Maternal Vitamin D Status and Preterm Birth

描述(由申请人提供)：1这项建议将通过关注孕妇的维生素D状况和维生素D受体(VDR)的基因变异，解决我们对早产中难以解决的种族差异的认识上的差距。我们已经证明，维生素D缺乏症在怀孕的黑人妇女中普遍存在，而在白人妇女中明显较少见。此外，有数据表明，维生素D在早产的发病机制中对炎症和其他5个已知的分子途径有直接和间接的影响。我们假设怀孕20周时母亲维生素D6缺乏和母亲VDR基因的基因变异与早产的风险有关。作为美国国立卫生研究院资助的赠款(R01 HD056999，8 PI：Bodnar)的一部分，我们在20世纪60年代对一大批美国怀孕患者生成的新的初步数据支持这一假设，并在一个现代的、种族多样化的队列中得到证实。10为了验证这一假设，我们将使用现有的母体血清样本和来自17,027名非西班牙裔白人和6,065名非西班牙裔黑人女性12的队列数据进行嵌套病例对照研究，这些女性12接受了产前筛查，并在宾夕法尼亚州匹兹堡的Magee-Women 13医院分娩了没有胎儿异常的单胎活产婴儿(1999-2010)。我们将选择所有早产病例(1539例白人和14例黑人)和等量的种族匹配的对照组，在妊娠20周时测定孕妇血清25-15羟基维生素D(25(OH)D)并进行基因分型。首先，我们将确定怀孕20周时孕妇维生素D状况与整个早产风险之间的独立关联，以及早产(32周)和晚期(32周和37周)早产、自然早产和指征早产的风险。18其次，我们将确定母亲维生素D状况对早产种族差异的贡献。19最后，我们将确定母亲维生素D受体基因的遗传变异对母亲维生素D状态和早产风险的影响。21成功完成这些目标将解决国际移民组织2010年钙和维生素D饮食参考摄入量委员会提出的一些最紧迫的研究22建议，23包括探讨维生素D在妊娠非骨骼健康结果中的作用；并阐明基因变异，包括种族/族裔群体中维生素D对健康结果的影响。我们非常适合进行这项研究，因为我们对胎龄的严格评估，对早产26个临床亚型的表型能力，亚型分析的统计能力，以及大量的白人和27名黑人女性。我们的研究团队在成功完成与早产和维生素D相关的项目方面拥有现有的基础设施、经过验证的合作和重要的经验。由于改善孕妇怀孕期间的维生素D状况是安全、廉价和直接的，因此探索维生素D如何导致出生结果的种族差异可能会对公众健康产生重大影响。

DESCRIPTION (provided by applicant): 1 This proposal will address gaps in our understanding of the intractable racial disparities in preterm birth 2 by focusing on maternal vitamin D status and vitamin D receptor (VDR) genetic variation. We have shown that 3 vitamin D deficiency is pervasive among pregnant black women and is significantly less common among white 4 women. Further, data indicate that vitamin D has direct and indirect influences on inflammation and other 5 known molecular pathways in the pathogenesis of preterm birth. We hypothesize that maternal vitamin D 6 deficiency at d20 weeks gestation and maternal genotypic variation in the VDR gene are associated with risk of 7 preterm birth. Novel preliminary data that we have generated as part of an NIH-funded grant (R01 HD056999, 8 PI: Bodnar) on a large cohort of U.S. pregnancies in the 1960s support this hypothesis and warrant 9 confirmation in a modern, ethnically-diverse cohort. 10 To test this hypothesis, we will conduct a nested case-control study using existing banked maternal 11 serum samples and data from a cohort of 17,027 non-Hispanic white and 6,065 non-Hispanic black women 12 who received prenatal screening and delivered singleton, live births with no fetal anomalies at Magee-Womens 13 Hospital in Pittsburgh, Pennsylvania (1999-2010). We will select all cases of preterm birth (n=1539 white and 14 n=805 black cases) and an equal number of race-matched controls for the assay maternal serum 25- 15 hydroxyvitamin D (25(OH) D) at d20 weeks gestation and genotyping. First, we will determine the independent 16 association between maternal vitamin D status at d20 weeks gestation and the risk of preterm birth overall, as 17 well as early (<32 weeks) and late (32-<37 weeks) preterm birth, and spontaneous and indicated preterm birth. 18 Second, we will determine the contribution of maternal vitamin D status to the racial disparity in preterm birth. 19 Finally, we will determine the effect of maternal genetic variation in the vitamin D receptor gene on maternal 20 vitamin D status and on the risk of preterm birth. 21 The successful completion of these aims will address some of the most urgent research 22 recommendations from the 2010 IOM Committee on Dietary Reference Intakes for Calcium and Vitamin D, 23 including exploring the role of vitamin D in non-skeletal health outcomes of pregnancy; and elucidating the 24 effect of genetic variation, including that among racial/ethnic groups, of vitamin D on health outcomes. We are 25 ideally suited to conduct this study because of our rigorous assessment of gestational age, ability to phenotype 26 clinical subtypes of preterm birth, statistical power for subtype analyses, and large numbers of both white and 27 black women. Our research team has the existing infrastructure, proven collaboration, and significant 28 experience in the successful completion of projects related to both preterm birth and vitamin D. Because it is 29 safe, inexpensive, and straightforward to improve maternal vitamin D status in pregnancy, exploring how 30 vitamin D contributes to racial disparities in birth outcomes could have a major public health impact.