ß-Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study.

Background: ß-Blockers are a class of antihypertensive medications that are commonly used in pregnancy. Objective: To estimate the risks for major congenital malformations associated with first-trimester exposure to ß-blockers. Design: Cohort study. Setting: Health registries in the 5 Nordic countries and the U.S. Medicaid database. Patients: Pregnant women with a diagnosis of hypertension and their offspring. Measurements: First-trimester exposure to ß-blockers was assessed. Outcomes were any major congenital malformation, cardiac malformations, cleft lip or palate, and central nervous system (CNS) malformations. Propensity score stratification was used to control for potential confounders. Results: Of 3577 women with hypertensive pregnancies in the Nordic cohort and 14 900 in the U.S. cohort, 682 (19.1%) and 1668 (11.2%), respectively, were exposed to ß-blockers in the first trimester. The pooled adjusted relative risk (RR) and risk difference per 1000 persons exposed (RD1000) associated with ß-blockers were 1.07 (95% CI, 0.89 to 1.30) and 3.0 (CI, -6.6 to 12.6), respectively, for any major malformation; 1.12 (CI, 0.83 to 1.51) and 2.1 (CI, -4.3 to 8.4) for any cardiac malformation; and 1.97 (CI, 0.74 to 5.25) and 1.0 (CI, -0.9 to 3.0) for cleft lip or palate. For CNS malformations, the adjusted RR was 1.37 (CI, 0.58 to 3.25) and the RD1000 was 1.0 (CI, -2.0 to 4.0) (based on U.S. cohort data only). Limitation: Analysis was restricted to live births, exposure was based on dispensed medication, and cleft lip or palate and CNS malformations had few outcomes. Conclusion: The results suggest that maternal use of ß-blockers in the first trimester is not associated with a large increase in the risk for overall malformations or cardiac malformations, independent of measured confounders. Primary Funding Source: The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Söderström König Foundation.

Social inequalities and smoking-associated breast cancer - Results from a prospective cohort study.

OBJECTIVE: The association between smoking and breast cancer has been found in most recent, large cohort studies. We wanted to investigate how smoking-associated breast cancer varies by level of education, a well-established measure of socioeconomic status. METHODS: We included 302,865 women with 7490 breast cancer cases. Participants were assigned to low, moderate or high level of education and analyzed by smoking status (ever/never), and stratified by birth cohorts (≤1950>). We used Cox proportional hazard to estimate hazard ratios (HRs) and confidence intervals (CIs), adjusting for age, number of children, age at first childbirth, BMI, age at enrollment and physical activity. RESULTS: Women born ≤1950 with low and moderate levels of education had a 40% increase in smoking-associated breast cancer risk (HR=1.40, 95% CI 1.25-1.57 and HR=1.14, 95% CI 1.05-1.24, respectively). Women in the same age group with high level of education did not have an increase in risk. No increased breast cancer risk was found among women born after 1950 for any level of education, when analyzed by smoking status. Longer duration of smoking before first childbirth was consistently associated with increasing risk of breast cancer in all three categories of education (all p for trends<0.01). CONCLUSION: Smoking for several years before first childbirth increases the risk of breast cancer, regardless of educational level.

Medical abortion with mifepristone and home administration of misoprostol up to 63 days' gestation.

OBJECTIVE: To evaluate the acceptability and efficacy of medical abortion at home up to 63 days' gestation without limits on travel distance to a registered institution. DESIGN: Observational prospective study. SETTING: Haukeland University Hospital between May 2006 and May 2009. POPULATION: A total of 1018 women requesting abortion before 63 days' gestation who chose medical termination with mifepristone and home administration of misoprostol. METHODS: The women took 200 mg mifepristone under nurse supervision and self-administered 800 µg misoprostol vaginally 36-48 h later at home. All were contacted by phone for follow-up and assessment of bleeding, pain and acceptability. MAIN OUTCOME MEASURES: Evacuation rate, pain, bleeding, acceptability, influence of distance on treatment. RESULTS: Median gestational age was 50 (range 35-63) days and 70 (7.1%) of the women lived more than 60 min travel from the clinic. The rate of completed abortion was 93.6% and surgical evacuation was performed in 50 (4.9%) cases. Two women requested treatment on the day of misoprostol use. Moderate to strong pain was experienced by 68.4%, and 74.7% reported moderate to heavy bleeding. Parous women experienced less pain than nulliparous women (odds ratio 0.27; 95% confidence interval 0.19-0.34). In all, 95.1% of the women were satisfied with staying at home. Travel distance did not influence treatment outcome variables. CONCLUSIONS: In our experience, home administration of misoprostol is an effective and acceptable method for abortion up to 63 days of gestation and women should be eligible for this treatment option regardless of their travel distance from hospital.

[Changes in the sale and use of flunitrazepam in Norway after 1999]. / Endringer i salg og bruk av flunitrazepam etter 1999.

BACKGROUND: In Norway there has in later years been much discussion of misuse of flunitrazepam. From 1 January 2003 the drug was moved up one level in the schedule of controlled substances. On 1 August 2004 the manufacturer of the Rohypnol brand withdrew it from the Norwegian market. How did these two events influence the sales and use of drugs containing flunitrazepam? MATERIALS AND METHODS: Sales figures for drugs containing flunitrazepam from the statistics database at the Norwegian Institute of Public Health were studied. The Norwegian prescription database was used to describe new (incident) users of flunitrazepam and the two brands of this drug sold in Norway in 2004. RESULTS AND DISCUSSION: Restrictions on the prescription status of flunitrazepam lead to a decrease in sales from 7.2 defined daily doses (DDD) per 1000 inhabitants per day in 2002 to 3.0 DDD per 1000 inhabitants per day in 2003. This decrease was only partly compensated for by an increase in the sales of nitrazepam (from 5.0 to 6.0 DDD per 1000 inhabitants per day). During the years 1999 to 2004 there was a steady increase in the sales of benzodiazepine-related hypnotics (zopiclone and zolpidem). This shift could mean a change from flunitrazepam to zopiclone. The withdrawal of Rohypnol in August 2004 had only minor effects on the total sales of flunitrazepam. The decline in sales of Rohypnol was almost compensated for by the increase in the overall sales of Flunipam. This was reflected in the fact that in the later months of 2004 there were many new (incident) users of Flunipam, but few new users of flunitrazepam-containing drugs in total. It could be concluded that the restrictions on prescription status of flunitrazepam had a much higher impact than the withdrawal of the Rohypnol brand.