Pregnancy outcome after first trimester exposure to domperidone-An observational cohort study.

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.

Pregnancy outcomes after first-trimester exposure to fluoroquinolones: Findings based on an integrated database from two Japanese institutions.

Given the paucity of safety data on fluoroquinolone antibiotics in pregnancy, a prospective observational cohort study was conducted in pregnant women who sought help and advice on drug use at two teratology information institutes in Japan. The primary endpoint of the study was the incidence of major congenital anomalies. The study population included pregnant women exposed to (i) fluoroquinolones (fluoroquinolone group), (ii) ß-lactams (infectious control group), or (iii) other agents considered to be nonteratogenic in humans (nonteratogenic control group) during the first trimester. The frequency of major congenital anomalies was compared across groups using a logistic regression model that adjusted for maternal age, smoking status, drinking status, facility consulted, and time of consultation. The fluoroquinolone group consisted of 411 women who had 383 children born alive. The infectious control and nonteratogenic control groups consisted of 1416 and 1482 women who had 1322 and 1401 children born alive, respectively. The incidence of major congenital anomalies was 1.5%, 2.0%, and 1.6% in the fluoroquinolone group, infectious control, and nonteratogenic control groups, respectively. Logistic regression showed that fluoroquinolone exposure is not a significant risk factor for major congenital anomalies. In conclusion, first-trimester exposure to fluoroquinolone antibiotics was not associated with increased maternal or fetal risks.

Risk of major birth defects after first-trimester exposure to carbocisteine and ambroxol: A multicenter prospective cohort study using counseling data for drug safety during pregnancy.

To assess the risk of major birth defects after first-trimester exposure to carbocisteine and ambroxol during pregnancy, we conducted a prospective cohort study using counseling data for drug use during pregnancy provided by the Japan Drug Information Institute in Pregnancy and Toranomon Hospital. Counseling information, including drug usage and participants' demographic information, was collected between April 1988 and December 2017. Pregnancy outcome data, including major birth defects, were obtained using a questionnaire administered 1 month after delivery. The risks of major birth defects after first-trimester exposure to carbocisteine (n = 588) and ambroxol (n = 341) were compared with those of nonteratogenic drug use during the first trimester (n = 1525). The adjusted odds ratio (aORs) for major birth defects was calculated using a multiple logistic regression analysis adjusted for confounders. The incidence of major birth defects was 1.2% (7/588) and 2.1% (7/341) in the carbocisteine and ambroxol groups, respectively, which was comparable to the control group (26/1525, 1.7%). Results of multiple logistic regression demonstrated similar nonsignificant risks for both carbocisteine (aOR: 0.66, 95% confidence interval [CI]: 0.40-1.1, p = 0.11) and ambroxol (aOR: 1.1, 95% CI: 0.18-7.2, p = 0.88). No specific major birth defects were reported in the carbocisteine or ambroxol groups. This study demonstrated that carbocisteine and ambroxol exposure during the first trimester was not associated with an increased risk of major birth defects. These results could help in counseling for the use of these drugs during pregnancy and further alleviate anxiety in patients.

The safety of pranlukast and montelukast during the first trimester of pregnancy: A prospective, two-centered cohort study in Japan.

For leukotriene receptor antagonists (LTRAs), especially pranlukast, safety data during pregnancy is limited. Therefore, we conducted a prospective, two-centered cohort study using data from teratogen information services in Japan to clarify the effects of LTRA exposure during pregnancy on maternal and fetal outcomes. Pregnant women who being counseled on drug use during pregnancy at two facilities were enrolled. The primary outcome of this study was major congenital anomalies. The incidence of major congenital anomalies in women exposed to montelukast or pranlukast during the first trimester of pregnancy was compared with that of controls. Logistic regression analysis was performed to analyze the effects of maternal LTRA use during the first trimester of pregnancy on major congenital anomalies. The outcomes of 231 pregnant women exposed to LTRAs (montelukast n = 122; pranlukast n = 106; both n = 3) and 212 live births were compared with those of controls. The rate of major congenital anomalies in the LTRA group was 1.9%. Multivariable logistic regression analysis revealed that LTRA exposure was not a risk factor for major congenital anomalies (adjusted odds ratio, 0.78; 95% confidence interval, 0.23-2.05; p = 0.653). In addition, no significant difference was detected in stillbirth, spontaneous abortion, preterm birth, and low birth weight between the two groups. The present study revealed that montelukast and pranlukast were not associated with the risk of major congenital anomalies. Our findings suggest that LTRAs could be safely employed for asthma therapy during pregnancy.