Time-varying restless legs syndrome and risk of incident perinatal depression.

PURPOSE: Previous studies have reported associations between restless legs syndrome (RLS) and perinatal depressive symptoms. However, no study has used diagnostic instruments to examine changes in RLS status during pregnancy in relation to the incidence of perinatal depression. This study aimed to investigate whether time-varying RLS status is associated with an increased risk of incident perinatal depression. METHODS: This prospective cohort study analyzed data from 2435 Japanese pregnant women in the control group of a randomized controlled trial on perinatal depression. Time-varying RLS status was assessed using data obtained in the second and third trimesters with the short form of the Cambridge-Hopkins diagnostic questionnaire. Incident major depressive episodes and depressive symptoms from the second trimester to 3 months postpartum were assessed using the self-administered World Health Organization Composite International Diagnostic Interview 3.0 and the Edinburgh Postnatal Depression Scale (EPDS), respectively. Associations were examined using Cox proportional hazards models with time-varying covariates. RESULTS: The prevalence of RLS was 40 (1.6%) in the second trimester and 60 (3.5%) in the third trimester. During a mean follow-up of 6.5 months (SD, 3.2), 69 participants developed perinatal depression. Time-varying RLS status was significantly associated with an increased risk of incident perinatal depression (hazard ratio [HR], 3.04; 95% CI, 1.22-7.58) and depressive symptoms (EPDS ≥ 13; HR, 2.12; 95% CI, 1.28-3.51). These associations remained robust after adjustment for potential confounders. CONCLUSION: RLS, modeled as a time-varying condition, was associated with an increased risk of incident perinatal depression, suggesting the importance of screening for RLS during pregnancy for the prevention of perinatal depression. CURRENT KNOWLEDGE/STUDY RATIONALE: RLS is common during pregnancy and has been linked to depressive symptoms, possibly through shared pathophysiological mechanisms such as sleep disturbances and iron deficiency; however, longitudinal evidence using diagnostic instruments remains limited. This study examined whether time-varying RLS status is associated with incident perinatal depression. STUDY IMPACT: Pregnant women with RLS, particularly in the third trimester, had an increased risk of perinatal depression, suggesting the clinical importance of routine RLS screening to support timely treatment and potentially prevent perinatal depression. Increased awareness of RLS among pregnant women and healthcare providers may promote early identification of individuals at higher risk. However, whether RLS treatment can reduce perinatal depression risk requires further investigation.