A new study, published in the journal Nutrients, has concluded that exclusive breastfeeding for extended periods without adequate multivitamin supplementation may not provide sufficient B vitamin levels for premature infants.
The research, in part funded by the Foundation to Promote Research into Functional Vitamin B12 Deficiency, evaluated B-vitamin status in premature VLBW infants from term age to 12 months corrected age, comparing exclusive breastfeeding with partial or exclusive formula feeding.
Vitamin gaps in premature VLBW infants
Premature infants with VLBW (defined as weighing less than 1500 g) begin life with limited vitamin stores and must undergo rapid catch-up growth, which increases their need for energy and essential nutrients.
While human milk provides optimal nutrition for all infants, including those with VLBW, it often doesn’t meet their nutritional requirements during hospitalization as they can only tolerate small feeding volumes. Therefore, clinicians will often add multinutrient fortifiers, which include protein, carbohydrates, minerals and vitamins.
Breastmilk remains the gold standard for infant feeding; however, it contains low levels of vitamins K1 and D and may also provide insufficient amounts of vitamins B12, B6, and B2, the report said. The concentrations of B vitamins in human milk depend on maternal status and decline during the first months of lactation, except for folate. Maternal B-vitamin deficiency directly lowers milk vitamin concentrations and increases the risk of infant deficiency during prolonged exclusive breastfeeding.
Vitamin levels normally change as infants grow: babies usually have high vitamin levels early in life, and these levels drop during the first year as growth increases and vitamin stores are used up.
According to the researchers, current recommendations for vitamin supplementation in premature infants vary widely, and recent surveys indicate that routine supplementation focuses mainly on vitamin D, with limited attention to B vitamins.
Cobalamin (Vit B12), folate (B9), vitamin B6, and riboflavin (B2) play critical roles in cellular metabolism, DNA synthesis and methylation, neurodevelopment, and growth. However, studies examining B-vitamin status, particularly vitamin B6 and riboflavin, during follow-up of premature VLBW infants are scarce, stated the report.
“A relevant question is whether the recommendations for premature VLBW infants ensure an adequate B vitamin status,” the researchers wrote.
Exclusive breastfeeding linked to B vitamin deficiency
The researchers recruited 64 premature infants with VLBW to a longitudinal observational study at Haukeland University Hospital in Bergen, Norway.
They recorded growth and nutritional data during the neonatal stay and invited all infants and mothers to follow-up visits at term, and at two, six and 12 months corrected age. At each visit, mothers completed questionnaires on nutrition and supplementation, clinicians measured infant growth, and staff collected blood samples from both infants and mothers.
While in the hospital, infants were fed according to standard care. Once they could digest milk properly, doctors added extra nutrients to breast milk or formula, and this continued until the infants weighed about 2 kg. After leaving the hospital, doctors recommended only breastfeeding until six months corrected age, although mothers chose how to feed their infants.
Doctors gave vitamin supplements once the infants could handle full milk feeds. Early on, infants received folic acid and multivitamins, and later they received vitamin D and iron during the first year of life. Infants who received formula were given lower doses of multivitamins than those who were breastfed.
The researchers took blood samples from the infants and measured levels of several vitamins and related markers.
About one-third of the premature infants were exclusively breastfed from term to 6 months corrected age. These infants had lower levels of vitamin B12, vitamin B6, and riboflavin than infants who received formula, and most of these exclusively breastfed infants showed signs of vitamin B12 deficiency during the first six months.
Data revealed exclusive breastfeeding strongly predicted lower levels of cobalamin, vitamin B6, and riboflavin, and higher homocysteine levels, compared with formula feeding. Vitamin supplements improved vitamin B6 and riboflavin levels but did not improve cobalamin or folate levels, and signs of cobalamin deficiency were much more common in exclusively breastfed infants than in formula-fed infants during early infancy.
“Deficiency of cobalamin, folate, vitamin B6, and vitamin B2 are associated with hypomethylation, and while DNA methylation is essential for viability in human cells, global hypomethylation has a wide spectrum of effects that include genetic, epigenetic, and metabolic alterations, and is associated with the occurrence and progression of cancer and metabolic diseases, rendering it important to secure an adequate B vitamin status during growth and development,” the researchers explained.
Adequate B vitamin intake is especially important during growth and development, they noted.
Low levels of cobalamin, folate, vitamin B6, and vitamin B2 reduce DNA methylation, which is essential for human cell survival. Reduced methylation levels can cause genetic, epigenetic, and metabolic changes linked to the development and progression of metabolic diseases.
“Exclusive breastfeeding for extended periods, with inadequate multivitamin supplementation and no specific recommendation for introduction of solid food, does not seem to provide an adequate B vitamin status in infants born prematurely with VLBW,” the researchers concluded.
“Improved nutrition with regular control of B vitamin status is warranted during the early period of life in premature VLBW infants.”
Source: Nutrients doi: 10.3390/nu18030423 “Exclusive Breastfeeding Is Not Ensuring an Adequate Vitamin B Status in Premature Infants with Very Low Birth Weight”; Authors: A. Bjørke-Monsen et al.




