| Folic acid compared with calcium lactate for sickle cell (SS) disease |
| Patient or population: 117 children with homozygous sickle cell (SS) disease Settings: hospital Intervention: folic acid 5 mg Comparison: calcium lactate (placebo) |
| Folate concentration Serum folate levels, measured between 6 and 12 months after entry to the study | 1. values in excess of 18 pg/L occurring in 6/39 (15%) children in the placebo group. 2. levels below 5 pg/L occurring in 15/39 (39%) | 1. values in excess of 18 pg/L occurring in 33/41 (81 %) in
the folic acid group. 2. levels below 5 pg/L None in the folic acid group. | NA | 80/115 (70%) (1 study) | ⊕⊕⊝⊝ low2 | There were marked differences between trial groups in the distribution of serum folate levels. |
| Haemoglobin concentration Haematological analyses were performed in the 100/115 (87%) children in whom baseline (within 2 months of entry to study) and 1 year (between 10 and 14 months after entry) | See comment | See comment | NA | 100/115 (87%) (1 study) | ⊕⊕⊝⊝ low2 | There were no significant differences in total haemoglobin (Hb) either at baseline or after 1 year. |
| Adverse events ‐ acute splenic sequestration Clinical events experienced by children during the 1 year period commencing at entry to the trial | 8/56 Total episodes 15 | 9/59 Total episodes 12 | RR 1.07 (95% CI 0.44 to 2.57) | 115 (1 study) | ⊕⊕⊝⊝ low2 | There were no significant differences in these measures of growth between the folic acid and placebo groups. |
| Adverse events ‐ painful episodes Clinical events experienced by children during the 1 year period commencing at entry to the trial | 18/56 Total episodes 27 | 22/59 Total episodes 39 | RR 1.16 (95% CI 0.70 to 1.92) | 115 (1 study) | ⊕⊕⊝⊝ low2 | There were no significant differences in painful episodes
between the folic acid and placebo groups. |
| Adverse events ‐ minor Infections Clinical events experienced by children during the 1 year period commencing at entry to the trial | 48 out of 56 children Total episodes/child: 2.3 | 50 out of 59 children Total episodes/child: 2.7 | RR 0.99 (95% CI 0.85 to 1.15) | 115 (1 study) | ⊕⊕⊝⊝ low2 | There were no differences in minor infections
between the folic acid and placebo groups. |
| Adverse events ‐ major infections Clinical events experienced by children during the 1 year period commencing at entry to the trial | 15 out of 56 children Total episodes/child: 19 | 14 out of 59 children Total episodes/child: 18 | RR 0.89 (95% CI 0.47 to 1.66) | 115 (1 study) | ⊕⊕⊝⊝ low2 | There were no differences in major infections
between the folic acid and placebo group. |
| Adverse events ‐ dactylitis Clinical events experienced by children during the 1 year period commencing at entry to the trial | 17 out of 56 children Total episodes: 32 | 12 out of 59 children Total episodes:15 | RR 0.67 (95% CI 0.37 to 1.27) | 115 (1 study) | ⊕⊕⊝⊝ low2 | There were no differences in dactylitis events
between the folic acid and placebo group. |
| *The basis for the assumed risk is the risk in the control group. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio. |
| GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate. |
