Investigation of connection between taking tranquilizer benzodiazepine in early stage of pregnancy and teratogenesis of newborn
by Research Team of Professor Shin Ju-Young from School of Pharmacy

-Confirmed connection between dose of benzodiazepine during early stage of pregnancy and teratogenesis of newborn

-Paper published on renowned international medicine journal ‘PLOS Medicine’

[Image] Prof. Ju-Young Shin, Dr. Yoon-Ha Noh, Dr. Hye-Eung Lee, Researcher Ah-Hyung Choi (From the left) 

SKKU (President Shin Dong-Ryeol) announced that professor Shin Ju-Young’s research team from School of Pharmacy (co-first author: Dr. No Yoon-Ha, Dr. Lee Hye-Sung, co-author: Researcher Choi Ah-Hyung) confirmed dose of benzodiazepine in early stage of pregnancy can increase the risk of newborn teratogenesis through large-scale stability research of pregnant women using domestic health care big data.

Benzodiazepine has been widely used for curing or alleviating mental illnesses such as insomnia, anxiety disorder, panic disorder ever since its first sale on market in the 1960s. Domestically, it is also used for neurotic-gastrointestinal or musculoskeletal diseases and according to an OECD report, the domestic elderly benzodiazepine prescription rate is about three times higher than OECD nations average rate.

Benzodiazepine not only accumulates in fetal tissue by penetrating through placenta but also gets involved in cell multiplication and differentiation. About 1-2% out of total pregnant women have received prescription of benzodiazepine, meaning that a substantial number of pregnant women are taking it in their early stages of pregnancy. However, despite the drug’s long history and its wide usage, the dosage of benzodiazepine during pregnancy was not proved safe clearly.

Thus, the research team conducted joint research with Seoul National University Hospital Neuropsychiatry Professor Kwon Jun-soo and Korea University, College of Medicine, Preventive Medicine Professor Choe Seung-Ah. And to prepare high-quality safety basis of benzodiazepine usage during pregnancy, the research team carried out large scale cohort study of pregnant woman using Health Insurance Claim Data of Health Insurance Review and Assessment Service.

Among all the pregnant women who have birth record from 2011 to 2018, the research team compared pregnant woman who took benzodiazepine (exposure group, 40,846) and those who did not (control group, 3,053,831) and the comparison result concluded a correlation that dosage of benzodiazepine increases teratogenesis and cardiac anomaly risks by 1.09 and 1.15 times, accordingly. Especially, overall teratogenesis increases to 1.26 times the original in >2.5mg/day group compared to average daily dosage <1 mg/day group, inferring that more daily average dosage of benzodiazepine can result in higher risk of teratogenesis.

Professor Shin Ju-Young asserted, “Taking Benzodiazepine in the early stage of pregnancy significantly increases risk of overall teratogenesis, especially cardiac anomaly, and risks aggravate in high dosage group than that of low dosage group. However, among total teratogenesis, population attributable risk of benzodiazepine is small, 0.36%, implying that benzodiazepine is not the major teratogenic drug.

The research team said, “Keep in mind that the research result does not prohibit the use of benzodiazepine in the early stage of pregnancy. This research assesses the risk of the drug and thus it must be evaluated with therapeutic effects as well. But high dosage does appear to have higher risks so if usage of benzodiazepine is inevitable, then minimum effective dose prescription must be prioritized to reduce potential threats on fetus.”

This research paper was published on renowned international medicine journal ‘PLOS Medicine (Impact Factor=11.069, JCR ranking Top 5.7%)’, on March 3rd.

※ Paper Title: First-trimester exposure to benzodiazepines and risk of congenital malformations in offspring: A population-based cohort study in South Korea

※ Original Paper: https://doi.org/10.1371/journal.pmed.1003945