to determine the prevalence of RLS in the pregnant population and the risk factors for RLS among pregnant Saudi women.
Methods
A cross-sectional study was conducted to assess the presence of restless leg syndrome in consecutive pregnant women who attended obstetric clinics at King Abdul-Aziz Medical City in Riyadh (KAMC-Riyadh) between June and November 2014. This study was reviewed and approved by the Institutional Review Board. The coinvestigator conducted the study by conducting personal interviews with the participants, using prestructured questionnaires. These questionnaires include demographic information, characteristics such as age, gender, educational level, duration of pregnancy, number of pregnancies, and parities. Furthermore, we asked about associated comorbidities. The diagnosis of RLS was based on the four criteria designated by the International RLS Study Group (IRLSSG).[8 ]
These four diagnostic criteria are: (i) A desire to move the extremities usually associated with some definable discomfort, (ii) Motor restlessness, (iii) Worsening of symptoms while at rest with at least temporary relief by activity, and (iv) Worsening of symptoms later in the day or at night. A diagnosis of RLS is confirmed only in the presence of all four criteria. We also assessed RLS severity using the IRLSSG.[32 ] The RLS severity was defined by 10 items with each rated on a scale of 5 points: None to very severe. We also assessed daytime sleepiness using the Epworth Sleepiness Scale (ESS). An ESS score of more than 10 would indicate excessive daytime sleepiness (EDS).[33 ],[34 ] Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI).[35 ] These questionnaires have been validated and used in previous studies.[18 ],[20 ],[21 ],[34 ],[36 ] Exclusion criteria were pregnant women with a history of neuropathy and a prepregnancy diagnosis of RLS or other sleep disorders. The sample size was calculated according to a precision of 2%, prevalence of 5%[18 ] and 95% confidence interval (CI), while the minimum required sample size was 457 subjects. A total of 517 of 600 pregnant women gave informed consent and enrolled in the analysis, with a response rate of 86%.
Statistical analysis
The data were presented as the mean and standard deviation or number and percent, as appropriate. To assess the possible influence of demographic and other variables on the prevalence of RLS, we used either the unpaired t-test or the Mann–Whitney U-test for nonparametric data, as appropriate. A stepwise multivariate logistic regression analysis was used to assess the risk of RLS while controlling for other characteristics. The variables associated at P < 0.05 level in bivariate analysis were included in the final multivariate model.
Results
The sample mean age was 30.11 ± 5.42 years (age range: 17–47 years) with 58% of participants younger than 30 years of age and 37% in the 31–39 year age group. The mean ESS was 7.8 ± 4.8 (score range: 0–24). The mean PSQI was 42.4 ± 10.4 (score range: 4–72).
Education-wise, 83% of the patients had high school or higher education. The majority of the participants were in the third trimester (72%) of pregnancy. Regular and daily tea and coffee intake was reported as 48% and 75%, respectively. The most common comorbidities reported were anemia 19%, asthma 11%, diabetes 7%, and hypertension 5%, with other demographic characteristics shown in [Table 1 ].
Table 1
Sample characteristics and restless leg syndrome among pregnant Saudi women
Characteristics
Overall
No
Yes
P
*Significant at α=0.05. DM: Diabetes mellitus, HTN: Hypertension, EDS: Excessive daytime sleepiness, PSQI: Pittsburgh Sleep Quality Index, SD: Standard deviation
Demographic (mean±SD) Age (17-47 years)
30.l±5.4
30.l±5.4
30.l±5.6
0.947
Education level university or more, n (%) No
236 (46.9)
l87 (79.2)
49 (20.8)
0.573
Yes
267 (53.l)
206 (77.2)
6l (22.8)
Co-morbidities and potential risk factors, n (%) Coffee intake No
l28 (24.8)
l04 (8l.3)
24 (l8.8)
0.42l
Yes
389 (75.2)
303 (77.9)
86 (22.l)
Tea intake No
268 (51.8)
2l7 (8l)
5l (l9)
0.l95
Yes
249 (48.2)
l90 (76.3)
59 (23.7)
Third trimester No
143 (27.7)
l23 (86)
20 (l4)
0.0l2*
Yes
374 (72.3)
284 (75.9)
90 (24.l)
Obese
No
238 (47.3)
l85 (77.7)
53 (22.3)
0.757
Yes
265 (52.7)
209 (78.9)
56 (2l.l)
Abortion
No
