Charlotte Olesen

Drug use in first pregnancy and lactation : a population-based survey among Danish women

AbstractObjective: To examine the drug prescription pattern in Danish women from 12 weeks prior to conception until 12 weeks post-partum. Method: A drug utilization study based on The North Jutland Prescription Database. The Danish pharmacies use a computerized accounting system for all subsidized drugs and this was linked to the Danish Medical Birth Registry concerning prescription patterns for all women who had given birth in the county of North Jutland from 1991 to 1996. Results: The analysis included 16 001 primiparous women, who had redeemed 34 834 prescriptions prior to, during and after pregnancy. During pregnancy 44.2% of the women received prescriptions for at least one drug. Users received 2.6 prescriptions on average during pregnancy; 5% of the users redeemed 24.2% of all prescriptions. The proportion of women who redeemed prescriptions for more than three different drugs was 2.7%. The majority of prescriptions were for antibiotics (28.7%), gynaecological drugs (13.3%) and anti-asthma drugs (7.6%). The post-partum prescription proportion was 34.0% and the majority of the prescriptions during this period were for penicillins (20.1%), opthalmologicals (15.5%) and corticosteroids for dermatological use (5.7%). Conclusion: A high proportion of the women received drugs during pregnancy. The pattern of drug use within the Anatomical Therapeutical Chemical (ATC) groups changed, i.e. the amount of broad spectrum antibiotics decreased and the proportion of prescriptions for local use increased. A small proportion of women redeemed prescriptions for more than three different drugs during pregnancy.

Do pregnant women report use of dispensed medications

Surveillance of drug safety in pregnancy often draws on administrative prescription registries. Noncompliance in the use of prescribed medication may be frequent among pregnant women owing to their fear of fetotoxic side effects. To estimate compliance in the use of prescription drugs dispensed during pregnancy, we compared prescription data from the North Jutland Prescription Database with information on drug use provided by pregnant women to the Danish National Birth Cohort (DNBC), which is a health interview survey. We used the North Jutland Prescription Database to identify all prescription drugs dispensed during pregnancy for the 2,041 women who were enrolled in the DNBC in the County of North Jutland, Denmark. Compliance was defined as the probability of reporting drug use in DNBC after purchasing a dispensed prescription drug. The overall compliance to drugs purchased within 120 days before the interview was 43% (95% confidence interval = 40–46). Drugs used for treating chronic diseases, for example, beta-blockers, insulin, thyroid hormones, and diuretic and antiepileptic drugs, were always reported to be used, but compliance was low for drugs used for local or short-term treatment such as antihistamines, antibiotics, antacids, nonsteroid anti-inflammatory drugs, and gynecologic drugs. Thus, for the latter drug groups the prescription database may provide an incomplete identification of exposure. Neither data source is unbiased regarding actual drug intake. Nevertheless, our results indicate that for some drug groups risk assessment studies based on prescription data may produce false negative results as a result of noncompliance.

Pregnancy Outcome Following Prescription for Sumatriptan

Background.– Some 2.5% of fertile Danish women use sumatriptan, and the drug is also taken during pregnancy. Although sumatriptan reacts selectively in brain vessels, the possibility of reactions with placental blood flow and uterotonic activity cannot be ruled out. The aim of our study was to examine the association between sumatriptan exposure during pregnancy and the risk of preterm delivery and low birth weight.

A population-based Prescription study of asthma drugs during pregnancy : Changing the intensity of asthma therapy and perinatal outcomes

Background: Among the goals of gestational asthma, therapy is optimisation of pulmonary function. According to the US Food and Drug Administration, no asthma drugs can be considered ‘safe’ during pregnancy. Fear of adverse fetal effects may thus lead to restrictive use of asthma drugs during pregnancy, and no population-based studies concerning gestational asthma therapy exist. Objectives: To examine whether asthma drugs or changing intensity of asthma therapy during pregnancy was associated with deviations from expected values of gestational age, birth weight, length at birth, or malformations. Methods: The Birth Registry was used to identify all 15,756 primiparous women who gave birth in the County of North Jutland between 1991 and 1996. According to the North Jutland Prescription Database, 303 of these women received prescriptions for asthma drugs during pregnancy. Women who did not purchase any prescription drugs during pregnancy constituted the reference group. Conclusion: Women who received prescriptions for asthma drugs during pregnancy gave birth to infants with birth weight and length at birth within the expected limits. Reducing intensity of asthma treatment during pregnancy was associated with lower birth weight and length at birth. This may indicate that pregnant women chose to discontinue therapy although their disease severity justifies continuation of treatment. However, analyses did not take into account important clinical variables, and results could also be due to confounding factors or chance.

