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

Ingrid Kristin Torsvik, Per Magne Ueland, Trond Markestad, Øivind Midttun, Anne-Lise Bjørke Monsen, Ingrid Kristin Torsvik, Per Magne Ueland, Trond Markestad, Øivind Midttun, Anne-Lise Bjørke Monsen

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.

Clinical trial registration: ClinicalTrials.gov, number NCT01201005.

Figures

Fig. 1
Fig. 1
a. Dose-response relationship of cobalamin, folate, PLP, riboflavin, tHcy and MMA at 6 months with months of exclusive breastfeeding by Generalized additive models (GAM), adjusted for gender, infant weight at 6 months and iron and folate supplementation. The solid line shows the fitted model and the shaded areas indicate 95 % CIs. PLP, pyridoxal 5´phosphate; tHcy, total homocysteine; MMA, methylmalonic acid. b. Dose-response relationship of tHcy and MMA at 6 months with AIMS scores at 6 months by Generalized Additive Models (GAM), adjusted for gender, infant weight at 6 months and iron and folate supplementation. The solid line shows the fitted model and the shaded areas indicate 95 % CIs. tHcy, total homocysteine; MMA, methylmalonic acid

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