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Restless legs syndrome/Willis-Ekbom disease during pregnancy and lactation

Author
Daniel L Picchietti, MD
Section Editor
Alon Y Avidan, MD, MPH
Deputy Editor
April F Eichler, MD, MPH

INTRODUCTION

Restless legs syndrome, also known as Willis-Ekbom disease (RLS/WED), is very common during pregnancy, affecting approximately one in five women at some point during the course of their pregnancy. It varies widely in severity, from a minor nuisance in some women to severe, disruptive symptoms in others. Symptoms tend to peak during the third trimester and remit or markedly improve after delivery.

RLS/WED commonly impacts sleep during pregnancy, and emerging data indicate that RLS/WED is associated with increased rates of gestational hypertension, preeclampsia, cesarean delivery, and depressed mood [1-5].

This topic will review aspects of the diagnosis and treatment of RLS/WED that are unique to pregnancy. Clinical features, diagnosis, and treatment of RLS/WED in the general population are discussed elsewhere. (See "Clinical features and diagnosis of restless legs syndrome/Willis-Ekbom disease and periodic limb movement disorder in adults" and "Treatment of restless legs syndrome/Willis-Ekbom disease and periodic limb movement disorder in adults" and "Restless legs syndrome/Willis-Ekbom disease and periodic limb movement disorder in children".)

PREVALENCE AND RISK FACTORS

The prevalence of restless legs syndrome/Willis-Ekbom disease (RLS/WED) during pregnancy is two- to threefold higher than the prevalence in the general population [6-8]. RLS/WED affects approximately 15 to 25 percent of pregnant women in Western countries and a somewhat lower proportion in most Asian countries, where general population rates are typically lower [6].

The majority of cases are of new onset during pregnancy, with preexisting RLS/WED accounting for 4 to 33 percent of cases [1,7,9-13]. Risk factors for RLS/WED during pregnancy include preexisting RLS/WED, a family history of RLS/WED, RLS/WED during a prior pregnancy, and low ferritin [9,12,14].

                         

