A Randomized Controlled Trial to Study the Effect of Folic Acid Supplementation in Pregnant Women Having Thalassaemia Trait

Folic acid supplementation is well established for its role in prevention of neural tube defects (NTD) when taken periconceptionally up to 12 weeks of gestation. The naturally occurring form, folate, is a water soluble B vitamin (B9) that is mostly present in dark green leafy vegetables and legumes. However, it is only 50% bioavailable. Folic acid, on the contrary, as a synthetic form of folate is almost completely bioavailable especially when administered in an empty stomach. It has been endorsed by World Health Organisation that RBC folate cutoff of 906 nmol/L (400ng/mL) is required for reduction of NTD. This level is only achievable by taking Folic acid supplementation of 0.4mg/day. Women at higher risk of having recurrent NTD is recommended to take higher dose at 4mg/day.

Patients with thalassaemia have an increased rate of erythropoiesis and chronic haemolysis. They are believed to have a higher rate of folate turnover and consequentially higher risk of folate deficiency. Guideline from Royal College of Obstetricians and Gynaecologists recommends daily intake of 5mg folic acid preconceptionally to prevent NTD. But, it does not specify whether this dosage is applicable to all types and degrees of thalassaemias and research data on the optimal dosage is lacking.

In addition to prevention of NTD, the supplementation of folic acid is also recommended for pregnant thalassaemia women for prevention of antenatal anaemia. In a retrospective study of Chinese population reported in 1989, women with beta-thalassaemia minor taking additional 5mg folic acid had higher pre-delivery haemoglobin concentration of 10.1 g/dL compared to haemoglobin level of 9.7 g/dL in the group taking Obimin (a pregnancy supplement containing 0.25mg folic acid and 90 mg ferrous fumarate). However, there was no further randomised controlled trial to validate this observation. Though a higher folic acid supplementation was believed to be beneficial in prevention of antenatal anaemia, unmetabolized folic acid were detected in maternal and fetal blood when daily dosage greater than 0.8-1mg was taken. Moreover, a higher rate of urinary excretion of folic acid was also observed in pregnant women receiving higher dosage of folic acid supplementation.

In non-pregnant beta thalassaemia major patients, folic acid supplementation at 1 mg daily was advised as cessation of which could lead to a significant reduction in serum folate. This has been counter-proposed by the observation of normal to high serum folate levels in transfusion dependent thalassaemia receiving optimal transfusion. Indeed, folic acid supplementation should be considered for non-transfusion dependent thalassaemia as excessive erythropoiesis is required to maintain satisfactory haemoglobin.

Folate level drops during pregnancy to puerperal period. Information on folate level of thalassaemia trait in pregnancy is scanty. In a paper published in 1985, no difference in serum folate was found between normal women and women with thalassaemia trait, and hence usual supplementation was suggested.