Download PDF
CC BY-NC-ND 4.0 · Sleep Sci 2022; 15(04): 471-479
DOI: 10.5935/1984-0063.20220080
REVIEWS

Possible etiologies of restless legs syndrome in pregnancy: a narrative review

Ana Mendes
1   Centro Hospitalar De Trás-Os-Montes E Alto Douro, E.P.E., Pulmonology - Vila Real - Portugal
,
Vitória Silva
1   Centro Hospitalar De Trás-Os-Montes E Alto Douro, E.P.E., Pulmonology - Vila Real - Portugal
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an urgent need to move the legs, due to the presence of a discomfort sensation in the lower limbs, especially at rest. Generally, it relieves with movement. There are several studies that argue the existence of an association between this syndrome and pregnancy. However, the pathophysiological mechanisms of this disorder in pregnancy are misunderstood. The objective of this narrative review is to identify and discuss some possible etiologies of RLS in pregnancy. A literature search was performed in the PubMed and ResearchGate databases by using the following search strategies: “restless legs syndrome”, “restless legs syndrome in pregnancy”, “pregnancy and vitamin D deficiency” and “pregnancy and zinc”. The publications were initially sorted through their title. After the initial process, inclusion and exclusion criteria were applied. The included articles were sorted by authors, year, journal of publication, type of study, and organized by chronological order of publication. Among the main findings, hormonal changes, iron metabolism, vitamin D deficiency, genetic factors, zinc and magnesium fluctuations have been some of the hypotheses supporting the development or worsening of this disorder in pregnancy. Dopamine also appears to be correlated with hormonal changes, iron metabolism, ferritin, folic acid and vitamin D deficiency. In conclusion, there are several hypotheses trying to link restless legs syndrome with pregnancy. The most covered were hormonal fluctuations and iron metabolism. However, this thematic is still highly discussed, creating the need for additional and thorough research.

Restless Legs Syndrome - Pregnancy - Hormones - Elements - Vitamin D - Genetics


Publication History

Received: 30 March 2021

Accepted: 07 February 2022

Article published online:
01 December 2023

© 2023. Brazilian Sleep Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • REFERENCES

