Objective This contribution addresses the risk associated with exposure to statins during pregnancy.Design Multicentre observational prospective controlled study. Setting European Network of Teratology Information Services.Population Pregnant women who contacted one of 11 participating centres, seeking advice about exposure to statins during pregnancy, or to agents known to be nonteratogenic.Methods Pregnancies exposed during first trimester to statins were followed up prospectively, and their outcomes were compared with a matched control group.Main outcome measures Rates of major birth defects, live births, miscarriages, elective terminations, preterm deliveries and gestational age and birthweight at delivery.Results We collected observations from 249 exposed pregnancies and 249 controls. The difference in the rate of major birth defects between the statin-exposed and the control groups was small and statistically nonsignificant (4.1% versus 2.7% odds ratio [OR] 1.5; 95% confidence interval [95% CI] 0.5-4.5, P = 0.43). In an adjusted Cox model, the difference between miscarriage rates was also small and not significant (hazard ratio 1.36, 95% CI 0.63-2.93, P = 0.43). Premature birth was more frequent in exposed pregnancies (16.1% versus 8.5%; OR 2.1, 95% CI 1.1-3.8, P = 0.019). Nonetheless, median gestational age at birth (39 weeks, interquartile range [IQR] 37-40 versus 39 weeks, IQR 38-40, P = 0.27) and birth weight (3280 g, IQR 2835-3590 versus 3250 g, IQR 2880-3630, P = 0.95) did not differ between exposed and non-exposed pregnancies.Conclusions This study did not detect a teratogenic effect of statins. Its statistical power remains insufficient to challenge current recommendations of treatment discontinuation during pregnancy.

This multicenter, observational prospective cohort study addresses the risk associated with exposure to mirtazapine during pregnancy. Pregnancy outcomes after exposure to mirtazapine were compared with 2 matched control groups: (1) exposure to any selective serotonin reuptake inhibitor (SSRI, control subjects with a psychiatric condition) and (2) no exposure to medication known to be teratogenic or any antidepressant (general control subjects). Data were collected by members of the European Network of Teratology Information Services between 1995 and 2011. Observations from 357 exposed pregnancies were compared with 357 pregnancies from each control group. The rate of major birth defects between the mirtazapine and the SSRI group did not differ significantly (4.5% vs 4.2%; odds ratio [OR], 1.1; 95% confidence interval [95% CI], 0.5-2.3; P = 0.9). A trend toward a higher rate of birth defects in the mirtazapine group compared with general control subjects (4.5% vs 1.9%; OR, 2.4; 95% CI, 0.9-6.3; P = 0.08) reached statistical significance after exclusion of chromosomal or genetic anomalies (4.1% vs 1.3%; OR, 3.3; 95% CI, 1.04-10.3; P = 0.03), but this difference became again nonsignificant if cases of exposure not comprising the first trimester were excluded from the analysis (3.4% vs 1.9%; OR, 1.8; 95% CI, 0.6-5.0; P = 0.26). The crude miscarriage rate did not differ significantly between the mirtazapine, the SSRI, and the general control groups (12.1% vs 12.0% vs 9.3%; P = 0.44). However, a higher rate of elective pregnancy termination was observed in the mirtazapine group compared with SSRI and general control subjects (7.8% vs 3.4% vs 5.6%; P = 0.03). This study did not observe a statistically significant difference in the rate of major birth defects after first-trimester exposure between mirtazapine, SSRI-exposed, and nonexposed pregnancies. A marginally higher rate of birth defects was, however, observed in the mirtazapine and SSRI groups compared with the low rate of birth defects in our general control subjects. Overall pregnancy outcome after mirtazapine exposure was similar to that of the SSRI-exposed control group.

Pregnant women with pre-gestational diabetes on metformin are at a higher risk for adverse pregnancy outcomes than the general population. This appears to be due to the underlying diabetes since women on metformin for other indications do not present meaningfully increased risks.

This study, in agreement with earlier smaller studies, suggests that the new macrolides do not pose a significantly increased risk of major congenital malformations or cardiac malformations.

Titlbach M., E. Maňáková: Development of the Rabbit Pancreas with Particular Regard to the argyrophilic Cells. acta vet. Brno 2007, 76: 509-517.The aim of the study was the description of the prenatal development of rabbit pancreas, cell modifications, and changes in their volume and mitotic activity.immunohistochemical, light and electron microscopic procedures were employed. Stereological methods were used for estimation of cellular and nuclear volumes. hits on epithelial cells, tubular lumens, and endocrine progenitor cells were counted by systematic field sampling using test grid. Number of mitoses was registered in various cellular types after colchicine treatment. Data obtained were converted to 1 mm 3 tissue. First granules were observed in cells on day 10 and 18 hours, however two different granular types are distinguishable by electron microscopy only on day 15, when insulin and glucagon can be detected immunohistochemically. Cellular volume increased remarkably in harmony with findings of granules in serous cells. Number of epithelial cells increased also exponentially. The increase was more rapid between days 13 and 15, later it appeared exponential. value of mitotic index and length of cell cycle did not change considerably between days 15 and 24. Mitoses were observed in ductal, exocrine, as well as endocrine cells. The dividing endocrine cells were those that contained fine dense granules (progenitor cells).The sub-population of progenitor cells is able to divide, however, this source of cells appears insufficient for exponential growth. Results after colchicine treatment show the increase of cell population but the life-span and a period necessary for volume multiplication vary. Mitoses decrease in both sub-populations during the prenatal period. The progenitor cells arise probably by differentiation from the ducts, because their number increases proportionally to the main cell population.