Maternal Vitamin D Status and Preterm Birth

这项提案将解决我们对早产中棘手的种族差异的理解上的差距。 2关注孕妇维生素D状况和维生素D受体(VDR)基因变异。我们已经证明了 3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 4名女性。此外，数据表明，维生素D对炎症和其他疾病有直接和间接的影响 早产发病机制中已知的5条分子途径。我们假设孕妇体内的维生素D 妊娠d20周缺乏和母体vdr基因变异与患糖尿病的风险相关。 7例早产。我们作为NIH资助拨款的一部分生成的新的初步数据(R01HD056999， 8 PI：Bodnar)在20世纪60年代的一大批美国怀孕人群中的研究支持这一假设并证明 9在一个现代的、种族多元化的队列中进行确认。 为了验证这一假设，我们将使用现有的母体银行进行嵌套病例对照研究。 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的11份血清样本和数据 12名接受产前筛查并在Magee妇女医院分娩的无胎儿异常的单胎活产婴儿 宾夕法尼亚州匹兹堡13医院(1999-2010)。我们将选择所有早产病例(n=1539例白人和 14n=805个黑人病例)和等量的种族匹配的对照进行母体血清的检测 妊娠20周时给予15羟基维生素D(25(OH)D)并进行基因分型。首先，我们将确定独立的 16怀孕20周时母亲维生素D状况与早产风险之间的关系，如 17以及早产(32周)和晚期(32周和37周)早产，以及自然早产和先兆早产。 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，我们将确定母体维生素D受体基因的遗传变异对母体 20维生素D状况和早产风险。 这些目标的成功完成将解决一些最紧迫的研究 2010年国际移民组织关于钙和维生素D饮食参考摄入量委员会的22项建议， 23包括探讨维生素D在妊娠的非骨骼健康结局中的作用；以及阐明 24维生素D的遗传变异，包括种族/族裔群体之间的遗传变异对健康结果的影响。我们是 25非常适合进行这项研究，因为我们对胎龄、表型能力的严格评估 早产的26个临床亚型，亚型分析的统计能力，以及大量的白人和 27名黑人女性。我们的研究团队拥有现有的基础设施、成熟的协作和重要的 28成功完成与早产和维生素D有关的项目的经验，因为它是 29安全、廉价和直接地改善孕妇怀孕期间的维生素D状况，探索如何 30维生素D导致出生结果的种族差异可能会对公共健康产生重大影响。

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 birthoverall, 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.