  • 1 Garbazza C, Manconi M. Management strategies for restless legs syndrome/Willis-Ekbom disease during pregnancy. Sleep Med Clin. 2018 Sep;13(3):335-48.
  • 2 Cimsir MT, Savas HB. Investigation of biochemical data in pregnant women diagnosed with restless legs syndrome. J Clin Exp Investig. 2021;12(2):em00767.
  • 3 Yildirim E, Apaydin H. Zinc and magnesium levels of pregnant women with restless leg syndrome and their relationship with anxiety: a casecontrol study. Biol Trace Elem Res. 2021 May;199(5):1674-85.
  • 4 Devaraj D, Devaraj U, Bothello M, Ramachandran P, D’Souza G. Prevalence of restless leg syndrome in pregnancy - a follow up study (Pearls study). Sleep Med. 2017 Dec;40:e78.
  • 5 Darvishi N, Daneshkhah A, Khaledi-Paveh B, Vaisi-Raygani A, Mohammadi M, Salari N, et al. The prevalence of restless legs syndrome/ Willis-Ekbom disease (RLS/WED) in the third trimester of pregnancy: a systematic review. BMC Neurol. 2020 Apr;20(1):132.
  • 6 Gupta R, Dhyani M, Kendzerska T, Pandi-Perumal SR, BaHammam AS, Srivanitchapoom P, et al. Restless legs syndrome and pregnancy: prevalence, possible pathophysiological mechanisms and treatment. Acta Neurol Scand. 2016 May;133(5):320-9.
  • 7 Attarian H, Viola-Saltzman M. Sleep disorders in women: a guide to practical management. 3rd ed. Totowa: Humana Press; 2020.
  • 8 Chen SJ, Shi L, Bao YP, Sun YK, Lin X, Que JY, et al. Prevalence of restless legs syndrome during pregnancy: a systematic review and metaanalysis. Sleep Med Rev. 2018;40:43-54.
  • 9 Viquez LEG, Segura JLC. Sindrome de piernas inquietas. Neuroeje. 2017;30:2.
  • 10 Srivanitchapoom P, Pandey S, Hallett M. Restless legs syndrome and pregnancy: a review. Parkinsonism Relat Disord. 2014 Jul;20(7):716-22.
  • 11 Panvatvanich S, Lolekha P. Restless legs syndrome in pregnant Thai women: prevalence, predictive factors, and natural course. J Clin Neurol. 2019 Jan;15(1):97-101.
  • 12 Prosperetti C, Manconi M. Restless legs syndrome/Willis-Ekbom disease and pregnancy. Sleep Med Clin. 2015 Sep;10(3):323-9.
  • 13 Kondori MJ, Kolla BP, Moore KM, Mansukhani MP. Management of restless legs syndrome in pregnancy and lactation. J Prim Care Community Health. 2020 Jan/Dec;11:1-8.
  • 14 Akba. P, Sozbir .Y. Restless legs syndrome and quality of life in pregnant women. Rev Assoc Med Bras. 2019;65(5):618-24.
  • 15 Khan FH, Ahlberg CD, Chow CA, Shah DR, Koo BB. Iron, dopamine, genetics, and hormones in the pathophysiology of restless legs syndrome. J Neurol. 2017 Aug;264(8):1634-41.
  • 16 Shang X, Yang J, Guo Y, Ma S, Jia Z, Xue R. Restless legs syndrome among pregnant women in China: prevalence and risk factors. Sleep Breath. 2015 Sep;19(3):1093-9.
  • 17 Seeman MV. Why are women prone to restless legs syndrome? Int J Environ Res Public Health. 2020 Jan;17(1):368.
  • 18 Dzaja A, Wehrle R, Lancel M, Pollmacher T. Elevated estradiol plasma levels in women with restless legs during pregnancy. Sleep. 2009 Feb;32(2):169-74.
  • 19 Tunc T, Karada. YS, Do.ulu F, .nan LE. Predisposing factors of restless legs syndrome in pregnancy. Mov Disord. 2007 Apr;22(5):627-31.
  • 20 Hubner A, Krafft A, Gadient S, Werth E, Zimmermann R, Bassetti CL. Characteristics and determinants of restless legs syndrome in pregnancy: a prospective study. Neurology. 2013 Feb;80(8):738-42.
  • 21 Grover A, Clark-Bilodeau C, D’Ambrosio CM. Restless leg syndrome in pregnancy. Obstet Med. 2015 Sep;8(3):121-5.
  • 22 Garcia-Borreguero D, Larrosa O, Granizo JJ, Llave Y, Hening WA. Circadian variation in neuroendocrine response to L-dopa in patients with restless legs syndrome. Sleep. 2004 Jun;27(4):669-73.
  • 23 Pereira Junior JC, Pradella-Hallinan M, Pessoa HL. Imbalance between thyroid hormones and the dopaminergic system might be central to the pathophysiology of restless legs syndrome: a hypothesis. Clinics. 2010;65(5):548-54.
