Reproductive Care in Women with Sickle Cell Disease - Use of Secondary Data to Investigate Risk of Contraception-Related Thrombosis and the Impact of Hydroxyurea on Pregnancy Outcomes

项目摘要/摘要 随着医学进步改善镰状细胞病(SCD)的发病率和死亡率，改善生殖健康 变得越来越重要。知识差距包括激素避孕的安全信息有限，以及 孕前使用羟基尿素对妊娠结局的影响。含雌激素避孕药 增加血栓栓塞症(TE)的风险，而且几乎没有证据表明仅使用孕激素的安全性 为患有SCD的妇女提供避孕措施。缺乏安全数据可能成为提供避孕措施的障碍 医学上复杂的女性。考虑到死亡风险的增加，这对患有SCD的妇女来说是一个特别令人担忧的问题 和怀孕期间的发病率，以及计划外怀孕的高比率。在怀孕期间，患有 与种族匹配的同龄人相比，SCD有更高的死亡率、先兆子痫和早产风险。 然而，这些数据大多是10-25岁时使用的HU，一种高效的疾病修饰剂 治疗，大大降低了。而HU对预后的影响，如血管闭塞危机和急性 胸部综合征已被很好地描述，但孕前使用HU对妊娠结局的影响尚不清楚。 这个R21应用程序的目标是结合我们在大型数据库研究和方法方面的经验 我们在女性血液学和SCD方面的内容专业知识，利用健康声明数据来研究避孕安全性 SCD妇女的妊娠结局。本申请的具体目的是：1)比较 通过确定开具处方的妇女中TE的风险率，了解SCD妇女的避孕选择 仅使用孕激素、含雌激素或不使用激素避孕，以及2)比较 妊娠前有无HU暴露的SCD妇女和SCD妇女的结局比较 年龄和种族匹配的对照。我们假设只使用孕激素避孕的妇女有时间接受治疗。 在不使用避孕措施的妇女中，无论年龄或SCD严重程度，将不逊于TE时间。我们 同样的假设是，没有使用HU的妇女怀孕并发症会更高 控制年龄和SCD严重程度。最后，我们假设目前先兆子痫和先兆子痫的相对风险 与历史数据相比，患有SCD的女性足月分娩将显著低于对照组。 拟议的工作具有创新性，因为它解决了既没有研究过的问题(影响 孕前HU暴露对临床结果的影响)或仅在非常小的队列中进行研究(避孕安全性)。 完成这项裁决将产生以下预期结果：1)了解 SCD中与避孕有关的TE和确定最安全的避孕形式，以及2)示范 孕前使用胡敏素对妊娠结局的影响。拟议的工作意义重大，因为 了解避孕安全性是消除咨询和处方障碍的第一步 不良妊娠结局风险增加的患者群体。同时，更好地理解 孕前使用HU对妊娠的影响可能是促进HU使用和坚持的关键。

PROJECT SUMMARY / ABSTRACT As medical advances improve morbidity and mortality in sickle cell disease (SCD), improving reproductive health is of increasing importance. Knowledge gaps include limited safety information for hormonal contraception and the impact of pre-pregnancy hydroxyurea (HU) use on pregnancy outcomes. Estrogen-containing contraceptives increase the risk of thromboembolism (TE), and there is little evidence on the safety of progestin-only contraceptives for women with SCD. Lack of safety data can be a barrier to provision of contraception for medically complex women. This is a particular concern for women with SCD, given the increased risk of mortality and morbidity during pregnancy, and the high rates of unplanned pregnancy. During pregnancy, women with SCD have increased risk of mortality, preeclampsia, and preterm delivery compared to race-matched peers. However, most of these data are 10-25 years old, when use of HU, a highly efficacious disease modifying therapy, was substantially lower. While the impact of HU on outcomes such as vaso-occlusive crises and acute chest syndrome is well described, the impact of pre-pregnancy HU use on pregnancy outcomes is unexplored. The objective of this R21 application is to combine our methodologic experience in large database research and our content expertise in women’s hematology and SCD to utilize health claims data to study contraception safety and pregnancy outcomes in women with SCD. The specific aims of this application are: 1) compare safety of contraceptive choices among women with SCD by identifying the hazard rate of TE in women prescribed progestin-only, estrogen-containing, or no hormonal contraception, and 2) compare pregnancy outcomes in women with SCD with and without HU exposure pre-pregnancy, and outcomes in women with SCD compared to age and race-matched controls. We hypothesize that time to TE in women using progestin-only contraception will be non-inferior to time to TE in women not using contraception, independent of age or SCD severity. We also hypothesize that pregnancy complications will be higher in women without HU use pre-pregnancy, again controlling for age and SCD severity. Finally, we hypothesize that current relative risks of preeclampsia and pre- term delivery in women with SCD compared to controls will be significantly lower compared to historical data. The proposed work is innovative because it addresses questions that have either not been studied (impact of pre-pregnancy HU exposure on clinical outcomes) or studied only in very small cohorts (contraception safety). Completion of this award will yield the following expected outcomes: 1) knowledge of the absolute risk of contraception-related TE in SCD and identification of the safest forms of contraception, and 2) demonstration of the impact of pre-pregnancy HU use on pregnancy outcomes. The proposed work is significant because understanding contraception safety is the first step to eliminating barriers to counseling and prescribing to a patient population with increased risks of adverse pregnancy outcomes. As well, better understanding of the impact of pre-pregnancy HU use on pregnancy may be key in promoting use of and adherence to HU.