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

镰状细胞病女性的生殖护理 - 利用二手数据调查避孕相关血栓形成的风险以及羟基脲对妊娠结局的影响

• 批准号: 10094247
• 负责人: SARAH H. OBRIEN
• 金额: $ 11.55万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-10 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10094247
• 关键词: Address; Adherence; Age; Area; Award; Benefits and Risks; Caring; Clinical; Complex; Contraceptive Agents; Contraceptive methods; Counseling; Data; Data Set; Databases; Disease; Estrogens; Exploratory/Developmental Grant for Diagnostic Cancer Imaging; Female Adolescents; Future; Goals; Guidelines; Health; Healthcare; Hematological Disease; Hematology; Hospitalization; Hospitalized Child; Knowledge; Maternal Mortality; Medicaid; Medical; Methodology; Modernization; Morbidity - disease rate; Myocardial Infarction; Outcome; Package Insert; Patients; Population; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Progestins; Race; Recording of previous events; Relative Risks; Reporting; Reproductive Health; Research; Risk; Safety; Severities; Severity of illness; Sickle Cell Anemia; Stroke; Thromboembolism; Thrombosis; Time; Transfusion; Woman; Women' s Health; Work; acute chest syndrome; adverse pregnancy outcome; clinically relevant; cohort; experience; fetal; hazard; hormonal contraception; hydroxyurea; improved; innovation; maternal risk; mortality; mortality risk; patient population; peer; prepregnancy; reproductive; safety outcomes; systematic review; thrombogenesis; unintended pregnancy; vaso-occlusive crisis; venous thromboembolism

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.

项目总结/摘要 随着医学进步改善镰状细胞病（SCD）的发病率和死亡率， 越来越重要。知识差距包括激素避孕的安全信息有限， 孕前使用羟基脲（HU）对妊娠结局的影响。含雌激素避孕药 增加血栓栓塞（TE）的风险，并且几乎没有证据表明仅使用孕激素的安全性 为患有SCD的女性提供避孕药。缺乏安全性数据可能是提供避孕措施的障碍， 医学上复杂的女人这是一个特别关注的妇女与SCD，鉴于增加的死亡风险 怀孕期间发病率和意外怀孕率高。怀孕期间，患有 与种族匹配的同龄人相比，SCD的死亡率、先兆子痫和早产风险增加。 然而，这些数据中的大多数是10-25岁，当使用HU时， 治疗，大大降低。虽然HU对血管闭塞性危象和急性 胸部综合征是很好的描述，孕前使用HU对妊娠结局的影响尚未探讨。 这个R21应用程序的目标是联合收割机结合我们在大型数据库研究中的方法学经验， 我们在女性血液学和SCD方面的内容专业知识，可利用健康声明数据研究避孕安全性 和妊娠结局。本申请的具体目的是：1）比较 通过确定处方妇女TE的危险率，在SCD妇女中选择避孕药 仅孕激素、含雌激素或无激素避孕，以及2）比较 妊娠前有和无HU暴露的SCD女性，以及SCD女性的结局比较 年龄和种族匹配的对照组。我们假设使用仅孕激素避孕的女性的TE时间 不劣效于未采取避孕措施的女性的至TE时间，与年龄或SCD严重程度无关。我们 我还假设怀孕前没有使用HU的妇女的妊娠并发症会更高， 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危险度是 与历史数据相比，SCD妇女的足月分娩率显著低于对照组。 拟议的工作是创新性的，因为它解决了一些尚未研究过的问题（ 妊娠前HU暴露对临床结局的影响）或仅在非常小的队列中进行研究（避孕安全性）。 完成此奖励将产生以下预期结果：1）了解 SCD中避孕相关TE和最安全避孕形式的识别，以及2）证明 孕前使用HU对妊娠结局的影响。这项工作意义重大，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人群。同时，更好地了解 孕前使用HU对妊娠的影响可能是促进使用和坚持HU的关键。

项目成果

Comparison of thromboembolism outcomes in patients with sickle cell disease prescribed hormonal contraception.

• DOI: 10.1182/bloodadvances.2023010204
• 发表时间: 2023-10-24
• 期刊: BLOOD ADVANCES
• 影响因子: 7.5
• 作者: Bala, Natasha S.;Stanek, Joseph R.;Vesely, Sara K.;Cronin, Robert M.;Creary, Susan E.;Roe, Andrea H.;Xu, Wendy;O'Brien, Sarah H.
• 通讯作者: O'Brien, Sarah H.