Among women with pregnancy-related RLS, around one third are already affected by RLS before pregnancy or already experienced the symptoms some time in their life [6]. Around 70–80% of these women report a worsening of RLS symptoms during pregnancy [6]. Considering the new onset cases, the incidence of RLS increases across pregnancy, with the highest rate reached in the third trimester, with an abrupt resolution of the symptoms occurring around the delivery, with very few cases continuing to be affected even in the puerperium [6, 10]. While the short-term prognosis of RLS is benign, the long-term one seems to be less favorable. After a follow up of approximately 7 years, Cesnik et al. [12] demonstrated that women who suffered of RLS during pregnancy have a 4 fold higher risk to develop an “idiopathic” RLS form compared to women who did not experience a pregnancy-related RLS. Besides, more than 60% of women who experienced RLS during pregnancy suffered of a relapse of RLS during a second pregnancy, while this percentage resulted of only around 3% for women who did not refer symptoms in a previous pregnancy [12]. Later on, Sarberg et al. [13], although after a shorter follow up of 3 years, substantially confirmed these results. The results obtained by these two long-term prospective studies evidently suggest a genetic predisposition behind the pregnancy RLS form [14].

The mechanism behind the pregnancy-related form is unknown. Few pathogenetic hypotheses have been postulated and concern the possible role of sexual hormones and iron deficiency during pregnancy [15, 16]. Particularly during the third trimester of pregnancy, when RLS symptoms are worst, estradiol, prolactin, and progesterone reach the highest blood level, and ferritin decreases at its minimum level [11]. Although with a pulsatile trend, prolactin keeps to stay at high levels also during puerperium, while estrogens and progesterone fall down quite dramatically around delivery, together with RLS symptoms [17]. Iron storage restore much gradually after delivery following a trend less comparable with RLS symptoms [18]. No solid experimental data are available in sustaining any role of the above-mentioned factors. The general idea consists in a genetic predisposition to the disease, while pregnancy may act as a precipitating factor for the symptoms appearance [11]. The genetic theory is supported by three findings: first, almost all pregnant women with a preexisting form of RLS get worst during pregnancy [6]; second, women with new pregnancy-related RLS have a high chance to develop an idiopathic not pregnancy-related RLS in the future [12, 13]; lastly, the chances to have a close familiar member affected by RLS is much higher in pregnant women with RLS than in pregnant women not affected [6, 19, 20]. The genetic hypothesis could be tested, and a study on the frequency of the already known allelic variants associated with idiopathic RLS is warrant [14, 21].

Other factors found to be associated with RLS during pregnancy are: leg cramps [6, 9], snoring [6] and daytime somnolence [6, 9, 22]. More uncertain is the role of age, smoking, body max index, and iron deficiency; herein, some studies found a significant differences in the above-listed parameters between pregnant with and without RLS [6, 19, 20, 22, 23]. Interesting is the influence of previous pregnancies on the chance to develop a pregnancy-related RLS form. Women who experienced RLS during a previous pregnancy have a higher risk for relapse in a following pregnancy [12]. The role of multiparity per sè is less clear. In more than few studies, the number of previous pregnancies was not a significant risk factor for RLS during the investigated pregnancy. However, a large epidemiological investigation found that multiparity per sè is a risk factor for the idiopathic, not pregnancy related, RLS form [24].

It is well known that idiopathic RLS has a significant impact on quality of life [25]. The impact of RLS is mainly mediated by the evening/night restlessness which limits all activities that require rest and reduces duration and quality of sleep. In a long-term prospective, RLS has a clear impact also on mood [26] and cognitive functions [27], while its role as a cardiovascular risk is likely but still under investigation [28–30]. Of course, the impact of RLS depends on the severity of symptoms, including its frequency and duration. Only few studies assessed the severity of RLS during pregnancy, finding unexpected results showing that in around 50% of women the standard RLS severity scale scored their symptoms as severe or very severe [10]. Prevalence of insomnia among pregnant women with RLS is higher than in women free of RLS [6]. In turn, a pour sleep quality during pregnancy is associated with a lower level of quality of life and possible consequences on pregnancy outcome. Preterm birth is more prevalent in women with pour quality of sleep during pregnancy compared to women without sleep complaint [31, 32]. Ramirez et al. [33] firstly found a significant association between RLS during pregnancy and pre-eclampsia. The other relevant pregnancy-related complications such as gestation diabetes, gestational hypertension, and eclampsia need still to be investigated in their relationship with RLS [34–36].

Recent data suggest that RLS during pregnancy significantly increases the risk of perinatal depression, which are common and important complications affecting around 10–15% of pregnant women in different level of severity [37]. When untreated, perinatal depression increases the risk of preterm delivery, smoking and substance use, shortening of breast feed, abusive behavior toward children, and can have significant negative effects on partner’s relationship and emotional and cognitive development of infants [38].

The problem of RLS management during pregnancy has been underestimated for a long time, this was due to three important aspects: the pour knowledge of the syndrome, especially among gynecologists, which led to under diagnose the disease; the frequent transiency of symptoms which usually disappear around delivery, that led to consider RLS as a “normal” pregnancy-related phenomenon not well distinguishable from others such as ankle edema, fatigue, or insomnia, and therefore to be endured with patience by women until the end of pregnancy; the false belief of the low severity of symptoms. Indeed, symptoms can be severe with significant impact on women and potentially on the outcome of pregnancy, and, more importantly, even when RLS is mild and does not need to be treated, it should be recognize and well explained to women, who often are simply worried about their symptoms. Concerning this latter issue, the first and crucial step for a physician is to perform an accurate diagnosis of RLS. The recommendation is to use always the standard diagnostic criteria currently valid for idiopathic RLS [39]. There are no reasons to consider these criteria inadequate for pregnancy-related RLS. In both, idiopathic and pregnancy-related forms, the anatomical distribution and the other main features of symptoms are similar and a possible genetic vulnerability for RLS is suggested also for the pregnancy-related form, which is often associated with a positive family history and represents a risk for the onset of an idiopathic RLS in the future [12, 40]. The last version of the diagnostic criteria included a new fifth criterion specifically established to limit the misdiagnosis of the disease, reminding to always rule out possible mimics [41]. This is particularly necessary during pregnancy, in order to discriminate between true RLS and other frequent complications such as positional discomfort, leg cramps, venous stasis, ankle edema, and compression neuropathies [42]. However, should be taken into account that all the above-mentioned conditions may also co-occur with a real RLS.

The second step, after the recognition of RLS, is to quantify the severity of symptoms and their impact on the quality of life of women. Using the current definition of RLS, symptoms should be considered as clinically relevant when “significant distress or impairment in social, occupational, educational, or other important areas of functioning by its impact on sleep, mood, cognition, health, daily activities, behavior, or energy/vitality” [41]. Also during pregnancy, the severity of symptoms can be measured using the standard RLS rating scale validated by the international RLS study group [43]. This instrument consists in a 10 questions, self-administered questionnaire, which produces a final score ranging from 0 to 40, where a score between 10 and 20 corresponds to “moderate,” from 20 to 30 to “severe” and over 30 to “very severe.” The frequency of occurrence of symptoms is another relevant feature to be considered in the management of RLS during pregnancy; a suggested threshold for a clinical significance is twice per week.