Teratogenicity of Drugs Most Commonly Used in Pregnancy

对乙酰氨基酚、阿司匹林、布洛芬和阿莫西林是怀孕期间最常用的药物，但这些药物对出生缺陷的安全性尚未确定。鉴于这些药物的广泛使用，即使出生缺陷风险的小幅增加也可能产生相当大的临床和公共卫生影响。我们建议评估这些药物与1)先前假设与每种药物相关的特定畸形，以及2)在一般人群中最常见的特定畸形之间的关系。此外，我们建议通过系统筛选与特定畸形风险相关的每次暴露来评估其他常用药物。通过利用北美现有的大型多中心出生缺陷病例对照监测项目，即Slone流行病学中心出生缺陷研究（BDS），可以以相对低廉的成本实现这些目标。BDS涉及四个大都市地区（波士顿、费城、多伦多和圣地亚哥）的大约95家机构，在25年多的时间里，采访了2万多名畸形婴儿母亲和4000多名非畸形婴儿母亲。BDS在三级医院和产科医院确定出生后5个月内患有各种畸形的婴儿，并在分娩后6个月内，研究护士就人口、生殖和医疗因素与母亲进行面谈；药物和维生素的使用；吸烟和饮酒；还有饮食摄入。该研究发现了可能的致畸作用，并随后得到了其他人的证实（例如，与胃裂有关的水杨酸盐）。在建议的分析中，我们将使用逻辑回归估计比值比和95%置信区间，并根据潜在的混杂因素对结果进行调整。研究结果将检验一些药物的假设，并为其他药物的进一步研究提供线索；这两个目标都旨在提高我们对孕妇常用药物相关风险的理解。

Acetaminophen, aspirin, ibuprofen, and amoxicillin are among the most commonly used drugs during pregnancy, but the safety of these medications with respect to birth defects is not established. Given the wide use of these drugs, even a small increase in the risk of birth defects may have considerable clinical and public health implications. We propose to evaluate the association between these drugs and 1) specific malformations previously hypothesized to be associated with each of them, and 2) specific malformations that occur most commonly in the general population. In addition, we propose to evaluate other commonly used medications by systematically screening each exposure in relation to the risk of specific malformations. These goals can be achieved at relatively modest cost by taking advantage of a large existing ongoing multicenter case-control surveillance program of birth defects in North America, the Slone Epidemiology Center Birth Defects Study (BDS). The BDS involves approximately 95 institutions in four metropolitan areas (Boston, Philadelphia, Toronto, and San Diego), and for over 25 years has interviewed over 20,000 mothers of malformed infants and over 4,000 mothers of non-malformed infants. The BDS identifies infants with a wide range of malformations within 5 months after birth at tertiary and birth hospitals, and within 6 months of delivery, study nurses interview mothers about demographic, reproductive, and medical factors; medication and vitamin use; cigarette smoking and alcohol consumption; and dietary intake. The study has discovered likely teratogenic effects that have subsequently been confirmed by others (e.g., salycilates in relation to gastroschisis). In the proposed analyses, we will estimate odds ratios and 95% confidence intervals using logistic regression, and results will be adjusted for potential confounders. Findings will test hypotheses about some drugs and provide leads for further research for others; both objectives seek to improve our understanding of risks associated with drugs commonly used by pregnant women.