Foundation for the Community of Control of Hereditary Diseases, Budapest, Hungary.
Clin Drug Investig. 2003;23(12):803-16. doi: 10.2165/00044011-200323120-00005.
To study the human teratogenic potential of oral aminophylline treatment during pregnancy.
The analysis of each case and its matched controls, as well as comparison of population or patient controls and cases with 25 groups of congenital abnormalities in the population-based data set of the large Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996.
38 151 pregnant women who had newborn infants without any congenital abnormalities (population control group), 22 843 pregnant women who had newborn infants or fetuses with congenital abnormalities, and 834 patient controls with Down's syndrome.
Prevalence of aminophylline use in cases with the 25 congenital abnormality groups compared with population control and patient control groups.
The prevalence of oral aminophylline treatment during pregnancy was similar in the case group (1374 pregnant women; 6.0%) and the population control group (2284 pregnant women; 6.0%) [crude prevalence odds ratio (POR) 1.0, 95% confidence interval (CI) 0.9-1.1], while it was higher in the patient control group (55 pregnant women; 6.6%). Comparisons of total population or patient control groups and cases with the 25 different congenital abnormality groups, as well as analysis of cases and their matched controls, indicated an association between aminophylline use and congenital abnormalities of the musculoskeletal system (crude POR 5.0, 95% CI 1.4-18.4, adjusted POR 4.7, 95% CI 1.3-17.2 for aminophylline treatment during the second through third months of gestation; crude POR 1.5, 95% CI 1.0-2.2, adjusted POR 1.5, 95% CI 0.9-2.2 for aminophylline treatment during the entire pregnancy), particularly pectus excavatum/carinatum (3.5 times excess). There was a possible association between aminophylline and clubfoot and posterior cleft palate. These findings may be connected with recall bias, although this bias was restricted by the evaluation of maternal drug use only during the critical period of the above congenital abnormalities and by evaluating medically recorded aminophylline treatment, as well as by the use of patient controls.
Our findings and previous animal investigations can only be regarded as a signal for the possible association between oral treatment with aminophylline during pregnancy and some congenital abnormalities of the skeletal system.
研究孕期口服氨茶碱治疗的人类致畸潜能。
在基于人群的大匈牙利出生缺陷病例对照监测 1980-1996 年数据集中，对每个病例及其匹配对照进行分析，并将人群或患者对照与 25 组先天性异常病例进行比较。
38151 名孕妇，其新生儿无任何先天性异常（人群对照组），22843 名孕妇，其新生儿或胎儿有先天性异常，834 名患者对照患有唐氏综合征。
与人群对照组和患者对照组相比，25 组先天性异常病例组中口服氨茶碱治疗的患病率。
病例组（1374 名孕妇；6.0%）和人群对照组（2284 名孕妇；6.0%）中口服氨茶碱治疗的患病率相似[粗患病率比值比（POR）1.0，95%置信区间（CI）0.9-1.1]，而患者对照组（55 名孕妇；6.6%）中患病率更高。将总人群或患者对照组与 25 种不同先天性异常组进行比较，以及对病例及其匹配对照进行分析，表明氨茶碱使用与骨骼系统先天性异常之间存在关联（氨茶碱在妊娠第二至第三个月使用的粗 POR 为 5.0，95%CI 为 1.4-18.4，调整 POR 为 4.7，95%CI 为 1.3-17.2；整个孕期使用氨茶碱的粗 POR 为 1.5，95%CI 为 1.0-2.2，调整 POR 为 1.5，95%CI 为 0.9-2.2），尤其是漏斗胸/鸡胸（过剩 3.5 倍）。氨茶碱与马蹄内翻足和后腭裂之间可能存在关联。这些发现可能与回忆偏倚有关，尽管这种偏倚受到限制，仅评估了上述先天性异常的关键时期内的母亲药物使用情况，以及评估了医学记录的氨茶碱治疗情况，以及使用了患者对照。
我们的发现和以前的动物研究只能被视为怀孕期间口服氨茶碱治疗与骨骼系统某些先天性异常之间可能存在关联的信号。
