Clinical trial NCT04856436: Maternal and Neonatal Outcomes Following Exposure to Benzodiazepines During Pregnancy
Official title: Maternal and Neonatal Outcomes Following Benzodiazepine Use During Pregnancy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pregnancy Related
Benzodiazepines Causing Adverse Effects in Therapeutic Use
Congenital Anomaly
Lead sponsor: Sungkyunkwan University
Sponsor class: OTHER
Collaborators: name: National Research Foundation of Korea
First posted: 2021-04-23
Enrollment: 3094227
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Pregnant women who gave birth in South Korea between 2011 and 2018

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Risk of congenital malformations
timeFrame: from the birth date until up to 8 years, death, or study end date (Dec 31, 2019)
Secondary outcomes:
Other outcomes:
Locations:
city: Suwon
country: Korea, Republic of
facility: Sungkyunkwan University
state: Gyeonggi-do
Study officials:
affiliation: Sungkyunkwan University
name: Ju-Young Shin, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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):18r12412. doi: 10.4088/JCP.18r12412.
citation: 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.
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. doi: 10.1176/appi.ps.53.1.39.
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.
citation: 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.