An internet based prospective study of time to pregnancy

描述（由研究者提供）：我们建议在丹麦夫妇中进行一项关于延迟妊娠时间（TTP）风险因素的前瞻性队列研究。大约10%至15%的夫妇患有不孕症，而且这种情况可能正在增加。不孕不育服务的使用构成了主要的经济负担，治疗成功率相对较低。因此，识别TTP延迟的危险因素，特别是可改变的因素，是一个重要的公共卫生目标。大多数延迟TTP的既往研究采用回顾性设计，这可能特别容易受到选择偏倚的影响。这项在丹麦进行的前瞻性队列研究将扩大一项非常成功的R21资助的试点研究，利用互联网招募并跟踪10，000名计划怀孕的女性及其男性伴侣。根据试点研究的结果，在前瞻性队列研究中，基于互联网的方法似乎是一种有效和具有成本效益的招募和随访手段，特别是对于计划怀孕的夫妇，他们不容易通过其他手段识别。基于互联网的前瞻性招募和与登记数据的联系相结合是一种强大的研究设计，可以减轻由于失访、召回以及暴露和结果的错误分类而导致的偏倚。由于丹麦独特的登记资源，建立该队列将允许在延长随访的情况下对其他终点（如儿童肥胖和哮喘）进行长期评价。在扩展研究中，女性和男性参与者都将完成基线问卷和每两个月一次的随访问卷，这些问卷收集了包括酒精消费、咖啡因摄入、体重指数、体力活动和久坐行为在内的广泛因素的数据。此外，在最近研究的指导下，我们将使用经过验证的食物频率问卷收集有关饮食因素的暴露数据，如脂肪酸，叶酸，乳制品和铁摄入量。其他目标将集中在几个常见的和越来越多地使用的药物，包括糖皮质激素，血清素再摄取抑制剂，和非甾体抗炎药。对于这些暴露，将流产以及TTP作为终点进行评价。我们优先考虑这些风险因素，因为它们是常见的，现有的研究与TTP和流产的关系是不确定的。将对夫妇进行随访，直到报告怀孕或长达12个月，这是不孕症的标准临床定义，也是通常寻求生育治疗的时间。我们将对随访期间怀孕的大多数夫妇进行流产分析。我们将收集关于性交频率、吸烟、产次、周期规律性、周期长度、最后一种避孕方法、职业、教育、压力和抑郁症状等因素的潜在混杂因素数据。登记数据将用于验证处方药、病史和生殖史的自我报告数据，并确定失访受试者的妊娠和出生结局。 公共卫生相关性：近15%的夫妇难以怀孕，约20%的怀孕以流产告终。尽管它们经常发生，但很少有因素与不孕症和流产的风险增加密切相关。确定不孕症和流产的可改变的风险因素是一个重要的公共卫生目标，特别是因为这些疾病的治疗效果相对较差。

DESCRIPTION (provided by investigator): We propose to conduct a prospective cohort study of risk factors for delayed time to pregnancy (TTP) among Danish couples. About 10-15 per cent of couples suffer from infertility, and the prevalence may be increasing. Use of infertility services constitutes a major economic burden, and success rates of treatment are relatively low. Thus, identifying risk factors for delayed TTP, especially modifiable factors, is an important public health goal. Most previous studies of delayed TTP have used retrospective designs, which may be particularly subject to selection bias. This prospective cohort study in Denmark will expand a highly successful R21-funded pilot study, using the internet to recruit and follow 10,000 women and their male partners who are planning a pregnancy. Based on results from the pilot study, internet-based methods appear to be an efficient and cost- effective means of recruitment and follow-up in a prospective cohort study, especially for couples planning a pregnancy who are not readily identifiable by other means. The combination of internet-based prospective recruitment and linkage to registry data is a powerful research design that can mitigate biases due to loss to follow-up, recall, and misclassification of exposures and outcomes. Owing to unique registry resources in Denmark, establishment of this cohort will allow, with extended follow-up, the long-term evaluation of other endpoints such as childhood obesity and asthma. In the expanded study, both female and male participants will complete a baseline questionnaire and bi-monthly follow-up questionnaires that collect data on a wide range of factors including alcohol consumption, caffeine intake, body mass index, physical activity and sedentary behavior. In addition, guided by recent research, we will collect exposure data on dietary factors, such as fatty acids, folic acid, dairy foods, and iron intake, using a validated food frequency questionnaire. Other objectives will focus on several common and increasingly used medications, including glucocorticoids, serotonin re-uptake inhibitors, and non-steroidal anti-inflammatory drugs. For these exposures, miscarriage as well as TTP will be evaluated as endpoints. We have given priority to these risk factors because they are common and existing studies of their relation to TTP and miscarriage are inconclusive. Couples will be followed until a pregnancy is reported or for up to twelve months, the standard clinical definition of infertility and the time when fertility treatment is typically sought. We will conduct miscarriage analyses among the majority subset of couples that conceive during the follow-up. We will collect potential confounder data on frequency of intercourse, smoking, parity, cycle regularity, cycle length, last method of contraception, occupation, education, stress and depressive symptoms, among other factors. Registry data will be used to validate self-reported data on prescription medications, medical history, and reproductive history and to ascertain pregnancies and birth outcomes among participants who are lost to follow-up. PUBLIC HEALTH RELEVANCE: Nearly 15 per cent of all couples have difficulty becoming pregnant and approximately 20 per cent of all pregnancies end in miscarriage. Despite their frequent occurrence, few factors have been firmly linked to an increased risk of infertility and miscarriage. Identifying modifiable risk factors for infertility and miscarriage is an important public health goal, especially because the effectiveness of treatments for these conditions is relatively poor.