Teratogenicity of drugs commonly used in pregnancy

描述（由申请人提供）：具有讽刺意味的是，减充血剂、抗组胺药和咳嗽（“咳嗽/感冒”）药物是妊娠期间最常用的药物，但其对出生缺陷的安全性尚未确定。鉴于这些药物的广泛使用，即使出生缺陷风险略有增加，也可能产生相当大的临床和公共卫生影响。因此，我们将评价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重大畸形和2）一般人群中常见的其他特定重大畸形之间的相关性。这些目标可以有效地实现利用数据，通过一个大的正在进行的多中心病例对照监测计划，在北美出生缺陷，斯隆流行病学中心出生缺陷研究（BDS）。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选定地区的100多家出生和三级医院，以及马萨诸塞州和纽约州的出生缺陷登记处，自1976年以来，已经采访了35，000多名有或没有出生缺陷婴儿的母亲。婴儿发育量表可以识别出各种各样的畸形婴儿（ICD编码740.0-759.9）和出生后5个月内的非畸形婴儿样本，研究护士采访分娩后6个月内的母亲，了解人口统计学、生殖和医学因素;吸烟和饮酒;饮食摄入;以及关于使用各种药物的详细信息，包括处方非处方药。这项研究成功地确定了选定的非处方药的风险和安全性，这一发现已被其他人证实。我们建议首先描述妊娠期间咳嗽/感冒药物的使用模式以及研究期间药物利用的变化。然后，我们将估计与妊娠早期接触特定的减充血剂、抗组胺药和咳嗽药相关的特定出生缺陷的风险。比值比和95%的置信区间将使用条件logistic回归模型计算，以调整潜在的混杂因素。这项工作的结果将提高我们对孕妇常用药物相关风险的理解，为治疗指南提供信息，并为进一步研究提供线索。公共卫生相关性：减充血剂，抗组胺药和咳嗽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。本研究将评估妊娠期使用这些药物是否与重大出生缺陷风险增加相关。研究结果将提高我们对这些药物相关风险的理解，帮助医疗保健提供者和孕妇做出明智的选择，并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.