Introduction: Nutritional anemia remains a global nutritional disease threatening children's health and is one of the common nutritional deficiencies in children.
Nutritional anemia refers to a condition where the body's hematopoietic function is reduced due to a relative or absolute decrease in essential nutrients required for blood production, such as iron, folic acid, and vitamins, leading to insufficient hemoglobin formation or red blood cell production. It commonly occurs in infants and young children aged 6 months to 2 years, women during pregnancy or lactation, and patients with gastrointestinal diseases that result in poor nutrient absorption. The harm of nutritional anemia to children's health is multifaceted, potentially causing growth retardation, intellectual development delay, behavioral deviations, and weakened immunity. The intellectual impairment caused in infants and young children is often irreversible. The Anemia Trio Panel refers to Folic Acid (FA), Vitamin B12 (VB12), and Serum Ferritin (SF). These three serological tests provide a comprehensive assessment of the cause and type of anemia, assisting clinicians in early diagnosis and treatment of anemic patients.
Folic Acid (FA)
Folic acid is a water-soluble vitamin, also known as vitamin B11, anti-anemia factor, vitamin Be, pteroylglutamic acid, etc. It participates in the synthesis and metabolism of numerous compounds and plays a vital role in protein synthesis, cell division, and growth.
As one of the essential vitamins for cell growth and reproduction, folic acid deficiency can impact normal physiological activities:
I. Folic Acid Deficiency and Birth Defects
Folic acid deficiency can cause neural tube defects in newborns and damage to critical areas of spinal development, leading to malformations such as spina bifida, anencephaly, and encephalocele. In 1991, the UK Medical Research Council first confirmed that folic acid supplementation before and during pregnancy can prevent neural tube defects (NTDs), reducing the incidence by 50-70%.
II. Folic Acid Deficiency and Megaloblastic Anemia
Folic acid deficiency inhibits the synthesis of red blood cell DNA, leading to insufficient nucleoprotein formation. Newly formed red blood cells in the bone marrow cannot mature properly, and the rate of cell division and proliferation slows down. Cells increase in volume, resulting in macrocytes. This causes megaloblastic anemia in pregnant women, infants, and young children, bringing significant harm such as habitual abortion, premature birth, low birth weight, and fetal digestive issues and growth retardation.
III. Folic Acid Deficiency and Other Diseases
Numerous literature reports suggest a link between folic acid deficiency and various brain-related conditions, including senile dementia, depression, and neurological abnormalities in newborns. Furthermore, folic acid deficiency may be associated with tumors (e.g., uterine, bronchial, esophageal, colorectal cancer), chronic atrophic gastritis, colitis, coronary heart disease, and cerebrovascular diseases. Symptoms can also include glossitis, poor growth, and mental regression.
Clinical Significance of Serum Folic Acid Testing:
Diagnosis of Megaloblastic Anemia: Measuring FA concentration reflects the body's recent demand for FA. Low FA values can impair DNA synthesis, causing delayed nuclear maturation and division. The nucleus of young red blood cells remains in a reticular structure without condensing, while the cytoplasm is unaffected, and hemoglobin synthesis continues. This leads to enlarged cells, resulting in megaloblastic anemia.
Inadequate Intake or Increased Demand: The daily human requirement for FA is approximately 50-200μg. As body stores of FA are limited (5-15mg) and FA is often lost during cooking, deficiency can occur with insufficient intake (e.g., during pregnancy, infancy, chronic alcoholism, liver cirrhosis) or increased demand (e.g., malignant tumors, hyperthyroidism).
Intestinal Malabsorption: Conditions like malabsorption syndrome, short bowel syndrome, and intestinal paralysis can lead to FA deficiency.
Pernicious Anemia and Aplastic Anemia: FA levels may be increased in these conditions. In contrast, FA levels are typically normal or elevated in anemia caused by iron deficiency, chronic inflammation, or malignant tumors. Therefore, FA measurement has significant clinical value in the differential diagnosis of anemia causes.
