Maternal and Neonatal Outcomes Following Exposure to Benzodiazepines During Pregnancy

Study Overview
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Brief Summary
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This is a nationwide cohort study to assess maternal and neonatal outcomes following exposure to benzodiazepines during pregnancy.

Detailed Description
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Benzodiazepines are widely used in pregnant women; however, their safety on congenital malformations in a real-world setting is still uncertain. We aimed to assess the association between benzodiazepine use in early pregnancy and the risk of congenital malformations. We will conduct a retrospective nationwide cohort study using the Health Insurance Review and Assessment (HIRA) database of South Korea, which covers the entire South Korean population.

Official Title
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Maternal and Neonatal Outcomes Following Benzodiazepine Use During Pregnancy

Conditions
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Pregnancy Related, Benzodiazepines Causing Adverse Effects in Therapeutic Use, Congenital Anomaly

Intervention / Treatment
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* Drug: Benzodiazepine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnancies with live birth, 2011-2018 Pregnancies linked to liveborn infants Pregnancies aged 20-45 years at delivery Exclusion Criteria: Pregnancies with a chromosomal abnormality Pregnancies with exposure to known teratogenic drugs (e.g. antineoplastic agent, warfarin, lithium, isotretinoin, misoprostol, thalidomide) during the first trimester Pregnancies with no benzodiazepine prescription during the first trimester, but with at least one benzodiazepine prescription during the 3 months before the pregnancy onset

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pregnant women with exposure to benzodiazepines<br>Women who gave birth during 2011-2018, were aged 20-45 years and were filled at least one benzodiazepine prescription during the first trimester (first 90 days of pregnancy). | Drug: Benzodiazepine<br>* Exposure to benzodiazepine during early pregnancy<br>|
| Pregnant women without exposure to benzodiazepines<br>Women who gave birth during 2011-2018, were aged 20-45 years and did not fill a benzodiazepine prescription during the 3 months before the pregnancy onset through the end of the first trimester | Drug: Benzodiazepine<br>* Exposure to benzodiazepine during early pregnancy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of congenital malformations | Overall congenital malformations and organ-specific congenital malformations in infants, which are confirmed by diagnostic records in the HIRA database. All infants were followed up for at least 1 year. | from the birth date until up to 8 years, death, or study end date (Dec 31, 2019) |