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Restless legs syndrome (RLS) in pregnancy is a common disorder with a multifactorial etiology. A neurological and obstetrical cohort of 308 postpartum women was screened for RLS within 1 to 6 days of childbirth and 12 weeks postpartum. Of the 308 young mothers, 57 (prevalence rate 19%) were identified as having been affected by RLS symptoms in the recently completed pregnancy. Structural and functional MRI was obtained from 25 of these 57 participants. A multivariate two-window algorithm was employed to systematically chart the relationship between brain structures and phenotypical predictors of RLS. A decreased volume of the parietal, orbitofrontal and frontal areas shortly after delivery was found to be linked to persistent RLS symptoms up to 12 weeks postpartum, the symptoms' severity and intensity in the most recent pregnancy, and a history of RLS in previous pregnancies. The same negative relationship was observed between brain volume and not being married, not receiving any iron supplement and higher numbers of stressful life events. High cortisol levels, being married and receiving iron supplements, on the other hand, were found to be associated with increased volumes in the bilateral striatum. Investigating RLS symptoms in pregnancy within a brain-phenotype framework may help shed light on the heterogeneity of the condition.

Phenotypical predictors of pregnancy-related restless legs syndrome and their association with basal ganglia and the limbic circuits