The prevalence and clinical relevance of hyperhomocysteinemia suggesting vitamin B12 deficiency in presumed healthy infants

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

doi:10.1016/j.ejpn.2021.10.008

The prevalence and clinical relevance of hyperhomocysteinemia suggesting vitamin B12 deficiency in presumed healthy infants

Eur J Paediatr Neurol. 2021 Nov:35:137-146. doi: 10.1016/j.ejpn.2021.10.008. Epub 2021 Oct 16.

Authors

Affiliations

¹ Institute of Clinical Medicine, University of Oslo, Postbox 1171 Blindern, NO-0318 Oslo, Norway; Department of Pediatrics, Vestfold Hospital Trust, Postbox 1068, NO-3103, Tønsberg, Norway. Electronic address: ulf.wike.ljungblad@siv.no.
² Department of Rehabilitation and Physiotherapy, Vestfold Hospital Trust, Postbox 1068, NO-3103, Tønsberg, Norway. Electronic address: hepaul@siv.no.
³ Institute of Clinical Medicine, University of Oslo, Postbox 1171 Blindern, NO-0318 Oslo, Norway; Department of Medical Biochemistry, Oslo, University Hospital, Norway. Electronic address: lamo2@ous-hf.no.
⁴ Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, 0424, Oslo, Norway. Electronic address: rdpetter@ous-hf.no.
⁵ Department of Medical Biochemistry, Vestfold Hospital Trust, Postbox 1068, NO-3103, Tønsberg, Norway. Electronic address: helle.hager@siv.no.
⁶ Department of Medical Biochemistry, Vestfold Hospital Trust, Postbox 1068, NO-3103, Tønsberg, Norway. Electronic address: morten.lindberg@siv.no.
⁷ Department of Pediatrics and Adolescent Medicine, Sorlandet Hospital Trust, Postbox 416, NO-4604, Kristiansand, Norway. Electronic address: henriette.astrup@sshf.no.
⁸ Department of Pediatrics, Clinical Sciences, Lund, Lund University, 221 84, Lund, Sweden. Electronic address: erik.eklund@med.lu.se.
⁹ Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway. Electronic address: almo@helse-bergen.no.
¹⁰ Institute of Clinical Medicine, University of Oslo, Postbox 1171 Blindern, NO-0318 Oslo, Norway; Department of Pediatrics, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, 0424, Oslo, Norway. Electronic address: trootwel@ous-hf.no.
¹¹ Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, 0424, Oslo, Norway; Department of Pediatrics, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, 0424, Oslo, Norway. Electronic address: ttangera@ous-hf.no.

PMID: 34717141
DOI: 10.1016/j.ejpn.2021.10.008

Abstract

Background: Previous studies have demonstrated a high prevalence of biochemical vitamin B12 deficiency in infants in Norway. Increased total homocysteine (tHcy) is the most important marker of B12 deficiency in infants. There is a need to evaluate its clinical relevance.

Aims: To investigate the prevalence of hyperhomocysteinemia (S-tHcy > 8 μmol/L) suggestive of suboptimal B12 status and the prevalence of clinically relevant hyperhomocysteinemia in presumed healthy infants in Norway. Further, to evaluate risk factors, presence of symptoms and psychomotor development in these children.

Methods: In a prospective study we clinically examined 252 infants aged 3-7 months using standardized neurological and psychomotor tests prior to analyzing biochemical B12 deficiency markers in 250 infants.

Results: Twenty-five of 250 (10%) infants had hyperhomocysteinemia combined with clinically relevant symptoms suggestive of B12 deficiency. Hyperhomocysteinemia was associated with tremor, excessive sleep, and sub-normal scores in the fine motor section of the Ages and Stages Questionnaire. One-hundred and fourteen of 250 (46%) infants had hyperhomocysteinemia. Multiple regression analysis showed months of infant formula use as the strongest negative predictor for hyperhomocysteinemia.

Conclusion: We have demonstrated associations between symptoms suggestive of infant B12 deficiency and increased levels of tHcy in presumed healthy infants The combination of hyperhomocysteinemia and associated relevant symptoms suggestive of B12 deficiency was a common finding, albeit most infants with hyperhomocysteinemia did not show symptoms.

Keywords: B12 deficiency; Breastfeeding; Cobalamin; Homocysteine; Infant; Infant nutrition; Tremor; Vitamin B12.

MeSH terms

Folic Acid
Humans
Hyperhomocysteinemia* / complications
Hyperhomocysteinemia* / epidemiology
Prevalence
Prospective Studies
Vitamin B 12
Vitamin B 12 Deficiency* / complications
Vitamin B 12 Deficiency* / epidemiology

Substances

Folic Acid
Vitamin B 12