Breastfed Infants With Spells, Tremor, or Irritability: Rule Out Vitamin B12 Deficiency

Ulf Wike Ljungblad; Henriette Astrup; Lars Mørkrid; Helle Borgstrøm Hager; Morten Lindberg; Erik A Eklund; Anne-Lise Bjørke-Monsen; Terje Rootwelt; Trine Tangeraas

doi:10.1016/j.pediatrneurol.2022.03.003

Breastfed Infants With Spells, Tremor, or Irritability: Rule Out Vitamin B12 Deficiency

Pediatr Neurol. 2022 Jun:131:4-12. doi: 10.1016/j.pediatrneurol.2022.03.003. Epub 2022 Mar 21.

Authors

Ulf Wike Ljungblad¹, Henriette Astrup², Lars Mørkrid³, Helle Borgstrøm Hager⁴, Morten Lindberg⁴, Erik A Eklund⁵, Anne-Lise Bjørke-Monsen⁶, Terje Rootwelt⁷, Trine Tangeraas⁸

Affiliations

¹ Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Pediatrics, Vestfold Hospital Trust, Tønsberg, Norway. Electronic address: ulf.wike.ljungblad@siv.no.
² Department of Pediatrics and Adolescent Medicine, Sørlandet Hospital Trust, Kristiansand, Norway.
³ Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital, Norway.
⁴ Department of Medical Biochemistry, Vestfold Hospital Trust, Tønsberg, Norway.
⁵ Department of Pediatrics, Clinical Sciences, Lund University, Lund, Sweden.
⁶ Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
⁷ Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Pediatric and Adolescent Medicine, Department of Pediatrics, Oslo University Hospital, Oslo, Norway.
⁸ Division of Pediatric and Adolescent Medicine, Norwegian National Unit for Newborn Screening, Oslo University Hospital, Oslo, Norway.

PMID: 35439713
DOI: 10.1016/j.pediatrneurol.2022.03.003

Abstract

Background: In Norway, 5-10% of neonates and infants have biomarkers suggesting vitamin B12 deficiency from newborn screening tests and unselected clinical screening, respectively.

Aims: The aims were to identify risk factors and describe presenting symptoms and biochemical profiles in infants diagnosed with vitamin B12 deficiency.

Methods: In this case-control study, we searched hospital medical records for infants younger than one year born in 2011-2018, diagnosed with vitamin B12 deficiency. We compared 85 cases with a control group of 252 infants aged 3-7 months. Parents completed questionnaires.

Results: Of the 85 cases with vitamin B12 deficiency, 80% presented with spells (37%) of apneas, motor seizures, or absences within the first two months of life. Tremor (29%) and irritability (18%) were the most common findings at the first examination. Serum total homocysteine ≥10 μmol/L was found in 77% of cases compared to 28% of controls (P < 0.001). None of the mothers were vegetarians, but 25% reported a previous history of vitamin B12 deficiency and 7% had celiac disease. The dose of nitrous oxide given during labor was significantly associated with infant serum total homocysteine level at diagnosis (r = 0.37, 95% confidence interval = 0.16-0.55, P < 0.001) for cases, but not for controls.

Conclusion: Spells, tremor, and irritability are common findings in early infant vitamin B12 deficiency. Nitrous oxide given during labor is proposed as a contributing risk factor to the development of early infant vitamin B12 deficiency.

Keywords: Apnea; Breastfeeding; Cobalamin; Formula; Infant; Nitrous oxide; Seizure; Vitamin B12.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Feeding
Case-Control Studies
Child
Female
Homocysteine
Humans
Infant
Infant, Newborn
Nitrous Oxide / adverse effects
Seizures / complications
Tremor / chemically induced
Tremor / etiology
Vitamin B 12 Deficiency* / complications
Vitamin B 12 Deficiency* / diagnosis
Vitamin B 12*

Substances

Homocysteine
Nitrous Oxide
Vitamin B 12