Teratogenicity of drugs commonly used in pregnancy

描述（由申请人提供）：具有讽刺意味的是，减充血药、抗组胺药和咳嗽（“咳嗽/感冒”）药物是怀孕期间最常用的药物，但它们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。因此，我们将评估子宫内暴露于这些药物与1)先前假设与每种药物相关的特定主要畸形之间的关系，以及2)一般人群中常见的其他特定主要畸形。通过利用北美正在进行的大型多中心出生缺陷病例对照监测项目Slone流行病学中心出生缺陷研究（BDS）提供的数据，可以有效地实现这些目标。BDS涉及波士顿、费城、多伦多、圣地亚哥等大都市地区和爱荷华州部分地区的100多家妇产医院和三级医院，以及马萨诸塞州和纽约州的出生缺陷登记处，自1976年以来，访问了3.5万多名有或无出生缺陷婴儿的母亲。BDS确定了各种畸形婴儿（ICD代码740.0-759.9）和出生后5个月内的非畸形婴儿样本，并研究护士在分娩后6个月内对母亲进行了关于人口、生殖和医疗因素的访谈；吸烟和饮酒；饮食摄入量;以及各种药物的使用细节，包括处方非处方药。这项研究成功地确定了某些非处方药的风险和安全性，这一发现也得到了其他人的证实。我们建议首先描述怀孕期间咳嗽/感冒药的使用模式以及研究期间药物使用的变化。然后，我们将评估与孕早期接触特定减充血剂、抗组胺药和咳嗽药物相关的特定出生缺陷的风险。比值比和95%置信区间将使用条件逻辑回归模型计算，以调整潜在的混杂因素。这项工作的发现将提高我们对孕妇常用药物相关风险的理解，将为治疗指南提供信息，并为进一步的研究提供线索。公共卫生相关性：减充血药、抗组胺药和止咳药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。这项研究将评估孕期使用这些药物是否与主要出生缺陷的风险增加有关。研究结果将提高我们对这些药物相关风险的理解，将帮助卫生保健提供者和孕妇做出明智的选择，并将为进一步的研究提供线索。

DESCRIPTION (provided by applicant): It is ironic that decongestant, antihistamine and cough ("cough/cold") medications are among the most commonly used drugs during pregnancy, yet their safety 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. Thus, we will evaluate the association between in utero exposure to these drugs and 1) specific major malformations previously hypothesized to be associated with each of them, and 2) other specific major malformations that occur commonly in the general population. These goals can be efficiently achieved by taking advantage of data available through a large ongoing multicenter case-control surveillance program of birth defects in North America, the Slone Epidemiology Center Birth Defects Study (BDS). The BDS has involved over 100 birth and tertiary hospitals in the greater metropolitan areas of Boston, Philadelphia, Toronto, San Diego, and selected regions in Iowa, as well as birth defects registries in Massachusetts and New York State, and has, since 1976, interviewed more than 35,000 mothers of babies with and without birth defects. The BDS identifies infants with a wide range of malformations (ICD codes 740.0-759.9) and a sample of non-malformed infants within 5 months after birth, and study nurses interview mothers within 6 months of delivery about demographic, reproductive, and medical factors; cigarette smoking and alcohol consumption; dietary intake; and details about use of a wide range of medications, including prescription over-the-counter drugs. The study has successfully identified both risks and safety of selected over-the-counter medications-findings which have been confirmed by others. We propose to first characterize the patterns of use of cough/cold medications during pregnancy and the changes in drug utilization over the study period. We then will estimate the risk of specific birth defects associated with first trimester exposure to specific decongestant, antihistamine and cough medications. Odds ratios and 95 per cent confidence intervals will be calculated using conditional logistic regression models to adjust for potential confounders. Findings from this effort will improve our understanding of risks associated with drugs commonly used by pregnant women, will inform therapeutic guidelines, and will provide leads for further research. PUBLIC HEALTH RELEVANCE: Decongestant, antihistamine and cough medications are among the most commonly used drugs during pregnancy, but the safety of these medications with respect to birth defects is not established. This study will evaluate whether use of these drugs in pregnancy is associated with an increased risk of major birth defects. Findings will improve our understanding of risks associated with these drugs, will help health care providers and pregnant women make informed choices, and will provide leads for further research.