Newborn bloodspot results: predictive value of screen positive test for thalassaemia major

Abstract

Aim: There are limited published data on the performance of the percentage of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. This paper aims to analyse data derived from a national newborn bloodspot screening programme for sickle cell disease on the performance of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. Methods: Newborn bloodspot sickle cell screening data from 2,288,008 babies were analysed. Data reported to the NHS Sickle Cell and Thalassaemia Screening Programme in England for the period 2005 to 2012 were also reviewed to identify any missed cases (4,599,849 babies). Results: Within the cohort of 2,288,008 births, 170 babies were identified as screen positive for beta thalassaemia major using a cut-point of 1.5% HbA. There were 51 identified through look-back methods and 119 prospectively identified from 4 screening laboratories. Among 119 babies with prospective data, 7 were lost to follow up and 15 were false positive results. Using a cutoff value of 1.5% Hb A as a percentage of the total haemoglobin as a screening test for beta thalassaemia major in the newborn provides an estimated sensitivity of 99% (from the look back arm of the study) with a positive predictive value of 87% (from the prospective arm of the study). Excluding infants born before 32 weeks gestation, the positive predictive value rose to 95%. Conclusion: A haemoglobin A value of less than 1.5% is a reliable screening test for beta thalassaemia major in the newborn period.

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

“…The putative identification of newborns affected with SCD is simple and very sensitive with the methods used. 16 14,15,19 In our study, all SCD-positive screening tests were confirmed, except for two patients not retrieved despite much effort. We did not observe, however, a high false-positive result even in the few cases of extremely preterm newborns, as described elsewhere.…”

“…Our chosen screening cutoff related to the low HbA value is currently under prospective validation (study in progress). With the expression of Hb percentages in MoM, a single threshold independent of term of pregnancy could potentially be used, in contrast to other studies where different thresholds have been chosen based on the distribution of HbA% in normal full‐term neonates …”

Evaluation of newborn sickle cell screening programme in England: 2010–2016

“…Several of the deaths were in affected babies who were born prematurely, had interuterine growth retardation or other complications as noted elsewhere. 30 31 …”

Newborn Screening for Sickle Cell Disease in Europe

“…Beta thalassemia continues to be reported when found in NBS for SCD, and this has been due to lack of available evidence on the efficacy of detection and the clinical justification for early detection. There is now improved evidence on the sensitivity and specificity of the test [9,10]. However published clinical evidence remains scarce.…”