Nutritional megaloblastic anemia, also known as nutritional macrocytic anemia, is primarily caused by a deficiency of vitamin B12 or (and) folic acid. Both vitamin B12 and folic acid act as coenzymes in the synthesis of nucleoproteins. Their deficiency disrupts nucleic acid metabolism, leading to abnormal development of blood cell nuclei and resulting in megaloblastic anemia. Vitamin B12 deficiency can also cause neurological symptoms.

bubble_chart Clinical Manifestations

1. Age characteristics: Mostly seen in infants, with about 2/3 of the total cases occurring between 6 to 12 months of age.
2. Feeding history: Infants exclusively breastfed without timely introduction of complementary foods, or those fed with goat's milk, as well as children with a history of picky eating, are more prone to developing the condition.
3. Clinical manifestations: The onset is gradual, with complexion progressively turning pale-yellow, easy fatigue, poor responsiveness to the external environment, drowsiness, apathy, reduced crying and laughter, absence of tears when crying, delayed intellectual and motor development, or even "regression phenomena." In cases caused by vitamin B12 deficiency, tremors in the limbs, head, lips, or even the entire body may occur, along with involuntary movements, increased muscle tone, hyperactive tendon reflexes, diminished superficial reflexes, and even pathological reflexes. Additionally, affected children often exhibit sparse, dry, and yellowish hair, "puffy" appearance, as well as digestive symptoms such as diarrhea, poor appetite, glossitis, or stomatitis. The liver and spleen are often mildly to grade II enlarged.

bubble_chart Auxiliary Examination

1. Blood picture: The decrease in red blood cell count is more pronounced than the decline in hemoglobin. Most red blood cells are larger in size, with ample hemoglobin, presenting as macrocytic anemia (MCV > 94fl, MCH >32pg, normal MCHC). Reticulocytes are normal or reduced, with frequent observation of polychromatic red cells and basophilic stippling. The total white blood cell count is normal or decreased, and hypersegmentation of neutrophils (shift to the right) may be observed. The presence of neutrophils with 5 or more lobes accounting for more than 3% of the total granulocytes is diagnostically significant, and giant band neutrophils may be seen. Platelets may be reduced, and giant platelets can be observed.
2. Bone marrow findings: Erythroid hyperplasia is present. All stages of erythroblasts exhibit "megaloblastic changes," characterized by enlarged cell size, coarse and loose nuclear chromatin, and nuclear maturation lagging behind cytoplasmic maturation. The nuclei of late erythroblasts are often malformed. In the granulocytic series, myelocytes, metamyelocytes, and band neutrophils are larger in size with abnormal nuclear morphology and loose chromatin. Megakaryocytes may show excessive nuclear lobulation.
3. Generation and transformation assays: Serum vitamin B12 or (and) folate levels are reduced (vitamin B12< 1OOpg/ml，葉酸<3 ng/ml有診斷意義)。維生素B12缺乏者尿中甲基丙二酸(MMA)增多，在纈氨酸負荷後更為明顯(正常值每24小時尿中含0～0.35mg)。葉酸缺乏者組氨酸負荷試驗示尿中甲亞胺基穀氨酸(FIGLU)排泄量增加(正常值<2mg/h)。

bubble_chart Treatment Measures

1. General Treatment: Strengthen nursing care, prevent and treat infections. Gradually increase foods rich in vitamin B12 and folic acid in the diet, such as meat, liver, egg yolks, and leafy greens. Since affected children often exhibit significant loss of appetite or even refusal to eat, it is necessary to feed them patiently. If required, nasogastric feeding may be used for the first 2–3 days, gradually increasing complementary foods as appetite improves, and correcting poor feeding habits.
2. Use of Vitamin B12 and Folic Acid: For patients with prominent neurological symptoms, vitamin B12 should be the primary treatment, as using folic acid alone may worsen symptoms. Vitamin B12 can be administered intramuscularly at 50–100 μg, 2–3 times per week for 2–4 weeks, or until blood parameters normalize. Some have used a single intramuscular injection of 500 μg vitamin B12 with good efficacy, which is more suitable for children who cannot receive frequent injections. If concurrent folic acid deficiency is suspected, oral folic acid can be added at 5 mg per dose, three times daily for 2–3 weeks, then reduced to once daily for a total of 4–5 weeks to restore sufficient body reserves. If the diet has normalized, medication can be discontinued. However, if the underlying condition affecting vitamin B12 or folic acid absorption and metabolism persists, appropriate medication should still be administered to prevent relapse. Within 24–48 hours after treatment begins, megaloblastic changes in bone marrow cells show significant improvement. Mental status improves within 2–3 days, and reticulocyte counts in peripheral blood peak at 5–7 days, followed by increases in red blood cell count and hemoglobin levels, generally returning to normal within 4–8 weeks. Neurological symptoms recover more slowly; in some cases, tremors may temporarily worsen after treatment but gradually improve with continued medication, sometimes taking months to fully resolve.
3. Other Medications: Vitamin C should be administered concurrently to aid in the conversion of folic acid to tetrahydrofolate, enhancing efficacy. For patients with pronounced neurological symptoms, vitamin B6 should be added. In severe cases, potassium supplementation is necessary. During the convalescent stage of anemia, iron supplements should be given to prevent iron deficiency during rapid red blood cell proliferation.
4. Blood Transfusion Therapy: Severe cases complicated by heart failure or other conditions may require appropriate blood transfusions, following the same principles as for iron-deficiency anemia.

bubble_chart Differentiation

Attention should be paid to differentiating from liver disease, hypothyroidism, hypopituitarism, juvenile pernicious anemia, erythroleukemia, and various congenital abnormalities causing non-nutritional megaloblastic anemia.