Racial difference in preterm birth and low birthweight: Towards a new hypothesis involving the interaction of 25-hydroxyvitamin D with maternal fat mass

Preterm birth (PB) and low birthweight (LBW) remain a leading cause of infant mortality worldwide. Persistent racial disparities in prevalence rates have been reported, with the highest values observed in Subsaharan Africa and South Asia. In United States, non-Hispanic Black women are more likely to have a premature or low-birth-weight baby. Beyond the speculative debate on factors explaining such racial disparity, the key-question remains about the path from race to birth outcomes. Several hypotheses emerged from the published literature to explain the racial difference in likelihood for PB and LBW. However, the 'Hispanic paradox' remains unexplained. We relied here on published data to hypothesize that the racial disparity in PB/LBW is a consequence to the joint influence of 25-hydroxyvitamin D and fat mass. Beyond its role as a source of 1,25-dihydroxyvitamin D, the 25-hydroxyvitamin D is directly implicated in the fetal growth and the normal completion of pregnancy. Because of its lipophilic property, a large part of 25-hydroxyvitamin D is swiftly trapped into fat mass and the circulating fraction impact the body development during fetal period. We postulate that the positive effect of vitamin D to prevent PB/LBW is less beneficial for women with high fat mass, independent of race. The core problem may be related to bioavailable 25-hydroxyvitamin D, not directly to race.