STUDY QUESTION Is preconception vitamin D level associated with the risk of miscarriage? SUMMARY ANSWER Preconception vitamin D levels are not associated with the risk of miscarriage in a population of women conceiving naturally. WHAT IS KNOWN ALREADY In humans, low vitamin D has been associated with prolonged menstrual cycles, delayed ovulation and a lower probability of conception. Animal and in vitro data indicate that vitamin D may affect implantation. STUDY DESIGN, SIZE, DURATION This prospective time-to-pregnancy study included 362 women who were trying to conceive naturally between 2008 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included participants who had been trying to conceive naturally for 3 months or less at enrollment and aged 30–44 years. A preconception blood sample was collected and 25-hydroxyvitamin D [25(OH)D] was measured. Women who conceived (N = 362) were at risk of a miscarriage from the day of a reported positive pregnancy test until either a participant-reported pregnancy loss or 20 weeks post day of last menstrual period, whichever came first. Gestational age was defined by ovulation. Time to miscarriage (days) or censoring was modeled using a multivariate Cox proportional hazards model. Multiple imputation was performed for missing covariates and missing day of ovulation. MAIN RESULTS AND THE ROLE OF CHANCE The mean age was 33 years (SD: 3.0 years). Mean 25(OH)D was lower among those who reported their race as African-American and those with a higher BMI. After adjustment for age, race, BMI, education, exercise, alcohol and caffeine intake, compared to the referent group (30–<40 ng/ml), the hazard ratio (HR) and 95% CI for those with a low 25(OH)D level (<30 ng/ml) was 1.10 (CI: 0.62, 1.91). Among participants with a higher 25(OH)D level (≥40 ng/ml), the HR was 1.07 (CI: 0.62, 1.84). LIMITATIONS, REASONS FOR CAUTION This study was limited by a 25(OH)D measurement at only a single time point. A large percentage of women in this study had sufficient vitamin D levels, which may have limited our power to detect an effect of deficiency. Women in this study were older (30–44 years), and predominantly reported their race as White which may limit generalizability. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study do not suggest an association between preconception vitamin D and miscarriage. Future research should focus on women at greater risk for miscarriage or in populations at risk for vitamin D deficiency or on supplementation. STUDY FUNDING/COMPETING INTEREST(S) This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01ES103333). This research was also supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) under award numbers R00HD079659 and R01HD067683. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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一项前瞻性队列研究中的孕前维生素 D 和流产

研究问题 孕前维生素 D 水平与流产风险有关吗？摘要答案 孕前维生素 D 水平与自然受孕女性的流产风险无关。已知信息 在人类中，低维生素 D 与月经周期延长、排卵延迟和受孕概率较低有关。动物和体外数据表明维生素 D 可能影响着床。研究设计、规模、持续时间 这项前瞻性妊娠时间研究包括 2008 年至 2015 年间尝试自然受孕的 362 名女性。参与者/材料、环境、方法 本研究包括尝试自然受孕 3 个月或 3 个月的参与者入学时较少，年龄在 30-44 岁之间。采集了孕前血样并测量了 25-羟基维生素 D [25(OH)D]。怀孕的妇女 (N = 362) 从妊娠试验报告呈阳性之日起至参与者报告流产或末次月经后 20 周（以先到者为准）都有流产风险。胎龄由排卵定义。使用多变量 Cox 比例风险模型对流产时间（天）或审查时间进行建模。对缺失的协变量和缺失的排卵日进行多重插补。主要结果和机会的作用 平均年龄为 33 岁（标准差：3.0 岁）。在报告自己种族为非裔美国人和 BMI 较高的人群中，平均 25(OH)D 较低。在根据年龄、种族、BMI、教育、锻炼、酒精和咖啡因摄入量进行调整后，与参照组 (30–<40 ng/ml) 相比，25(OH)D 水平较低 (<30 ng/ml) 的患者的风险比 (HR) 和 95% CI 为 1.10（CI： 0.62、1.91）。在 25(OH)D 水平较高 (≥40 ng/ml) 的参与者中，HR 为 1.07 (CI: 0.62, 1.84)。局限性、谨慎的原因 本研究仅限于在单个时间点进行 25(OH)D 测量。本研究中很大一部分女性维生素 D 水平充足，这可能限制了我们检测缺乏影响的能力。这项研究中的女性年龄较大（30-44 岁），并且主要报告她们的种族是白人，这可能会限制普遍性。研究结果的更广泛意义 本研究的结果并未表明孕前维生素 D 与流产之间存在关联。未来的研究应侧重于流产风险较高的女性或存在维生素 D 缺乏或需要补充剂风险的人群。研究资金/竞争利益 这项研究部分得到了 NIH 的校内研究计划的支持，国家环境健康科学研究所 (Z01ES103333)。这项研究还得到了美国国立卫生研究院 (NIH) 的 Eunice Kennedy Shriver 国家儿童健康和人类发展研究所的支持，奖励编号为 R00HD079659 和 R01HD067683。作者没有利益冲突。试用注册号 N/A。国家环境健康科学研究所 (Z01ES103333)。这项研究还得到了美国国立卫生研究院 (NIH) 的 Eunice Kennedy Shriver 国家儿童健康和人类发展研究所的支持，奖励编号为 R00HD079659 和 R01HD067683。作者没有利益冲突。试用注册号 N/A。国家环境健康科学研究所 (Z01ES103333)。这项研究还得到了美国国立卫生研究院 (NIH) 的 Eunice Kennedy Shriver 国家儿童健康和人类发展研究所的支持，奖励编号为 R00HD079659 和 R01HD067683。作者没有利益冲突。试用注册号 N/A。