Medication use in pregnancy: a cross-sectional, multinational web-based study

Objectives: Intercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. his study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use. Design: Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire. Setting: Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia. Participants: Pregnant women and new mothers with children less than 1 year of age. Primary and secondary outcome measures: Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use. Results: The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of ute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than nonimmigrants. Conclusions: In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used

The Empirical Landscape of Trade Policy

This chapter surveys empirically the broad features of trade policy in goods for 31 major economies that collectively represented 83 percent of the world's population and 91 percent of the world's GDP in 2013. We address five questions: Do some countries have more liberal trading regimes than others? Within countries, which industries receive the most import protection? How do trade policies change over time? Do countries discriminate among their trading partners when setting trade policy? Finally, how liberalized is world trade? Our analysis documents the extent of cross-sectional heterogeneity in applied commercial policy across countries, their economic sectors, and their trading partners, over time. We conclude that substantial trade policy barriers remain as an important feature of the world economy.antidumpin

Serum concentrations of paliperidone after administration of the long-acting injectable formulation

Background: The pharmacokinetics of long-acting intramuscular paliperidone in a naturalistic setting is not well documented. The objective of this study was to investigate the relationship between dose and serum concentrations of paliperidone using data from a routine therapeutic drug monitoring service. Methods: Serum concentration measurements in 310 samples from 110 male and 75 female patients receiving depot injections of paliperidone were retrospectively retrieved from the therapeutic drug monitoring database. Results: The median dose was 100 mg every 28 days. The median concentration/dose (C/D) ratio of paliperidone was 16.1 (nmol/L)/(mg/d), with a 10–90 percentile range of 7.8–31.0 (nmol/L)/(mg/d). Dose-adjusted serum concentrations were 33% higher in patients 65 years or older and more than 50% lower in patients taking the p-glycoprotein inducer carbamazepine. There were no significant effects of sex or dose on the C/D ratio. The median serum concentrations of paliperidone at the end of the dose interval were 31 nmol/L at an intramuscular dose of 50 mg/28 d, 53 nmol/L after a dose of 75 mg/28 d, 59 nmol/L after a dose of 100 mg/28 d, and 93 nmol/L after a dose of 150 mg/28 d. Forty-five percent of the measurements were lower than the suggested therapeutic range of 20–60 ng/mL (47–140 nmol/L). Conclusions: The data show a 4-fold interindividual difference in dose-adjusted serum concentrations within the 10–90 percentile range and illustrate the significant effects of age and p-glycoprotein induction on the pharmacokinetics of paliperidone. The study also indicates that at least in some patients, it might take longer time than anticipated to reach steady state.publishedVersionCopyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non CommercialNo Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

Depression and antidepressant treatment in the development of hypertensive disorders of pregnancy: Results from a prospective cohort study

Background: Hypertensive disorders of pregnancy are associated with longer term cardiovascular risk. Understanding if depression or antidepressant use in pregnancy is associated with HDP is important in identifying those potentially vulnerable to poorer health in later life. This study examines if depression and antidepressants are associated with HDP. Methods: In all, 815 pregnant women were recruited within an Australian pregnancy cohort study at less than 20 weeks of pregnancy, all undertook the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and were assigned to four groups for this paper: those with unmedicated depression meeting criteria for current depression (n = 97), those taking selective serotonin reuptake inhibitors in early pregnancy (n = 101), those taking serotonin and noradrenaline reuptake inhibitors in early pregnancy (n = 31), and those without depression or taking antidepressant medication (control; n = 586). Women were then assessed again following birth. Hypertensive disorders of pregnancy were diagnosed according to the Society of Obstetric Medicine in Australia and New Zealand Guidelines. Results: Use of serotonin and noradrenaline reuptake inhibitors (SNRIs) (adjusted risk ratio = 9.10, 95% confidence interval = [3.82, 21.67]) and unmedicated depression (adjusted risk ratio = 3.11, 95% confidence interval = [1.32, 7.35]) were independently associated with significantly higher risk for developing hypertensive disorders of pregnancy compared to controls. Selective serotonin reuptake inhibitors (SSRIs) use did not confer any increased risk. Higher doses of SNRIs, but not selective serotonin reuptake inhibitors, were associated with significantly higher risk for developing HDP (adjusted risk ratio = 4.83, 95% confidence interval = [1.50, 15.58]). Conclusions: Our findings suggest that those with depression in pregnancy and/or on an serotonin and noradrenaline reuptake inhibitor should have closer surveillance for the development of hypertensive disorders of pregnancy. These findings support treatment of depression in pregnancy, however, also the consideration of class of antidepressant.acceptedVersio