Birth outcome following maternal use of fluoroquinolones

The aim of the study was to examine fetal risk associated with intrauterine exposure to fluoroquinolones. By using on record linkage between a Prescription Database and the Birth Registry in Denmark, the offspring of 57 users of fluoroquinolones and of 17259 patients who had no prescriptive medication during pregnancy, were compared in a cohort study. Among the users, the prevalence rate ratios of congenital abnormalities, preterm birth and low birth weight were 1.30 (95% CI: 0.30-5.30),1.53 (95% CI: 0.62-3.80) and 1.17 (95% CI: 0.15-8.90), respectively. The risk of congenital abnormalities among users of fluoroquinolones during pregnancy was close to unity. Despite these limitations of statistical analysis the study suggested that the use of fluoroquinolones during pregnancy may not be a major risk factor to the foetus.

Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplications. Although previous studies exist, each was of small size, and it remains to be determined whether there are parent-of-origin biases for the de novo 22q11.2 deletion. To address this question, we genotyped a total of 389 DNA samples from 22q11DS-affected families. A total of 219 (56%) individuals with 22q11DS had maternal origin and 170 (44%) had paternal origin of the de novo deletion, which represents a statistically significant bias for maternal origin (p = 0.0151). Combined with many smaller, previous studies, 465 (57%) individuals had maternal origin and 345 (43%) had paternal origin, amounting to a ratio of 1.35 or a 35% increase in maternal compared to paternal origin (p = 0.000028). Among 1,892 probands with the de novo 22q11.2 deletion, the average maternal age at time of conception was 29.5, and this is similar to data for the general population in individual countries. Of interest, the female recombination rate in the 22q11.2 region was about 1.6-1.7 times greater than that for males, suggesting that for this region in the genome, enhanced meiotic recombination rates, as well as other as-of-yet undefined 22q11.2-specific features, could be responsible for the observed excess in maternal origin.

Associations between socio-economic factors and the use of prescription medication during pregnancy

ObjectiveTo examine the association between socio-economic factors and use of prescription medication during pregnancy in a population of Danish women.MethodsThis was a population-based cohort study. Using record linkage from public administrative registries, we described the use of prescription medication during pregnancy and the financial and educational resources for each pregnant woman in the cohort.ResultsThe analyses included all 19,874 primiparous women delivering singletons in North Jutland county, Denmark, in 1991–1998. We identified 24,243 prescriptions filled by the women during their pregnancies. The highest overall prescription medication use was among women with basic schooling (OR 1.3; 95% CI 1.2–1.4), and lowest among women with the highest education (OR: 0.8; 95% CI 0.7–0.9) compared with women who had vocational education. Stratified analysis of therapeutic subgroups revealed that socio-economic factors were associated with the use of anti-infective and anti-asthmatic medications during pregnancy.ConclusionMaternal educational level, and to a lesser degree household income, paternal educational level and cohabitation status, was associated with the use of prescription medication during pregnancy. However, the analyses did not take into account important clinical variables such as maternal illness, and the results could be affected by differential misclassification of exposure information, by confounding or chance.

How Do We Best Detect Toxic Effects of Drugs Taken During Pregnancy? A EuroMap Paper

It is a major clinical and public health problem that there is no clear strategy as to how we best make use of information obtained when pregnant women take drugs. For this reason, some pregnant women are not treated as they should be and some are given drugs they should not use. We suggest a monitoring system that combines some of the available datasets in Europe. Using these sources as a starting point, one can develop a system that has sufficient power to detect even rare diseases like congenital malformations and sufficient diversity to detect several possible outcomes from spontaneous abortions to childhood disorders. We also suggest that case-crossover designs should be used in case-control monitoring systems that carry a high risk of recall bias. These considerations are based upon our results from a European Union-funded concerted action called EuroMaP (Medicine and Pregnancy).

Drug Use in Pregnancy. Principal Problems and a Review of Newer Utilization Studies

AbstractThe thalidomide disaster set focus on the problems of drug utilization and safety during pregnancy, particularly with respect to malformations, but other, and more subtle, side effects may also occur as a result of drug consumption in pregnancy. Our knowledge of adverse drug effects in pregnancy is still sparse, especially with respect to side-effects other than malformations. As consumption of medicine in pregnancy is common we need large epidemiological studies are needed to address this issue. Our knowledge of the long-term effects of drugs on the childs function, its mental and motor development, is at best sporadic. Studies on drug use by pregnant women have shown that at least 50% take one or often several drugs during pregnancy, most of the drugs have been analgesics and antibiotics. In summary, our knowledge in this field is limited and insufficient. Hopefully three new Danish studies will give more insight in this very complex subject with substantial public health relevance.