Restless Legs Syndrome is 2 to 3 times more common in pregnant women than in the general population.
- Symptoms become more common and often worsen as pregnancy progresses.
Most symptoms occur in the third trimester.
- Restless Legs Syndrome significantly complicates falling asleep, decreases sleep quality and causes daytime sleepiness.
- The aetiology of the syndrome is partially unclear, but iron deficiency anemia during pregnancy is a major risk factor.
- During pregnancy, non-medicated treatments are preferred. Adequate iron and folic acid intake must be ensured.
Restless Legs Syndrome (RLS), or Willis Ekbom disease (WED), is a neurosensory movement disorder that diminishes sleep and quality of sleep. Its aetiology is not yet fully understood, but the condition has been linked to low levels of dopamine in the brain and iron deficiency anemia. It is more common in women than in men. In the general population, the prevalence of the syndrome is between 5% and 15%, but during pregnancy the incidence increases and the symptoms become more severe.
How to diagnose Restless Legs Syndrome?
Symptoms of Restless Legs Syndrome include unpleasant sensations such as tingling, itching and burning sensations, especially in the lower limbs. Symptoms appear at rest and worsen towards evening and night. Walking, moving your body, or stretching your legs will usually give you a momentary relief of symptoms and therefore patients will feel a strong need to move their limbs. Symptoms range from mild to intolerable and impair the quality and quantity of sleep. The International Diagnostic Criteria for Restless Legs Syndrome developed by The International Restless Legs Study Group (TIRLSG) are presented in Table 1 as well as features to support diagnosis in Table 2.
Restless Legs Syndrome can be diagnosed clinically, without neurophysiological measurements. Electrolyte disturbances, peripheral neuropathy and vasculopathy, nerve impingement, and spinal radiation pains should be taken into account in differential diagnostics. Symptoms should also be distinguished from nocturnal leg cramps and postural numbness.
Etiology and risk factors of Restless Legs Syndrome
Restless Legs Syndrome distinguishes between primary and secondary forms. The primary form is often idiopathic, but in 40% of cases it has been found to have a genetic background.
The syndrome has been found to be related to changes in the central nervous system dopamine metabolism: Medicines that increase the amount or activity of dopamine alleviate the symptoms, and on the other hand, dopamine antagonists can worsen them. Symptoms follow a daily pattern similar to normal dopamine metabolism: dopamine levels and dopamine receptor activity are highest in the morning and lowest in the late evening.
Studies on the pathophysiology of Restless Legs Syndrome have shown an association with brain iron levels and metabolism. Iron acts as a cofactor in the production of tyrosine hydroxylase, which in turn regulates the conversion of levodopa to dopamine (Figure 1). Folate is also needed for the production of dopamine.
Studies have shown that restless legs syndrome is increasing in iron deficiency situations. During normal pregnancy, the need for iron and folate increases significantly. This contributes to the involvement of iron and folate deficiency in the pathophysiology of the syndrome during pregnancy.
Risk factors for Restless Legs Syndrome during pregnancy include obesity, high age, family history, smoking, alcohol usage, history of growth pain in childhood. The incidence of the syndrome has also been found to increase with increasing levels of estrogen. However, some studies have also shown conflicting results: for example, in a Swiss follow-up study, hemoglobin or estrogen levels did not correlate with the syndrome or pregnancy.
Prevalence of Restless Legs Syndrome during pregnancy
Restless Legs Syndrome during pregnancy is 2 to 3 times more common than in the general population. In studies, the prevalence has varied between 12 and 34%, mainly due to differences in diagnostic criteria. The incidence of symptoms increases as pregnancy progresses, peaking during the third trimester.
According to an Italian follow-up study, almost two-thirds of women did not start to develop their symptoms until after pregnancy. Symptoms often become more severe as the pregnancy progresses and during pregnancy. According to one study, of the women who did not have the syndrome before pregnancy, 13% had symptoms in the first trimester, 18% in the second, and 23% in the third. Researcher Suzuki found a clear link between Restless Legs Syndrome and pregnancy duration in a study of 16,000 women: symptoms occurred in 15% of the first and second trimester and 23% at the end of the last trimester. Similar results were also found in Researcher Sarberg’s prospective study of 500 women: 17% of the subjects had symptoms in the first trimester, 27% in the second and 30% in the third.
After childbirth, symptoms of primary Restless Legs Syndrome usually return to pre-pregnancy levels. Symptoms of pregnancy-induced syndrome usually disappear shortly after delivery. However, for some new patients, the disorder is prolonged: according to the Japanese study, 3% still had symptoms after one month, in the Italian study, 5% after six months, and in the Swedish study up to 31% after three years. This finding may explained by the fact that those suffering from symptoms are more likely to respond to queries. On the other hand, pregnancy symptoms may be indicative of an increased risk of the syndrome; according to one study, the risk was up to four times higher. Secondary Restless Legs Syndrome has been found to recur in subsequent pregnancies in approximately 30% of women.
