A Paper-Based Test for Screening Newborns for Sickle Cell Disease

Nathaniel Z Piety,Sonia Serrano,Silvina Kahan,Palka R Patel,Alex George,Gladstone Airewele,Maria P Noli,Maria R Lanzi,João F Camanda,Sergey S Shevkoplyas,Damian Nirenberg

doi:10.1038/srep45488

Abstract

The high cost, complexity and reliance on electricity, specialized equipment and supplies associated with conventional diagnostic methods limit the scope and sustainability of newborn screening for sickle cell disease (SCD) in sub-Saharan Africa and other resource-limited areas worldwide. Here we describe the development of a simple, low-cost, rapid, equipment- and electricity-free paper-based test capable of detecting sickle hemoglobin (HbS) in newborn blood samples with a limit of detection of 2% HbS. We validated this newborn paper-based test in a cohort of 159 newborns at an obstetric hospital in Cabinda, Angola. Newborn screening results using the paper-based test were compared to conventional isoelectric focusing (IEF). The test detected the presence of HbS with 81.8% sensitivity and 83.3% specificity, and identified SCD newborns with 100.0% sensitivity and 70.7% specificity. The use of the paper-based test in a two-stage newborn screening process could have excluded about 70% of all newborns from expensive confirmatory testing by IEF, without missing any of the SCD newborns in the studied cohort. This study demonstrates the potential utility of the newborn paper-based test for reducing the overall cost of screening newborns for SCD and thus increasing the practicality of universal newborn SCD screening programs in resource-limited settings.

Highlights

Universal newborn screening, in combination with early intervention for affected infants, has nearly eliminated early childhood mortality due to sickle cell disease (SCD; HbSS) in high-income developed countries[1,2,3]
We describe a test based on the same principles which is optimized to detect the low levels of sickle hemoglobin (HbS) present in the blood of newborns, allowing the direct screening of newborns for SCD and sickle cell trait
The limit of detection (LOD) for the adult test was about 15% HbS15, which was insufficient for detecting the very low percentages of HbS typically found in newborn samples −6 .5 ± 2.8% for SCT (HbFAS) and 10.2 ± 3.9% for SCD (HbFS)[16]

Summary

Introduction

In combination with early intervention for affected infants, has nearly eliminated early childhood mortality due to sickle cell disease (SCD; HbSS) in high-income developed countries[1,2,3]. The major barriers limiting the expansion of these highly successful pilot screening programs are the high cost and technical complexity of conventional diagnostics methods (e.g. HPLC, high-performance liquid chromatography[8], or IEF, isoelectric focusing electrophoresis9), and their dependence on specialized equipment, stable infrastructure and well-trained laboratory personnel[4,5,10]. Because of these limitations, newborn screening for SCD remains confined to only a few specialized clinical laboratories in major population centers, almost entirely missing the majority of all births occurring out of hospital[7,11,12]. We report on the feasibility and diagnostic accuracy of the paper-based newborn test as performed by local health workers in a resource-limited clinical setting in Cabinda, Angola

Methods

Results

Conclusion