Cleft Centre, Clinic of Plastic Surgery, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic;
Institute of Anatomy, First Faculty of Medicine, Charles University, Prague, Czech Republic.
In Vivo. 2021 May-Jun;35(3):1451-1460. doi: 10.21873/invivo.12397.
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.
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.
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.
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.
我们有一个病例，连续三胎均为患有口腔裂的婴儿。其母亲患有支气管哮喘，在怀孕期间使用信必可（皮质类固醇布地奈德加支气管扩张剂福莫特罗）进行治疗。提出了一个假设：这些哮喘药物可能会在实验模型中诱发口腔裂。
在鸡胚孵化的第 4 或第 5 天，将信必可、布地奈德或福莫特罗的五种递增剂量（包括治疗剂量）中的一种单次注入羊膜。总共对 600 个胚胎进行了抗哮喘药的致畸/致死作用评估。
对于布地奈德，致畸/致死作用始于每个胚胎 0.003μg 的剂量，对于福莫特罗为 0.3μg，对于信必可为 0.03μg。所有三种抗哮喘药暴露后均出现口腔裂和腹裂。暴露后还出现了心脏隔缺损。
目前的结果支持那些临床/流行病学研究指出，在人类产前发育过程中，哮喘药物有诱发口腔裂、腹裂和心脏畸形的潜力。
