Maternal characteristics and pregnancy outcomes among pregnancies exposed to a teratogenic drug.

Maternal characteristics and pregnancy outcomes among pregnancies exposed to a teratogenic drug.</p

Flow chart.

ObjectiveDescribe the trends of exposure to harmful drugs during pregnancy over recent years in France.DesignNationwide cohort study.SettingThe French National administrative health Data System (SNDS).PopulationPregnancies starting between 2013 and 2019 and outcomes corresponding to live births, medical terminations of pregnancy, and stillbirths.MethodsEach pregnancy was divided into a preconceptional period of 90 days before conception and three trimesters from conception to birth. Harmful drugs were defined according to their risks to the fetus: teratogenicity or fetotoxicity. Exposure was defined using the critical period during pregnancy for each type of harmful drug: preconceptional period or first trimester for teratogenic drugs and second or third trimesters for fetotoxic drugs.Main outcome measuresPrevalence of pregnancies exposed to at least one harmful drug.ResultsAmong 5,253,284 pregnancies, 204,402 (389 per 10,000) pregnancies were exposed to at least one harmful drug during the critical periods: 48,326 (92 per 10,000) pregnancies were exposed to teratogenic drugs during the preconceptional period or the first trimester, and 155,514 (299 per 10,000) pregnancies were exposed to fetotoxic drugs during the second or third trimesters. Teratogenic drugs were mainly retinoids for topical use (44 per 10,000 pregnancies), antiepileptics (13 per 10,000 pregnancies) and statins (13 per 10,000 pregnancies). Fetotoxic drugs were mainly non-steroidal anti-inflammatory drugs (NSAIDs), for systemic (128 per 10,000 pregnancies) and topical use (122 per 10,000 pregnancies). Exposure to teratogenic drugs decreased from the preconceptional period to the first trimester. Exposure to fetotoxic drugs decreased from the second to the third trimester. Between 2013 and 2019, we found a decrease in harmful drug exposure overall, mainly for topical and systemic NSAIDs and for topical retinoids.ConclusionsIn this nationwide study, about one in 25 pregnancies was exposed to at least one harmful drug, mainly NSAIDs and topical retinoids. Although the prevalence of harmful drug exposure decreased over the study period, NSAID exposure in the second and third trimester remains of concern.</div

Trends of exposure to fetotoxic drugs during the second or the third trimester for pregnancies starting between 2013 and 2019 in France.

The p-values indicate whether a statistically significant trend was observed between 2013 and 2019. A. Overall fetotoxic drugs. Overall fetotoxic drugs with topical NSAIDs and overall fetotoxic drugs without topical NSAIDs. Trends were significant for: all fetotoxic drugs (p−3), and all fetotoxic drugs without topical forms (p−3). B. Any fetotoxic drug. Trends were significant for: contraceptives (p−3), non-steroids anti-inflammatory drugs for systemic use (p−3), non-steroids anti-inflammatory drugs for topical use (p−3), sex hormones (p−3). C. NSAIDs for systemic use. Trends were significant for: acetylsalicylic acid (p−3), diclofenac (p−3), flurbiprofen (p−3). D. NSAIDs for topical use. Trends were significant for: diclofenac (p−3), ibuprofen (p−3), ketoprofen (p−3), niflumic acid (p−3). E. Sex hormone. Trends were significant for: clomifene (p−3), promestriene (p−3).</p

Teratogenic drug exposure according to pregnancy period.

Number of pregnancies (rate per 10,000 pregnancies). (PDF)</p

Maternal and pregnancy outcome characteristics among pregnancies exposed to at least one teratogenic drug (sensitivity analysis without topical retinoids).

Maternal and pregnancy outcome characteristics among pregnancies exposed to at least one teratogenic drug (sensitivity analysis without topical retinoids).</p

Trends in teratogenic drug exposure during pregnancy between 2013 and 2019.

Number of pregnancies (rate per 10,000 pregnancies). (PDF)</p

Maternal characteristics and pregnancy outcomes according to exposure to harmful drugs.

Maternal characteristics and pregnancy outcomes according to exposure to harmful drugs.</p

Maternal and pregnancy outcome characteristics among pregnancies exposed to at least one fetotoxic drug (sensitivity analysis without topical NSAIDs).

Maternal and pregnancy outcome characteristics among pregnancies exposed to at least one fetotoxic drug (sensitivity analysis without topical NSAIDs).</p

Trends in foetotoxic drug exposure during pregnancy between 2013 and 2019.

Number of pregnancies (rate per 10,000 pregnancies). (PDF)</p

List of harmful drugs.

ObjectiveDescribe the trends of exposure to harmful drugs during pregnancy over recent years in France.DesignNationwide cohort study.SettingThe French National administrative health Data System (SNDS).PopulationPregnancies starting between 2013 and 2019 and outcomes corresponding to live births, medical terminations of pregnancy, and stillbirths.MethodsEach pregnancy was divided into a preconceptional period of 90 days before conception and three trimesters from conception to birth. Harmful drugs were defined according to their risks to the fetus: teratogenicity or fetotoxicity. Exposure was defined using the critical period during pregnancy for each type of harmful drug: preconceptional period or first trimester for teratogenic drugs and second or third trimesters for fetotoxic drugs.Main outcome measuresPrevalence of pregnancies exposed to at least one harmful drug.ResultsAmong 5,253,284 pregnancies, 204,402 (389 per 10,000) pregnancies were exposed to at least one harmful drug during the critical periods: 48,326 (92 per 10,000) pregnancies were exposed to teratogenic drugs during the preconceptional period or the first trimester, and 155,514 (299 per 10,000) pregnancies were exposed to fetotoxic drugs during the second or third trimesters. Teratogenic drugs were mainly retinoids for topical use (44 per 10,000 pregnancies), antiepileptics (13 per 10,000 pregnancies) and statins (13 per 10,000 pregnancies). Fetotoxic drugs were mainly non-steroidal anti-inflammatory drugs (NSAIDs), for systemic (128 per 10,000 pregnancies) and topical use (122 per 10,000 pregnancies). Exposure to teratogenic drugs decreased from the preconceptional period to the first trimester. Exposure to fetotoxic drugs decreased from the second to the third trimester. Between 2013 and 2019, we found a decrease in harmful drug exposure overall, mainly for topical and systemic NSAIDs and for topical retinoids.ConclusionsIn this nationwide study, about one in 25 pregnancies was exposed to at least one harmful drug, mainly NSAIDs and topical retinoids. Although the prevalence of harmful drug exposure decreased over the study period, NSAID exposure in the second and third trimester remains of concern.</div