An internet-based preconception cohort study in North America and Denmark

摘要 不孕不育和自然流产是重要的公共卫生问题，影响高达20%的 处于生育年龄的夫妇。随着夫妇越来越多地将生育推迟到晚年，许多人 寻求治疗不孕不育的成功率相对较低，在美国，估计每年花费50亿美元。 在美国，并与不良妊娠结局有关。也应对不孕不育的压力 对受影响的夫妇造成可测量的情感损失。确定不孕症和SAB的可改变的危险因素 是一项重要的公共卫生目标。众所周知，计划怀孕的夫妇很难招募到 使用传统方法的研究性学习。我们已经表明，注册和跟进预科 在北美和丹麦，通过互联网进行受孕夫妇是可行的、有效的和成本效益高的。 我们建议统一来自丹麦三个相互关联的前瞻性先入为主的队列研究的数据 (Snart Gravid和Snart Foraeldre)和北美(Presto)评估是否选择了饮食因素 而药物会影响女性和男性的生育力，以及SAB的风险。为了将我们的统计能力提高到 为了实现这些目标，我们将利用我们现有的NICHD支持的基于网络的基础设施来收集额外的 来自6000名女性和2000名男性伴侣的数据。有有限的证据表明常用的 抗生素、哮喘药物、抗抑郁药和镇痛剂等药物会影响生育和SAB，尽管 育龄夫妇越来越多地使用药物带来的潜在的巨大归因风险。 此外，缺乏关于饮食因素和从优化设计的队列中繁殖的研究 对积极尝试怀孕的夫妇的研究。感兴趣的饮食因素包括高血糖负荷/指数、大豆、 女性为鱼/海鲜，男性为红肉和加工肉类、乳制品和反式脂肪酸。多数 TTP和SAB的研究在设计上具有回溯性，容易出现分类错误、左截断和选择 和回忆偏见。现有的为数不多的关于TTP和SAB的前瞻性研究规模小，动力不足。这个 将大型先入为主的队列与类似的设计相协调，将提供极好的能力来评估 广泛的假设范围。在夫妇怀孕之初登记可以确定关键时间段 暴露易感性。利用社交媒体和与健康有关的网站进行招聘是创新和 与传统方法相比，性价比非常高。纳入男性是一种创新，因为它允许 评估双方暴露的单独和联合影响，并允许更好地控制 令人困惑。利用登记册数据将能够收集更多的暴露和结果数据、数据 验证，确定那些失去后续行动的人，以及评估选择偏向和泛化。这 将是对TTP和SAB可修改的风险因素进行的最大规模的前瞻性先入为主的队列研究 约会。拟议研究的结果可能会对该领域产生重大和持续的影响，并将 为夫妇提出可行的建议，以提高他们的生育力，降低他们患上SAB的风险。

ABSTRACT Infertility and spontaneous abortion (SAB) are important public health problems, affecting up to 20% of reproductive age couples. As couples increasingly postpone childbearing to the later reproductive years, many seek infertility treatment, which has relatively low success rates, costs an estimated $5 billion per year in the United States, and is associated with adverse pregnancy outcomes. Coping with the stress of infertility also exacts a measurable emotional toll in affected couples. Identifying modifiable risk factors for infertility and SAB is an important public health goal. Couples planning a pregnancy are notoriously difficult to recruit into research studies using traditional methods. We have shown that enrollment and follow-up of pre- conception couples via the internet in North America and Denmark is feasible, valid, and cost-efficient. We propose to harmonize data from three interrelated prospective preconception cohort studies in Denmark (Snart Gravid and Snart Foraeldre) and North America (PRESTO) to evaluate whether selected dietary factors and medications influence female and male fecundity, and SAB risk. In order to increase our statistical power to accomplish these aims, we will use our existing NICHD-supported web-based infrastructure to collect additional data from 6,000 females and 2,000 of their male partners. There is limited evidence on whether commonly-used medications, such as antibiotics, asthma drugs, antidepressants, and analgesics affect fertility and SAB, despite the potentially large attributable risk due to increasing use of medications among couples of reproductive age. In addition, there is a scarcity of research on dietary factors and reproduction from optimally-designed cohort studies of couples actively trying to conceive. Dietary factors of interest include high glycemic load/index, soy, and fish/seafood among females and red and processed meats, dairy, and trans-fatty acids among males. Most studies of TTP and SAB are retrospective in design and prone to misclassification, left truncation, and selection and recall biases. The few existing prospective studies of TTP and SAB are small and underpowered. The harmonization of large preconception cohorts with similar designs will provide excellent power to evaluate a broad range of hypotheses. Enrolling couples at the start of their pregnancy attempt can identify critical windows of exposure susceptibility. The use of social media and health-related websites for recruitment is innovative and extremely cost-effective relative to traditional methods. Inclusion of males is innovative because it allows for the assessment of individual and joint effects of exposures in both partners, and permits better control for confounding. Utilization of registry data will enable the collection of additional exposure and outcome data, data validation, identification of those lost to follow-up, and assessment of selection bias and generalizability. This will be the largest prospective preconception cohort study of modifiable risk factors for TTP and SAB to date. Findings from the proposed research are likely to have a large and sustained impact on the field and will result in actionable recommendations for couples to improve their fertility and lower their risk of SAB.