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

Abstract

Chinese herbal medicines (CHM) 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. The aim of this descriptive cohort study was to systematically investigate the use of CHM throughout the pregnancy and their safety profiles. We developed a large medication use cohort by linking a population-based pregnancy registry and a population-based pharmacy database, which documented all prescriptions both at outpatients and inpatients from conception to 7 days after delivery, including pharmaceutical drugs and processed CHM formula that were approved by regulatory authority and prepared under the guidance of national quality standards. We investigated the prevalence of CHM formula use, prescription pattern and combination use of pharmaceutical drugs throughout the pregnancy life course. Multivariable log-binomial regression was conducted to assess temporal trend, and further explore the potential characteristics associated with the CHM use. Two authors independently conducted a qualitative systematic review of patientpackageinserts (PPI) of top 100 CHM formula use to identify their safety profiles. Our study included 199,710 pregnancies; of those, 65.71% (131,235/199,710) were administered with CHM formula, including 26.13% during pregnancy (corresponding to 14.00%, 8.91% and 8.26% in the first, second, and third trimesters), and 55.63% at post-delivery. The peak uses of CHM occurred between the 5th and 10th weeks. The use of CHM significantly increased over the years (63.28% in 2014 to 69.59% in 2018, adjusted relative risk [aRR]: 1.11, 95% CI: 1.10-1.13), which was particularly great during pregnancy (18.47% to 32.46%, 1.84, 95% CI: 1.77-1.90). Our study observed 291,836 prescriptions involving 469 CHM formula, and the 100 mostly used CHM 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 injections. However, CHM were very often prescribed in combination with pharmaceutical drugs (overall 94.96%), involving 1,175 pharmaceutical drugs with 1,667,459 prescriptions. A median of 10 (IQR: 5-18) pharmaceutical drugs was prescribed in combination with CHM per pregnancy. The systematic review of drug patient package inserts found that the 100 most frequently prescribed CHM contained a total of 240 herb constituents (median 4.5); 7% 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 medication has any reproductive toxicity, is excreted in human milk or may cross the placenta. The use of CHM was prevalent throughout the pregnancy and increased over years. The CHM use peaked at the first trimester and was very often used in combination with pharmaceutical drugs. However, their safety profiles were mostly unclear or incomplete, warranting a strong need for post-approval surveillance for CHM use during pregnancy life course.