Anemias in Premature Babies – Guide for Parents

Anemia in newborns

Many premature babies suffer from anemias while they receive treatment in a NICU. This article will give you a definition of anemia, describe common types of it, and talk about diagnosis and treatment. 

Background Information

Blood consists of cellular components and liquid. The liquid part (also called plasma or serum) includes water and various chemical components such as electrolytes, protein, fat, sugars, etc. The cellular part comprises red blood cells, white blood cells, and platelets. The primary function of red blood cells (RBCs) is to carry oxygen from the lungs to the tissues; white blood cells defend us from infections, and platelets help us stop bleeding after blood vessels get injured. 

We define anemia as having an abnormally low number of healthy red blood cells responsible for carrying oxygen to our tissues. Depending on each patient’s age, what is normal, and what is abnormal number will differ. 

Types of anemias

There may be numerous causes of anemia in a premature baby. I will focus only on the most common situations occurring in the NICU. 

Blood loss during the delivery process

A baby may lose a significant amount of blood in the following situations:

  • placenta previa – placenta covering the cervix or positioned very close to it resulting in ruptured vessels and bleeding
  • abruptio placentae – detachment of the placenta from the uterus leading to bleeding
  • accidental trauma to the placenta during the cesarean section 
  • rupture of umbilical cord vessels
  • Feto-maternal bleeding – in essence, it is a pathologic situation in which a baby “donates” its blood to the mother. It occurs due to specific abnormalities in the placenta allowing for the mixing between the baby’s and mother’s blood. 
  • twin-to-twin transfusion – similar to the above situation, except that one twin is donating its blood to another twin

Blood loss after birth, during hospitalization

A baby may lose a lot of blood after birth due to frequent blood draws required to test the baby while providing necessary treatments. A high number of blood tests adds up quickly and may lead to the need for a blood transfusion within weeks after birth. 

Additionally, certain complications during the neonatal period, such as intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), spleen or liver rupture, and bleeding problems, can lead to blood loss (my article on IVH, and article on NEC). 

Increased or premature destruction of red blood cells, also called hemolysis

Blood incompatibilities

Sometimes the difference between blood groups of a baby and its mother may lead to the presence of maternal antibodies in the baby and premature destruction of its red cells. That often occurs when the mother has blood type Rh-negative, and the baby is Rh-positive; or when the mother is “O” and the baby is “A” or “B.” Blood incompatibilities may lead not only to severe anemia but also to life-threatening newborn jaundice. I wrote separate articles on both topics, and you can find them here: ABO-incompatibility, and RH-incompatibility. Of note, some other blood incompatibilities between mother and her baby also can lead to anemias and jaundice, but they are rarer and of lesser importance.

Congenital disorders of red blood cells

Congenital disorders rarely cause anemia; nevertheless, they are possible. Lets at least look at three different categories of inheritable defects leading to anemia:

  • Membranes defects – those are diseases in which due to structural defects in the wall of red cells, they become misshaped and consequently more prone to premature destruction. Examples are spherocytosis and ovalocytosis.
  • Metabolic defect – due to enzymatic defect, red cells’ life span is shortened. G6PD-deficiency or pyruvate kinase deficiency are examples.
  • Hemoglobinopathies – hemoglobin is an essential protein component of red cells; therefore, congenital defects in its structure can contribute to anemias. Thalassemias and sickle cell anemias are examples of these diseases; however, sickle cell anemia does not affect newborn babies.

Diminished production of red cells in bone marrow

Certain genetic conditions, infections, and drugs negatively influence bone marrow, leading to less robust production of red blood cells.

Diagnosis of anemia

While diagnosing anemia, we need to review clinical symptoms present in premature babies and conduct blood tests.

Clinical symptoms

Clinical symptoms will vary depending on if the onset of anemia was sudden or it developed chronically over time. 

Acute and severe anemia, particularly if it occurred due to blood loss during birth, may result in severely low blood pressure, the arrest of breathing, and significant skin paleness. Often, affected babies will need resuscitation, fluid boluses to maintain their blood pressure, and urgent blood transfusion after birth. 

When a baby develops anemia slowly over time, they usually get better adapted to it. Initially, symptoms may not be obvious, but with time they will become more apparent. A baby may appear pale, have slow feedings, and get more tired with feedings, develop more frequent apneas, and a faster resting heart rate. When anemia progresses further, the baby may be lethargic and have low blood pressure as well.

Blood tests

Blood tests that we conduct to diagnose anemia may be divided into two groups: 1. general, and 2. identifying the cause of anemia.

General blood tests

Three numerical values allow us to say that a baby has anemia: 

  • the number of red blood cells
  • amount of Hemoglobin in the blood
  • hematocrit

All three listed above values can be obtained from the test called Complete Blood Count (CBC). In addition to red blood cells, the CBC test also evaluates the numbers of white cells and platelets. 

Hemoglobin is a protein, an essential component of red blood cells responsible for carrying oxygen to peripheral tissues. Therefore, the amount of hemoglobin is an indirect measure of the number of red blood cells.  

Hematocrit is a percentage ratio of red blood cell volume to total blood volume. Again, it is an indirect indicator of the number of red blood cells in the blood. 

