(280) Miscarriage Preventing Herbal Medicines and the Risk of Birth Defects: A Population-Based Cohort Study of 195,824 Pregnancies

Background: Herbal medicines have a long history of use for pregnant women around the world. However, their uses at the early gestation are often questioned regarding safety on offspring.

Objectives: To examine whether miscarriage-preventing herbal medicines, the main type of herbal medicines used at the early gestation, are associated higher risk of birth defects.

Methods: This is a population-based cohort study, which included pregnancies registered at a population-based and long-term follow-up database (i.e., REPRESENT) and underwent live births between January 2013 and December 2018, by linking a population-based drug prescription database covered all the hospitals in Xiamen, China. The exposure of interest was defined as consecutive administration of one or more prescriptions of herbal medicines for preventing miscarriage during the first trimester. The overall birth defects (excluding chromosomal malformations) and 23 individual types by national surveillance were the main outcomes. To facilitate comparison, we included blank (non-use) and active control. The association between miscarriage-preventing herbal medicines and birth defects was accessed by using a propensity score matching (PSM) based Poisson regression. Several sensitivity analyses and negative control analyses were conducted to examine the robustness.

Results: The final cohort included 195,824 pregnancies, and 29,063 (14.8%) were prescribed with an herbal medicine at early pregnancy among which 3,024 (1.5%) received a monotherapy of miscarriage preventing herbal medicine. In total, 2,795 birth defects were identified. Compared to no use of drug (i.e., blank control), herbal medicine monotherapy was not associated with a higher risk of overall birth defects (risk ratio [RR] 1.25, 95% CI 0.69-2.29). Compared to progesterone monotherapy (i.e., active control), pregnancies with herbal medicine monotherapy showed a similar risk (RR 1.28, 95% CI 0.57-2.90). Consistent results were shown in sensitivity analyses.

Conclusions: The current evidence did not suggest increased risk of birth defects when using herbal medicines at early pregnancy for preventing miscarriage. Although larger studies are desirable, the current study was the first case that involved a population-based data for assessing the safety of herbal medicines used during pregnancy.