A trial of folate supplementation in children with homozygous sickle cell disease

Abstract

A double blind controlled trial of supplementation with folic acid has been performed in 117 children with homozygous sickle cell (SS) disease aged 6 months to 4 years over a 1 year period. No megaloblastic change was observed in either group. At the end of the study period the folate supplemented group showed no significant differences in haemoglobin, growth characteristics, or in the proportion of children affected by major or minor infections, acute splenic sequestration, dactylitis or episodes of bone or abdominal pain. However, the folate supplemented group showed a significantly lower mean cell volume and the placebo group contained a significant excess of children experiencing multiple episodes of dactylitis. The results are compatible with mild folate deficiency in some patients in the placebo group but the absence of striking effects on haematology or growth suggest that the policy of regular folate supplementation in children with SS disease should be critically reviewed.

Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review

“…1968 and 2016, of which 15 trials were published before the year 2000 37,[42][43][44][45][46][47][48][49][50][51][52][53][54][55] and 8 in the last 5 years. [56][57][58][59][60][61][62][63] Three studies did not use a placebo intervention for their control group.…”

“…43,54,56 A majority of studies were performed in North America (n 5 10), 33,46,47,51,61,62,[64][65][66][67][68] Africa (n 5 9), 38,42,52,55,56,59,[69][70][71] and Latin America (n 5 8). 40,44,48,49,53,54,57,72 Four studies were performed on multiple continents. 58,60,63,73 The number of patients per study ranged from 9 to 341.…”

“…A majority of studies were limited to patients with the HbSS or HbSb 0 genotype (n 5 26). 37,38,42,44,45,[48][49][50][51][52][53][54][55][56][57][59][60][61]63,64,66,67,[69][70][71]74 A summary overview of the characteristics, risk of bias, and primary outcomes of the included studies is provided in Table 1. The complete results of our risk-of-bias assessment and a detailed overview of the primary and secondary outcomes of this review per study are provided in supplemental Tables 2 and 3, respectively.…”

“…[58][59][60]66,69,72,73 Fourteen studies scored a high risk of bias on at least 1 of the items of the quality assessment, in particular on incomplete outcome data (n 5 8) and blinding of participants (n 5 6) and personnel for intervention (n 5 6). 37,[43][44][45]48,49,51,54,56,63,64,70,71,74 Anticoagulation. A total of 7 studies assessed interventions targeting coagulation activation.…”

“…Four studies assessed the therapeutic value of dietary supplements. Rabb et al 48 assessed the effect of folic acid supplementation on VOCs and dactylitis in children with HbSS disease in Jamaica (N 5 115). 48 In this non-RCT, there was no effect of folate on the proportion of patients with VOCs.…”