Clinical trial NCT00479479: Cobalamin Supplementation During Infancy; Effect on B-vitamin Status, Growth and Psychomotor Development
Official title: Cobalamin Supplementation During Infancy; Effect on B-vitamin Status, Growth and Psychomotor Development
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vitamin B 12 Deficiency
Keywords: cobalamin
methylmalonic acid
homocysteine
folate
newborns
infants
Deficiency Disease
Breastfeeding
Infant
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: Norwegian Foundation for Health and Rehabilitation
name: Foundation to Promote Research into Functional Vitamin B12 Deficiency, Bergen, Norway
First posted: 2007-05-28
Enrollment: 107
Sex: ALL
Minimum age (years): 4
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Adequate levels of vitamin B12 (cobalamin) is necessary for normal growth and development in infants. We have earlier investigated cobalamin status in healthy children and we observed metabolic evidence of impaired cobalamin status during the first 6 months, but not later in life.

The purpose of this study is to determine if cobalamin supplementation may influence the metabolic profile related to cobalamin status in infants.

Detailed description: During fetal life and infancy, an adequate cobalamin status is important for normal growth and central nervous system development. A metabolic profile consistent with impaired cobalamin status is prevalent in breast-fed infants. Whether this profile reflects immature organ systems or cobalamin deficiency has not been clarified.

Low levels of cobalamin, elevated levels of total homocysteine (tHcy), cystathionine and/or methylmalonic acid (MMA) in the blood are measures of impaired cobalamin status.

The purpose of this randomized, controlled study is to determine if cobalamin supplementation may influence the metabolic profile related to cobalamin status in infants.

Six weeks old infants will be randomly assigned to receive either an intramuscular injection with 400 µg cobalamin or no intervention. Concentrations of cobalamin and folate in serum, and total homocysteine (tHcy), methylmalonic acid (MMA) and cystathionine in plasma will be determined at inclusion and at the age of 4 months. A questionnaire on infant and maternal nutrition, vitamin supplementation, growth parameters, parity and maternal use of tobacco will be completed.

Eligibility criteria: Inclusion Criteria:

* 6 weeks old infants
* The infant should be healthy and not have any serious malformations
* The mother should be healthy and not have any serious disorders or use any daily medications
* The mother should have an ordinary omnivorous diet

Exclusion Criteria:

* If there are evidence of serious infant disease during the study period, the infant should be excluded from the study

Primary outcomes:
measure: Measure: Outcome is related to changes in Cobalamin status: serum levels of cobalamin and folate, and the metabolic markers, plasma-tHcy, cystathionine and MMA
timeFrame: Infant age 6 weeks - 4 months
Secondary outcomes:
measure: Outcome is related to changes in growth parameters; weight, length, head circumference
timeFrame: Infant age: 6 weeks - 4 months
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Laboratory of Clinical Biochemistry and Department of Pediatrics; Haukeland University Hospital
Study officials:
affiliation: Haukeland University Hospital
name: Anne-Lise Bjørke Monsen, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bjorke Monsen AL, Ueland PM, Vollset SE, Guttormsen AB, Markestad T, Solheim E, Refsum H. Determinants of cobalamin status in newborns. Pediatrics. 2001 Sep;108(3):624-30. doi: 10.1542/peds.108.3.624.
citation: Monsen AL, Refsum H, Markestad T, Ueland PM. Cobalamin status and its biochemical markers methylmalonic acid and homocysteine in different age groups from 4 days to 19 years. Clin Chem. 2003 Dec;49(12):2067-75. doi: 10.1373/clinchem.2003.019869.
citation: Allen LH. Vitamin B12 metabolism and status during pregnancy, lactation and infancy. Adv Exp Med Biol. 1994;352:173-86. doi: 10.1007/978-1-4899-2575-6_14.
citation: Rosenblatt DS, Whitehead VM. Cobalamin and folate deficiency: acquired and hereditary disorders in children. Semin Hematol. 1999 Jan;36(1):19-34.
citation: Bjorke-Monsen AL, Torsvik I, Saetran H, Markestad T, Ueland PM. Common metabolic profile in infants indicating impaired cobalamin status responds to cobalamin supplementation. Pediatrics. 2008 Jul;122(1):83-91. doi: 10.1542/peds.2007-2716.