Congenital clubfoot in Europe: A population-based study.

We aimed to assess prevalence, birth outcome, associated anomalies and prenatal diagnosis of congenital clubfoot in Europe using data from the EUROCAT network, and to validate the recording of congenital clubfoot as a major congenital anomaly by EUROCAT registries. Cases of congenital clubfoot were included from 18 EUROCAT registries covering more than 4.8 million births in 1995-2011.

Insulin analogues use in pregnancy among women with pregestational diabetes mellitus and risk of congenital anomaly: a retrospective population-based cohort study.

Objectives: To evaluate the risk of major congenital anomaly associated with first-trimester exposure to insulin analogues compared with human insulin in offspring of women with pregestational diabetes.

Design And Setting: A population-based cohort of women with pregestational diabetes (n=1661) who delivered between 1996 and 2012 was established retrospectively from seven European regions covered bythe European Surveillance of Congenital Anomalies (EUROCAT) congenital anomaly registries.

Primary Outcome Measures: The risk of non-chromosomal major congenital anomaly in live births, fetal deaths and terminations for a fetal anomaly exposed to insulin analogues in the first trimester of pregnancy was compared with the risk in those exposed to human insulin only.

The Risk of Specific Congenital Anomalies in Relation to Newer Antiepileptic Drugs: A Literature Review.

Background: More information is needed about possible associations between the newer anti-epileptic drugs (AEDs) in the first trimester of pregnancy and specific congenital anomalies of the fetus.

Objectives: We performed a literature review to find signals for potential associations between newer AEDs (lamotrigine, topiramate, levetiracetam, gabapentin, oxcarbazepine, eslicarbazepine, felbamate, lacosamide, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, vigabatrin, and zonisamide) and specific congenital anomalies.

Methods: We searched PubMed and EMBASE to find observational studies with pregnancies exposed to newer AEDs and detailed information on congenital anomalies.

Prescribing of Antidiabetic Medicines before, during and after Pregnancy: A Study in Seven European Regions.

Aim: To explore antidiabetic medicine prescribing to women before, during and after pregnancy in different regions of Europe.

Methods: A common protocol was implemented across seven databases in Denmark, Norway, The Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK. Women with a pregnancy starting and ending between 2004 and 2010, (Denmark, 2004-2009; Norway, 2005-2010; Emilia Romagna, 2008-2010), which ended in a live or stillbirth, were identified.

Lamotrigine use in pregnancy and risk of orofacial cleft and other congenital anomalies.

Objective: To test previous signals of a risk of orofacial cleft (OC) and clubfoot with exposure to the antiepileptic lamotrigine, and to investigate risk of other congenital anomalies (CA).

Methods: This was a population-based case-malformed control study based on 21 EUROCAT CA registries covering 10.1 million births (1995-2011), including births to 2005 in which the clubfoot signal was generated and a subsequent independent study population of 6.

EUROmediCAT signal detection: an evaluation of selected congenital anomaly-medication associations.

Aims: To evaluate congenital anomaly (CA)-medication exposure associations produced by the new EUROmediCAT signal detection system and determine which require further investigation.

Methods: Data from 15 EUROCAT registries (1995-2011) with medication exposures at the chemical substance (5th level of Anatomic Therapeutic Chemical classification) and chemical subgroup (4th level) were analysed using a 50% false detection rate. After excluding antiepileptics, antidiabetics, antiasthmatics and SSRIs/psycholeptics already under investigation, 27 associations were evaluated.

Asthma medication prescribing before, during and after pregnancy: a study in seven European regions.

Objectives: To explore utilisation patterns of asthma medication before, during and after pregnancy as recorded in seven European population-based databases.

Design: A descriptive drug utilisation study.

Setting: 7 electronic healthcare databases in Denmark, Norway, the Netherlands, Italy (Emilia Romagna and Tuscany), Wales, and the Clinical Practice Research Datalink representing the rest of the UK.

