Bangladesh
Saifuddin Ahmed, Bloomberg School of Public Health
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Half of all under-five deaths in South Asia occur in the neonatal period, and about half of these are due to bacterial infections (e.g., sepsis, pneumonia), highlighting the pressing need for antenatal interventions to reduce the risk of neonatal infections in resource-poor settings. Antenatal nutritional interventions can alter the neonate's resistance against bacterial infection by influencing the development of the fetal immune system and newborn micronutrient status. Vitamin D is a candidate micronutrient because of its proven role as a potent modulator of immune functions in laboratory studies, including lymphocyte proliferation, T helper cell differentiation, and phagocyte activity. More recently, activated vitamin D (l,25-dihydroxyvitamin D) was shown to be an essential cofactor in the endogenous synthesis of a human antimicrobial peptide, termed cathelicidin, which is expressed in newborn skin, vernix caseosa, saliva and breast milk. However, the effect of improvements in maternal/fetal/neonatal vitamin D status on biomarkers of neonatal immune function has not been studied. We therefore propose to conduct a small scale randomized placebo-controlled double-blind clinical trial in rural Bangladesh to test the hypothesis that fetal/neonatal vitamin D supplementation upregulates the local expression of cathelicidin at sites of potential bacterial invasion (e.g., umbilical cord), modulates lymphocyte proliferation, and optimizes the T helper cell (Th 1 versus Th2) balance. Evidence in support of these hypotheses would justify larger¬ scale community trials of antenatal interventions to determine whether improvements in fetal/neonatal vitamin D status can reduce the enormous burden of neonatal infection-related morbidity and mortality in South Asia. >> See all 2007 Faculty Grant in Global Health winners | 
