Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Internet Explorer is no longer a supported browser.

This website may not display properly with Internet Explorer. For the best experience, please use a more recent browser such as the latest versions of Google Chrome, Microsoft Edge, and/or Mozilla Firefox. Thank you.

COVID-19 is an emerging, rapidly evolving situation.

Get the latest public health information from CDC. Get the latest research information from NIH.

Your Environment. Your Health.

Publication Detail

Title: Metabolome-wide association study of anti-epileptic drug treatment during pregnancy.

Authors: Walker, Douglas I; Perry-Walker, Kayla; Finnell, Richard H; Pennell, Kurt D; Tran, Vilinh; May, Ryan C; McElrath, Thomas F; Meador, Kimford J; Pennell, Page B; Jones, Dean P

Published In Toxicol Appl Pharmacol, (2019 01 15)

Abstract: Pregnant women with epilepsy (PWWE) require continuous anti-epileptic drug (AED) treatment to avoid risk to themselves and fetal risks secondary to maternal seizures, resulting in prolonged AED exposure to the developing embryo and fetus. The objectives of this study were to determine whether high-resolution metabolomics is able to link the metabolite profile of PWWE receiving lamotrigine or levetiracetam for seizure control to associated pharmacodynamic (PD) biological responses. Untargeted metabolomic analysis of plasma obtained from 82 PWWE was completed using high-resolution mass spectrometry. Biological alterations due to lamotrigine or levetiracetam monotherapy were determined by a metabolome-wide association study that compared patients taking either drug to those who did not require AED treatment. Metabolic changes associated with AED use were then evaluated by testing for drug-dose associated metabolic variations and pathway enrichment. AED therapy resulted in drug-associated metabolic profiles recognizable within maternal plasma. Both the parent compounds and major metabolites were detected, and each AED was correlated with other metabolic features and pathways. Changes in metabolites and metabolic pathways important to maternal health and linked to fetal neurodevelopment were detected for both drugs, including changes in one‑carbon metabolism, neurotransmitter biosynthesis and steroid metabolism. In addition, decreased levels of 5-methyltetrahydrofolate and tetrahydrofolate were detected in women taking lamotrigine, which is consistent with recent findings showing increased risk of autism spectrum disorder traits in PWWE using AED. These results represent a first step in development of pharmacometabolomic framework with potential to detect adverse AED-related metabolic changes during pregnancy.

PubMed ID: 30521819 Exiting the NIEHS site

MeSH Terms: Adult; Anticonvulsants/pharmacology*; Anticonvulsants/therapeutic use; Carbon/metabolism; Epilepsy/drug therapy*; Epilepsy/metabolism; Female; Fetus/drug effects; Fetus/metabolism*; Folic Acid/metabolism; Humans; Lamotrigine/pharmacology; Lamotrigine/therapeutic use; Levetiracetam/pharmacology; Levetiracetam/therapeutic use; Metabolic Networks and Pathways/drug effects; Metabolome/drug effects*; Metabolomics; Neurotransmitter Agents/biosynthesis; Pregnancy; Pregnancy Complications/drug therapy*; Pregnancy Complications/metabolism; Prospective Studies; Steroids/metabolism; Treatment Outcome

Back
to Top