Findings Uncover Disparity in Alpha-Thalassemia Screening Procedures in Newborns

September 17, 2020

The methodologies used to screen sickle cell disease are also able to detect alpha-thalassemia, which is currently not a core condition of the United States Recommended Uniform Screening Panel.

Alpha-thalassemia screening practices in newborns are found to vary widely in methodologies and reporting strategies across screening programs, according to a new US Centers for Disease Control and Prevention (CDC) report on a survey conducted in 2016.

These findings suggest a potential need to establish more uniform technical and reporting procedures that could help further illuminate the condition’s public health impact as well as optimize outcomes and clinical care.

These methodologies to detect alpha-thalassemia are also used to identify sickle cell disease, a core condition on the United States Recommended Uniform Screening Panel. Despite occurring in a similar population as sickle cell as well as having a global prevalence of 5%, alpha-thalassemia currently has no standardized procedures for detection.

The aim of the nationwide survey, which was the first of its kind conducted by the Association of Public Health Laboratories’ Hemoglobinopathy Workgroup, was to better understand the practices of US newborn screening programs. To do this, they sent an 8-question survey to all 53 programs. The response rate was 83%.

All responding programs had indicated use of methods capable of screening for alpha-thalassemia, but 93% reported results.

As many as 57% of the programs used two modalities for screening, which, as noted by the investigators, ensures maximization in the number of patients identified with Hemoglobin (Hb) Bart’s levels associated with alpha-thalassemia. Additionally, 32% reported use of only one modality. 

Furthermore, among those that used two modalities for screening, 60% used isoelectric focusing (IEF) as their first test, and 40% used high performance liquid chromatography (HPLC) as a second test. For those programs that only used 1 test, 57% used IEF and 43% used HPLC.

The investigators reported that there was great variance among the programs in percentage thresholds for Hb Bart's levels used for classifying alpha-thalassemia types.

For example, the minimum cutoff of Hb Bart’s for Alpha-thalassemia major was 25%, and the maximum was 100%. For silent alpha-thalassemia carriers, the minimum was 3%, and the maximum was 11%.

In addition to these ranges of thresholds, programs differed in the means of reporting of results. While some only reported the presence of Hb Bart’s, others reported a single form of suspected alpha-thalassemia, as well as multiple suspected forms.

There was also a noted discrepancy in the way results were communicated or disseminated. The diverse types of recipients included newborn screening follow-up programs, birthing hospitals, hematologists, regional sickle cell specialty centers, and contracted specialists.

It was especially rare for programs to directly notify the parents of the infant’s status, a limitation which has also been found in cases of screening results that indicate sickle cell disease and the sickle cell trait.

And finally, up to 80% of the programs that did report results indicated that they provided recommendations for patient re-testing or follow-up.

Overall, the investigators stressed the implications of the findings and the potential for creating a more streamlined, uniform screening procedure. 

“The infrastructure for universal newborn screening and reporting of alpha-thalassemia in the United States already exists, and there are many opportunities for standardizing and streamlining the process,” they wrote. “The results of this survey could guide further discussion, development of definitions, and dissemination of evidence-based best practices and expert guidelines for improving upon this work.”

The study, "Newborn Screening Practices and Alpha-Thalassemia Detection — United States, 2016," was published online in the CDC’s Morbidity and Mortality Weekly Report.