Screening for sickle cell disease in newborns: a systematic review

Background: Sickle cell disease (SCD) is an inherited autosomal recessive disorder caused by the replacement of normal haemoglobin (HbA) by mutant Hb (sickle Hb, HbS). The sickle-shaped red blood cells lead to haemolysis and vaso-occlusion. Especially in the first years of life, patients with SCD are at high risk of life-threatening complications. SCD prevalence shows large regional variations; the disease predominantly occurs in sub-Saharan Africa. We aimed to systematically assess the evidence on the benefit of newborn screening for SCD followed by an earlier treatment start. Methods: We systematically searched bibliographic databases (MEDLINE, EMBASE, Cochrane Databases, and the Health Technology Assessment Database), trial registries, and other sources to identify systematic reviews and randomised controlled trials (RCTs) or non-randomised trials on newborn screening for SCD. The last search was in 07/2020. Two reviewers independently reviewed abstracts and full-text articles and assessed the risk of bias of the studies included. Data were extracted by one person and checked by another. As meta-analyses were not possible, a qualitative summary of results was performed. Results: We identified 1 eligible study with direct evidence: a Jamaican retrospective study evaluating newborn screening for SCD followed by preventive measures (prevention of infections and education of parents). The study included 500 patients with SCD (intervention group, 395; historical control group, 105). Although the results showed a high risk of bias, the difference between the intervention and the control group was very large: mortality in children decreased by a factor of about 10 in the first 5 years of life (0.02% in the intervention group vs. 0.19% in the control group, odds ratio 0.09; 95% confidence interval [0.04; 0.22], p < 0.001). Conclusion: The results are based on a single retrospective study including historical controls. However, the decrease of mortality by a factor of 10 is unlikely to be explained by bias alone. Therefore, in terms of mortality, data from this single retrospective study included in our systematic review suggest a benefit of newborn screening for SCD (followed by preventive measures) versus no newborn screening for SCD (weak certainty of conclusions).