Approach to anemia in the newborn and infant (underproduction): Clinical sciences

Anemia is a condition characterized by a decrease in healthy red blood cells, or RBCs, indicated by low hemoglobin and hematocrit or a low RBC count. Based on the mean corpuscular volume, or MCV for short, anemia can be classified as microcytic, normocytic, or macrocytic.

When a pediatric patient presents with a chief concern suggesting anemia, you should first perform an ABCDE assessment to determine if the patient is unstable or stable. If unstable, stabilize the airway, breathing, and circulation, obtain IV access, and give IV fluids. Next, place your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry; and, if indicated, consider transfusion of blood products, such as packed RBCs. If needed, provide supplemental oxygen to maintain oxygen saturation above 90%.

Here’s a clinical pearl! When a patient with anemia is unstable, be sure to look for active bleeding due to trauma, as well as signs of internal bleeding such as hematochezia, melena, or hematuria.

Now, let’s go back to the ABCDE and look at stable patients. First, obtain a focused history and physical examination and order labs, including CBC with indices, and a reticulocyte count. History could reveal symptoms like fatigue, malaise, palpitations, or dyspnea; while the physical exam might demonstrate tachycardia or pallor. Next, check the CBC, and if results reveal a low hemoglobin and hematocrit for gestational and postnatal age, you can diagnose anemia.

Alright, your next step is to assess the reticulocyte count. A reticulocyte count above the reference range indicates the body is actively producing new RBCs, which is suggestive of anemia due to RBC destruction, like hemolysis; or blood loss, like hemorrhage.

On the other hand, a reticulocyte count within or below the reference range is suggestive of anemia due to RBC underproduction. In this case, your next step is to classify the anemia based on the size of the RBCs, so you should assess the MCV. Based on this, you can classify anemia as either microcytic, normocytic, or macrocytic.

First, let's focus on patients with an MCV below the reference range. We call this microcytic anemia because the RBCs are smaller than normal. To investigate the cause, order iron studies, including serum iron; ferritin; transferrin saturation or TSAT; and serum total iron binding capacity, or TIBC.

Now, the results will likely reveal low serum iron, ferritin, and TSAT levels, along with a high serum TIBC. In these patients, you should also order a blood lead level and a peripheral blood smear to identify the cause.

If the blood lead level is negative and the peripheral blood smear reveals microcytic and hypochromic RBCs, the diagnosis is iron deficiency anemia. Remember, iron deficiency is the most common cause of microcytic anemia!

Here’s a clinical pearl! Breast milk contains very little iron, so all breastfed infants should receive iron supplementation to prevent iron deficiency anemia, starting at 4 months of age and continuing until iron-containing foods are introduced.

On the other hand, if the blood lead level is positive and the peripheral blood smear shows basophilic stippling of the RBCs, diagnose anemia due to lead poisoning. Also, be sure to look at the patient's history for hints suggesting environmental lead exposure, such as living in a home built before 1978, after which lead-based paint was banned for residential use; or being exposed to soil contaminated with lead.

Here’s a high-yield fact! Lead poisoning can cause microcytic anemia through two mechanisms. The first one can clinically resemble iron deficiency because lead interferes with iron absorption in the intestines; while the second mechanism involves the inhibition of enzymes involved in heme synthesis, resulting in sideroblastic anemia.

Okay, let's turn our attention to patients with an MCV within the reference range. In this case, diagnose normocytic anemia, meaning the RBCs are of normal size. To determine the cause, you need to revisit the patient's history.

Let’s start with the physiologic anemia of infancy. These infants are usually born full-term and are incidentally found to have anemia in the first 8 to 12 weeks of life, with a hemoglobin level between 9 and 11 g/dL. In this case, you can diagnose physiologic anemia of infancy.

This is not a hematologic disorder; instead, it’s a physiologic response as the infant transitions from a relatively low-oxygen intrauterine environment to an oxygen-rich extrauterine environment.

This results in a negative feedback to erythropoietin production, a temporary reduction in erythropoiesis, and a physiologic hemoglobin nadir. These infants don’t exhibit signs of illness and don’t require treatment.

Next, let’s take a look at anemia of prematurity. These infants present with anemia around 4 to 8 weeks of life, with a hemoglobin level between 7 and 9 g/dL; findings which are highly suggestive of anemia of prematurity. In these infants, anemia is often due to an immature hematopoietic system, shorter RBC lifespan, as well as rapid growth; and it’s often exacerbated by frequent blood draws for laboratory testing.