Hematological findings associated with neurodevelopmental delay in infants with vitamin B12 deficiency

In adults with vitamin B12 deficiency, an inverse correlation between the severity of megaloblastic anemia and the degree of neurological dysfunction has been reported. We aimed to evaluate the association between hematological findings and the results of neurodevelopmental assessment in infants. Denver-II developmental screening test (DDST II) was performed in vitamin B12-deficient infants (n = 122), and its relationship with hematological findings was evaluated. DDST II was abnormal in 15 (12.3%), suspect in 20 (16.4%) and normal in 87 (71.3%) cases. Among the infants aged ≥ 4 months (n = 89), cases with an abnormal DDST II had lower levels of hemoglobin (7.49 ± 3.13 vs. 9.87 ± 1.77 g/dL; P = 0.015), whereas they had higher levels of mean corpuscular volume (MCV) (90.05 ± 19.31 vs. 69.90 ± 10.51 fL; P = 0.002), mean corpuscular hemoglobin (MCH) (28.96 ± 7.50 vs. 22.03 ± 4.58 pg; P = 0.001), homocysteine (44.31 ± 11.51 vs. 21.05 ± 9.23 µmol/L; P < 0.001), transferrin saturation index (25.84 ± 17.72 vs. 9.55 ± 6.38%; P = 0.004) and ferritin (87.28 ± 82.21 vs. 26.59 ± 31.67 ng/mL; P = 0.040) than those with a normal DDST II. The receiver operator characteristic analysis could distinguish infants with an abnormal DDST II from those with a normal DDST II by using a hemoglobin level < 8.75 g/dL [sensitivity: 71.4%, specificity: 76.4%; area under curve (AUC): 0.744], an MCV > 88.4 fL (sensitivity: 76.9%, specificity: 98.2%; AUC 0.813), an MCH > 28.5 pg (sensitivity: 76.9%, specificity: 96.4%; AUC: 0.822), and a homocysteine level > 27.35 µmol/L (sensitivity: 92.9%, specificity: 85.5%; AUC: 0.907). Even mild abnormalities of some commonly evaluated laboratory variables (such as MCV and MCH) in an infant should alert the physicians for the possibility of an underlying vitamin B12 deficiency with some degree of neurological impairment.