Peroneal Nerve Stimulation (Tonic Motor Activation) for Restless Legs Syndrome in Pregnancy: A Critical Narrative Review

Abstract

Restless legs syndrome affects a substantial proportion of pregnant women, most often emerging in the second or third trimester and imposing a considerable burden on sleep, mood, and possibly obstetric outcome. Management during pregnancy is constrained: dopamine agonists, gabapentinoids at higher doses, opioids, and benzodiazepines all carry theoretical or demonstrated concerns for the mother or fetus, leaving iron repletion and generic reassurance-based measures as the mainstay of first-line care, with a recognised residue of women whose symptoms remain inadequately controlled despite these steps. Peroneal nerve stimulation, delivered clinically as tonic motor activation, has recently emerged as a Food and Drug Administration-cleared, non-pharmacological, non-systemic therapy for moderate-to-severe medication-refractory restless legs syndrome in the general adult population, supported by randomised, sham-controlled trials, an open-label extension, and independent meta-analysis. Because the therapy avoids systemic drug exposure, it is mechanistically attractive for pregnancy, yet the pivotal trials establishing its evidence base explicitly excluded pregnant participants, and only a single small feasibility study in pregnant women has so far been registered. This review synthesises the epidemiological, pathophysiological, and therapeutic literature on restless legs syndrome in pregnancy; critically appraises the quality, consistency, and generalisability of the non-pregnant tonic motor activation evidence base; and evaluates the physiological plausibility and safety-extrapolation issues that arise when peripheral neuromodulation is considered during gestation. The review finds that although the mechanistic rationale and non-pregnant safety profile are reassuring, no efficacy or safety data specific to pregnant populations currently exist, and extrapolation from non-pregnant trials cannot substitute for dedicated study given physiological changes in connective tissue, dependent oedema, and neuromuscular excitability across gestation. Peroneal nerve stimulation represents a biologically plausible but presently unproven option for restless legs syndrome in pregnancy. Its future clinical role depends on the results of the ongoing feasibility trial and on subsequent adequately powered, safety-focused studies rather than on inference from adult populations that specifically excluded the population of interest.