Background: In the past years, we diagnosed subclinical vitamin B12 deficiency in infants with hypotonia, motor delay and/or infant malaise. These infants had elevated methylmalonic acid (MMA) in plasma and urine and plasma B12 in the low normal range for adults. They all responded very well to cobalamin supplements, with resolution of symptoms and catching up motor milestones within a few weeks.
Hypothesis: subclinical vitamin B12 deficiency may be an unrecognized cause of delayed motor development in early infancy and may originate already in pregnancy.
Aim of this pilot study: knowing the incidence of subclinical B12 deficiency in newborns.
Methods: we measured MMA in one drop of blood collected on filter paper in the 4th day of life of 100 healthy newborns at term. For 26/100 infants, we also measured MMA in urine.
Results: 7 newborns had elevated MMA in blood spot; in all of them, as well as in their mothers, vitamin B12 deficiency was confirmed by further investigation. All infants were supplemented with vitamin B12 and normalized their MMA level within 4 to 8 weeks.
Conclusions:
1) Subclinical vitamin B12 deficiency is relatively frequent (7%) in healthy newborns and starts already in pregnancy;
2) B12 deficiency should be considered in differential diagnosis of motor delay and infant malaise, even in the absence of anemia;
3) Screening for B12 deficiency is possible at the pediatrician praxis by MMA measurement in dried blood spot, which seems to be more sensitive than urine analysis.
Outlook: in order to demonstrate the impact of B12 deficiency on development of symptoms, we plan a larger prospective, randomized, placebo-controlled interventional study using dried blood spot MMA as a marker of B12 deficiency and with a clinical follow-up to 24 months of life.