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Literature review current through: Nov 2016. | This topic last updated: Wed Nov 04 00:00:00 GMT+00:00 2015.
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References
Top
  1. Vahdat M, Sariri E, Miri S, et al. Prevalence and associated features of restless legs syndrome in a population of Iranian women during pregnancy. Int J Gynaecol Obstet 2013; 123:46.
  2. Ramirez JO, Cabrera SA, Hidalgo H, et al. Is preeclampsia associated with restless legs syndrome? Sleep Med 2013; 14:894.
  3. Lee KA, Zaffke ME, Baratte-Beebe K. Restless legs syndrome and sleep disturbance during pregnancy: the role of folate and iron. J Womens Health Gend Based Med 2001; 10:335.
  4. Wesström J, Skalkidou A, Manconi M, et al. Pre-pregnancy restless legs syndrome (Willis-Ekbom Disease) is associated with perinatal depression. J Clin Sleep Med 2014; 10:527.
  5. Ma S, Shang X, Guo Y, et al. Restless legs syndrome and hypertension in Chinese pregnant women. Neurol Sci 2015; 36:877.
  6. Picchietti DL, Hensley JG, Bainbridge JL, et al. Consensus clinical practice guidelines for the diagnosis and treatment of restless legs syndrome/Willis-Ekbom disease during pregnancy and lactation. Sleep Med Rev 2015; 22:64.
  7. Alves DA, Carvalho LB, Morais JF, Prado GF. Restless legs syndrome during pregnancy in Brazilian women. Sleep Med 2010; 11:1049.
  8. Facco FL, Kramer J, Ho KH, et al. Sleep disturbances in pregnancy. Obstet Gynecol 2010; 115:77.
  9. Sikandar R, Khealani BA, Wasay M. Predictors of restless legs syndrome in pregnancy: a hospital based cross sectional survey from Pakistan. Sleep Med 2009; 10:676.
  10. Uglane MT, Westad S, Backe B. Restless legs syndrome in pregnancy is a frequent disorder with a good prognosis. Acta Obstet Gynecol Scand 2011; 90:1046.
  11. Minar M, Habanova H, Rusnak I, et al. Prevalence and impact of restless legs syndrome in pregnancy. Neuro Endocrinol Lett 2013; 34:366.
  12. Shang X, Yang J, Guo Y, et al. Restless legs syndrome among pregnant women in China: prevalence and risk factors. Sleep Breath 2015; 19:1093.
  13. Miri S, Rohani M, Vahdat M, et al. Presenting features of idiopathic versus secondary restless legs syndrome in pregnancy. Iran J Neurol 2014; 13:241.
  14. Neyal A, Senel GB, Aslan R, et al. A prospective study of Willis-Ekbom disease/restless legs syndrome during and after pregnancy. Sleep Med 2015; 16:1036.
  15. Trotti LM, Bhadriraju S, Rye DB. An update on the pathophysiology and genetics of restless legs syndrome. Curr Neurol Neurosci Rep 2008; 8:281.
  16. Earley CJ, Connor J, Garcia-Borreguero D, et al. Altered brain iron homeostasis and dopaminergic function in Restless Legs Syndrome (Willis-Ekbom Disease). Sleep Med 2014; 15:1288.
  17. Manconi M, Ulfberg J, Berger K, et al. When gender matters: restless legs syndrome. Report of the "RLS and woman" workshop endorsed by the European RLS Study Group. Sleep Med Rev 2012; 16:297.
  18. Pereira JC Jr, Rocha e Silva IR, Pradella-Hallinan M. Transient Willis-Ekbom's disease (restless legs syndrome) during pregnancy may be caused by estradiol-mediated dopamine overmodulation. Med Hypotheses 2013; 80:205.
  19. Minár M, Košutzká Z, Habánová H, et al. Restless legs syndrome in pregnancy is connected with iron deficiency. Sleep Med 2015; 16:589.
  20. Hübner A, Krafft A, Gadient S, et al. Characteristics and determinants of restless legs syndrome in pregnancy: a prospective study. Neurology 2013; 80:738.
  21. Neau JP, Porcheron A, Mathis S, et al. Restless legs syndrome and pregnancy: a questionnaire study in the Poitiers District, France. Eur Neurol 2010; 64:268.
  22. Kızılırmak A, Timur S, Kartal B. Insomnia in pregnancy and factors related to insomnia. ScientificWorldJournal 2012; 2012:197093.
  23. Manconi M, Govoni V, De Vito A, et al. Pregnancy as a risk factor for restless legs syndrome. Sleep Med 2004; 5:305.
  24. Goodman JD, Brodie C, Ayida GA. Restless leg syndrome in pregnancy. BMJ 1988; 297:1101.
  25. Cesnik E, Casetta I, Turri M, et al. Transient RLS during pregnancy is a risk factor for the chronic idiopathic form. Neurology 2010; 75:2117.
