Targeting adverse effects of antiseizure medication on offspring: current evidence and new strategies for safety

ABSTRACT

Introduction

For women with epilepsy of reproductive age, antiseizure medications (ASMs) are associated with an increased risk of offspring malformations. There are safety concerns for most anti-seizure medications in the perinatal period, and there is a clear need to identify safe medications. ASMs must transport through biological barriers to exert toxic effects on the fetus, and transporters play essential roles in trans-barrier drug transport. Therefore, it is vital to understand the distribution and properties of ASM-related transporters in biological barriers.

Areas covered

This study reviews the structure, transporter distribution, and properties of the blood-brain, placental, and blood-milk barrier, and summarizes the existing evidence for the trans-barrier transport mechanism of ASMs and standard experimental models of biological barriers.

Expert opinion

Ideal ASMs in the perinatal period should have the following characteristics: 1) Increased transport through the blood-brain barrier, and 2) Reduced transport of the placental and blood-milk barriers. Thus, only low-dose or almost no antiseizure medication could enter the fetus’s body, which could decrease medication-induced fetal abnormalities. Based on the stimulated structure and molecular docking, we propose a development strategy for new ASMs targeting transporters of biological barriers to improve the perinatal treatment of female patients with epilepsy.

KEYWORDS:

• Antiseizure medications
• blood-brain barrier
• blood-milk barrier
• placental barrier
• women of reproductive age

Article highlights

• Epilepsy is a chronic neurological disorder characterized by recurrent seizures and excessive or abnormal synchronous neuronal activity.

• Antiseizure medications generally have high transport capabilities across the blood-brain and placental barriers, leading to high concentrations of antiseizure medications in the fetus.

• For women with epilepsy of reproductive age, antiseizure medications (ASMs) are associated with an increased risk of offspring malformations

• Indeed, it is estimated that women with epilepsy are twice as likely to have fetal malformations than healthy women. The offspring of women with epilepsy also have an increased risk of cognitive impairment and autism.

• In the next five years, large cohort studies will be conducted to determine the safety and efficacy of existing anti-seizure medications for women of reproductive age with epilepsy. Novel, safer drugs will be designed and tested in preclinical trials.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.