Effectiveness and Safety of Tdap Immunization in Pregnancy

描述（由申请人提供）：最近在美国百日咳的复苏需要重新检查我们的方法来控制这种疾病。百日咳可导致住院治疗和死亡，特别是对于年龄太小而无法从免疫接种中受益的婴儿。为了减轻婴儿百日咳的负担，免疫实践咨询委员会（ACIP）于2011年6月建议所有孕妇在怀孕后期接受破伤风-白喉-无细胞百日咳（Tdap）加强剂。ACIP的建议是由免疫学研究提供的，这些研究表明母亲的抗百日咳抗体会转移到胎儿身上;然而，为了支持这些免疫学研究，还没有大规模的研究表明婴儿百日咳病例可以通过这种策略预防。一个重要的问题是，被动获得的母体抗体可能会在婴儿早期减弱婴儿自身对白喉-破伤风-无细胞百日咳（DTaP）系列的免疫反应，一旦这些被动获得的抗体减弱，婴儿可能会受到较差的保护。此外，关于Tdap在妊娠期的安全性或吸收的建议知之甚少。这项研究汇集了一组研究人员，以评估妊娠期Tdap免疫接种的吸收，有效性和安全性。我们提出了一个非实验性的研究设计，使用现有的商业保险索赔数据库，包括2011年6月至2013年12月期间超过100万名活产分娩的妇女。我们将首先描述自2011年6月以来在妊娠期使用Tdap的特征，并检查与遵守建议相关的个人，提供者和生态特征，以告知未来关于Tdap免疫接种障碍的研究。接下来，我们将比较a）妊娠期间接种Tdap的母亲，B）未接种Tdap的母亲，以及c）产后接种Tdap的母亲（如之前推荐的）所生的6个月以下婴儿的百日咳住院风险。我们将进一步研究妊娠期Tdap给药时间与百日咳住院风险之间的关系。最后，我们将通过比较免疫组和未免疫组孕妇及其各自婴儿之间不良妊娠和婴儿结局（如早产、死产和先天性畸形）的相对风险，评估Tdap在妊娠期的安全性。我们还将在孕妇接受Tdap给药后2周内使用新的数据驱动信号检测方法，以检测先前未报告的不良反应。该提案将推进用于分析疫苗安全性和有效性现有数据的统计方法，同时提供有关当前婴儿百日咳预防建议的重要信息。如果我们的研究结果表明，Tdap免疫接种在怀孕期间是安全和有效的，在预防婴儿百日咳，这可能有助于提高免疫接种覆盖率的孕妇，从而减少婴儿百日咳病例和死亡人数。

DESCRIPTION (provided by applicant): The recent resurgence of pertussis in the United States requires a reexamination of our approach to controlling this illness. Pertussis can result in hospitalization and death, especially among infants who are too young to benefit from immunization. To reduce the burden of pertussis in infants, the Advisory Committee on Immunization Practices (ACIP) recommended in June 2011 that all pregnant women should receive the tetanus-diptheria-acellular pertussis (Tdap) booster in late pregnancy. The ACIP recommendation was informed by immunological studies showing that maternal anti-pertussis antibodies are transferred to the fetus; however, to support these immunological studies, there have been no large-scale studies showing that infant pertussis cases can be prevented by this strategy. One important concern is that passively-acquired maternal antibodies may act to blunt the infant's own immune response to the diphtheria-tetanus-acellular pertussis (DTaP) series in early infancy, and once these passively-acquired antibodies wane, the infant may be left with inferior protection. Further, little is known about the safety or uptake of the Tdap in pregnancy recommendation. This study brings together a team of investigators to evaluate the uptake, effectiveness, and safety of Tdap immunization in pregnancy. We propose a non-experimental study design using an existing commercial insurance claims database, including over 1 million women with live-birth deliveries between June 2011 and December 2013. We will first characterize the use of Tdap in pregnancy since June 2011 and examine personal, provider, and ecologic characteristics associated with adherence to the recommendation, to inform future studies on barriers to Tdap immunization. Next, we will compare the risk of pertussis hospitalization among infants less than 6 months of age who were born to a) mothers immunized with Tdap during pregnancy, b) mothers unimmunized with Tdap, and c) mothers immunized with Tdap in the postpartum period (as previously recommended). We will further examine the relationship between the timing of Tdap administration in pregnancy and the risk of pertussis hospitalization. Finally, we will evaluate the safety of Tdap in pregnancy by comparing the relative risks of adverse pregnancy and infant outcomes, such as preterm delivery, stillbirth, and congenital anomalies between groups of immunized and unimmunized pregnant women and their respective infants. We will also use novel data-driven signal detection methods during the 2 week period after Tdap administration to pregnant women to detect previously unreported adverse reactions. This proposal will advance statistical methodologies for analyzing existing data on vaccine safety and effectiveness, while at the same time providing important information on the current recommendation for infant pertussis prevention. If our findings shows that Tdap immunization in pregnancy is safe and effective at preventing infant pertussis, this may help to increase immunization coverage among pregnant women, and thereby reduce the number of infant pertussis cases and deaths.