Biochemical, Nutritional, and Clinical Parameters of Vitamin B12 Deficiency in Infants: A Systematic Review and Analysis of 292 Cases Published between 1962 and 2022

Miriam Wirthensohn; Susanne Wehrli; Ulf Wike Ljungblad; Martina Huemer

doi:10.3390/nu15234960

Biochemical, Nutritional, and Clinical Parameters of Vitamin B12 Deficiency in Infants: A Systematic Review and Analysis of 292 Cases Published between 1962 and 2022

Nutrients. 2023 Nov 29;15(23):4960. doi: 10.3390/nu15234960.

Authors

Miriam Wirthensohn¹, Susanne Wehrli^{2

3

4

5}, Ulf Wike Ljungblad⁶, Martina Huemer^{1

7

8}

Affiliations

¹ Department of Pediatrics, Landeskrankenhaus Bregenz, 6900 Bregenz, Austria.
² Department of Psychosomatics and Psychiatry, University Children's Hospital, University of Zurich, 8032 Zurich, Switzerland.
³ Division of Child and Adolescent Health Psychology, Department of Psychology, University of Zurich, 8050 Zurich, Switzerland.
⁴ Children's Research Centre, University Children's Hospital Zurich, University of Zurich, 8032 Zurich, Switzerland.
⁵ University Research Priority Program "ITINERARE-Innovative Therapies in Rare Diseases", University of Zurich, 8032 Zurich, Switzerland.
⁶ Department of Pediatrics, Vestfold Hospital Trust, NO-3168 Tønsberg, Norway.
⁷ Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, University of Zurich, 8032 Zurich, Switzerland.
⁸ Vorarlberg University of Applied Sciences, Competence Area Healthcare and Nursing, 6850 Dornbirn, Austria.

Abstract

Pooled data from published reports on infants with clinically diagnosed vitamin B12 (B12) deficiency were analyzed with the purpose of describing the presentation, diagnostic approaches, and risk factors for the condition to inform prevention strategies. An electronic (PubMed database) and manual literature search following the PRISMA approach was conducted (preregistration with the Open Science Framework, accessed on 15 February 2023). Data were described and analyzed using correlation analyses, Chi-square tests, ANOVAs, and regression analyses, and 102 publications (292 cases) were analyzed. The mean age at first symptoms (anemia, various neurological symptoms) was four months; the mean time to diagnosis was 2.6 months. Maternal B12 at diagnosis, exclusive breastfeeding, and a maternal diet low in B12 predicted infant B12, methylmalonic acid, and total homocysteine. Infant B12 deficiency is still not easily diagnosed. Methylmalonic acid and total homocysteine are useful diagnostic parameters in addition to B12 levels. Since maternal B12 status predicts infant B12 status, it would probably be advantageous to target women in early pregnancy or even preconceptionally to prevent infant B12 deficiency, rather than to rely on newborn screening that often does not reliably identify high-risk children.

Keywords: breastfeeding; homocysteine; methylmalonic acid; newborn screening.

Publication types

Systematic Review
Review

MeSH terms

Breast Feeding
Child
Female
Homocysteine
Humans
Infant
Infant, Newborn
Methylmalonic Acid*
Pregnancy
Vitamin B 12 / therapeutic use
Vitamin B 12 Deficiency* / drug therapy

Substances

Methylmalonic Acid
Vitamin B 12
Homocysteine

Grants and funding

This is an academic study without specific financial support. No honoraria, grants, or other forms of payment were given to anyone to produce the manuscript. M.W. has no financial support to declare. S.W. received financial support from the University Research Priority Program of the University of Zurich (URPP) ITINERARE—Innovative Therapies in Rare Diseases, Switzerland. U.W.L. received funding from Vestfold Hospital Trust. M.H. has received unrestricted research grants from Nutricia Metabolics, SOBI, and Sanofi-Aventis for other projects, and consultancy honoraria not related to the content of this work from Aeglea, Nutricia Metabolics, Sanofi-Aventis, and Recordati.