Anaemia during pregnancy: could riboflavin deficiency be implicated?

Anaemia affects more than 36% of all pregnancies globally and is associated with significant maternal and neonatal morbidity and mortality. Iron deficiency is widely recognised as the most common nutritional cause of anaemia but other nutrient deficiencies are also implicated, including the B vitamin riboflavin, albeit its role is largely under-investigated and thus typically overlooked. Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), is required for numerous oxidation-reduction reactions, antioxidant function, and in the metabolism of other B vitamins and iron. While clinical deficiency of riboflavin is largely confined to low-income countries, sub-clinical (functional) deficiency is much more widespread, including in high-income countries, and is particularly common among women of reproductive age and during pregnancy. Limited observational evidence from high-income populations suggests that suboptimal riboflavin status contributes to an increased risk of anaemia. Furthermore, randomised controlled trials in pregnant women from low- and middle-income countries have demonstrated beneficial effects of riboflavin on haematological status and anaemia. Various mechanisms have been proposed to explain the contribution of riboflavin deficiency to anaemia, with the strongest evidence pointing to an adverse effect on iron metabolism, given that riboflavin co-factors are required for the release of iron from storage ferritin in the production of red blood cells. Overall, this review investigates riboflavin intakes and status during pregnancy in different populations and evaluates the available evidence for the under-recognised role of riboflavin in the maintenance of haemoglobin concentrations together with its potential to protect against the development of anaemia during pregnancy.