234 (55.2)
l85 (79.l)
49 (20.9)
0.9l7
Yes
190 (44.8)
l5l (79.5)
39 (20.5)
DM
No
482 (93.2)
380 (78.8)
l02 (2l.2)
0.8l3
Yes
35 (6.8)
27 (77.l)
8 (22.9)
HTN
No
493 (95.4)
39l (79.3)
l02 (20.7)
0.l39
Yes
24 (4.6)
l6 (66.7)
8 (33.3)
Depression
No
502 (97.1)
397 (79.l)
l05 (20.9)
0.332
Yes
15 (2.9)
l0 (66.7)
5 (33.3)
Bronchial asthma No
462 (89.4)
369 (79.9)
93 (20.l)
0.065
Yes
55 (10.6)
38 (69.l)
l7 (30.9)
Gravida (1-18)
3.8±2.6
3.8±2.5
4±2.9
0.44l
(mean±SD) Parity (0-16)
3±2
2.9±2
3.2±2.3
0.26
(mean±SD) Symptoms of sleep disorders, n (%) EDS No
351 (67.9)
285 (8l.2)
66 (l8.8)
0.046*
Yes
166 (32.l)
l22 (73.5)
44 (26.5)
Insomnia
No
371 (71.8)
3l7 (85.4)
54 (l4.6)
0.00l*
Yes
l46 (28.2)
90 (6l.6)
56 (38.4)
PSQI
Good sleep
95 (18.4)
86 (90.5)
9 (9.5)
0.002*
Poor sleep
422 (81.6)
32l (76.l)
l0l (23.9)
Berlin Low risk
325 (62.9)
266 (8l.8)
59 (l8.2)
0.024*
High risk
192 (37.l)
l4l (73.4)
5l (26.6)
The prevalence of RLS was 21.3% (95% CI: 17.83%–25.06%). As shown in [Figure 1 ], RLS symptoms were more common among women in the third trimester (24.1%) compared to the second (14.3%) or first trimester (13.6%), P = 0.012. When we compared the risk factors and clinical characteristics of participants with RLS to those without, there was no significant difference regarding age, number of pregnancies, or educational level. There was no significant association between RLS and gravid P = 0.441 or parities P = 0.26. We also did not find any association between drinking habit of coffee or tea and RLS P = 0.421 and 0.195, respectively. There was also no association between RLS and other medical problems; obesity, diabetes, hypertension, depression or age, P = 075, 0.813, 0.139, 0.332, 0.94, respectively.
Figure 1: Restless legs syndrome in relation to pregnancy term
Poor sleep quality as measured by PSQI and EDS as measured by ESS (>10) were significantly high among pregnant women with RLS, 23.9% (P = 0.002) and 26.5% (P = 0.046) [Figure 2 ] and [Figure 3 ].
Figure 2: Restless legs syndrome in relation to sleep quality
Figure 3: Restless legs syndrome in relation to risk for excessive daytime sleepiness
The stepwise multivariate logistic model [Table 2 ] identified insomnia (odds ratio [OR]: 3.6, 95% CI: 2.167–6.017, P = 0.001), and poor sleep quality (OR: 4.9, 95% CI: 1.473–16.454, P = 0.010) were associated with RLS. [Table 3 ] shows that RLS severity was associated with bronchial asthma (OR: 4.3, 95% CI: 1.130–16.684, P = 0.032).
Table 2
Factors associated with restless leg syndrome among pregnant Saudi women (n=517)
Reference
Univariate analysis
Multivariate analysis
P
OR
95% CI for OR
P
OR
95% CI for OR
*Significant at α=0.05. DM: Diabetes mellitus, HTN: Hypertension, EDS: Excessive daytime sleepiness, OR: Odds ratio, CI: Confidence interval
Age
0.947
1.0
0.961-1.038
Gravida
0.441
1.0
0.948-1.131
Parity
0.260
1.1
0.954-1.189
Third trimester
No
0.012*
1.9
1.149-3.307
Obese
No
0.757
0.9
0.612-1.43
University education or more
No
0.573
1.1
0.739-1.728
Coffee intake
No
0.421
1.2
0.743-2.037
Tea intake
No
0.195
1.3
0.866-2.016
Abortion
No
0.917
1.0
0.608-1.564
DM
No
0.813
1.1
0.487-2.503
HTN
No
0.139
1.9
0.798-4.603
Depression
No
0.332
1.9
0.633-5.65
Bronchial asthma
No
0.065
1.8
0.959-3.285
EDS
No
0.046*
1.6
1.007-2.41
Insomnia
No
0.001*
3.7
2.35-5.678
0.001*
3.6
2.167-6.017
Poor sleep
No
0.002*
3.0
1.46-6.19
Berlin
No
0.024*
1.6
1.064-2.499
0.010*
4.9
1.473-16.454
Table 3
Factors associated with severity of restless leg syndrome among pregnant Saudi women with restless leg syndrome (n=110)
Reference
Univariate analysis
Multivariate analysis
P
OR
95% CI for OR
P
OR
95% CI for OR
*Significant at α=0.05. DM: Diabetes mellitus, HTN: Hypertension, EDS: Excessive daytime sleepiness, OR: Odds ratio, CI: Confidence interval
Age
0.864
1.0
0.929-1.064
Gravida
0.880
1.0
0.857-1.141
Parity
0.966
1.0
0.836-1.206
Third trimester
No
0.347
1.6
0.598-4.303
Obese
No
0.337
1.5
0.68-3.094
University
No
0.780
1.1
0.523-2.369
Coffee intake
No
0.776
0.9
0.348-2.198
Tea intake
No
0.930
1.0
0.455-2.054
Abortion
No
0.942
1.0
0.444-2.398
DM
No
0.055
8.0
0.954-67.78
HTN
No
0.451
1.8
0.401-7.798
Depression
No
0.197
4.3
0.467-39.97
Bronchial asthma
No
0.022*
4.0
1.225-13.34
0.032*
4.3
1.130-16.684
EDS
No
0.506
1.3
0.601-2.804
Insomnia
No
0.152
1.7
0.816-3.716
Poor sleep
