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The Effect Of Fluconazole Prophylaxis In Very Low Birthweight Infants Is Over-Estimated By Before-After Studies
  1. W McGuire1,*,
  2. L Clerihew2
  1. 1 University of York, United Kingdom;
  2. 2 University of Dundee, United Kingdom
  1. Correspondence to: William McGuire, The Canberra Hospital, HYMS, University of York, York, YO10 5DD, United Kingdom; william.mcguire{at}


Background: The validity and applicability of before-after studies compared to randomised controlled trials of fluconazole prophylaxis for very low birthweight infants is uncertain.

Aims: We aimed to examine whether the study design (before-after studies compared to randomised controlled trials) affected the estimate of effect size yielded in meta-analyses and to explore possible causes for any differences detected.

Methods: We undertook a systematic review and meta-analysis of before-after studies that assessed the effect of fluconazole prophylaxis on the incidence of invasive fungal infection in very low birthweight infants. Data were compared with estimates generated from meta-analyses of randomised controlled trials. Funnel plots were examined for evidence of publication bias.

Results: Meta-analysis of eleven before-after studies found a reduced risk of invasive fungal infection following introduction of fluconazole prophylaxis: relative risk 0.19 (95% confidence interval 0.13 to 0.27). This estimate is significantly lower than the estimate from meta-analysis of randomised controlled trials: relative risk 0.48 (95% confidence interval 0.31 to 0.73). Funnel plot inspection of before-after studies revealed that smaller studies with large effects sizes contributed an excess of data points suggesting that publication bias contributes to the inflation of the effect size estimate.

Conclusions: Data from before-after studies should be interpreted and applied cautiously. Evidence to guide policy and practice for antifungal prophylaxis for very low birthweight infants should be derived from well-designed randomised controlled trials.

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