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• Methyldopa and amlodipine were the most frequently prescribed in the first trimester. • Nifedipine was the most frequently prescribed antihypertensive during pregnancy. • The MCM risk of first-trimester antihypertensives was not suggested. • The MCM risk of first-trimester amlodipine and methyldopa was not suggested. To evaluate the major congenital malformation (MCM) risk of first-trimester antihypertensive exposure, specifically of amlodipine and methyldopa. A large administrative claims database was used. The prevalence of antihypertensive prescriptions during pregnancy was described in 91,390 women giving birth between 2010 and 2019. The MCM risk of first-trimester antihypertensives was evaluated in 1,185 women diagnosed with hypertensive disorders in the first trimester. The MCM risk of first-trimester amlodipine and methyldopa was evaluated in 178 women who were prescribed antihypertensives in the first trimester. Antihypertensives were prescribed to 278 (0.30%) women during their first trimester. The prescription prevalence in the first trimester was highest for methyldopa (115, 0.13%), followed by amlodipine (55, 0.06%). Antihypertensives were prescribed to 2,955 (3.23%) women during pregnancy. Nifedipine (903, 0.99%) and nicardipine (758, 0.83%) were the most frequently prescribed oral and injectable antihypertensives during pregnancy, both with a significant increase in annual prevalence. Of the 1,185 women diagnosed with hypertensive disorders in the first trimester, antihypertensives were prescribed to 178 women. The adjusted odds ratio (aOR) of MCMs in the first-trimester prescription of any antihypertensive medication was 1.124 (95% confidence interval [CI], 0.618–2.045). Amlodipine and methyldopa were prescribed to 44 and 93 of the 178 women, respectively. The aORs of MCMs in the first-trimester prescription of amlodipine and methyldopa were 1.219 (95% CI, 0.400–3.721) and 0.921 (0.331–2.564), respectively. The MCM risk of first-trimester exposure to antihypertensives, including amlodipine and methyldopa, was not suggested. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the risk of major congenital malformations (MCMs) associated with first‐trimester exposure to propulsives with a special focus on domperidone using a large administrative database in Japan. Methods: A large claims database was used from January 2005 to August 2016. The dates of pregnancy onset and delivery were estimated using the developed algorithms. MCMs were defined according to the International Classification of Diseases, 10th revision codes. We compared the infants' risk of overall MCMs between women with or without first‐trimester prescriptions of propulsives and estimated the odds ratios (ORs) with unadjusted and adjusted analyses. We also compared the risk of overall MCMs between women with domperidone prescriptions and those with other propulsive prescriptions during the first trimester. Results: Among 38 270 women, propulsives were prescribed to 3197 women (8.4%) in the first trimester, including domperidone to 371 women (1.0%). Propulsive prescriptions in the first trimester were not significantly associated with an increased risk of overall MCMs (adjusted OR [aOR] 1.030, 95% confidence interval [CI] 0.843–1.257). Compared to the prescription of other propulsives in the first trimester, the prescription of domperidone in the first trimester was not associated with an increased risk of overall MCMs (aOR 0.724, 95% CI 0.363–1.447). Conclusions: The first‐trimester prescription of propulsives, including domperidone, was not associated with an increased risk of overall MCMs. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the prevalence of folic acid (FA) prescription to prenatal and postpartum women who have also been prescribed antiepileptic drugs (AED) in Japan. Methods: The data set used in this study included women covered by health insurance between 2005 and 2016. The prevalence of FA prescriptions between 180 days before pregnancy and 180 days postpartum was determined from a large administrative database, with the FA prescription classified according to dose and timing. Results: For 33,941 women meeting our eligibility criteria, the mean maternal age at delivery was 32.3 years. At least one AED was prescribed to 225 of 33,941 women between 180 days before pregnancy and 180 days postpartum. FA was prescribed to 32 of 225 women (14.2%) during the same period. FA was prescribed to 8.8% of women with AED within 90 days before pregnancy and to 19.8% during the first trimester. FA was prescribed to 10.9% during the first 30 days after conception, all of whom were prescribed FA before the pregnancy. The maximum FA dose prescribed within 90 days before pregnancy was 5 mg/day for 5 of 12 women (41.7%) and >5 mg/day for 4 of 12 women (33.3%). The maximum FA dose prescribed during the first trimester was 5 mg/day for 14 of 22 women (63.6%) and >5 mg/day for 8 of 22 women (36.4%). Conclusions: The concurrent prescription of FA with AEDs in Japan was an uncommon therapeutic approach both before and during pregnancy. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the prevalence and patterns of prescriptions of antiepileptic drugs (AEDs) to prenatal and postpartum women in Japan using a large administrative database. Methods: The dates of pregnancy onset and delivery were estimated using published algorithms and infant birth months. The prevalence of prescribed AEDs, the maximum dose of some AEDs, and the frequency of potential combination therapy with AEDs were evaluated for the 180 days before pregnancy onset, during pregnancy, and at 180‐day postpartum. Results: In total, 33 941 pregnant women were eligible for analysis. At least one AED was prescribed to 225 women (66 per 10 000 deliveries) between 180 days before pregnancy and 180‐day postpartum and for 135 women (40 per 10 000 deliveries) during pregnancy. The prevalence of AED prescription declined during the first and second trimesters and increased in the third trimester and postpartum. Valproate was the most frequently prescribed drug, followed by clonazepam, lamotrigine, and carbamazepine. Nine (18.4%) of the 49 women with at least one prescription record of valproate in the first trimester were prescribed more than 600 mg/day of valproate. Concerning potential combination therapy, 40 (12 per 10 000 deliveries) concurrently received two or more AEDs between 180 days before pregnancy and 180‐day postpartum, respectively, 31 (9 per 10 000 deliveries) women received these drugs during pregnancy. Conclusions: Various AEDs were prescribed to pregnant Japanese women. Women of reproductive age should select the appropriate AED before becoming pregnant, depending on the risk benefit profile. [ABSTRACT FROM AUTHOR]