  26. Sevim S, Dogu O, Kaleagasi H, et al. Correlation of anxiety and depression symptoms in patients with restless legs syndrome: a population based survey. J Neurol Neurosurg Psychiatry 2004; 75:226.
  27. Picchietti D, Winkelman JW. Restless legs syndrome, periodic limb movements in sleep, and depression. Sleep 2005; 28:891.
  28. Winkelmann J, Prager M, Lieb R, et al. "Anxietas tibiarum". Depression and anxiety disorders in patients with restless legs syndrome. J Neurol 2005; 252:67.
  29. Lee HB, Hening WA, Allen RP, et al. Restless legs syndrome is associated with DSM-IV major depressive disorder and panic disorder in the community. J Neuropsychiatry Clin Neurosci 2008; 20:101.
  30. Cho SJ, Hong JP, Hahm BJ, et al. Restless legs syndrome in a community sample of Korean adults: prevalence, impact on quality of life, and association with DSM-IV psychiatric disorders. Sleep 2009; 32:1069.
  31. Winkelman JW, Finn L, Young T. Prevalence and correlates of restless legs syndrome symptoms in the Wisconsin Sleep Cohort. Sleep Med 2006; 7:545.
  32. Allen RP, Picchietti DL, Garcia-Borreguero D, et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med 2014; 15:860.
  33. American Academy of Sleep Medicine. International Classification of Sleep Disorders, 3rd ed, American Academy of Sleep Medicine, Darien, IL 2014.
  34. Walters AS, LeBrocq C, Dhar A, et al. Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 2003; 4:121.
  35. Hening WA, Allen RP, Washburn M, et al. The four diagnostic criteria for Restless Legs Syndrome are unable to exclude confounding conditions ("mimics"). Sleep Med 2009; 10:976.
  36. Ramoz LL, Patel-Shori NM. Recent changes in pregnancy and lactation labeling: retirement of risk categories. Pharmacotherapy 2014; 34:389.
  37. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation, 9th ed, Lippincott Williams & Wilkins, Philadelphia 2011.
  38. Aukerman MM, Aukerman D, Bayard M, et al. Exercise and restless legs syndrome: a randomized controlled trial. J Am Board Fam Med 2006; 19:487.
  39. Deslandes A, Moraes H, Ferreira C, et al. Exercise and mental health: many reasons to move. Neuropsychobiology 2009; 59:191.
  40. Giannaki CD, Sakkas GK, Karatzaferi C, et al. Effect of exercise training and dopamine agonists in patients with uremic restless legs syndrome: a six-month randomized, partially double-blind, placebo-controlled comparative study. BMC Nephrol 2013; 14:194.
  41. Koltyn KF, Schultes SS. Psychological effects of an aerobic exercise session and a rest session following pregnancy. J Sports Med Phys Fitness 1997; 37:287.
  42. Centers for Disease Control and Prevention. Physical Activity Guidelines for Americans. 2008. www.cdc.gov/physicalactivity/everyone/guidelines/adults.html (Accessed on February 22, 2014).
  43. Garcia-Borreguero D, Stillman P, Benes H, et al. Algorithms for the diagnosis and treatment of restless legs syndrome in primary care. BMC Neurol 2011; 11:28.
  44. Gamaldo CE, Earley CJ. Restless legs syndrome: a clinical update. Chest 2006; 130:1596.
  45. Yang C, White DP, Winkelman JW. Antidepressants and periodic leg movements of sleep. Biol Psychiatry 2005; 58:510.
  46. Rottach KG, Schaner BM, Kirch MH, et al. Restless legs syndrome as side effect of second generation antidepressants. J Psychiatr Res 2008; 43:70.
  47. Jones CR. Diagnostic and management approach to common sleep disorders during pregnancy. Clin Obstet Gynecol 2013; 56:360.
  48. Delgado Rodrigues RN, Alvim de Abreu E Silva Rodrigues AA, Pratesi R, Krieger J. Outcome of restless legs severity after continuous positive air pressure (CPAP) treatment in patients affected by the association of RLS and obstructive sleep apneas. Sleep Med 2006; 7:235.
  49. Innes KE, Selfe TK. The Effects of a Gentle Yoga Program on Sleep, Mood, and Blood Pressure in Older Women with Restless Legs Syndrome (RLS): A Preliminary Randomized Controlled Trial. Evid Based Complement Alternat Med 2012; 2012:294058.
  50. Innes KE, Selfe TK, Agarwal P, et al. Efficacy of an eight-week yoga intervention on symptoms of restless legs syndrome (RLS): a pilot study. J Altern Complement Med 2013; 19:527.