  • 24 Cakmak B, Metin ZF, Karatas A, Ozsoy Z, Demirturk F. Restless leg syndrome in pregnancy. Perinatal J. 2014;22:1-5.
  • 25 Almeneessie AS, Alyousefi N, Alzahrani M, Alsafi A, Alotaibi R, Olaish AH, et al. Prevalence of restless legs syndrome among pregnant women: a case-control study. Ann Thorac Med. 2020;15(1):9-14.
  • 26 Neyal A, Senel GB, Aslan R, Nalbantoglu M, Acikgoz S, Yilmaz N, et al. A prospective study of Willis-Ekbom disease/restless legs syndrome during and after pregnancy. Sleep Med. 2015 Sep;16(9):1036-40.
  • 27 Ferre S, Quiroz C, Guitart X, Rea W, Seyedian A, Moreno E, et al. Pivotal role of adenosine neurotransmission in restless legs syndrome. Front Neurosci. 2018 Jan;11:722.
  • 28 Jimenez-Jimenez FJ, Alonso-Navarro H, Garcia-Martin E, Agundez JAG. Neurochemical features of idiopathic restless legs syndrome. Sleep Med Rev. 2019 Jun;45:70-87.
  • 29 Telarovi. S, .ondi. L. Frequency of iron deficiency anemia in pregnant and non-pregnant women suffering from restless legs syndrome. Hematology. 2019 Dec;24(1):263-7.
  • 30 Minar M, Ko.utzka Z, Habanova H, Rus.ak I, Planck K, Valkovi. P. Restless legs syndrome in pregnancy is connected with iron deficiency. Sleep Med. 2015 May;16(5):589-92.
  • 31 Sikandar R, Khealani BA, Wasay M. Predictors of restless legs syndrome in pregnancy: a hospital based cross sectional survey from Pakistan. Sleep Med. 2009 Jun;10(6):676-8.
  • 32 Morker M, Gossett D, McKnight TA, Patel B, Patel M, Attarian HP. Serum folic acid level and its relationship to gestational Willis-Ekbom disease (restless legs syndrome): a pilot study. J Reprod Med. 2017 Dec;62(6):593-7.
  • 33 Sa.lam G, Pekta. G, Karakullukcu S, Pekta. B, Aykut DS. The relationship between vitamin d deficiency and restless legs syndrome in pregnancy. J Turk Sleep Med. 2020;7(2):44-8.
  • 34 Tutuncu M, Tutuncu M. The effect of vitamin D on restless legs syndrome: Prospective self-controlled case study. Sleep Breath. 2020 Sep;24(3):1101-6.
  • 35 Wali S, Alsafadi S, Abaalkhail B, Ramadan I, Abulhamail B, Kousa M, et al. The association between vitamin D level and restless legs syndrome: a population-based case-control study. J Clin Sleep Med. 2018 Apr;14(4):557-64.
  • 36 Gur G, Abaci A, Koksoy AY, Anik A, Catli G, Ki.lal FM, et al. Incidence of maternal vitamin D deficiency in a region of Ankara, Turkey: a preliminary study. Turkish J Med Sci. 2014;44(4):616-23.
  • 37 Al-Faris NA. High prevalence of vitamin D deficiency among pregnant Saudi women. Nutrients. 2016 Feb;8(2):77.
  • 38 Cesnik E, Casetta I, Turri M, Govoni V, Granieri E, Strambi LF, et al. Transient RLS during pregnancy is a risk factor for the chronic idiopathic form. Neurology. 2010 Dec;75(23):2117-20.
  • 39 Iqbal S, Ali I, Rust P, Kundi M, Ekmekcioglu C. Selenium, zinc, and manganese status in pregnant women and its relation to maternal and child complications. Nutrients. 2020 Mar;12(3):725.
  • 40 Schwalfenberg GK, Genuis SJ. The importance of magnesium in clinical healthcare. Scientifica. 2017;2017:4179326.
  • 41 Soliman JSA, Amer AY, Soliman JSA. Association of zinc deficiency with iron deficiency anemia and its symptoms: results from a case-control study. Cureus. 2019 Jan;11(4):e3811.
  • 42 Kelkitli E, Ozturk N, Aslan NA, Kilic-Baygutalp N, Bayraktutan Z, Kurt N, et al. Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia. Ann Hematol. 2016 Apr;95(5):751-6.
  • 43 Szentkiralyi A, Stefani A, Hackner H, Czira M, Teismann IK, Volzke H, et al. Prevalence and associated risk factors of periodic limb movement in sleep in two German population-based studies. Sleep. 2019 Mar;42(3):zsy237.