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. RESULTS: During the first trimester, 870 fetuses (52.4%) were exposed to human insulin only, 397 fetuses (23.9%) to insulin analogues only and 394 fetuses (23.7%) to both human insulin and insulin analogues. The risk of major congenital anomaly in fetuses exposed to insulin analogues only was lower than those exposed to human insulin only; the relative risk adjusted for glycaemic control and region was 0.56 (95% CI 0.29 to 1.06). The significantly lower risk related to exposure of insulin analogues only was observed in congenital heart defects: adjusted relative risk 0.14 (95% CI 0.03 to 0.62). CONCLUSIONS: In this retrospective population-based cohort study across Europe, first-trimester exposure to insulin analogues did not increase the risk of major congenital anomaly compared with exposure to human insulin. A possible lower risk of congenital heart defects among fetuses exposed to insulin analogues only deserves further investigation.

Interval cancers in the Antwerp European randomised study of screening for prostate cancer study, using a 6 year screening interval.

BACKGROUND: The European randomised study of screening for prostate cancer (ERSPC) was initiated to evaluate the effect of Prostate Specific Antigen (PSA) screening on prostate cancer mortality. Variations in screening modalities between participating centres, such as the interval between screening rounds are likely to affect the outcome of screening. METHODS: The study describes the number and characteristics of interval cancers in men in the screening arm of the Antwerp ERSPC aged 55-65 years at the time of randomisation and participating in the screening rounds they were invited for. The interval between the first screening rounds was 6 years on average. Interval cancers were defined as cancers diagnosed during the screening interval but not detected by screening. Cases with a positive screening test were considered as interval cancers if diagnosis through biopsy occurred more than 1 year after screening. Interval cancer cases were identified through linkage with cancer registries. Aggressive interval cancer was defined as cancer with at least one of the following characteristics: stage M1 or N1, Gleason score higher than 7 or World Health Organisation (WHO) score of 3. RESULTS: The 10 year cumulative incidence of interval cancers was 3.0% (n=50) and the cumulative incidence of aggressive interval cancers was 0.5% (n=8). During the first screening interval 36 interval cancers were detected. Of these 20 (55.6%) were detected more than 4 years after the initial screening and 5 (13.9%) were considered aggressive. All aggressive interval cancers emerged more than 4 years after initial screening. CONCLUSION: The occurrence of interval cancers in this study was higher than in the ERSPC centres that used a shorter screening interval. Aggressive interval cancers only started to emerge 4 years after initial screening.