  51. Russell M. Massage therapy and restless legs syndrome. J Bodyw Mov Ther 2007; 11:146.
  52. Cuellar N, Galper DI, Taylor AG, et al. Restless legs syndrome. J Altern Complement Med 2004; 10:422.
  53. Lettieri CJ, Eliasson AH. Pneumatic compression devices are an effective therapy for restless legs syndrome: a prospective, randomized, double-blinded, sham-controlled trial. Chest 2009; 135:74.
  54. Eliasson AH, Lettieri CJ. Sequential compression devices for treatment of restless legs syndrome. Medicine (Baltimore) 2007; 86:317.
  55. Rajaram SS, Rudzinskiy P, Walters AS. Enhanced external counter pulsation (EECP) for restless legs syndrome (RLS): preliminary negative results in a parallel double-blind study. Sleep Med 2006; 7:390.
  56. Rajaram SS, Shanahan J, Ash C, et al. Enhanced external counter pulsation (EECP) as a novel treatment for restless legs syndrome (RLS): a preliminary test of the vascular neurologic hypothesis for RLS. Sleep Med 2005; 6:101.
  57. The Organization of Teratology Information Specialists (OTIS). Hyperthermia and Pregnancy fact sheet. Available at: www.otispregnancy.org (Accessed on March 28, 2015).
  58. Bothwell TH. Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr 2000; 72:257S.
  59. Pavord S, Myers B, Robinson S, et al. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol 2012; 156:588.
  60. Silber MH, Becker PM, Earley C, et al. Willis-Ekbom Disease Foundation revised consensus statement on the management of restless legs syndrome. Mayo Clin Proc 2013; 88:977.
  61. Garcia-Borreguero D, Ferini-Strambi L, Kohnen R, et al. European guidelines on management of restless legs syndrome: report of a joint task force by the European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society. Eur J Neurol 2012; 19:1385.
  62. Wang J, O'Reilly B, Venkataraman R, et al. Efficacy of oral iron in patients with restless legs syndrome and a low-normal ferritin: A randomized, double-blind, placebo-controlled study. Sleep Med 2009; 10:973.
  63. Sloand JA, Shelly MA, Feigin A, et al. A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis 2004; 43:663.
  64. Picchietti DL, Wang VC, Picchietti MA. Intravenous iron given prior to pregnancy for restless legs syndrome is associated with remission of symptoms. J Clin Sleep Med 2012; 8:585.
  65. Vadasz D, Ries V, Oertel WH. Intravenous iron sucrose for restless legs syndrome in pregnant women with low serum ferritin. Sleep Med 2013; 14:1214.
  66. Schneider J, Krafft A, Bloch A, et al. Iron infusion in restless legs syndrome in pregnancy. J Neurol 2011; 258:55.
  67. Allen RP, Earley CJ. The role of iron in restless legs syndrome. Mov Disord 2007; 22 Suppl 18:S440.
  68. Eskeland B, Baerheim A, Ulvik R, Hunskaar S. Influence of mild infections on iron status parameters in women of reproductive age. Scand J Prim Health Care 2002; 20:50.
  69. Barton JC, Wooten VD, Acton RT. Hemochromatosis and iron therapy of Restless Legs Syndrome. Sleep Med 2001; 2:249.
  70. Swaney P, Thorp J, Allen I. Vitamin C supplementation in pregnancy--does it decrease rates of preterm birth? A systematic review. Am J Perinatol 2014; 31:91.
  71. Grote L, Leissner L, Hedner J, Ulfberg J. A randomized, double-blind, placebo controlled, multi-center study of intravenous iron sucrose and placebo in the treatment of restless legs syndrome. Mov Disord 2009; 24:1445.
  72. Allen RP, Adler CH, Du W, et al. Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. Sleep Med 2011; 12:906.
  73. Cho YW, Allen RP, Earley CJ. Lower molecular weight intravenous iron dextran for restless legs syndrome. Sleep Med 2013; 14:274.
  74. Birgegård G, Schneider K, Ulfberg J. High incidence of iron depletion and restless leg syndrome (RLS) in regular blood donors: intravenous iron sucrose substitution more effective than oral iron. Vox Sang 2010; 99:354.
  75. Mehmood T, Auerbach M, Earley CJ, Allen RP. Response to intravenous iron in patients with iron deficiency anemia (IDA) and restless leg syndrome (Willis-Ekbom disease). Sleep Med 2014; 15:1473.
