Screening for glucose-6-phosphate dehydrogenase deficiency in neonates: a comparison between cord and peripheral blood samples

Abstract

BackgroundThe use of cord blood in the neonatal screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency is being done with increasing frequency but has yet to be adequately evaluated against the use of peripheral blood sample which is usually employed for confirmation. We sought to determine the incidence and gender distribution of G6PD deficiency, and compare the results of cord against peripheral blood in identifying G6PD DEFICIENCY neonates using quantitative enzyme activity assay.MethodsWe carried out a retrospective and cross-sectional study employing review of primary hospital data of neonates born in a tertiary care center from January to December 2008.ResultsAmong the 8139 neonates with cord blood G6PD assays, an overall incidence of 2% for G6PD deficiency was computed. 79% of these were males and 21% were females with significantly more deficient males (p < .001). Gender-specific incidence was 3.06% for males and 0.85% for females. A subgroup analysis comparing cord and peripheral blood samples (n = 1253) showed a significantly higher mean G6PD value for peripheral than cord blood (15.12 ± 4.52 U/g and 14.52 ± 4.43 U/g, respectively, p = 0.0008). However, the proportion of G6PD deficient neonates did not significantly differ in the two groups (p = 0.79). Sensitivity of cord blood in screening for G6PD deficiency, using peripheral G6PD assay as a gold standard was 98.6% with a NPV of 99.5%.ConclusionThere was no difference between cord and peripheral blood samples in discriminating between G6PD deficient and non-deficient neonates. A significantly higher mean peripheral G6PD assay reinforces the use of cord blood for neonatal screening since it has substantially low false negative results.

Diagnostic performances of the fluorescent spot test for G6PD deficiency in newborns along the Thailand-Myanmar border: A cohort study

“…Umbilical cord blood collection is easy, can spare the neonate unnecessary pain, and results of cord blood G6PD FST are comparable to that of peripheral blood drawn in the first week of life in a recent study 19 . However, there is evidence suggesting that the diagnosis performed at birth should be confirmed later in life, because of a potentially higher G6PD activity in neonates compared to adults 20 – 23 .…”

Immunohematology testing using umbilical cord blood: review of the literature, survey of practice and guidance development

“…CB, rather than PB, is the preferred sample for G6PD neonatal screening as fewer false negative results are reported from CB 53,54 . The normal G6PD reference range is reported to be lower in CB compared to PB 54 …”

“…Glucose-6-phosphate dehydrogenase (G6PD) CB, rather than PB, is the preferred sample for G6PD neonatal screening as fewer false negative results are reported from CB. 53,54 The normal G6PD reference range is reported to be lower in CB compared to PB. 54 Early assessment of G6PD activity is essential when the etiology of neonatal hyperbilirubinemia is unclear.…”

Functional Analysis of G6PD Variants Associated With Low G6PD Activity in the All of Us Research Program

“…This finding was not surprising based on previous reports that variation outside of the CDS or in splice sites does not contribute to G6PD deficiency 5 and suggests that the unexplained variability in G6PD activity for individuals without CDS variants likely comes from environmental or assay sources, which are established to contribute to variability of G6PD activity test results. [52][53][54] We incidentally observed some interesting results from the permutation testing and power simulations that we did in support of the G6PD association analysis. The drastically higher permuted false positive threshold compared to Bonferroni should serve as a signal that permutation testing in GWAS analyses is a better method for distinguishing false positives, especially when sequencing data is used without LD pruning.…”

“…This finding was not surprising based on previous reports that variation outside of the CDS or in splice sites does not contribute to G6PD deficiency 5 and suggests that the unexplained variability in G6PD activity for individuals without CDS variants likely comes from environmental or assay sources, which are established to contribute to variability of G6PD activity test results. 52–54…”