Is vagal-nerve stimulation safe during pregnancy? A mini review

Highlights

• Vagus nerve stimulation is the most common neuromodulation technique, widely used in all types of epilepsy.

• The parameters of VNS and the dosage of epileptic drugs can be adjusted properly during pregnancy.

• Vagus nerve stimulation appears to be safe for pregnant women and fetuses.

Abstract

Background

Vagus-nerve stimulation (VNS) is the most common neuromodulation technique and has been approved by the FDA for treating refractory epilepsy and refractory depression. Although VNS has been used for nearly 32 years, the impact of VNS on the safety of pregnant women and neonate remains to be evaluated.

Methods

We first analyze the relationship between the vagus nerve and the reproductive system (ovary and uterus) and then determine whether harm is inflicted to the reproductive system, thereby affecting the pregnancy. A comprehensive literature search is performed on PubMed/MEDLINE database, Web of Science, and Scopus. Ten articles are included in the study, and 44 pregnancies of 38 patients are analyzed.

Results

The vagus nerve is connected with the reproductive system, but VNS may have little effect on pregnancy. We analyze 10 articles (38 patients with 44 pregnancies) about VNS complications during pregnancy. Two of the 44 pregnancies (2/44, 4.5 %) are miscarriages, and two pregnancies have fetuses with congenital malformations (2/42, 4.8 %), which could also be attributed to polytherapy with antiepileptic drugs. The rest of the pregnant women have no postpartum complications, and their fetuses are healthy.

Conclusions

VNS may be relatively safe and effective for the fetus and mother during pregnancy, and turning off VNS during pregnancy is unnecessary. However, owing to the small sample size and short follow-up time in the present study, further research is needed.

Introduction

Vagus-nerve stimulation (VNS) is a common nerve-regulation technology (Boon et al., 2009; George et al., 2002; San-Juan et al., 2019; Starnes et al., 2019). VNS has been approved by FDA to treat refractory epilepsy and treatment-resistant depression (Ben-Menachem et al., 2013; Conway and Xiong, 2018; Howland, 2014; Morris et al., 2013; Nierenberg et al., 2008). VNS could also have therapeutic potential for other diseases of the central nervous system (Parkinson's disease, addiction, and ischemic stroke) (Farrand et al., 2017; García-Toro et al., 2011; Ma et al., 2019) and non-central nervous system (rheumatoid arthritis, inflammatory bowel disease, heart failure, and kidney disease) (Bonaz et al., 2016; Drewes et al., 2021; Hilderman and Bruchfeld, 2020; Kibleur et al., 2018; Wang et al., 2019). As of June 2018, about 100 000 patients worldwide had received VNS implantation (Toffa et al., 2020; Wheless et al., 2018). Although VNS is extensively used, little is known about the effect of VNS on pregnancy and fetal outcomes. VNS implantation during pregnancy is rarely reported or evaluated, with only over 40 cases reported in literature (Ben-Menachem et al., 1999; Galbarriatu et al., 2015; Kalayjian and Heck, 2005; Rodríguez-Osorio et al., 2017; Sabers et al., 2017).

The application of VNS during pregnancy generally involves two situations. One is pregnancy after VNS implantation, in which neurosurgeons have always been concerned about the possible adverse of VNS on fetuses and pregnant women. The other situation is that patients with epilepsy develop severe epilepsy or depression after pregnancy. The purpose of VNS implantation is to reduce seizures. VNS is particularly important for the safety evaluation of pregnant women and fetuses (Rodríguez-Osorio et al., 2017; Sabers et al., 2017).