Institute for Quality and Efficiency in Health Care, Cologne, Germany.
Institute for Evidence in Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Syst Rev. 2020 Oct 30;9(1):250. doi: 10.1186/s13643-020-01504-5.
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.
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.
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).
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).
镰状细胞病（SCD）是一种由正常血红蛋白（HbA）被突变血红蛋白（镰状血红蛋白，HbS）取代引起的常染色体隐性遗传疾病。这种镰状的红细胞导致溶血和血管阻塞。特别是在生命的最初几年，SCD 患者有发生危及生命的并发症的高风险。SCD 的流行情况存在很大的地域差异；该疾病主要发生在撒哈拉以南非洲。我们旨在系统评估新生儿筛查 SCD 并提前开始治疗的益处的证据。
我们系统地搜索了文献数据库（MEDLINE、EMBASE、Cochrane 数据库和卫生技术评估数据库）、试验登记处和其他来源，以确定关于 SCD 新生儿筛查的系统评价和随机对照试验（RCT）或非随机试验。最后一次搜索是在 2020 年 7 月。两名审查员独立审查摘要和全文文章，并评估纳入研究的偏倚风险。由一个人提取数据，另一个人进行核对。由于无法进行荟萃分析，因此对结果进行了定性总结。
我们确定了一项具有直接证据的合格研究：一项评估 SCD 新生儿筛查后采取预防措施（预防感染和父母教育）的牙买加回顾性研究。该研究纳入了 500 名 SCD 患者（干预组 395 例；历史对照组 105 例）。尽管结果显示存在高偏倚风险，但干预组和对照组之间的差异非常大：在生命的前 5 年，儿童死亡率降低了约 10 倍（干预组为 0.02%，对照组为 0.19%，比值比 0.09；95%置信区间 [0.04；0.22]，p<0.001）。
结果基于一项包括历史对照的单回顾性研究。然而，死亡率降低 10 倍不太可能仅归因于偏倚。因此，就死亡率而言，我们系统评价中纳入的这项单回顾性研究的数据表明，SCD 的新生儿筛查（伴预防措施）优于不进行 SCD 的新生儿筛查（结论确定性低）。
