Association Between Exposure to Kampo Medicines Containing Ephedra and Major Congenital Malformations: A Japanese Administrative Claims Database Study

Aim Traditional Japanese (Kampo) medicines containing ephedra (KE) are prescribed for cold during pregnancy; however, detailed safety information on their use in pregnant women is lacking. This study aimed to clarify the association between prescription of KE during the first trimester of pregnancy and major congenital malformations (MCMs) in newborns. Methods Data from a large Japanese administrative claims database were analyzed: we included records of pregnant women who continued to be covered in the same health insurance society from 3 months before pregnancy until delivery, who gave birth between 2010 and 2019; the selected records included data relating to the infants until first year from birth. Pregnant women who were prescribed acetaminophen, commonly used to treat colds, in the first trimester of pregnancy and their infants were treated as the controls in our analysis. Results Of 75,398 infants, 4607 (6.1%) were diagnosed with MCMs within the first year of birth. Among the 7820 infants whose mothers were prescribed acetaminophen, 497 (6.4%) had MCMs. Of the 4772 infants were born to women prescribed KE, among whom 327 (6.9%) had MCMs. adjusting for covariates with propensity score overlap weights identified no significant difference in MCM risk between the two types of prescriptions (overlap‐weighted odds ratio 1.077, 95% confidence interval 0.932−1.245). Conclusion The results of this study indicated that the risk of MCMs did not differ between women prescribed KE and those prescribed acetaminophen in the first trimester of pregnancy.