Miroslav Peterka1,2, Lucie Hubickova Heringova3, Andrej Sukop4, Renata Peterkova3. 1. Cleft Centre, Clinic of Plastic Surgery, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic; peterkamm@seznam.cz. 2. Institute of Anatomy, First Faculty of Medicine, Charles University, Prague, Czech Republic. 3. Institute of Histology and Embryology, Third Faculty of Medicine, Charles University, Prague, Czech Republic. 4. Cleft Centre, Clinic of Plastic Surgery, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Abstract
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 anti-asthmatics 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 anti-asthmatics 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 anti-asthmatics have the potential to induce orofacial clefts, gastroschisis and heart malformations during prenatal development in human. Copyright
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 anti-asthmatics 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 anti-asthmatics 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 anti-asthmatics have the potential to induce orofacial clefts, gastroschisis and heart malformations during prenatal development in human. Copyright
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