Oral Vitamin D supplementation as a safe, affordable treatment for profound vitamin D deficiency in pregnancy 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. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.