Insulin analogues in pregnancy and specific congenital anomalies: a literature review.

Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies.

Actual Use of Medications Prescribed During Pregnancy: A Cross-Sectional Study Using Data from a Population-Based Congenital Anomaly Registry.

Introduction And Aim: Data from prescription databases are increasingly being used to study associations between maternal medications used in pregnancy and congenital anomalies. We therefore investigated the extent to which prescriptions reflect the actual use of medication during pregnancy, and whether medicines used during pregnancy are taken according to the prescribed dosage and duration.

Methods: We performed a cross-sectional study in a population-based congenital anomaly register (EUROCAT Northern Netherlands).

Use of antibiotics in rural and urban regions in The Netherlands: an observational drug utilization study.

Background: Large livestock farms might increase the infection risk for the nearby human population because of an increased risk for disease outbreaks and because antibiotic-resistant bacteria are more likely to be present. We hypothesized that populations residing in rural areas have more contact with cattle compared with populations in urban areas, and will use more antibiotics or more frequently require a new course of antibiotics.

Methods: Using data from the prescription database IADB.

Maternal high-dose folic acid during pregnancy and asthma medication in the offspring.

Purpose: Low-dose folic acid supplementation (0.5 mg) taken during pregnancy has been associated with an increased risk for childhood asthma. The effect of high-dose folic acid (5 mg) advised to women at risk for having a child with neural tube defect has not been assessed so far.

Teratogenic mechanisms associated with prenatal medication exposure.

Birth defects may originate through multiple mechanisms and may be caused by a variety of possible exposures, including medications in early pregnancy. In this review, we describe six principal teratogenic mechanisms suspected to be associated with medication use: folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption, and specific receptor- or enzyme-mediated teratogenesis. Knowledge about these mechanisms, for some of which evidence is mainly derived from animal models, may not only be relevant for etiologic and post-marketing research, but may also have implications for prescribing behavior for women of reproductive age.

Healthcare databases in Europe for studying medicine use and safety during pregnancy.

Purpose: The aim of this study was to describe a number of electronic healthcare databases in Europe in terms of the population covered, the source of the data captured and the availability of data on key variables required for evaluating medicine use and medicine safety during pregnancy.

Methods: A sample of electronic healthcare databases that captured pregnancies and prescription data was selected on the basis of contacts within the EUROCAT network. For each participating database, a database inventory was completed.

Drugs associated with teratogenic mechanisms. Part II: a literature review of the evidence on human risks.

Study Question: What is the current state of knowledge on the human risks of drugs suspected to be associated with teratogenic mechanisms?

Summary Answer: Evidence for the presence or absence of human risks of birth defects is scarce or non-existent for the majority of drugs associated with teratogenic mechanisms.

What Is Known Already: Medical drugs suspected to be associated with teratogenic mechanisms are dispensed to a significant proportion of women in the first trimester of pregnancy. However, an overview of the current state of knowledge on the human teratogenic effects of these drugs is lacking.

Drugs associated with teratogenic mechanisms. Part I: dispensing rates among pregnant women in the Netherlands, 1998-2009.

Study Question: What are the dispensing rates of drugs suspected to be associated with teratogenic mechanisms among pregnant Dutch women?

Summary Answer: In a substantial proportion of pregnancies in our study population at least one drug associated with a teratogenic mechanism was dispensed in the first trimester of pregnancy.

What Is Known Already: The main teratogenic mechanisms of medical drugs that may affect fetal development in the first trimester of pregnancy have been described previously. However, information on the dispensing rate of such drugs among women at all stages of pregnancy is lacking.

Antibiotics prescribed before, during and after pregnancy in the Netherlands: a drug utilization study.

Purpose: To describe the prescription of antibiotics before, during and after pregnancy, and the trends over a 16-year period in the Netherlands, and to determine whether they were prescribed according to national guidelines.