  76. Schneider J, Krafft A, Manconi M, et al. Open-label study of the efficacy and safety of intravenous ferric carboxymaltose in pregnant women with restless legs syndrome. Sleep Med 2015; 16:1342.
  77. Saletu M, Anderer P, Saletu-Zyhlarz G, et al. Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam. Eur Neuropsychopharmacol 2001; 11:153.
  78. Montagna P, Sassoli de Bianchi L, Zucconi M, et al. Clonazepam and vibration in restless legs syndrome. Acta Neurol Scand 1984; 69:428.
  79. Weinstock L, Cohen LS, Bailey JW, et al. Obstetrical and neonatal outcome following clonazepam use during pregnancy: a case series. Psychother Psychosom 2001; 70:158.
  80. Lin AE, Peller AJ, Westgate MN, et al. Clonazepam use in pregnancy and the risk of malformations. Birth Defects Res A Clin Mol Teratol 2004; 70:534.
  81. Eros E, Czeizel AE, Rockenbauer M, et al. A population-based case-control teratologic study of nitrazepam, medazepam, tofisopam, alprazolum and clonazepam treatment during pregnancy. Eur J Obstet Gynecol Reprod Biol 2002; 101:147.
  82. Samrén EB, van Duijn CM, Christiaens GC, et al. Antiepileptic drug regimens and major congenital abnormalities in the offspring. Ann Neurol 1999; 46:739.
  83. Dostal M, Weber-Schoendorfer C, Sobesky J, Schaefer C. Pregnancy outcome following use of levodopa, pramipexole, ropinirole, and rotigotine for restless legs syndrome during pregnancy: a case series. Eur J Neurol 2013; 20:1241.
  84. Watanabe T, Matsubara S, Baba Y, et al. Successful management of pregnancy in a patient with Segawa disease: case report and literature review. J Obstet Gynaecol Res 2009; 35:562.
  85. Serikawa T, Shimohata T, Akashi M, et al. Successful twin pregnancy in a patient with parkin-associated autosomal recessive juvenile parkinsonism. BMC Neurol 2011; 11:72.
  86. Micromedex Inc. Micromedex healthcare series. Englewood, CO: Micromedex.
  87. Cornelius JR, Tippmann-Peikert M, Slocumb NL, et al. Impulse control disorders with the use of dopaminergic agents in restless legs syndrome: a case-control study. Sleep 2010; 33:81.
  88. Ohman I, Tomson T. Gabapentin kinetics during delivery, in the neonatal period, and during lactation. Epilepsia 2009; 50:108.
  89. Ohman I, Vitols S, Tomson T. Pharmacokinetics of gabapentin during delivery, in the neonatal period, and lactation: does a fetal accumulation occur during pregnancy? Epilepsia 2005; 46:1621.
  90. Kristensen JH, Ilett KF, Hackett LP, Kohan R. Gabapentin and breastfeeding: a case report. J Hum Lact 2006; 22:426.
  91. Kelly LE, Poon S, Madadi P, Koren G. Neonatal benzodiazepines exposure during breastfeeding. J Pediatr 2012; 161:448.
  92. Birnbaum CS, Cohen LS, Bailey JW, et al. Serum concentrations of antidepressants and benzodiazepines in nursing infants: A case series. Pediatrics 1999; 104:e11.
  93. Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry 2009; 31:403.
  94. Grote NK, Bridge JA, Gavin AR, et al. A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry 2010; 67:1012.
  95. Wisner KL, Sit DK, Hanusa BH, et al. Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Am J Psychiatry 2009; 166:557.
  96. Hornyak M. Depressive disorders in restless legs syndrome: epidemiology, pathophysiology and management. CNS Drugs 2010; 24:89.
  97. Hornyak M, Kopasz M, Berger M, et al. Impact of sleep-related complaints on depressive symptoms in patients with restless legs syndrome. J Clin Psychiatry 2005; 66:1139.
  98. Benes H, Mattern W, Peglau I, et al. Ropinirole improves depressive symptoms and restless legs syndrome severity in RLS patients: a multicentre, randomized, placebo-controlled study. J Neurol 2011; 258:1046.
  99. Fulda S, Kloiber S, Dose T, et al. Mirtazapine provokes periodic leg movements during sleep in young healthy men. Sleep 2013; 36:661.
  100. Bayard M, Bailey B, Acharya D, et al. Bupropion and restless legs syndrome: a randomized controlled trial. J Am Board Fam Med 2011; 24:422.
  101. Nofzinger EA, Fasiczka A, Berman S, Thase ME. Bupropion SR reduces periodic limb movements associated with arousals from sleep in depressed patients with periodic limb movement disorder. J Clin Psychiatry 2000; 61:858.