{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T04:49:23Z","timestamp":1770785363779,"version":"3.50.0"},"reference-count":34,"publisher":"The Pediatric Pharmacy Association","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p>Valproic acid, carbamazepine and topiramate have well-known teratogenic risk and all 3 rank among the top 10 teratogenic medications with the highest prenatal exposure risk. Importantly, pregnancies exposed to valproic acid are not dominated by patients with epilepsy but rather with less serious conditions such as migraine. In the United States, only a weight loss combination product containing topiramate has a mandatory pregnancy prevention program, a so-called Risk Evaluation and Mitigation Strategy (REMS), while prevention of fetal exposure to all three single ingredient products relies on information in the product labeling and a medication guide provided at dispensing.<\/jats:p>\n                  <jats:p>REMS have been avoided for antinconvulsants because of concerns about reduced medication access for patients with serious conditions such as epilepsy, hence weighting maternal harm due to uncontrolled disease against adverse pregnancy or infant outcomes. However, the broad and growing spectrum of indications for all three medications, paired with increasingly strict abortion laws that may not allow pregnancy termination if accidental fetal exposure occurs, may require re-assessment of the benefit-risk of REMS. Here we argue that formal quantitative approaches are needed that allow assessments of maternal and infant risk, considering maternal disease, adverse pregnancy outcomes and teratogenic effects on infants, and the overall public health impact of REMS for anticonvulsants. For valproic acid, given its broad use, high risk of fetal exposure, and profound impact on child health, we predict the public health impact of a REMS will be favorable.<\/jats:p>","DOI":"10.5863\/jppt-25-01204","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T13:56:51Z","timestamp":1750946211000},"page":"398-400","source":"Crossref","is-referenced-by-count":0,"title":["Risk Management of Valproate and Other Teratogenic Anticonvulsants in the Era of Proliferating Use"],"prefix":"10.5863","volume":"30","author":[{"given":"Almut G.","family":"Winterstein","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Outcomes and Policy, Department of Epidemiology, and Center for Drug Evaluation and Safety (CoDES), University of Florida, Gainesville, FL"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3883","reference":[{"issue":"14","key":"i2331-348X-30-3-398-b01","series-title":"Birth Defects Res","first-page":"1274","article-title":"Ascertainment of malformations in pregnancy registries: lessons learned in the North American AED Pregnancy Registry","volume":"115","author":"Holmes","year":"2023","unstructured":"Holmes LB, Quinn M, Conant S, et al. Ascertainment of malformations in pregnancy registries: lessons learned in the North American AED Pregnancy Registry. Birth Defects Res. 2023;115(14):1274\u20131283."},{"issue":"5","key":"i2331-348X-30-3-398-b02","series-title":"JAMA Neurol","first-page":"481","article-title":"Risk of major congenital malformations and exposure to antiseizure medication monotherapy","volume":"81","author":"Battino","year":"2024","unstructured":"Battino D, Tomson T, Bonizzoni E, et al. Risk of major congenital malformations and exposure to antiseizure medication monotherapy. JAMA Neurol. 2024;81(5):481\u2013489."},{"issue":"11","key":"i2331-348X-30-3-398-b03","series-title":"Cochrane Database Syst Rev","first-page":"CD010224","article-title":"Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child","volume":"11","author":"Weston","year":"2016","unstructured":"Weston J, Bromley R, Jackson CF, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev. 2016;11(11):CD010224."},{"issue":"10","key":"i2331-348X-30-3-398-b04","series-title":"Am J Epidemiol","first-page":"961","article-title":"Neural tube defects in relation to use of folic acid antagonists during pregnancy","volume":"153","author":"Hern\u00e1ndez-D\u00edaz","year":"2001","unstructured":"Hern\u00e1ndez-D\u00edaz S, Werler MM, Walker AM, Mitchell AA. Neural tube defects in relation to use of folic acid antagonists during pregnancy. Am J Epidemiol. 2001;153(10):961\u2013968."},{"key":"i2331-348X-30-3-398-b05","series-title":"Reprod Toxicol","first-page":"45","article-title":"First trimester exposure to topiramate and the risk of oral clefts in the offspring: a systematic review and meta-analysis","volume":"53","author":"Alsaad","year":"2015","unstructured":"Alsaad AM, Chaudhry SA, Koren G. First trimester exposure to topiramate and the risk of oral clefts in the offspring: a systematic review and meta-analysis. Reprod Toxicol. 2015;53:45\u201350."},{"issue":"1","key":"i2331-348X-30-3-398-b06","series-title":"Am J Obstet Gynecol MFM","first-page":"101245","article-title":"Common teratogenic medication exposures\u2014a population-based study of pregnancies in the United States","volume":"6","author":"Wang","year":"2024","unstructured":"Wang Y, Smolinski NE, Thai TN, et al. Common teratogenic medication exposures\u2014a population-based study of pregnancies in the United States. Am J Obstet Gynecol MFM. 2024;6(1):101245."},{"issue":"5","key":"i2331-348X-30-3-398-b07","series-title":"JAMA Netw Open","first-page":"e2412680","article-title":"Prenatal exposure to valproic acid across various indications for use","volume":"7","author":"Smolinski","year":"2024","unstructured":"Smolinski NE, Sarayani A, Thai TN, et al. 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Pharmacoepidemiol Drug Saf. 2015;24(5):518\u2013525."},{"issue":"4","key":"i2331-348X-30-3-398-b11","series-title":"Drug Saf","first-page":"447","article-title":"Real-world fetal exposure to acne treatments in the United States: a retrospective analysis from 2006 to 2015","volume":"44","author":"Albogami","year":"2021","unstructured":"Albogami Y, Sarayani A, Hincapie-Castillo JM, Winterstein AG. Real-world fetal exposure to acne treatments in the United States: a retrospective analysis from 2006 to 2015. Drug Saf. 2021;44(4):447\u2013454."},{"issue":"8","key":"i2331-348X-30-3-398-b12","series-title":"BMJ Qual Saf","first-page":"636","article-title":"Comparative effectiveness of risk mitigation strategies to prevent fetal exposure to mycophenolate","volume":"29","author":"Sarayani","year":"2020","unstructured":"Sarayani A, Albogami Y, Elkhider M, et al. Comparative effectiveness of risk mitigation strategies to prevent fetal exposure to mycophenolate. BMJ Qual Saf. 2020;29(8):636\u2013644."},{"issue":"4","key":"i2331-348X-30-3-398-b13","series-title":"Ann Intern Med","first-page":"443","article-title":"Assessment of the Risk Evaluation and Mitigation Strategy (REMS) for phentermine-topiramate to prevent exposure during pregnancy","volume":"176","author":"Sarayani","year":"2023","unstructured":"Sarayani A, Donahoo WT, Hampp C, et al. Assessment of the Risk Evaluation and Mitigation Strategy (REMS) for phentermine-topiramate to prevent exposure during pregnancy. Ann Intern Med. 2023;176(4):443\u2013454."},{"key":"i2331-348X-30-3-398-b14","series-title":"New Drug Application 22580: VI-0521 QNEXA (phentermine\/topiramate)","first-page":"200","article-title":"Endocrinologic and Metabolic Drugs Advisory Committee Meeting","year":"2012","unstructured":"Clinical Briefing Document. Endocrinologic and Metabolic Drugs Advisory Committee Meeting; February 22, 2012. New Drug Application 22580: VI-0521 QNEXA (phentermine\/topiramate). 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