Tests helping to identify the cause of anemia

In most cases, the cause of anemia can be presumed after gathering complete clinical history on the mother and baby. Most of the time, anemia in a premature baby is due to acute blood loss at birth, iatrogenic chronic blood loss for lab testing, blood group incompatibilities, and suppressed bone marrow due to prematurity or nutritional deficiency. Other causes rarely need to be considered, but obviously, we should not ignore them completely (Source).

Let’s review some tests that can help us in the differential diagnosis of anemias in premature babies:

Blood types in mother and baby – certain differences in blood groups between mother and baby may suggest blood incompatibility as anemia’s etiology. Only when the DAT test (direct antiglobulin test) is positive can this etiology be proven. 

Reticulocyte count – elevation of reticulocyte count- usually occurs in response to increased red blood cells’ destruction. Reticulocyte count may be elevated in blood type incompatibilities, membrane defects, enzymatic defects, or hemoglobinopathies (see above for explanations).

Red cells enzyme levels – if we suspect congenital enzymatic defects affecting red blood cells, we can actually measure levels of those enzymes to diagnose those diseases.

Nutrients’ deficiencies – we can measure levels of iron, vitamins, and micronutrients in the blood.

Treatment of anemia

Not all premature babies need treatment for the anemia. The decision when and how to treat anemia in any given patient will depend on the severity of anemia, the severity of symptoms, and the exact cause of the anemia. 

Blood transfusion

Acute anemia due to blood loss during birth leading to low blood pressure frequently will require an urgent blood transfusion. Criteria for a blood transfusion in chronic anemias will vary. They will depend on a baby’s age and general condition, including how much supplementary oxygen for breathing baby needs. For example, a premature baby, a “feeder-grower” without chronic lung disease, may be OK without blood transfusion until hematocrit drops down to 20%. On the other hand, a one-month-old baby with chronic lung disease, on a ventilator receiving 50% oxygen, may need to be transfused when hematocrit drops to 30%. 

Of note, we rarely transfuse whole blood. To treat anemia, we prefer to transfuse only red blood cells. The product comes from the blood bank and is called Packed Red Blood Cells (PRBC). In rare situations, particularly when blood transfusion is not urgent, it may be possible for a family member to donate blood for the baby. Of note, such blood is not considered safer than any other blood received from the blood bank. Family donors are screened and go through the same process as any other blood donor volunteering their blood. In fact, there may be some contraindications for some family donors to donate blood for their family members due to immunological considerations. 

Blood transfusion carries some risks; the most important are incompatibility due to human errors, allergic reactions, and infections. Hospitals instituted policies that two medical professionals have to check blood units before administering them to the patient to avoid human mistakes. Blood for transfusions from the blood banks is tested for many important infectious microorganisms, but unfortunately, it is never 100% safe. 

Other treatments of anemia


Erythropoietin is a hormone secreted by kidneys and stimulates the bone marrow to produce more red blood cells. It is available as medication, and we can administer it to small babies who suffer from anemia, or we expect, will become anemic in the near future. We can use it in extremely premature babies or newborns of parents who are Jehovah’s Witnesses and oppose blood transfusions in their children. Unfortunately, Erythropoietin works slowly, and its first effects may not be detectable until 2-4 weeks after the start of therapy. Thus, the baby may still need a blood transfusion.

Nutritional elements

Some babies develop anemia due to deficiency of nutritional elements such as iron, vitamins, or minerals. Also, even if anemia in a patient is not due to dietary deficiencies, nutrients are necessary for the baby to produce new red blood cells on its own. Therefore, the use of supplements such as iron, vitamin B12, folic acid, and vitamin E is critical in treating each premature baby with chronic anemia. 

Immunoglobulin (IgG)

If anemia in a baby is due to blood groups incompatibility between a mother and a baby, we can use immunoglobulin. The immunoglobulin role would be to stop the process in which maternal antibodies keep destroying red blood cells in the baby. Immunoglobulin will not cause an increase in the number of red cells; it only will stop further destruction of them. The baby still may need a supplementary blood transfusion.

Prognosis in anemia

In general, I can say that most anemias can be managed easily, and babies recover from them without long term consequences. However, there are a few notable exceptions. Congenital anemias due to genetic defects can’t be cured at this time. You should know that several pharmaceutical companies have some solutions under development, so that may change shortly. I expect that within 3-5 years, we may have FDA approved drugs for the genetic treatment of congenital sickle cell anemia or thalassemia. 

If a baby had low Apgar scores at birth and required prolonged resuscitation and blood transfusion due to acute blood loss during delivery, that baby will be at risk of having impaired developmental outcomes.


This article is only for general information purposes. It should not be viewed as any medical advice. There is a chance that information here may be inaccurate. It would be best if you always discussed all health-related matters with your doctor before making any decisions that may affect yours or your family members’ health.


Dr.Wisniewski is a board-certified pediatrician and neonatologist with over 20 years of clinical experience in the USA. He authored the book: "Babies Born Early - A guide for Parents of Babies Born Before 32 Weeks" Dr.Wisniewski loves educating parents on various health conditions affecting their newborn babies and children.

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