Anti-asthma Drugs Formoterol and Budesonide (Symbicort) Induce Orofacial Clefts, Gastroschisis and Heart Septum Defects in anIn VivoModel

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 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).

Role of Maternal Infections and Inflammatory Responses on Craniofacial Development

“…This was found to be linked to altered muscle growth and skeletal development in both human and animal models [ 93 , 94 ]. Exposure to corticosteroids during pregnancy has been associated with the risk of developing orofacial defects in animal models however, their effects in humans remain unclear [ 95 , 96 ].…”