The use of Chinese herbal medicines throughout the pregnancy life course and their safety profiles: a population-based cohort study.

BACKGROUND:Chinese herbal medicines have been long used among pregnant populations in China. However, despite the high susceptibility of this population to drug exposure, it continued to remain unclear about how often they were used, to what extent they were used at different pregnancy stages, and whether their use was based on sound safety profiles, particularly when used in combination with pharmaceutical drugs. OBJECTIVE:This descriptive cohort study aimed to systematically investigate the use of Chinese herbal medicines throughout pregnancy and their safety profiles. STUDY DESIGN:A large medication use cohort was developed by linking a population-based pregnancy registry and a population-based pharmacy database, which documented all prescriptions at both outpatients and inpatients from conception to 7 days after delivery, including pharmaceutical drugs and processed Chinese herbal medicine formulas that were approved by the regulatory authority and prepared under the guidance of national quality standards. The prevalence of the use of Chinese herbal medicine formulas, prescription pattern, and combination use of pharmaceutical drugs throughout pregnancy were investigated. Multivariable log-binomial regression was performed to assess temporal trends and further explore the potential characteristics associated with the use of Chinese herbal medicines. Of note, 2 authors independently conducted a qualitative systematic review of patient package inserts of the top 100 Chinese herbal medicine formulas used to identify their safety profiles. RESULTS:This study included 199,710 pregnancies; of those pregnancies, 131,235 (65.71%) used Chinese herbal medicine formulas, including 26.13% during pregnancy (corresponding to 14.00%, 8.91%, and 8.26% in the first, second, and third trimesters of pregnancy) and 55.63% after delivery. The peak uses of Chinese herbal medicines occurred between 5 and 10 weeks of gestation. The use of Chinese herbal medicines significantly increased over the years (from 63.28% in 2014 to 69.59% in 2018; adjusted relative risk, 1.11; 95% confidence interval, 1.10-1.13), which was particularly great during pregnancy (from 18.47% in 2014 to 32.46% in 2018; adjusted relative risk, 1.84; 95% confidence interval, 1.77-1.90). Our study observed 291,836 prescriptions involving 469 Chinese herbal medicine formulas, and the top 100 most used Chinese herbal medicines accounted for 98.28% of the total prescriptions. Of those, a third (33.39%) were dispensed at outpatient visits; 6.79% were external use, and 0.29% were administered intravenously. However, Chinese herbal medicines were very often prescribed in combination with pharmaceutical drugs (94.96% overall), involving 1175 pharmaceutical drugs with 1,667,459 prescriptions. The median of pharmaceutical drugs prescribed in combination with Chinese herbal medicines per pregnancy was 10 (interquartile range, 5-18). The systematic review of drug patient package inserts found that the 100 most frequently prescribed Chinese herbal medicines contained a total of 240 herb constituents (median, 4.5); 7.00% were explicitly indicated for pregnancy or postpartum conditions; 43.00% were reported with efficacy or safety data from randomized controlled trials. Information was lacking about whether the medications had any reproductive toxicity, were excreted in human milk, or crossed the placenta. CONCLUSION:The use of Chinese herbal medicines was prevalent throughout pregnancy and increased over the years. The use of Chinese herbal medicines peaked in the first trimester of pregnancy and was very often used in combination with pharmaceutical drugs. However, their safety profiles were mostly unclear or incomplete, suggesting a strong need for postapproval surveillance for the use of Chinese herbal medicines during pregnancy.