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

Ulf Wike Ljungblad; Morten Lindberg; Erik A Eklund; Ingjerd Sæves; Carlos Sagredo; Anne-Lise Bjørke-Monsen; Trine Tangeraas

doi:10.3390/ijns8040066

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

Int J Neonatal Screen. 2022 Dec 14;8(4):66. doi: 10.3390/ijns8040066.

Authors

Ulf Wike Ljungblad^{1

2}, Morten Lindberg³, Erik A Eklund⁴, Ingjerd Sæves⁵, Carlos Sagredo⁶, Anne-Lise Bjørke-Monsen^{7

8

9}, Trine Tangeraas⁵

Affiliations

¹ Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318 Oslo, Norway.
² Department of Pediatrics, Vestfold Hospital Trust, P.O. Box 1068, 3103 Tønsberg, Norway.
³ Department of Medical Biochemistry, Vestfold Hospital Trust, P.O. Box 1068, 3103 Tønsberg, Norway.
⁴ Department of Pediatrics, Clinical Sciences, Lund, Lund University, 221 84 Lund, Sweden.
⁵ Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, 0424 Oslo, Norway.
⁶ Department of Pharmacology, Division of Laboratory Medicine, Oslo University Hospital, 0424 Oslo, Norway.
⁷ Laboratory of Medical Biochemistry, Innlandet Hospital Trust, 2609 Lillehammer, Norway.
⁸ Laboratory of Medical Biochemistry, Førde Central Hospital, 6812 Førde, Norway.
⁹ Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, 1400 Bergen, Norway.

Abstract

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 (N₂O) 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 N₂O compared to in hospitals not providing N₂O, with median total homocysteine 4.0 µmol/L compared to 3.5 µmol/L (n = 434, 95% CI 0.04-0.87, p = 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 N₂O may impact total homocysteine at NBS.

Keywords: homocysteine; infant; newborn screening; nitrous oxide; second-tier; vitamin B12; vitamin B12 deficiency.

Grants and funding

N/A/Sykehuset i Vestfold