B Vitamin Status in Premature and Small for Gestational Age(SGA) Infants

Premature birth and low birth weight implies insufficient intrauterine growth and fetal malnutrition. During the first months of life where the infant is breastfed, the low stores aquired during fetal life, may cause specific B vitamin deficiencies. In this study infants with a birth weight below 3000 g will be studied at 6 weeks, 4 and 6 months. At 6 months infants with biochemical signs of impaired cobalamin status (i.e.: tHcy > 97.5 percentile for cobalamin treated infants, i.e.: tHcy>6.5 µM/L) will be randomised to cobalamin treatment or placebo. At 7 months the investigators will evaluate the effect of cobalamin or placebo treatment according to infant biochemical status and neurodevelopment. Study hypothesis: Cobalamin treatment given to infants with biochemical cobalamin deficiency will normalize biochemical status and cause improved motor neurodevelopment.

Hydroxycobalamin 400 µg (Vitamin B12 depot, Nycomed Pharma) is given as a singel intramuscular injection. The syringe is covered so it is impossible to see whether it contains any substance

The controls receive an intramuscular "injection": which is merely an introduction of the needle into the muscle whithout any injection. The syringe is covered so it is not possible to see whether the syringe contains any substance

Hydroxycobalamin 400 µg (Vitamin B12 depot, Nycomed Pharma ) is given as a single intramuscular injection

Bloodsamples for analysis of B vitamin status are drawn before intervention and after 4 weeks Neurological evaluation (AIMS test) of the infants is done before intervention and after 4 weeks

Maternal evaluation of changes in infant behaviour will be tested by using a maternal questionnaire, Ages and Stages (ASQ), a highly rated child screening and monitoring system, before and after intervention

Inclusion Criteria: Birthweight < 3000 grams Age 6 months (+/- 0.5 months) Plasma total homocysteine > 6.5 umol/L Exclusion Criteria: Plasma total homocysteine < 6.5 umol/L

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.

Torsvik IK, Ueland PM, Markestad T, Midttun O, Bjorke Monsen AL. Motor development related to duration of exclusive breastfeeding, B vitamin status and B12 supplementation in infants with a birth weight between 2000-3000 g, results from a randomized intervention trial. BMC Pediatr. 2015 Dec 18;15:218. doi: 10.1186/s12887-015-0533-2.

Torsvik IK, Markestad T, Ueland PM, Nilsen RM, Midttun O, Bjorke Monsen AL. Evaluating iron status and the risk of anemia in young infants using erythrocyte parameters. Pediatr Res. 2013 Feb;73(2):214-20. doi: 10.1038/pr.2012.162. Epub 2012 Nov 20.