Background: Vitamin B12 is essential for many metabolic reactions in humans and deficiency results in impaired neurologic functions and disruption in hematopoiesis. Infants are particularly prone to vitamin B12 deficiency due to depleted maternal stores during pregnancy and low vitamin B12 concentrations in the breastmilk. Megaloblastic anemia is a common complication of vitamin B12 deficiency, however hematologic changes are not clearly defined in infants. Our aim was to identify hematologic changes in infants associated with vitamin B12 deficiency.
Method: We retrieved laboratory results including complete blood cell count concomitant with serum B12 and ferritin measurements of infants younger that 1 year of age. The vitamin B12 deficiency was defined as levels below serum concentration of 203 pg/ml. Neutropenia was defined as absolute neutrophil count of ≤ 1000 for infants ≤6 months of age and ≤ 1500 for infants >6 months of age. Continuous variables were expressed as median and interquartile range) and compared by Mann Whitney U test. Associations were analyzed by Spearman correlation and linear regression. Statistical analysis was performed using SPSS 20.0. The study was approved by the ethical committee of the University.
Results: Results of 864 infants were analyzed after exclusion of infants with missing data. Median age of the infants was 6 months (interquartile range: 5-6 months). Vitamin B12 deficiency was detected in 480 infants (55.6%). Serum vitamin B12 concentration showed a weak positive correlation with increasing age (rs=0.09, p=0.006). Vitamin B12 deficient patients had significantly lower white blood cell (WBC) count (9,400/μL, 7,800-11,100 /μL vs 9,900/μL, 8,300-12,175/μL, p=0.001) and absolute neutrophil count (ANC) (2,200/μL, 1,600-3,100 /μL vs 2,500/μL, 1,800-3,500/μL, p=0.001) compared to the vitamin B12 sufficient patients. Vitamin B12 levels were weakly and positively correlated with ANC (rs=0.11, p<0.001), WBC count (rs=0.11, p=0.001), ferritin (rs=0.08, p=0.01) and mean corpuscular volume (MCV) (rs=0.07, p=0.02). In a multiple regression model assessing the ability of hematologic parameters (WBC count, ANC, absolute lymphocyte count, hemoglobin concentration, MCV, and platelet count) to predict vitamin B12 levels, none of the variables were able to predict vitamin B12 levels in infants. In another model assessing the ability of neutrophil count to predict vitamin B12 level after controlling for age, ANC was a statistically significant predictor of vitamin B12 level (beta: 0.11, p: 0.01). However there were no statistical difference between vitamin B12 levels of neutropenic patients (n=66, 178.50 pg/ml, IQR:127.75- 247.75 pg/ml) and patients with normal neutrophil count (n=798, 189.0 pg/ml, IQR:132.0-316.0 pg/ml).
Conclusion: Although hematologic abnormalities characterized by megaloblastic anemia is expected to be seen in vitamin B12 deficiency, complete blood cell counts of infants with vitamin B12 deficiency may not reveal any signs of it, except for neutrophil count corrected for age. Given the common prevalence of vitamin B12 deficiency in infants and considering the severe sequela associated with neurological impairments in developing infant, clinicians should consider to monitor vitamin B12 levels during anemia screening in well child visits, since complete blood cell count may not indicate clues for vitamin B12 deficiency. Besides, low neutrophil counts in infants should drive the clinicians to check for vitamin B12 deficiency.