Co-prescription of metoprolol and CYP2D6-inhibiting antidepressants before and after implementation of an optimized drug interaction database in Norway

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Association between low body weight and cytochrome P-450 enzyme activity in patients with anorexia nervosa

Very little is known to which extent severe underweight could affect cytochrome P-450 (CYP) enzyme activity. In this study, 24 patients with anorexia nervosa at two occasions ingested single oral doses of five test drugs known to be metabolized by CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, respectively. A mixed model analysis was used to evaluate the effect of changes in body mass index (BMI) on the metabolic activities of these enzymes. The primary end point was the change in drug/metabolite ratio of each of the test drugs per kg/m2 change in BMI. With increasing BMI, the metabolic activity of CYP3A4 decreased (change in the CYP3A4 drug/metabolite ratio per unit change in BMI = 0.056; 95% confidence interval [CI] 0.011 to 0.102; P = .017). For CYP1A2, increasing BMI increased the metabolic activity with borderline significance (change in the CYP1A2 drug/metabolite ratio per unit change in BMI = –0.107; CI –0.220 to 0.005; P = .059). For CYP2C9, CYP2C19, and CYP2D6, no significant changes were seen. The clinical impact of these findings for drug treatment in patients with anorexia nervosa and other severely underweight patients needs to be further studied by examining the pharmacokinetics of specific drugs. This might be particularly relevant for drugs metabolized by CYP1A2 and/or CYP3A4.publishedVersio

Using the Norwegian Mother and Child Cohort Study to determine risk factors for delayed development and neuro-psychiatric symptoms in the offspring of parents with epilepsy

Introduction: Antiepileptic drug (AED) teratogenicity is suspected to be the main cause of impaired development in children of women with epilepsy. However, many factors may confound the reported risks. The purpose of this review is to characterize the epilepsy cohort in the Norwegian Mother and Child Cohort Study (MoBa) and show how it can be used to detangle various risk factors for adverse outcome in children of mothers with epilepsy. Methods: MoBa is a large, long-term prospective, family-based cohort study. The database is linked to the Medical Birth Registry of Norway. The epilepsy cohort consists of mothers and their children representing more than 700 pregnancies. Blood samples were obtained from the mother during pregnancy and from the umbilical cord after delivery, and AED concentrations were measured. Validated screening tools determined the frequency of maternal confounding risk factors and adverse offspring outcomes. Risk estimates were reported as adjusted odds ratios with confidence intervals using the remaining MoBa cohort as a reference (n=107,597). Outcome in offspring of women with epilepsy without AED treatment in pregnancy and of fathers with epilepsy were used to separate the effect of epilepsy from the effect of in utero exposure to AEDs. Results: Socioeconomic and psychiatric risk factors for adverse offspring outcomes were more frequent in mothers with epilepsy. The frequency of adverse offspring outcome was increased at 6, 18 and 36 months for verbal, motor and social development. Children of women with epilepsy without AED treatment and of fathers with epilepsy were generally similar to children of women without epilepsy. Conclusion: Children of mothers with epilepsy are at risk of adverse outcomes. AED exposure emerges as the most important risk factor.publishedVersio