Sickle cell disease: folic acid had no clear effect on symptomatic episodes.

Clinical bottom line (level 2b-)

  1. Children with sickle cell disease who were given folic acid, had no clear difference in painful episodes, infection, acute splenic sequestration or dactylitis, than those given placebo.
Rabb et al: British Journal of Hematology 1983; 54: 589-594
Expires February 2003

The study

Double-blinded ?concealed un-randomised trial without intention-to-treat
Setting: maternity hospital, Jamaica

117 patients (aged range 6 to 47 months, 56% male) children with sickle cell disease (diagnosed from cord blood screening programme) between 1979 and 1981

Excluded if
  • resident in areas remote from the study centre
  • incomplete follow-up data


    • Control Group: (n = 56, 56 analysed): placebo tablet ( calcium lactate ) taken once a day for one year
    Experimental Group: (n = 59, 59 analysed): folic acid, 5 mg, taken once a day for a year

    98% followed for 12 months

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    painful episodes 12 months 18
    (32.1%)    		 22
    (37.3%)    		 -16.0%
    (-92.0% to 30.0%)    		 -5.15%
    (-22.5% to 12.2%)    		 -19
    (NNT = 8 to infinity;
    NNH = 4 to infinity)
    major infections 12 months 15
    (26.8%)    		 14
    (23.7%)    		 11.0%
    (-66.0% to 53.0%)    		 3.06%
    (-12.8% to 18.9%)    		 33
    (NNT = 5 to infinity;
    NNH = 8 to infinity)
    acute splenic sequestration 12 months 8
    (14.3%)    		 9
    (15.3%)    		 -7.00%
    (-157% to 56.0%)    		 -0.97%
    (-13.9% to 12.0%)    		 -103
    (NNT = 8 to infinity;
    NNH = 7 to infinity)
    dactylitis 12 months 17
    (30.4%)    		 12
    (20.3%)    		 33.0%
    (-27.0% to 65.0%)    		 10.0%
    (-5.81% to 25.9%)    		 10
    (NNT = 4 to infinity;
    NNH = 17 to infinity)
    minor infections 12 months 48
    (85.7%)    		 50
    (84.8%)    		 1.00%
    (-15.0% to 15.0%)    		 0.97%
    (-12.0% to 13.9%)    		 103
    (NNT = 7 to infinity;
    NNH = 8 to infinity)

    Comments

    1. There was a concomitant trial in this cohort which used penicillin V and pneumococcal vaccine as the treatment arms. Folic acid and placebo tablets were given so that treatment and placebo groups were evenly distributed across the other trials different arms.
    2. The folic acid group had a significantly lower mean cell volume than the placebo group.
    3. Analysis of height and weight (age-adjusted) showed no difference between the groups 103/115 children.
    4. One year follow-up was not long enough (for children with a life long disease) to detect a small difference between groups. This may be especially so in a small, non-randomised trial.

    Citation

    1. Rabb LM, Grandison Y, Mason K, et al: A trial of folate supplementation in children with homozygous sickle cell disease. British Journal of Hematology 1983; 54: 589-594
    Contributor: Nick Shenker and Clare Wotton, February 2000
    Reviewer:

    Clinical Question.
    Patient sickle cell disease
    Intervention or Exposure folic acid
    Comparison placebo
    Outcome painful episodes