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Introduction <p>Preventing fetal exposure to teratogenic medications is a public health priority. The Teratogenic Risk Impact Mitigation (TRIM) tool has been developed to support regulatory decisions regarding risk mitigation programs. One of the explicit TRIM criteria requires medication-specific quantification of fetal exposure risk.</p> Objective <p>To develop and compare population-based estimates of fetal exposure risk for medications with known teratogenicity.</p> Methods <p>This retrospective US population-based cohort study used claims data from Medicaid and MarketScan<sup>®</sup> databases from 01/2014 to 12/2018. Data were analyzed from 12/2023 to 12/2024. We included female patients aged 12–55 years with ≥&#xa0;1 teratogenic medication prescription. A validated algorithm identified pregnancies that ended with a live or non-live outcome among medication users. We estimated the fetal exposure rate as the number of pregnancies per at-risk medication exposure time, accounting for teratogenic risk profiles (e.g., ACE inhibitors exert risk in 2nd/3rd trimesters). Rates were averaged across databases to generate tertiles of high/medium/low fetal exposure risk.</p> Results <p>Among 59,815,213 female enrollees (31,905,714 Medicaid; 27,909,499 MarketScan), 12,819,073 used ≥&#xa0;1 teratogenic medication. Fetal exposure rates ranged from 0–1512 per 1000 user-years (tertiles: 2.9 and 11.5), with higher rates observed in Medicaid. Medications that exhibited high rates included fluconazole (1512/1000 user-years, 95% CI 1504.5–1518.6) and sulfamethoxazole/trimethoprim (295, 95% CI 233.6–492.2), vedolizumab (53, 95% CI 46.7–60.2) and several anticonvulsants. Two medications, phentermine-topiramate, with a current risk mitigation program, and fingolimod, with a released risk management program, were also ranked in the highest tertile. Fetal exposures to medications prescribed for acute conditions occurred more frequently through initiation during pregnancy, while those for chronic medications occurred mostly because of conception during treatment.</p> Conclusions <p>Fetal exposure risks differed across medications and populations, influenced by treatment chronicity, relevant teratogenic risk periods, and patient demographics, which can inform the development of risk mitigation programs. Data gleaned from this analysis will be used as an ordinal “fetal exposure risk” criterion score in our development of the TRIM decision tool.</p>

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Risk of Fetal Exposure to Teratogenic Medications: Development of Evidence for the Teratogenic Risk Impact and Mitigation (TRIM) Tool

  • 期刊论文

  • 发表日期：

    2026年4月17日

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  • Yanning Wang,
  • Celeste L. Y. Ewig,
  • Nicole E. Smolinski,
  • Gita A. Toyserkani,
  • Cynthia LaCivita,
  • Esther H. Zhou,
  • Gerald J. Dal Pan,
  • Thuy Nhu Thai,
  • Judith C. Maro,
  • Sonja A. Rasmussen,
  • Almut G. Winterstein

摘要

Introduction

Preventing fetal exposure to teratogenic medications is a public health priority. The Teratogenic Risk Impact Mitigation (TRIM) tool has been developed to support regulatory decisions regarding risk mitigation programs. One of the explicit TRIM criteria requires medication-specific quantification of fetal exposure risk.

Objective

To develop and compare population-based estimates of fetal exposure risk for medications with known teratogenicity.

Methods

This retrospective US population-based cohort study used claims data from Medicaid and MarketScan® databases from 01/2014 to 12/2018. Data were analyzed from 12/2023 to 12/2024. We included female patients aged 12–55 years with ≥ 1 teratogenic medication prescription. A validated algorithm identified pregnancies that ended with a live or non-live outcome among medication users. We estimated the fetal exposure rate as the number of pregnancies per at-risk medication exposure time, accounting for teratogenic risk profiles (e.g., ACE inhibitors exert risk in 2nd/3rd trimesters). Rates were averaged across databases to generate tertiles of high/medium/low fetal exposure risk.

Results

Among 59,815,213 female enrollees (31,905,714 Medicaid; 27,909,499 MarketScan), 12,819,073 used ≥ 1 teratogenic medication. Fetal exposure rates ranged from 0–1512 per 1000 user-years (tertiles: 2.9 and 11.5), with higher rates observed in Medicaid. Medications that exhibited high rates included fluconazole (1512/1000 user-years, 95% CI 1504.5–1518.6) and sulfamethoxazole/trimethoprim (295, 95% CI 233.6–492.2), vedolizumab (53, 95% CI 46.7–60.2) and several anticonvulsants. Two medications, phentermine-topiramate, with a current risk mitigation program, and fingolimod, with a released risk management program, were also ranked in the highest tertile. Fetal exposures to medications prescribed for acute conditions occurred more frequently through initiation during pregnancy, while those for chronic medications occurred mostly because of conception during treatment.

Conclusions

Fetal exposure risks differed across medications and populations, influenced by treatment chronicity, relevant teratogenic risk periods, and patient demographics, which can inform the development of risk mitigation programs. Data gleaned from this analysis will be used as an ordinal “fetal exposure risk” criterion score in our development of the TRIM decision tool.