MOTOR-Maternal Oral Therapy to Reduce Obstetric Risk

描述（申请人提供）：最近的研究证实，母体牙周病与导致早产的妊娠并发症之间存在相关性[例如，胎龄（GA）<37周：校正比值比2.1（CI 95%：1.12，4.09），GA<28周的OR=4.2（CI 95%：1.42，12.6）]和胎儿体重下降[例如，在35-37周之间分娩GA的母亲中，牙周病患者（4+个部位，PD 5+mm，AL 2+mm）的新生儿小13.8%（p=0.004）。母体牙周感染对妊娠的有害影响在非裔美国人中尤其明显，并且可能部分地解释了这些不幸并发症的患病率的差异。妊娠早期牙周病的存在不仅会增加风险，而且妊娠期间牙周病的恶化-一种相对频繁的事件（814例分娩中的35.5%）似乎独立地增加了胎儿暴露于牙周病原体（如胎儿脐带血IgM抗体对母体口腔病原体的证明）和早产的风险（OR=5.0，CI 95%：2.22，11.3）。这些数据表明，牙周病及其进展可能代表感染和炎症暴露，可能在怀孕期间产生严重的有害影响。从科学的角度来看，要确定牙周病是否与早产有因果关系，并赋予任何可改变的风险，关键是要证明治疗孕妇牙周病会降低早产和生长受限的发生率。我们的中心假设是，在妊娠中期接受牙周治疗的牙周炎母亲的早产率较低，早产儿的平均出生体重较高。我们建议进行一项为期5年的随机、2组临床试验，在3个医疗/牙科中心（ESTA/杜克、UAB和UTHSCSA）完成1800名母亲，联合收割机结合牙周和妇产科临床试验专业知识。我们建议将1800名患有牙周病的孕妇随机分配到两个治疗组中的一个：1）在第二个三个月期间进行刮治和根面平整术或2）产后进行刮治和根面平整术。将在研究进行期间采集生物样本并存档，以便将来进行研究，进一步阐明母体口腔和阴道感染对妊娠的作用。我们推测，妊娠期牙周治疗将显著降低GA<35周早产的发生率，并增加GA<37周早产的平均体重。在UAB进行的一项试点研究的结果进一步支持了这项研究的动力，该研究表明，刮治和根面平整将GA<35周的发生率从未治疗组的6.4%降低到0.81%。这项名为MOTOR（降低产科风险的产妇口服疗法）的申请包括5个独立的组成部分：一个行政监督项目（MUNDental School），3个临床试验执行地点（MUNDental/杜克医疗，UAB Dental & Medical和UTHSCSA Dental & Medical）以及一个临床试验数据和统计协调中心（MUNDental Collaborative Studies Coordinating Center，School of Public Health）。

DESCRIPTION (provided by applicant): Recent studies have confirmed that there is an association between maternal periodontal disease and pregnancy complications that result in premature delivery [e.g. gestational age (GA)<37 weeks: adjusted odds ratio 2.1(CI95%:1.12, 4.09)and OR=4.2 for GA<28 weeks (CI95%: 1.42,12.6)] and decreased fetal weight [e.g. among mothers with births of GA between 35-37 weeks, those with periodontal disease (4+ sites with 5+mm PD and 2+mm AL) have neonates that are 13.8% smaller (p=0.004). The deleterious effect of maternal periodontal infection on pregnancy is particularly pronounced among African Americans and may, in part, account for some of the disparities in the prevalence of these unfortunate complications. Not only does the presence of periodontal disease early in pregnancy confer risk, but the worsening of periodontal disease during pregnancy - a relatively frequent event (35.5% of 814 deliveries) appears to independently enhance the risk of fetal exposure to periodontal pathogens (as evidenced by fetal cord blood IgM antibody to maternal oral pathogens) and preterm birth (OR=5.0, CI95%:2.22,11.3). These data suggest that periodontal disease and its progression may represent an infectious and inflammatory exposure that could have serious deleterious effects during pregnancy. Scientifically, to determine whether periodontal disease is causally related to preterm delivery and confers any modifiable risk, it will be critical to demonstrate that treating periodontal disease in pregnant mothers results in a decreased incidence of preterm birth and growth restriction. It is our central hypothesis that mothers with periodontitis that receive periodontal treatment during the second trimester of pregnancy will experience a lower rate of preterm delivery and a higher mean birth weight of the premature infants. We propose to conduct a 5-year randomized, 2-armed, clinical trial completing 1800 mothers at 3 medical/dental centers (UNC/Duke, UAB & UTHSCSA) that combine both periodontal and Obstetrics/Gynecology clinical trial expertise. We propose to randomly assign 1800 pregnant mothers with periodontal disease to one of two treatment arms 1) scaling and root planning during the second trimester or 2) scaling and root planning post-partum. Biological samples will be collected and archived during the conduct of the study to enable future investigations that will seek to further elucidate the role of maternal oral and vaginal infections on pregnancy. We hypothesize that periodontal treatment during pregnancy will significantly reduce the incidence of preterm deliveries of GA<35 weeks and also enhance the mean weight of those of GA<37 weeks. The impetus for this study is further supported by results from a pilot study conducted at UAB that demonstrated that scaling and root planning reduced the rate of GA<35 weeks from 6.4% in the untreated group to 0.81%. This application entitled MOTOR (Maternal Oral Therapy to Reduce Obstetric Risk) includes 5 separate components: an administrative oversight project (UNC Dental School), 3 clinical trial performance sites (UNC Dental/Duke Medical, UAB Dental & Medical and UTHSCSA Dental & Medical) and a clinical trials data and statistical coordinating center (UNC Collaborative Studies Coordinating Center, School of Public Health).