Vitamin B12 (VB12)
Vitamin B12, also known as cobalamin, is one of the B vitamins. It is an essential nutrient with key physiological functions: participating in the production of bone marrow red blood cells, preventing pernicious anemia, and protecting the nervous system from damage. Vitamin B12 deficiency primarily affects the hematopoietic and nervous systems.
I. Vitamin B12 Deficiency and the Hematopoietic System
VB12 deficiency leads to megaloblastic anemia, clinically presenting as puffiness, waxy pallor, sparse and dry hair, and noticeably pale conjunctiva, lips, and nails. Common symptoms include fatigue, dizziness, palpitations, and shortness of breath. It is most common in pregnant women aged 20-40 and infants aged 6 months to 2 years.
II. Vitamin B12 Deficiency and the Nervous System
VB12 deficiency can cause numbness, weakness, or a crawling sensation in the hands and feet; ataxia; hypoesthesia; incontinence; irritability; forgetfulness; and mental disturbances. Early signs in children include emotional changes, listlessness, reduced crying or fussing, slow response, and increased sleepiness, ultimately leading to anemia.
III. Vitamin B12 Deficiency and the Digestive System
VB12 deficiency can cause glossitis and tongue pain, with the tongue appearing "smooth and beefy red" due to atrophy of the papillae. Other symptoms include loss of appetite, abdominal bloating, and diarrhea.
Clinical Significance of Serum Vitamin B12 Testing:
Decreased Levels:
Megaloblastic Anemia: Impaired intestinal absorption due to intrinsic factor deficiency disrupts nucleic acid synthesis, affecting red blood cell division and causing megaloblastic anemia.
Chronic Pancreatitis: Trypsin deficiency prevents the degradation of R-protein, which then competes with intrinsic factor and inhibits VB12 absorption.
Zollinger-Ellison Syndrome: Low pH in the small intestine affects VB12 absorption.
Drug Effects: Medications like aminosalicylic acid and neomycin can interfere with VB12 absorption, leading to decreased blood levels.
Other Conditions: Neural tube defects, recurrent aphthous ulcers, stomatitis, alcoholism, pregnancy, chronic renal insufficiency, gastric cancer, acute lymphocytic leukemia, diabetes, etc.
Increased Levels:
Leukemia: Serum VB12 can be nearly 10 times higher than normal, possibly related to the release of VB12 from the massive destruction of leukemic cells.
Polycythemia Vera: Serum VB12 levels are elevated.
Lymphoma and Hyperplastic Anemia.
Liver Diseases: Such as cirrhosis, biliary cirrhosis, portal cirrhosis.
Malignant Tumors.
Serum Ferritin (SF)
Serum ferritin is the most iron-rich protein in the body and a crucial indicator for assessing body iron stores. Serum ferritin testing is significant for diagnosing iron deficiency anemia, iron overload, and evaluating nutritional status. As a tumor marker, ferritin also provides valuable reference information for diagnosing certain clinical malignancies.
Clinical Significance of Serum Ferritin (SF) Testing:
Differential Diagnosis of Anemia: In iron deficiency anemia, serum SF is significantly decreased. SF < 12 μg/mL is considered indicative of depleted iron stores, and levels below 50 μg/mL suggest possible iron deficiency. In aplastic anemia and thalassemia, SF levels are typically normal or elevated.
Chronic Diseases: In anemia associated with chronic infection, inflammation, connective tissue diseases, or malignancies, iron metabolism abnormalities manifest as low serum iron with normal or elevated ferritin levels.
Hematologic Malignancies: SF levels can be elevated in aplastic anemia, acute/chronic leukemia, and malignant lymphoma.
Tumor Marker: Ferritin can serve as a tumor marker. In cancers such as hepatocellular carcinoma, lung cancer, pancreatic cancer, and leukemia, increased synthesis of ferritin by cancer cells leads to elevated serum ferritin levels.