New approach to accurate interpretation of sickle cell disease newborn screening by applying multiple of median cutoffs and ratios

Allaf, Bichr; Patin, Franck; Élion, Jacques; Costédoat-Chalumeau, Nathalie

doi:10.1002/pbc.27230

Cited by 14 publications

(12 citation statements)

References 20 publications

(42 reference statements)

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“…The cut-off of HbA<5% is efficient also for preterm newborns. The percentages of HbA and HbF were in agreement with previous reports [21,22], which found a great variability according to the maternal ethnic origin and the gestational age.…”

Section: Discussionsupporting

confidence: 92%

Evaluation of Technical Issues in a Pilot Multicenter Newborn Screening Program for Sickle Cell Disease

Martella

Viola

Azzena

et al. 2018

IJNS

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A multicenter pilot program for universal newborn screening of Sickle cell disease (SCD) was conducted in two centres of Northern Italy (Padova and Monza). High Performance Liquid Chromatography (HPLC) was performed as the first test on samples collected on Guthrie cards and molecular analysis of the β-globin gene (HBB) was the confirmatory test performed on the HPLC-positive or indeterminate samples. 5466 samples of newborns were evaluated. Of these, 5439/5466 were submitted to HPLC analysis and the molecular analysis always confirmed in all the alteration detected in HPLC (62/5439 newborns); 4/5439 (0.07%) were SCD affected, 37/5439 (0.68%) were HbAS carriers and 21/5439 (0.40%) showed other hemoglobinopathies. Stored dried blood spots were adequate for HPLC and β-globin gene molecular analysis. Samples were suitable for analysis until sixteen months old. A cut-off of A1 percentage, in order to avoid false negative or unnecessary confirmation tests, was identified. Our experience showed that several technical issues need to be addressed and resolved while developing a multicenter NBS program for SCD in a country where there is no national neonatal screening (NBS) program for SCD and NBS programs occur on a regional basis.

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Section: Discussionsupporting

confidence: 92%

Evaluation of Technical Issues in a Pilot Multicenter Newborn Screening Program for Sickle Cell Disease

Martella

Viola

Azzena

et al. 2018

IJNS

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“…HbA levels range from 6 to 40% with an average of 19%, showing inter-individual variations. HbA levels in newborns are dependent on gestational age and date of sampling, reflecting the stage of hemoglobin switch [6,12]. In Table 1, patterns of the detected hemoglobins are listed in the order of highest percentage to the lowest.…”

Section: Interpretation Of Newborn Screening Results and Hemoglobin Pmentioning

confidence: 99%

“…Additionally, precise quantification is a problem close to the detection limit of a variant for HPLC and CE [5,7]. To standardize quantitative interpretation of screening results, cut-offs and ratios can be expressed as multiples of median (MoM) [12]. IEF is a method with a very high resolution, but it sometimes hampers precise quantification and correct classification of bands, and there is a slight tendency to over-detect variants of no significance, e.g., modified HbA or γ-variants [5,16].…”

Section: Sickle Cell Diseasementioning

confidence: 99%

“…Babies who received blood transfusions show increased percentages of adult hemoglobin HbA and HbA 2 and the presence of a severe hemoglobinopathy may be masked. Therefore, it seems essential that transfused babies can be identified using either HbA levels above the 2.5 multiples of median (MoM) dependent on gestational age or ratios of HbF/HbA [12].…”

Section: Pre-analyticsmentioning

confidence: 99%

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Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies: A Short Review on Classical Laboratory Methods—Isoelectric Focusing, HPLC, and Capillary Electrophoresis

Frömmel

2018

IJNS

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Sickle cell disease (SCD) and other hemoglobinopathies are a major health concern with a high burden of disease worldwide. Since the implementation of newborn screening (NBS) for SCD and other hemoglobinopathies in several regions of the world, technical progress of laboratory methods was achieved. This short review aims to summarize the current practice of classical laboratory methods for the detection of SCD and other hemoglobinopathies. This includes the newborn screening technologies of high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and isoelectric focusing (IEF).

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“…The accuracy of newborn screening for hemoglobinopathies can be improved by quantitative interpretation of Hb separation results using ratios or multiple of median cut-offs [5]. Alternatively, genetic testing can distinguish between HbAS and HbSβ + (and identify any hemoglobinopathy) at any age, with a clinical laboratory turn-around time of 3-4 weeks (using our testing strategy).…”

Section: Discussionmentioning

confidence: 99%

Clinical Utility of Confirmatory Genetic Testing to Differentiate Sickle Cell Trait from Sickle-β+-Thalassemia by Newborn Screening

Shook

Haygood

Quinn

2020

IJNS

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Hemoglobin separation techniques are the most commonly used laboratory methods in newborn screening and confirmatory testing programs for hemoglobinopathies. However, such protein-based testing cannot accurately detect several hemoglobinopathies in newborns, especially when β-thalassemia mutations are involved. Here, we describe a consecutive cohort of newborns who were identified by newborn screening to have a likely diagnosis of sickle-β+-thalassemia (having an “FSA” pattern) who were determined to have sickle cell traits by confirmatory and genetic testing. We illustrate the clinical utility of genetic testing to make a correct and timely diagnosis in the setting of newborn screening for hemoglobinopathies.

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New approach to accurate interpretation of sickle cell disease newborn screening by applying multiple of median cutoffs and ratios

Abstract: This new approach introduces tools for a quantitative interpretation in SCD NBS by HPLC methods and could allow standardization of interpretation between centers.

Cited by 14 publications

References 20 publications

Evaluation of Technical Issues in a Pilot Multicenter Newborn Screening Program for Sickle Cell Disease

Evaluation of Technical Issues in a Pilot Multicenter Newborn Screening Program for Sickle Cell Disease

Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies: A Short Review on Classical Laboratory Methods—Isoelectric Focusing, HPLC, and Capillary Electrophoresis

Clinical Utility of Confirmatory Genetic Testing to Differentiate Sickle Cell Trait from Sickle-β+-Thalassemia by Newborn Screening

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