A Retrospective Evaluation of the Predictive Value of Newborn Screening for Vitamin B12 Deficiency in Symptomatic Infants Below 1 Year of Age

Background: The sensitivity of newborn screening (NBS) in detecting infants that later develop symptomatic vitamin B12 deficiency is unknown. We evaluated the predictive value using NBS algorithms in detecting infants that later were clinically diagnosed with symptomatic B12 deficiency. Furthermore,...

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Main Authors: Ulf Wike Ljungblad, Morten Lindberg, Erik A. Eklund, Ingjerd Sæves, Carlos Sagredo, Anne-Lise Bjørke-Monsen, Trine Tangeraas
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:International Journal of Neonatal Screening
Subjects:
Online Access:https://www.mdpi.com/2409-515X/8/4/66
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author Ulf Wike Ljungblad
Morten Lindberg
Erik A. Eklund
Ingjerd Sæves
Carlos Sagredo
Anne-Lise Bjørke-Monsen
Trine Tangeraas
author_facet Ulf Wike Ljungblad
Morten Lindberg
Erik A. Eklund
Ingjerd Sæves
Carlos Sagredo
Anne-Lise Bjørke-Monsen
Trine Tangeraas
author_sort Ulf Wike Ljungblad
collection DOAJ
description Background: The sensitivity of newborn screening (NBS) in detecting infants that later develop symptomatic vitamin B12 deficiency is unknown. We evaluated the predictive value using NBS algorithms in detecting infants that later were clinically diagnosed with symptomatic B12 deficiency. Furthermore, we investigated whether being born in a hospital using nitrous oxide (N<sub>2</sub>O) as pain relief in labor may have had an impact on total homocysteine at NBS. Methods: We retrospectively retrieved NBS data and analyzed total homocysteine, methylmalonic acid and methyl citrate on stored NBS dried blood spots (DBS) of 70 infants diagnosed with symptomatic B12 deficiency and compared them to 646 matched and 434 unmatched DBS controls to evaluate the Austrian and Heidelberg B12 NBS algorithms. Results: The sensitivity of NBS in detecting infants later diagnosed with symptomatic B12 deficiency at median age 10.9 weeks was ≤10%. Total homocysteine was higher in DBS for the unmatched controls who were born in hospitals providing N<sub>2</sub>O compared to in hospitals not providing N<sub>2</sub>O, with median total homocysteine 4.0 µmol/L compared to 3.5 µmol/L (n = 434, 95% CI 0.04–0.87, <i>p</i> = 0.03). Conclusion: NBS algorithms were unable to identify most infants diagnosed with symptomatic B12 deficiency after the neonatal period. Being born in hospitals providing N<sub>2</sub>O may impact total homocysteine at NBS.
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spelling doaj.art-202808ac5ff54ac18e51c226866bf4ec2023-11-24T15:35:33ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2022-12-01846610.3390/ijns8040066A Retrospective Evaluation of the Predictive Value of Newborn Screening for Vitamin B12 Deficiency in Symptomatic Infants Below 1 Year of AgeUlf Wike Ljungblad0Morten Lindberg1Erik A. Eklund2Ingjerd Sæves3Carlos Sagredo4Anne-Lise Bjørke-Monsen5Trine Tangeraas6Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318 Oslo, NorwayDepartment of Medical Biochemistry, Vestfold Hospital Trust, P.O. Box 1068, 3103 Tønsberg, NorwayDepartment of Pediatrics, Clinical Sciences, Lund, Lund University, 221 84 Lund, SwedenNorwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, 0424 Oslo, NorwayDepartment of Pharmacology, Division of Laboratory Medicine, Oslo University Hospital, 0424 Oslo, NorwayLaboratory of Medical Biochemistry, Innlandet Hospital Trust, 2609 Lillehammer, NorwayNorwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, 0424 Oslo, NorwayBackground: The sensitivity of newborn screening (NBS) in detecting infants that later develop symptomatic vitamin B12 deficiency is unknown. We evaluated the predictive value using NBS algorithms in detecting infants that later were clinically diagnosed with symptomatic B12 deficiency. Furthermore, we investigated whether being born in a hospital using nitrous oxide (N<sub>2</sub>O) as pain relief in labor may have had an impact on total homocysteine at NBS. Methods: We retrospectively retrieved NBS data and analyzed total homocysteine, methylmalonic acid and methyl citrate on stored NBS dried blood spots (DBS) of 70 infants diagnosed with symptomatic B12 deficiency and compared them to 646 matched and 434 unmatched DBS controls to evaluate the Austrian and Heidelberg B12 NBS algorithms. Results: The sensitivity of NBS in detecting infants later diagnosed with symptomatic B12 deficiency at median age 10.9 weeks was ≤10%. Total homocysteine was higher in DBS for the unmatched controls who were born in hospitals providing N<sub>2</sub>O compared to in hospitals not providing N<sub>2</sub>O, with median total homocysteine 4.0 µmol/L compared to 3.5 µmol/L (n = 434, 95% CI 0.04–0.87, <i>p</i> = 0.03). Conclusion: NBS algorithms were unable to identify most infants diagnosed with symptomatic B12 deficiency after the neonatal period. Being born in hospitals providing N<sub>2</sub>O may impact total homocysteine at NBS.https://www.mdpi.com/2409-515X/8/4/66vitamin B12 deficiencyhomocysteineinfantnewborn screeningnitrous oxidesecond-tier
spellingShingle Ulf Wike Ljungblad
Morten Lindberg
Erik A. Eklund
Ingjerd Sæves
Carlos Sagredo
Anne-Lise Bjørke-Monsen
Trine Tangeraas
A Retrospective Evaluation of the Predictive Value of Newborn Screening for Vitamin B12 Deficiency in Symptomatic Infants Below 1 Year of Age
International Journal of Neonatal Screening
vitamin B12 deficiency
homocysteine
infant
newborn screening
nitrous oxide
second-tier
title A Retrospective Evaluation of the Predictive Value of Newborn Screening for Vitamin B12 Deficiency in Symptomatic Infants Below 1 Year of Age
title_full A Retrospective Evaluation of the Predictive Value of Newborn Screening for Vitamin B12 Deficiency in Symptomatic Infants Below 1 Year of Age
title_fullStr A Retrospective Evaluation of the Predictive Value of Newborn Screening for Vitamin B12 Deficiency in Symptomatic Infants Below 1 Year of Age
title_full_unstemmed A Retrospective Evaluation of the Predictive Value of Newborn Screening for Vitamin B12 Deficiency in Symptomatic Infants Below 1 Year of Age
title_short A Retrospective Evaluation of the Predictive Value of Newborn Screening for Vitamin B12 Deficiency in Symptomatic Infants Below 1 Year of Age
title_sort retrospective evaluation of the predictive value of newborn screening for vitamin b12 deficiency in symptomatic infants below 1 year of age
topic vitamin B12 deficiency
homocysteine
infant
newborn screening
nitrous oxide
second-tier
url https://www.mdpi.com/2409-515X/8/4/66
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