No
0.107
3.8
0.751-19.15
Berlin
No
0.392
1.4
0.653-2.963
Discussion
The reported prevalence of RLS in pregnancy varies and ranges from 1% to 30%.[10 ],[19 ],[22 ],[23 ],[24 ],[25 ],[28 ],[29 ],[31 ] The variation in reported prevalence in the literature is due to various factors including study populations, ethnicity, and methodology used to collect information, diagnostic criteria used for the definition of RLS, and the gestational age at study time.
Significantly, the number of criteria used for the diagnosis of RLS also differed among studies.[10 ],[19 ],[22 ],[23 ],[24 ],[25 ],[26 ],[27 ],[28 ],[29 ],[30 ] The prevalence of RLS in our study was found to be 21.3% which is similar in range to other published studies. A study from Turkey reported a prevalence of 10%,[24 ] while a study from Pakistan [19 ] reported a prevalence of 30%. In this study, RLS was 13.6% in the first trimester, 14.3% in the second, and 24.1% in the third, which is similar to many other studies.[23 ],[28 ],[37 ],[38 ]
A potential mechanism for the higher prevalence of RLS in pregnancy may be threefold to fourfold increase in iron requirements in pregnancy.[10 ],[27 ] As the mother is the sole source of nutrients to the fetus, the placenta upregulates its iron transfer systems to maintain an adequate supply for the fetus, which often occurs at the expense of the mother's stores. This upregulation is more pronounced under conditions of maternal iron deficiency. Iron deficiency in the brain has been demonstrated in MRI studies with RLS patients, where reduced cerebrospinal fluid concentrations of ferritin and transferrin have also been found.[4 ],[39 ] Multiple gravid and parties associated with risk for anemia and therefore risk of developing RLS.[40 ] In our sample, 82.4% of the women had multiple pregnancies, but we did not find any association between number of gravid or parities and RLS. This could be because all participants were followed at antenatal care from early pregnancy and any commodities include anemia identified and treated early. However, the diagnosis of anemia in our study was not confirmed by laboratory tests and only based on history taken from the patients and iron supplement information. Therefore, we do not include anemia as a risk factor for RLS in our participants. In this study, age has no effect on the prevalence of RLS which similar to our previous study in general population where age has no effect on the prevalence of RLS.[21 ] On concurrence with our previous study in general population in this study, we did not find any association between coffee, tea intake, diabetes, hypertension, obesity, and asthma.[21 ]
There are other impacts of RLS on quality of sleep in our study. Some women with RLS reported higher sleep latency, EDS, lower total sleep time, frequent insomnia, and poor sleep quality as measured by PSQI, as compared with unaffected pregnant subjects.[27 ],[31 ],[37 ] In our study, we found that 23.9% of pregnant women with RLS had poor quality of sleep. This is similar to other studies but is much lower than the study conducted by Chen et al. among the Taiwan population.[31 ] Sleep disruption or deprivation during pregnancy is considered a significant risk factor for the occurrence of mood disturbances and recurrence of depression.[41 ],[42 ],[43 ] However, we did not assess for depression in this study, as this was beyond the scope of our study.
The strength of our current study is the large number of patients, an interview-based data collection according to international RLS standards, and being the first study of its kind in the pregnant Saudi population. We also recognized the potential weakness of being a single-center study as well as the lack of a control group (e.g., nonpregnant women population). Early detection and adequate treatment of severe RLS is very important to prevent maternal discomfort, poor sleep, and possible health risks. The questionnaire method is a simple, reliable diagnostic tool for diagnosis of RLS.
Conclusion
RLS occurs in two of ten pregnant women visiting obstetric clinics at KAMC-Riyadh and is associated with insomnia and poor sleep quality. Future studies are needed to explore the causality of these associations.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
