Cobalamin Status in Young Children With Developmental Delay

Cobalamin Status in Young Children With Developmental Delay and Regression

During fetal life and infancy, an adequate cobalamin status is important for normal growth and central nervous system development. During the last years we have detected cobalamin deficiency in a number of infants admitted to the Pediatric Department with various symptoms, including neurological symptoms and feeding problems. Cobalamin treatment is given to the infants with biochemical cobalamin deficiency, and leads to loss of symptoms and in improved physical condition.

In this study we want to establish the prevalence of cobalamin deficiency in infants with developmental delay and regression and other vague neurological symptoms. Cobalamin status will be investigated in all children aged 8 months and younger, admitted to the Pediatric Department with these symptoms. In a randomised intervention trial we will evaluate the effect of cobalamin supplementation in children with these symptoms and metabolic evidence of impaired cobalamin status.

Study hypothesis: Cobalamin treatment given to the infants with biochemical cobalamin deficiency, will lead to loss of symptoms and in improved physical condition.

Study Overview

• Status: Completed
• Conditions: Vitamin B 12 Deficiency
• Intervention / Treatment: Dietary supplement: Hydroxycobalamin (Vitamin B12 Depot, Nycomed Pharma)

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway, 5021
    • Department of Pediatrics, Haukeland University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children below 8 months of age
• Clinical diagnosis or symptoms: developmental delay and regression and other vague neurological symptoms

Exclusion Criteria:

• Children with syndromic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; 400 µg hydroxycobalamin (Vitamin B12 Depot, Nycomed Pharma) given as a single intramuscular injection. The syringe is covered so it is impossible to see whether or not it contains any substance.	Dietary supplement: Hydroxycobalamin (Vitamin B12 Depot, Nycomed Pharma); 400 µg hydroxycobalamin (Vitamin B12 Depot, Nycomed Pharma), as a single intramuscular injection; Other Names: Vitamin B12; Cobalamin; B vitamins
Sham Comparator: 2; The controls receive an intramuscular "injection", however, it is only an introduction of the needle into the muscle, but no injections are given. The syringe is covered so it is impossible to see whether or not it contains any substance.	Dietary supplement: Hydroxycobalamin (Vitamin B12 Depot, Nycomed Pharma); 400 µg hydroxycobalamin (Vitamin B12 Depot, Nycomed Pharma), as a single intramuscular injection; Other Names: Vitamin B12; Cobalamin; B vitamins

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Outcome Measure: Changes in cobalamin and folate status, including metabolic markers, hematological parameters, neurological evaluation and growth parameters	Reevalutation after 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Maternal evaluation of infant behaviour	After 4 weeks

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Collaborators: Norwegian Foundation for Health and Rehabilitation; Foundation to Promote Research into Functional Vitamin B12 Deficiency, Bergen, Norway

Publications and helpful links

General Publications

• 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. Erratum In: Pediatrics 2002 Oct;110(4):853.
• Rosenblatt DS, Whitehead VM. Cobalamin and folate deficiency: acquired and hereditary disorders in children. Semin Hematol. 1999 Jan;36(1):19-34.
• 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.
• Graham SM, Arvela OM, Wise GA. Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants. J Pediatr. 1992 Nov;121(5 Pt 1):710-4. doi: 10.1016/s0022-3476(05)81897-9.
• Casella EB, Valente M, de Navarro JM, Kok F. Vitamin B12 deficiency in infancy as a cause of developmental regression. Brain Dev. 2005 Dec;27(8):592-4. doi: 10.1016/j.braindev.2005.02.005.
• Grattan-Smith PJ, Wilcken B, Procopis PG, Wise GA. The neurological syndrome of infantile cobalamin deficiency: developmental regression and involuntary movements. Mov Disord. 1997 Jan;12(1):39-46. doi: 10.1002/mds.870120108.
• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: July 2, 2008
• First Submitted That Met QC Criteria: July 3, 2008
• First Posted (Estimate): July 4, 2008

Study Record Updates

• Last Update Posted (Estimate): August 16, 2010
• Last Update Submitted That Met QC Criteria: August 13, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Nutrition; Infant; Neurodevelopment; Neurological symptoms; Cobalamin deficiency; Cobalamin supplementation
• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin B Deficiency; Vitamin B 12 Deficiency; Physiological Effects of Drugs; Micronutrients; Hematinics; Vitamins; Vitamin B 12; Hydroxocobalamin; Vitamin B Complex
• Other Study ID Numbers: 19072