Maternal and Neonatal Outcomes Following Exposure to Benzodiazepines During Pregnancy

NCT04856436 | Completed

• 1 other identifier: SKKU-2021-PREG-BZ
• Study Type: observational
• Target: 3,094,227
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pregnancy Related; Benzodiazepines Causing Adverse Effects in Therapeutic Use; Congenital Anomaly

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (2)

Pregnant women with exposure to benzodiazepines

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

Pregnant women without exposure to benzodiazepines

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

Interventions

Benzodiazepine DRUG

Exposure to benzodiazepine during early pregnancy

Pregnant women with exposure to benzodiazepines; Pregnant women without exposure to benzodiazepines

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Pregnant women who gave birth in South Korea between 2011 and 2018

You may qualify if:

• Pregnancies with live birth, 2011-2018
• Pregnancies linked to liveborn infants
• Pregnancies aged 20-45 years at delivery

You may not qualify if:

• 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

Sponsors & Collaborators

• Sungkyunkwan University: lead
• National Research Foundation of Korea: collaborator

Study Sites (1)

Sungkyunkwan University

Suwon, Gyeonggi-do, 16419, South Korea

Location

Related Publications (6)

• 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.

  PMID: 23044244 BACKGROUND

• 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):18r12412. doi: 10.4088/JCP.18r12412.

  PMID: 31294935 BACKGROUND

• 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.

  PMID: 32217339 BACKGROUND

• 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. doi: 10.1176/appi.ps.53.1.39.

  PMID: 11773648 BACKGROUND

• 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.

  PMID: 30628916 BACKGROUND

• Noh Y, Lee H, Choi A, Kwon JS, Choe SA, Chae J, Kim DS, Shin JY. First-trimester exposure to benzodiazepines and risk of congenital malformations in offspring: A population-based cohort study in South Korea. PLoS Med. 2022 Mar 2;19(3):e1003945. doi: 10.1371/journal.pmed.1003945. eCollection 2022 Mar.

  PMID: 35235572 DERIVED

MeSH Terms

Conditions

Congenital Abnormalities

Interventions

Benzodiazepines

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ju-Young Shin, PhD

  Sungkyunkwan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: April 23, 2021
• Study Start: December 1, 2020
• Primary Completion: June 30, 2021
• Study Completion: July 30, 2021
• Last Updated: March 7, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)