Miscarriage Preventing Herbal Medicines and the Risk of Birth Defects: a Population-based Cohort Study

Using data from a population-based medicine use cohort in Xiamen, China, this retrospective cohort study will investigate whether herbal medicines used to prevent miscarriage are associated with increased risk of birth defects.

Study Overview

• Status: Active, not recruiting
• Conditions: Pregnancy; Birth Defects; Drug Exposures
• Intervention / Treatment: Drug: Herbal medicines (e.g., Yunkang granules, Duzhong granules)

Detailed Description

Herbal medicines have a long history of use for pregnant women both in China and around the world. However, the safety of herbal medicines used at the early gestation is often questioned regarding their impact on offspring. Therefore, the aim of this study is to investigate whether miscarriage preventing herbal medicines associated with increased risk of birth defects.

A large medication use cohort will be developed by linking a population-based pregnancy registry (i.e., REPRESENT) and a population-based pharmacy database, which documented all prescriptions at both outpatients and inpatients from conception to delivery. This cohort will include herbal medicines formula which were granted approval by the Chinese National Medical Products Administration.

Using data from this cohort, the investigators will investigate the prevalence of the use of herbal medicine formulas and prescription patterns at the first trimester. This study will then investigate the association between miscarriage preventing herbal medicines and the risk of birth defects. A propensity score matching (PSM) based Poisson regression will be used to estimate the relative risk. To ensure the robustness of the results investigators will perform several sensitivity analyses and negative control analyses, such as restricting the population to women with singleton pregnancies, excluding individuals who had undergone in vitro fertilization (IVF), and considering those women who were prescribed herbal medicines during the middle and late stages of pregnancy as the negative exposure control group.

• Study Type: Observational
• Enrollment (Estimated): 200000

Contacts and Locations

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361008
      • Xiamen Health and Medical Big Data Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Between January 2013 and December 2018, all pregnant women who registered at the REPRESENT in Xiamen was included in this cohort.

Description

Inclusion Criteria:

• Pregnancies registered at REPRESENT and underwent live births between January 2013 and December 2018 were included.

Exclusion Criteria:

• (1) those with the first antenatal visit occurring after 20 gestational weeks, (2) those without timing records of the last menstrual period or delivery dates, (3) those with known factors related to birth defects (e.g.,syphilis positive, epilepsy), (4) those prescribed known medications associated with birth defects (e.g.,dezocine, diazepam).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Drug exposure; Herbal medicines	Drug: Herbal medicines (e.g., Yunkang granules, Duzhong granules); Herbal medicines (e.g., Yunkang granules, Duzhong granules) exposure at the early gestation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall birth defects (excluding chromosomal malformations)	Number of births with birth defects	From conception to 42 days after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
National monitored 23 main types of birth defects	Number of births with 23 major births defects defined by National Health Standard Criteria in the China national universal surveillance system	From conception to 42 days after delivery

Collaborators and Investigators

• Sponsor: West China Hospital
• Collaborators: Xiamen Health Commission; Xiamen Health and Medical Big Data Center
• Investigators: Study Chair: Xin Sun, PHD, Chinese Evidence-based Medicine Center, West China Hospital, Sichuan

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: September 14, 2023
• First Submitted That Met QC Criteria: September 14, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Cohort study; Birth defects; Herbal medicines; Drug exposures
• Additional Relevant MeSH Terms: Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital Abnormalities; Abortion, Spontaneous
• Other Study ID Numbers: HERB and BD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Following the policy of Xiamen Health Commission, research institutions could apply for data access by submitting a formal study protocol, subjected to approval by the Xiamen Health and Medical Big Data Center and the Chinese Evidence-based Medicine Center. Ethical review and research registration are mandatory for all studies.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No