Methods: The IADB (http://iadb.nl) contains prescriptions dispensed by community pharmacies in the Netherlands.

Identifying associations between maternal medication use and birth defects using a case-population approach: an exploratory study on signal detection.

Background: The effects of many drugs on the unborn child are unknown. In a case-population design, drug exposure of cases is compared with that of a source population; this kind of study can be useful for generating signals.

Objective: To see whether a comparison of drug use rates from the birth defect registry EUROCAT NNL (cases) with prescription rates from a population-based prescription database, the IADB (population), could be used to detect signals of teratogenic risk of drugs.

The population-based prescription database IADB.nl: its development, usefulness in outcomes research and challenges.

Research databases with large numbers of prescriptions in observational settings can provide valuable information in addition to the initial randomized controlled trials. This paper reports on the development of prescription database IADB, formerly known as InterAction Database. IADB contains prescriptions from 54 community pharmacies in The Netherlands and covers a population of 500,000 people.

Assessing the effect of a guideline change on drug use prevalence by including the birth cohort dimension: the case of benzodiazepines.

Purpose: The aim of this study was to investigate whether including the birth cohort dimension in time series analysis leads to a more accurate estimation of the (long-term) effect of a guideline change on the trend of benzodiazepine use.

Methods: We calculated age-specific (20-84 years) and sex-specific prevalence of benzodiazepine use per 1000 population per quarter year (1998 to 2008) using a prescription database set in the Netherlands. We studied the prevalence over time by age group and within birth cohorts through interrupted time series analyses to estimate the effect of the guideline change in 2001.

Inhaled corticosteroids and the occurrence of oral candidiasis: a prescription sequence symmetry analysis.

Objectives: The primary aim of the study was to gain insight into the relative risk of clinically relevant oral candidiasis following inhaled corticosteroid (ICS) initiation over time. A secondary aim was to analyse the influence of patient characteristics and co-medication on the occurrence of this adverse effect.

Methods: Drug prescription data from 1994 to 2011 were retrieved from the IADB.

The effects of antitussive treatment of ACE inhibitor-induced cough on therapy compliance: a prescription sequence symmetry analysis.

Background: A common adverse effect of angiotensin-converting enzyme inhibitors (ACEI) is a persistent dry cough. Physicians and pharmacists who fail to recognise dry cough to be ACEI related may prescribe antitussives, instead of recommended ACEI substitution.

Objective: The aim of this study was to determine the influence of antitussive treatment of ACEI-induced cough on ACEI therapy compliance.

A population analysis of prescriptions for asthma medications during pregnancy.

Background: It is important to control asthma during pregnancy. However, some studies indicate that women stop or change their asthma medications when they become pregnant.

Objective: We used a population database to analyze changes in prescriptions for asthma medications to patients before, during, and after pregnancy.

[Peri-pregnancy folic acid supplementation must be improved].

The correct usage of folic acid (FA) supplements to prevent neural tube defects (NTDs) increased from 28% in 1996 to 50% in 2005 and remained stable until 2009. Recent data from national birth defect registries show a decrease of NTD prevalence from 13.2 (per 10,000) in 1997 to 8.

Inclusion of the birth cohort dimension improved description and explanation of trends in statin use.

Objective: Including the birth cohort dimension improves trend studies of mortality and health. We investigated the effect of including the birth cohort dimension in trend studies of prescription drug use by studying prevalence of statin use among adults.

Study Design And Setting: Data from a drug prescription database in the Netherlands (IADB.

A comparison of pharmacoepidemiological study designs in medication use and traffic safety research.

In order to explore how the choice of different study designs could influence the risk estimates, a case-crossover and case-time-control study were carried out and their outcomes were compared with those of a traditional case-control study design that evaluated the association between the exposure to psychotropic medications and the risk of having a motor vehicle accident (MVA). A record-linkage database availing data for 3,786 cases and 18,089 controls during the period 2000-2007 was used. The study designs (i.