Maternal and Neonatal Outcomes Following Exposure to Benzodiazepines During Pregnancy

Pregnancy Related Clinical Trial

Official title:

Maternal and Neonatal Outcomes Following Benzodiazepine Use During Pregnancy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04856436
• Other study ID #: SKKU-2021-PREG-BZ
• Status: Completed
• Start date: December 1, 2020
• Est. completion date: July 30, 2021

Study information

• Verified date: March 2022
• Source: Sungkyunkwan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3094227
• Est. completion date: July 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Congenital Abnormalities
• Congenital Anomaly
• Pregnancy Related

Intervention

Drug:
• Benzodiazepine
Exposure to benzodiazepine during early pregnancy

Locations

Country	Name	City	State
Korea, Republic of	Sungkyunkwan University	Suwon	Gyeonggi-do

Sponsors (2)

Lead Sponsor	Collaborator
Sungkyunkwan University	National Research Foundation of Korea

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (5)

Bais B, Molenaar NM, Bijma HH, Hoogendijk WJG, Mulder CL, Luik AI, Lambregtse-van den Berg MP, Kamperman AM. Prevalence of benzodiazepines and benzodiazepine-related drugs exposure before, during and after pregnancy: A systematic review and meta-analysis. J Affect Disord. 2020 May 15;269:18-27. doi: 10.1016/j.jad.2020.03.014. Epub 2020 Mar 5. Review. — View Citation

Bellantuono C, Tofani S, Di Sciascio G, Santone G. Benzodiazepine exposure in pregnancy and risk of major malformations: a critical overview. Gen Hosp Psychiatry. 2013 Jan-Feb;35(1):3-8. doi: 10.1016/j.genhosppsych.2012.09.003. Epub 2012 Oct 6. Review. — View Citation

Grigoriadis S, Graves L, Peer M, Mamisashvili L, Dennis CL, Vigod SN, Steiner M, Brown C, Cheung A, Dawson H, Rector N, Guenette M, Richter M. Benzodiazepine Use During Pregnancy Alone or in Combination With an Antidepressant and Congenital Malformations: Systematic Review and Meta-Analysis. J Clin Psychiatry. 2019 Jul 9;80(4). pii: 18r12412. doi: 10.4088/JCP.18r12412. — View Citation

Iqbal MM, Sobhan T, Ryals T. Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant. Psychiatr Serv. 2002 Jan;53(1):39-49. Review. — View Citation

Shyken JM, Babbar S, Babbar S, Forinash A. Benzodiazepines in Pregnancy. Clin Obstet Gynecol. 2019 Mar;62(1):156-167. doi: 10.1097/GRF.0000000000000417. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)