title: 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.
abstract: BACKGROUND
  Exclusive breastfeeding for 6 months is assumed to ensure adequate micronutrients for term infants. Our objective was to investigate the effects of prolonged breastfeeding on B vitamin status and neurodevelopment in 80 infants with subnormal birth weights (2000-3000 g) and examine if cobalamin supplementation may benefit motor function in infants who developed biochemical signs of impaired cobalamin function (total homocysteine (tHcy) > 6.5 μmol/L) at 6 months.
  
  
  METHODS
  Levels of cobalamin, folate, riboflavin and pyridoxal 5´-phosphate, and the metabolic markers tHcy and methylmalonic acid (MMA), were determined at 6 weeks, 4 and 6 months (n = 80/68/66). Neurodevelopment was assessed with the Alberta Infants Motor Scale (AIMS) and the parental questionnaire Ages and Stages (ASQ) at 6 months. At 6 months, 32 of 36 infants with tHcy > 6.5 μmol/L were enrolled in a double blind randomized controlled trial to receive 400 μg hydroxycobalamin intramuscularly (n = 16) or sham injection (n = 16). Biochemical status and neurodevelopment were evaluated after one month.
  
  
  RESULTS
  Except for folate, infants who were exclusively breastfed for >1 month had lower B vitamin levels at all assessments and higher tHcy and MMA levels at 4 and 6 months. At 6 months, these infants had lower AIMS scores (p = 0.03) and ASQ gross motor scores (p = 0.01). Compared to the placebo group, cobalamin treatment resulted in a decrease in plasma tHcy (p < 0.001) and MMA (p = 0.001) levels and a larger increase in AIMS (p = 0.02) and ASQ gross motor scores (p = 0.03).
  
  
  CONCLUSIONS
  The findings suggest that prolonged exclusive breastfeeding may not provide sufficient B vitamins for small infants, and that this may have a negative effect on early gross motor development. In infants with mild cobalamin deficiency at 6 months, cobalamin treatment significantly improvement cobalamin status and motor function, suggesting that the observed impairment in motor function associated with long-term exclusive breastfeeding, may be due to cobalamin deficiency.
  
  
  BACKGROUND
  ClinicalTrials.gov, number NCT01201005.
authors.affiliation: Department of Pediatrics, Haukeland University Hospital, N-5021, Bergen, Norway. ingrid.kristin.torsvik@helse-bergen.no.
authors.forename: Ingrid Kristin
authors.initials: IK
authors.lastname: Torsvik
authors.affiliation: Laboratory of Clinical Biochemistry, Haukeland University Hospital, N-5021 Bergen, Norway. per.ueland@kb.uib.no.|Institute of Medicine, Faculty of Medicine and Dentistry, University of Bergen, N-5021, Bergen, Norway. per.ueland@kb.uib.no.
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.affiliation: Department of Pediatrics, Haukeland University Hospital, N-5021, Bergen, Norway. trond.jacob.markestad@helse-bergen.no.|Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, N-5021 Bergen, Norway. trond.jacob.markestad@helse-bergen.no.
authors.forename: Trond
authors.initials: T
authors.lastname: Markestad
authors.affiliation: Bevital AS, N-5021 Bergen, Norway. Bjorn.Midttun@med.uib.no.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Midttun
authors.affiliation: Laboratory of Clinical Biochemistry, Haukeland University Hospital, N-5021 Bergen, Norway. anne-lise.bjorke.monsen@helse-bergen.no.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Bjørke Monsen
mesh_terms: D001942:Breast Feeding; D002657:Child Development; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007223:Infant; D007230:Infant, Low Birth Weight; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood; D009048:Motor Skills; D011732:Pyridoxal Phosphate / Q000097:blood; D012256:Riboflavin / Q000097:blood; D013997:Time Factors; D014805:Vitamin B 12 / Q000097:blood / Q000627:therapeutic use*; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000188:drug therapy*; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex; D011732:Pyridoxal Phosphate; D008764:Methylmalonic Acid; D005492:Folic Acid; D014805:Vitamin B 12; D012256:Riboflavin