Purpose The purpose of the study is to evaluate the status of prescribed antihypertensives primarily during pregnancy, but also before pregnancy and after delivery, using a large claims database in Japan. Methods: The dates of pregnancy onset and delivery were identified using reported algorithms and the birth months of infants. The prevalence and timing of prescribed antihypertensives during pregnancy were descriptively evaluated. Time trends in prescriptions were evaluated using multivariate logistic regression analyses. We also evaluated the prevalence of antihypertensives prescribed within 180 days before pregnancy and 180 days after delivery among women who were covered by health insurers during the entire period. Results: At least one antihypertensive agent was prescribed for 1144 (2.74%) of 41 693 pregnant women. The most frequently prescribed oral antihypertensive during pregnancy was nifedipine, followed by methyldopa, hydralazine, and furosemide. Drugs targeting the renin‐angiotensin system were prescribed for 21 pregnant women (0.05%), including angiotensin II receptor blockers that were prescribed for 19 (0.05%) of them. Nicardipine was the most frequently prescribed injectable antihypertensive during pregnancy, followed by furosemide, hydralazine, and nitroglycerin. Annual prescription trends remained similar except for a significant decrease in those for oral and injectable furosemide and an annual increase in those for organic nitrate. Based on an evaluation of 33 941 pregnant women, the number of prescriptions for antihypertensives increased particularly during the third trimester, then decreased from 91 to 180 days after delivery. Conclusions: Various types of antihypertensives are prescribed for Japanese pregnant women. The effects of exposing pregnant Japanese women to these agents should be evaluated. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To develop and assess algorithms to determine the onset of pregnancy and delivery date using health administrative data from a university hospital in Japan. Methods: All women who were hospitalized in the maternity ward and had at least one pregnancy that ended with a delivery during the period of January 2014 and December 2015 were included in this study. The true delivery date was obtained from the electronic medical records and was used as a gold standard. The onset of pregnancy was calculated by subtracting the gestational age at birth from the delivery date based on the electronic medical records and was also used as a gold standard. The administrative data‐based algorithms to identify (1) the onset of pregnancy estimated from the gestational age recorded as part of a diagnosis during a specific visit and (2) the delivery date estimated using the delivery‐related diagnosis, procedure, or prescription were compared with the gold‐standard data. Results: Of the 1705 women included in this study, the onset of pregnancy was determined in 1704 subjects with 1582 (92.8%) within ± 7 days from the gold‐standard date of pregnancy onset. The delivery date was determined in 1654 subjects, and 1594 (96.4%) were within ± 7 days before the true delivery date using the algorithm of “selected” diagnosis and a surgical procedure followed by some other delivery‐related data. Conclusions: The algorithms developed in this study are expected to accelerate future studies for real‐world exposure and quantify drug safety during pregnancy using Japanese health care administrative databases. [ABSTRACT FROM AUTHOR]

Background: The prevalence and pattern of perinatal antidepressant prescriptions in Japan are unknown.Methods: The prevalence of antidepressant prescriptions between 180 days before pregnancy onset and 180 days postpartum was evaluated using a large administrative database. The dates of pregnancy onset and delivery were estimated using developed algorithms.Results: Of 33,941 women, at least one antidepressant was prescribed to 451 (133/10,000 deliveries) between 180 days before pregnancy and 180 days postpartum and to 241 (71/10,000 deliveries) during pregnancy. The prevalence of antidepressant prescriptions decreased during the first and second trimesters and increased in the postpartum period. Of 339 women with antidepressant prescriptions before pregnancy, 151 (44.5%) discontinued it during pregnancy. Selective serotonin-reuptake inhibitors were the most frequently prescribed class of antidepressants in the time period studied (356 women, 105/10,000 deliveries), followed by tricyclic/non-tricyclic antidepressants (101 women, 30/10,000 deliveries). Of the 57 women who had at least one record of paroxetine prescription in the first trimester, 13 (22.8%) were prescribed >25 mg/day. Fifty-seven women (17/10,000 deliveries) were concurrently prescribed two or more classes of antidepressants between 180 days before pregnancy and 180 days postpartum.Limitations: It may not always have been the case that the prescribed antidepressants were used. Women whose pregnancy ended in an abortion or stillbirth were not included.Conclusions: Various antidepressants were prescribed to prenatal and postpartum women in Japan. Approximately half of pregnant women discontinued treatment with antidepressants after becoming pregnant. Women of childbearing age should select an appropriate antidepressant considering the risk/benefit profile. [ABSTRACT FROM AUTHOR]