Protocol of a prospective and multicentre China Teratology Birth Cohort (CTBC): association of maternal drug exposure during pregnancy with adverse pregnancy outcomes

Abstract

Background As reported, 27-93 % of pregnant women take at least one drug during pregnancy. However, drug exposure during pregnancy still lacks sufficient foetal safety evidence of human origin. It is urgent to fill the knowledge gap about medication safety during pregnancy for optimization of maternal disease treatment and pregnancy drug consultation. Methods and analysis The China Teratology Birth Cohort (CTBC) was established in 2019 and is a hospital-based open-ended prospective cohort study with the aim of assessing drug safety during pregnancy. Pregnant women who set up the pregnancy health records in the first trimester or who seek drug consultation regardless of gestational age in the member hospitals are recruited. Enrolled pregnant women need to be investigated four times, namely, 6–14 and 24–28 weeks of gestational age, before discharge after hospital delivery, and 28–42 days after birth. Maternal medication exposure during pregnancy is the focus of the CTBC. For drugs, information on the type, name, and route of medication; start and end time of medication; single dose; frequency of medication; dosage form; manufacturer; and reason for medication is collected. The adverse pregnancy outcomes collected in the study include birth defects, stillbirth, spontaneous abortion, preterm birth, post-term birth, low birth weight, macrosomia, small for gestational age, large for gestational age and low Apgar score. CTBC uses an electronic questionnaire for data collection and a cloud system for data management. Biological samples are collected if informed consents are obtained. Multi-level logistic regression, mixed-effect negative binomial distribution regression and spline function regression are used to explore the effect of drugs on the occurrence of birth defects. Discussion The findings of the study will assist in further understanding the risk of birth defects and other adverse pregnancy outcomes associated with maternal drug exposure and developing the optimal treatment plans and drug counselling for pregnant women. Trial registration This study was approved by the Research Ethics Committee of the West China Second Hospital of Sichuan University and registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx, registration number ChiCTR1900022569).

The maternal drug exposure birth cohort (DEBC) in China

“…However, internationally, there have been very rare cohorts specifically focusing on maternal medication exposure during pregnancy. China Teratology Birth Cohort (CTBC), which was expected to recruit at least 300,000 participants 12 , was a hospital-based, open-ended prospective cohort study with the aim to assess the risk of birth defects and other adverse pregnancy outcomes associated with maternal environmental and behavioral exposures during pregnancy. The current maternal drug exposure birth cohort (DEBC) was a sub-cohort of CTBC, aiming to explore the impact of maternal drug exposure during pregnancy on pregnancy outcomes, and to establish a biobank of high-quality and well-annotated human biospecimens for further research on the mechanisms of fetal health and diseases.…”

“…The cohort study was launched on August 1, 2018, and aimed to recruit 150,000 pregnant women. The recruitment was implemented with the cooperation of 49 hospitals at different levels (including tertiary or secondary hospitals) from 15 Provinces in China, of which Sichuan Province made the major contribution 12 .…”

“…4 ). The designed structured questionnaires were given at each pregnancy stage through a mobile APP or face-to-face interviews 12 . Maternal medical charts, clinical laboratory measurements from each follow-up and the pregnancy outcomes were abstracted from medical records by our obstetricians or investigators.…”

“…The health status part of the questionnaire focused on the detailed information about drug exposure, including drug name, exposure time and duration, route, dose, frequency, and reason of administration during pregnancy. The detailed information in this questionnaire has been reported 12 . The questionnaires given in the second and the third trimester mainly focused on the medication, pregnancy complications, nutraceuticals, and sleep condition.…”