{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:50:44Z","timestamp":1786114244473,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>Canada's 2009 risk management plan (RMP) framework has not been evaluated for prenatal exposure impact. Conversely, widely used drugs such as nonsteroidal anti\u2010inflammatory drugs (NSAIDs) lack RMPs. We assessed first\u2010trimester exposure to RMP\u2010regulated medications following regulatory interventions and to NSAIDs following safety publications. We conducted interrupted time series analyses using data from the Qu\u00e9bec Pregnancy Cohort (1998\u20132022), including pregnancies among individuals aged 15\u201345\u2009years with continuous public prescription drug insurance. First\u2010trimester exposure was defined as dispensed prescriptions overlapping or initiated during gestational weeks 0\u201314. Exposures included RMP\u2010regulated medications (overall, retinoids, and valproic acid) and prescription NSAIDs. RMP dates served as interruption points. Monthly incidence rates were analyzed using segmented Poisson regression to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs). Among 559,215 eligible pregnancies, 6,215 and 87,820 involved first\u2010trimester exposure to RMP\u2010regulated medications and NSAIDs, respectively. The Canadian RMP framework was associated with an immediate 45.3% reduction (IRR: 0.547, 95% CI: 0.403\u20130.743) and a sustained 1.3% monthly decline (IRR: 0.987, 95% CI: 0.981\u20130.994). Retinoid exposure declined by 12.5% per month post\u2010SMART RMP (IRR: 0.875, 95% CI: 0.772\u20130.993), with reductions post\u2010iPLEDGE RMP (IRR: 0.949, 95% CI: 0.932\u20130.966). Valproic acid exposure declined after the strengthened FDA boxed warning (IRR: 0.869, 95% CI: 0.836\u20130.903) and migraine prophylaxis contraindication (IRR: 0.754, 95% CI: 0.543\u20131.046). NSAID publications yielded transient effects. RMPs were associated with sustained prenatal exposure reductions, whereas safety publications were associated with transient effects, highlighting the need for reinforced risk\u2010management strategies.<\/jats:p>","DOI":"10.1002\/cpt.70353","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:50:49Z","timestamp":1780635049000},"page":"721-730","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reducing Exposure Before Birth: An Interrupted Time Series Study of Prenatal Exposure to Fetotoxic Medications Under Risk Management Plans in Canada"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0716-9590","authenticated-orcid":false,"given":"Nahiyan Saiyara","family":"Khan","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy University of Montreal  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Research Center Sainte\u2010Justine University Hospital Center  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6784-2080","authenticated-orcid":false,"given":"Odile","family":"Sheehy","sequence":"additional","affiliation":[{"name":"Research Center Sainte\u2010Justine University Hospital Center  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4151-8960","authenticated-orcid":false,"given":"Lisiane Freitas","family":"Leal","sequence":"additional","affiliation":[{"name":"Research Center Sainte\u2010Justine University Hospital Center  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4391-5166","authenticated-orcid":false,"given":"Vanina","family":"Tchuente","sequence":"additional","affiliation":[{"name":"Research Center Sainte\u2010Justine University Hospital Center  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7535-5517","authenticated-orcid":false,"given":"Anick","family":"B\u00e9rard","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Montreal  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Research Center Sainte\u2010Justine University Hospital Center  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12884-015-0745-3"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2021.1893296"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajo.13044"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.54298"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30315-6"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20132"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2022.01.004"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr088"},{"key":"e_1_2_10_9_1","unstructured":"Council for International Organizations of Medical Sciences (CIOMS).Practical approaches to risk minimisation for medicinal products. 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