The effect of Restless Legs Syndrome on the health of a pregnant woman
Restless Legs Syndrome significantly affects the quality of sleep of a pregnant mother. Uncomfortable sensations in the legs make it harder to fall asleep, the time to fall asleep is longer and the night’s sleep shortens. There are more symptoms of insomnia and daytime fatigue than healthy pregnant women. Lee and other researchers found that expecting mothers with restless legs syndrome had a longer sleep delay and a longer delay to the first phase of REM sleep than non-symptomatic expecting mother. Those suffering from the symptoms also had more depression. There is a proven link between Restless Legs Syndrome and the symptoms of depression, especially if the syndrome causes sleep disorders and
decrease in sleep quality.
Restless Legs Syndrome and snoring both increase during pregnancy and towards the end of pregnancy, and both reduce the quality of sleep. Sarberg and other researchers investigated their relationship in different stages of pregnancy. According to the study, snoring during the first trimester increased the incidence of Restless Legs Syndrome in all trimesters, second trimester snoring increased the incidence of the syndrome in the second and third trimester, but there was no association between third trimester snoring and the syndrome.
The cause of snoring and Restless Legs Syndrome is not clear. Typically, snoring during pregnancy is due to obstruction of the upper airways. Difficulty in breathing during sleep leads to a reduction in blood oxygen saturation and further peripheral hypoxia. Studies of the involvement of peripheral hypoxia and hypercapnia in the pathophysiology of Restless Legs Syndrome have shown that peripheral hypoxia is clearly associated with the occurrence of the syndrome.
Effect of restless legs on pregnancy, childbirth and neonatal prognosis
There is only limited research on the independent influence of Restless Legs Syndrome on the course of pregnancy and childbirth and the prognosis of the newborn. Syndrome worsens sleep quality and shortens sleep duration. In addition, symptoms are often at their worst in the third trimester, just before delivery.
High blood pressure and preeclampsia, premature births and C-sections have been found to be more common in patients with the syndrome than in asymptomatic patients. On the other hand, in the syndrome, the duration of pregnancy has been found to be shorter and the birth weight of the newborn child lower. Sleep disorders have also been found to prolong the duration of labor and increase pain awareness during labor.
Treatment of Restless Legs Syndrome during pregnancy
The goal of treatment for Restless Legs Syndrome is to relieve symptoms and improve sleep and quality of life. The expectant mother should be informed of the benign nature of the symptoms and the high rate of spontaneous recovery. In most cases, the symptoms are quite mild, and in this case, there are sufficient lifestyle guidelines for treatment: avoiding coffee, alcohol and tobacco and exercising regularly. Non-drug treatments include walking, stretching and massage of the feet, various relaxation techniques, thermal treatments such as a warm bath before bed. In addition, infrared light and pneumatic compression are recent treatment options.
If the patient’s iron stores are low as measured by ferritin, the preferred treatment is replacement iron therapy in combination with vitamin C and folic acid. In the most severe cases (S-ferritin <30 μg / l), administration of iron into a vein may be considered, but the assessment and implementation of treatment is a matter of specialist medical care. Oral or intravenous administration of magnesium may also be beneficial, although the International RLS Study Group (IRLSSG) considers research evidence to be insufficient to treat Restless Legs Syndrome with folic acid, magnesium, vitamins C, D, or E. If iron and vitamin C combination and folic acid replacement therapy are not effective, the patient should be referred to specialist medical care.
Dopamine agonists are the most effective drugs for relieving the symptoms of Restless Legs Syndrome in non-pregnant women, but their safety during pregnancy is limited and its use is not recommended. According to IRLSSG recommendations, carbidopa / levodopa may be used in the treatment of severe Restless Legs Syndrome.
Opioids (oxycodone) or benzodiazepines (clonazepam) can be used for very severe symptoms. However, they can cause fetal malformations, so treatment should be restricted to the second and third trimesters of pregnancy at the lowest possible dose. In addition, they can also cause withdrawal symptoms and breathing difficulties in a newborn baby if the treatment is used during the final pregnancy.
There is too little research to recommend the use of gabapentin during pregnancy. During breast-feeding, gabapentin can be used, because of its excretion in breast milk is only limited.
Summary of pregnancy and Restless Legs Syndrome
There is limited research on the effects of Restless Legs Syndrome on pregnancy, delivery, and newborn wellbeing, but it has been associated with at least preeclampsia, premature labor, and increased risk of caesarean section and lower birth weight. There is also limited experience of treating the syndrome during pregnancy, but often the symptoms are moderate and thus manageable by non-drug methods. Therefore, in order to avoid side effects, drug treatment should be limited to very severe symptoms.
1. An urge to move the legs usually but not always accompanied by or felt to be caused by uncomfortable and unpleasant sensations in the legs.
2. The urge to move the legs and any accompanying unpleasant sensations begin or worsen during periods of rest or inactivity such as lying down or sitting.
3. The urge to move the legs and any accompanying unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.
4. The urge to move the legs and any accompanying unpleasant sensations during rest or inactivity only occur or are worse in the evening or night than during the day.
5. The occurrence of the above features are not solely accounted for as symptoms primary to another medical or a behavioral condition (e.g., myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort, habitual foot tapping). Criteria through 1-5 must be met in order for the syndrome to be diagnosed.
- Walking brings quick and lasting relief to your symptoms
- The syndrome has occurred in the family
- Response to dopaminergic medication
- Intermittent limb movements during sleep or at night while awake