CP-induced cytotoxicity manifested by dose-dependent disturbance of cell-cycle resulted in an overall depression of proliferation activity clearly associated with the occurrence of malformations and embryonic death. Although a non-significant depression of mitotic activity appeared sufficient to produce malformations on Day 2, remarkably deeper disturbance was needed to interfere with the development of the embryos in more advanced stages. Changes in proliferation rate appear to be a primary and most important event in teratogenesis induced by general toxic agents.
Background: We had a case in which three consecutive pregnancies resulted in birth of three children with an orofacial cleft. Their mother suffered from bronchial asthma and was treated using symbicort (corticosteroid budesonide plus bronchodilator formoterol) during her pregnancies. A hypothesis was assessed: these antiasthmatics can induce an orofacial cleft in experimental model. Materials and Methods: A single administration of one of five increasing doses (including therapeutically used ones) of Symbicort, budesonide or formoterol was injected into the amnion of a chick embryo on day 4 or 5 of incubation. The teratogenic/lethal effects of the antiasthmatics were assessed on a total of 600 embryos. Results: For budesonide, the teratogenic/lethal effect started at a dose 0.003 μg per embryo, for formoterol at 0.3 μg and for Symbicort 0.03 μg. Orofacial clefts and gastroschisis after exposure were found for all three anti-asthmatics. Heart septum defects occurred after exposure to formoterol. Conclusion: The present results support those clinical/epidemiological studies pointing out that antiasthmatics have the potential to induce orofacial clefts, gastroschisis and heart malformations during prenatal development in human.Bronchial asthma affects between 7 to 16% of pregnant women and its prevalence exhibits an increasing trend (1-3).
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