Oral Vitamin D supplementation as a safe, affordable treatment for profound vitamin D deficiency in pregnancy

背景资料：在印度次大陆的不同地理区域，妊娠期维生素D缺乏症非常严重，据报道，缺乏水平在70-100%之间，并且与多种不良结局（包括母亲妊娠合并症）相关。（例如先兆子痫、早产和妊娠糖尿病）;母亲和婴儿感染增加;佝偻病、出生体重不足和婴儿身长不足以及3-5岁儿童呼吸道症状增加。美国的妊娠期维生素D临床试验提供的证据表明：（i）补充比印度目前推荐的每日摄入量高10倍的维生素D是安全的，并且大多数（>80%）孕妇都能获得充足的维生素D;和（ii）从怀孕早期开始每天补充对改善母亲和她的孩子的不良临床结果具有最大的效果。印度早期的研究主要集中在妊娠晚期的推注给药。我们建议在印度每天补充更高水平的维生素D将对母亲和孩子的健康结果产生重大影响。然而，印度对这些较高水平的补充剂存在担忧，该提案旨在直接解决这些担忧。假设：在印度，确保孕妇从怀孕早期到足月都有充足的维生素D，可改善孕妇在怀孕期间和婴儿出生后第一年的健康状况。目标1。进行一项初步可行性研究，以确定在班加罗尔的圣约翰医学院医院（SJHMC），补充维生素D的最高可接受水平（妊娠10-14周，每天2000 IU）（略低于美国试验研究的一半）是否会导致孕妇维生素D补充不足。我们已经获得了机构伦理委员会和印度政府对此类研究的批准。目标二。形成一个由科学家、临床医生、卫生保健工作者、政策制定者组成的跨印度网络，参加为期3天的研讨会。我们将邀请该领域的国际专家，他们参加了妊娠期高剂量维生素D补充剂的全球试验。我们的目标是讨论全球研究的异质性和印度国内对妊娠期维生素D剂量和补充方案的担忧，以克服印度更高水平补充的障碍。我们的研讨会旨在提供在全球维生素D试验结果的背景下对印度维生素D临床研究的荟萃分析，并计划进行一项具有影响国家战略潜力的高影响力审查。我们的研讨会计划将包括一个基于实验室的方法的培训部分，这些方法支持维生素D补充如何使母亲和婴儿的临床参数受益的科学，以及可能支持这一点的生物学途径，以加强知识转移和能力建设。这些目标将使我们的假设在未来的GCRF的应用测试。我们的目标是进行一项大规模的临床研究，以确定针对印度弱势孕产妇和新生儿群体的安全和廉价公共卫生干预措施的潜力。

Background: Vitamin D deficiency in pregnancy is profound across distinct geographical areas of the Indian subcontinent, where levels of deficiency between 70-100% are reported and is detrimentally associated with multiple adverse outcomes including co-morbidities of pregnancy in the mother (e.g. preeclampsia, pre-term birth and gestational diabetes); increased infections in mother and baby; rickets, low birth weight and baby length and increased respiratory symptoms in the child at 3-5 years. Clinical trials of vitamin D in pregnancy in the USA provide evidence that (i) supplementation with ~10 fold higher levels of vitamin D than those currently within the recommended daily allowance in India are safe and achieve vitamin D sufficiency in the majority (>80%) of pregnant women; and (ii) daily supplementation from early in pregnancy has the greatest effect in improving adverse clinical outcomes in both mother and her child. Earlier studies in India focused largely on bolus administration in late pregnancy. We propose that daily supplementation with higher levels of vitamin D in India will have a major impact on health outcomes for both the mother and her child. However concerns exist in India about these higher levels of supplementation and this proposal aims to address these concerns directly. Hypothesis: Ensuring vitamin D sufficiency in pregnant women in India from early pregnancy till term improves maternal health outcomes in pregnancy and in her baby during the first year of life. Aim 1. To perform a pilot feasibility study to determine whether the highest acceptable level of vitamin D supplementation (2000 IU/daily from 10-14 weeks of gestation), which is slightly less than half of that studied in USA trials, leads to vitamin D repletion in pregnant women at St. John's Medical College Hospital (SJHMC), Bangalore. We have obtained Institutional Ethics Committee and Government of India approvals for such a study. Aim 2. Form a cross India network comprising scientists, clinicians, health care workers, policy makers to participate in a 3-day workshop. We will invite international experts in the field who have participated in global trials of high dose vitamin D supplementation in pregnancy. Our goal is to discuss the heterogeneity in global studies and concerns within India of vitamin D dose and supplementation regimens in pregnancy to potentially overcome the perceived roadblock to higher levels of supplementation in India. Our workshop is designed to provide a meta-analysis of vitamin D clinical studies in India in the context of global vitamin D trial outcomes and a projected high impact review with the potential to influence national strategy is planned. Our workshop program will include a training component on laboratory-based methods that underpin the science of how vitamin D supplementation benefits clinical parameters in both mother and baby and biological pathways likely to underpin this, to enhance knowledge transfer and capacity building. Together these aims will empower testing of our hypothesis in a future application to the GCRF. Our goal will be to perform a large-scale clinical study to determine the potential of a safe and inexpensive public health intervention targeted to a vulnerable maternal and neonatal populations across India.