Kayoko Hishinuma1, Ritsuko Yamane1, Ikuko Yokoo2, Takahide Arimoto2, Kunihiko Takahashi3, Mikako Goto4, Yoshiyuki Saito5, Ken Nakajima6, Atsuko Murashima7, Masahiro Hayashi1. 1. Department of Pharmacy, Toranomon Hospital, Minato-ku, Tokyo, Japan. 2. Department of Obstetrics and Gynecology, Toranomon Hospital, Minato-ku, Tokyo, Japan. 3. Department of Biostatistics, M&D Data Science Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan. 4. The Japan Drug Information Institute in Pregnancy, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan. 5. Human Health Sciences, Kyoto University Graduate School of Medicine, Sakyo-ku, Tokyo, Japan. 6. Department of Pharmacy, Yokohama Minami Kyousai Hospital, Yokohama, Kanagawa, Japan. 7. Center of Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan.
Abstract
AIM: To assess the teratogenic risk of domperidone by comparing the incidence of major malformation with domperidone to a control. METHODS: Pregnancy outcome data were obtained for women at two Japanese facilities that provide counseling on drug use during pregnancy between April 1988 and December 2017. The incidence of major malformation was calculated among infants born to women taking domperidone (n = 519), nonteratogenic drugs (control, n = 1673), or metoclopramide (reference, n = 241) during the first trimester of pregnancy. Using the control group as reference, the crude odds ratio (OR) of the incidence of major malformation in the domperidone and metoclopramide groups was calculated using univariable logistic regression analysis. Adjusted OR was also calculated using multivariable logistic regression analysis adjusted for various other factors. RESULTS: The incidence of major malformation was 2.9% (14/485, 95% confidence interval [CI]: 1.6-4.8) in the domperidone group, 1.7% (27/1554, 95%CI: 1.1-2.5) in the control group, and 3.6% (8/224, 95%CI: 1.6-6.9) in the metoclopramide group. The adjusted multivariable logistic regression analysis showed no significant difference in incidence between the control and domperidone groups (adjusted OR: 1.86 [95%CI: 0.73-4.70], p = 0.191) or between the control and metoclopramide groups (adjusted OR: 2.20 [95%CI: 0.69-6.98], p = 0.183). CONCLUSIONS: This observational cohort study showed that domperidone exposure during the first trimester was not associated with increased risk of major malformation in infants. These results may help alleviate the anxiety of patients who took domperidone during pregnancy.
AIM: To assess the teratogenic risk of domperidone by comparing the incidence of major malformation with domperidone to a control. METHODS: Pregnancy outcome data were obtained for women at two Japanese facilities that provide counseling on drug use during pregnancy between April 1988 and December 2017. The incidence of major malformation was calculated among infants born to women taking domperidone (n = 519), nonteratogenic drugs (control, n = 1673), or metoclopramide (reference, n = 241) during the first trimester of pregnancy. Using the control group as reference, the crude odds ratio (OR) of the incidence of major malformation in the domperidone and metoclopramide groups was calculated using univariable logistic regression analysis. Adjusted OR was also calculated using multivariable logistic regression analysis adjusted for various other factors. RESULTS: The incidence of major malformation was 2.9% (14/485, 95% confidence interval [CI]: 1.6-4.8) in the domperidone group, 1.7% (27/1554, 95%CI: 1.1-2.5) in the control group, and 3.6% (8/224, 95%CI: 1.6-6.9) in the metoclopramide group. The adjusted multivariable logistic regression analysis showed no significant difference in incidence between the control and domperidone groups (adjusted OR: 1.86 [95%CI: 0.73-4.70], p = 0.191) or between the control and metoclopramide groups (adjusted OR: 2.20 [95%CI: 0.69-6.98], p = 0.183). CONCLUSIONS: This observational cohort study showed that domperidone exposure during the first trimester was not associated with increased risk of major malformation in infants. These results may help alleviate the anxiety of patients who took domperidone during pregnancy.