Clinical trial NCT05005897: Early Infant Micronutrition and Development
Official title: Vitamin B12 Status in Infancy and the Effect of Providing Vitamin B12 to Infants With Signs of Suboptimal Vitamin B12 Status - a Registry-based, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Vitamin B 12 Deficiency
Keywords: Nutrition
Vitamins
Breastfeeding
Infant
Neurodevelopment
Growth
Clinical trial
Lead sponsor: Sykehuset Innlandet HF
Sponsor class: OTHER
Collaborators: name: University of Bergen
name: University of Oslo
name: Inland Norway University of Applied Sciences
First posted: 2021-08-16
Enrollment: 600
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Globally, vitamin B12 deficiency is one of the most common micronutrient deficiencies. Poor status is also seen in affluent countries such as in Norway. Vitamin B12 is crucial for normal cell division and differentiation and necessary for the development and myelination of the central nervous system. Deficiency is also associated with impaired fetal and infant growth. In the proposed study we will measure the effect of daily oral vitamin B12 supplementation infants on neurodevelopment. We also aim to measure the impact of B12 supplementation on several other outcomes.

Study design: Individually randomized double-blind placebo-controlled trial breastfed infants who will be assigned to a screening group (in which measurements will be obtained immediately) or a control group (in which serum will be stored and measurements done after one year).

Pregnant women will be informed about the study during their first antenatal visit at the clinic and that we will re-approach them on their 6-week visit to their public health nurse. Infants who are deficient will be treated with peroral or intramuscular injections with 400 µg cyano-cobalamin.

Infants in the control group will not be offered any intervention their blood sample will be stored for one year and then analyzed for the same nutrients as the intervention group.

Outcomes: Primary: (i) neurodevelopment in children measured at 12 months of age (ii) growth in children measured by attained weight and length at 12 months. Secondary: (i) neurodevelopment and cognitive functioning in children later in life


Eligibility criteria: Inclusion Criteria:

1. Availability of informed verbal consent
2. Plan to reside in the defined study area for the next 12 months
3. Mothers intend to breastfeed their children for at least 8 months, and exclusively for 4 months

Exclusion Criteria:

1. Severe systemic illness requiring hospitalization
2. Growth retardation
3. Severe congenital malformations
4. Plasma cobalamin concentration \<148 pmol/L (These children will be treated for vitamin B12 deficiency and not included in the RCT, but will be included in the cohort design)

Primary outcomes:
measure: Neurodevelopment
timeFrame: 12 months of age
measure: Prevalence of vitamin B12 deficiency
timeFrame: 1-3 months of age
measure: Prevalence of other vitamin deficiencies
timeFrame: 1-3 months of age
Secondary outcomes:
measure: Neurodevelopment measured by the Ages and Stages Questionaire
timeFrame: 4-12 months of age
measure: Vagal tone
timeFrame: 12 months of age
measure: Eye tracking
timeFrame: 12 months of age
measure: Neurodevelopment later in childhood
timeFrame: 5 years
measure: Adverse events
timeFrame: 3 months after treatment with vitamin B12
Other outcomes:
measure: Thyroid function
timeFrame: 12 months of age
Locations:
city: Lillehammer
country: Norway
facility: Innlandet Hospital Trust
Study officials:
affiliation: Sykehuset Innlandet HF
name: Tor A Strand, M.D. / Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hay G, Johnston C, Whitelaw A, Trygg K, Refsum H. Folate and cobalamin status in relation to breastfeeding and weaning in healthy infants. Am J Clin Nutr. 2008 Jul;88(1):105-14. doi: 10.1093/ajcn/88.1.105.
citation: Torsvik I, Ueland PM, Markestad T, Bjorke-Monsen AL. Cobalamin supplementation improves motor development and regurgitations in infants: results from a randomized intervention study. Am J Clin Nutr. 2013 Nov;98(5):1233-40. doi: 10.3945/ajcn.113.061549. Epub 2013 Sep 11.
citation: Dror DK, Allen LH. Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. Nutr Rev. 2008 May;66(5):250-5. doi: 10.1111/j.1753-4887.2008.00031.x.
citation: Kvestad I, Taneja S, Kumar T, Hysing M, Refsum H, Yajnik CS, Bhandari N, Strand TA; Folate and Vitamin B12 Study Group. Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial. PLoS One. 2015 Jun 22;10(6):e0129915. doi: 10.1371/journal.pone.0129915. eCollection 2015.
citation: Bjorke-Monsen AL. Is exclusive breastfeeding ensuring an optimal micronutrient status and psychomotor development in infants? Clin Biochem. 2014 Jun;47(9):714. doi: 10.1016/j.clinbiochem.2014.05.022. Epub 2014 May 17. No abstract available.
citation: Forssman L, Ashorn P, Ashorn U, Maleta K, Matchado A, Kortekangas E, Leppanen JM. Eye-tracking-based assessment of cognitive function in low-resource settings. Arch Dis Child. 2017 Apr;102(4):301-302. doi: 10.1136/archdischild-2016-310525. Epub 2016 Aug 22.
citation: Graziano P, Derefinko K. Cardiac vagal control and children's adaptive functioning: a meta-analysis. Biol Psychol. 2013 Sep;94(1):22-37. doi: 10.1016/j.biopsycho.2013.04.011. Epub 2013 May 4.
citation: Strand TA, Taneja S, Ueland PM, Refsum H, Bahl R, Schneede J, Sommerfelt H, Bhandari N. Cobalamin and folate status predicts mental development scores in North Indian children 12-18 mo of age. Am J Clin Nutr. 2013 Feb;97(2):310-7. doi: 10.3945/ajcn.111.032268. Epub 2013 Jan 2.