Neonatal Isoerythrolysis in Foals: Causes, Treatment & Prevention

Neonatal isoerythrolysis (NI) is a potentially fatal, but preventable, condition affecting newborn foals. Foals develop NI when they consume colostrum containing antibodies against their blood type, resulting in destruction of their red blood cells.

This condition will only occur if the mare and foal have different blood types, and the mare’s immune system produces antibodies that target the foal’s blood type.

The main symptoms of NI include rapid breathing, increased heart rate, and jaundice of the gums and skin. Laboratory testing is the best method to confirm a diagnosis.

Treatment requires intensive management, including blood transfusions to restore red blood cell levels. Neonatal isoerythrolysis generally has a good prognosis if caught early and treated promptly, however many foals die before symptoms develop.

This condition is entirely preventable by identifying mares at risk of producing affected foals and testing the foal after it is born. If there is a risk of NI, an alternative source of colostrum should be provided.

Neonatal Isoerythrolysis in Foals

Neonatal isoerythrolysis (NI) is a serious, potentially fatal condition in newborn foals. In foals with NI, antibodies from the mare cause destruction of the foal’s red blood cells shortly after the foal consumes colostrum, the mare’s first milk.

Most of the time, NI occurs in foals born to mares that have multiple previous foals, but in rare cases it can occur in foals born to maiden mares. ^[1] Estimates suggest that NI affects around 1% of horse foals, and around 10% of mule foals. ^[2]

The root cause of NI stems from the mare producing antibodies that target the blood type of her foal. ^[1] Several events must occur for NI to develop: ^[1][3]

• The mare must have a different blood type than the foal she is carrying
• The mare must have been previously exposed to another blood type
• The foal must inherit the previously exposed blood type from its sire

Disease Development

Horses have seven red blood cell groups, also called “systems”. In addition, over 40 different factors on the surface of red blood cells have been identified. ^[2] Therefore, the likelihood of a foal having a different blood type than its dam is very high. However, NI is rare because it only occurs when the mare’s immune system has a previous exposure to another blood type. ^[1]

Like other species, horses typically do not have antibodies against other blood types in their bloodstream. But there are exceptions, such as if a horse has received a blood transfusion during emergency situations in the past. ^[4]

In most cases, exposure to other blood types is a result of a previous pregnancy in which the mare carried a foal with a different blood type. ^[1][4] As the foal grows, small amounts of the foal’s blood may leak into the maternal bloodstream through the placenta, stimulating the mare to produce antibodies. ^[4].

After exposure to the foreign blood type, the mare’s immune system begins producing antibodies against that blood type. Foals in utero are protected because the placenta does not allow antibodies to cross over to the fetus. ^[1][4]

During late pregnancy, these antibodies begin to accumulate in the colostrum, the mare’s first milk.

Once the newborn foal is born and consumes this colostrum, the antibodies from the mare target the foal’s red blood cells, resulting in their destruction. ^[1][4]. This destruction of red blood cells (isoerythrolysis) is what ultimately causes the symptoms associated with neonatal isoerythrolysis.

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Prevalence

Some blood types have a higher risk of developing NI than others. The vast majority of NI cases involve foals with blood types containing Aa or Qa factors, likely because these factors induce a particularly strong antibody response. ^[4]

Aa and Qa factors refer to specific blood group antigens found on the surface of red blood cells in horses. Blood group antigens are molecular structures that can be recognized by the immune system, and each blood type has its own set of specific antigens.

Mules also have a very high risk of NI because they often have donkey blood types containing donkey factor, which is highly stimulating to the immune system of horses. ^[1][3][4] Approximately 10% of mule foals have some degree of NI due to the incompatibility caused by donkey factor. ^[1]

There are also reports of non-specific antibody production in mares that generally targets all other blood types, rather than specific blood types. ^[5]

Clinical Signs

Foals with neonatal isoerythrolysis are healthy at birth. They only begin to show symptoms of NI at around 24-36 hours old, after drinking colostrum from their dam. ^[1]

Common symptoms include: ^[1][4][6]

• Lethargy
• Rapid or laboured breathing
• Weakness
• Repetitive yawning
• Seizures
• Jaundice of the gums and skin
• Blood in the urine
• Elevated heart rate

Diagnosis

If you suspect your foal has NI, contact your veterinarian immediately for an accurate diagnosis. In particular, foal showing signs of jaundice within the first few days of life should be tested for NI.

Laboratory testing is the most effective diagnostic technique and has the lowest risk of false-negative results. ^[4] For laboratory analysis, blood or colostrum samples from the mare and a blood sample from the foal are submitted for testing. ^[1]

Because NI is an emergency and can rapidly cause death in affected foals, it is common for veterinarians to perform a crude on-farm test for the condition, known as a jaundiced foal agglutination (JFA) test. However, this test has a high rate of false-negatives, and requires careful interpretation.

To perform the JFA test, different concentrations of colostrum from the mare are mixed with blood from the foal or the sire. ^[1][3][7] A tentative diagnosis of NI is made based on the concentration of colostrum that stimulates red blood cells to clump together. ^[1]

This test allows for prompt treatment if the results suggest NI. However, a negative result does not necessarily indicate that the foal is negative for NI.

Foals that test negative on the JFA test require further testing for confirming their NI status. ^[1]

Treatment

Typically, by the time the foal develops symptoms of NI, the level of antibodies in the mare’s milk has declined to the point where further consumption by the foal will not affect their health.

Treatment focuses on addressing the loss of red blood cells experienced by the foal, rather than preventing further colostrum consumption. ^[1] The main treatment for NI is a blood transfusion to restore red blood cell levels.

Blood Transfusion

Selection of a blood donor can be complex in cases of NI. The donor must “match” the foal’s blood type, but also not be a target for the mare’s antibodies. A straightforward blood donor source is the mare’s blood, since her blood type will not react with antibodies that she produces. ^[1][4]

However, for the mare’s blood to be an effective treatment, the plasma component of the blood that contains antibodies must be removed. Otherwise, administering the mare’s blood would only introduce more red blood cell-targeting antibodies into the foal, preventing recovery. ^[1][2]

Since using the mare’s blood requires additional processing completed by a veterinarian, it is not always available as a treatment option.

Alternatively, some veterinary clinics have access to a universal donor horse that can donate blood on short notice. ^[1][4] A universal horse has a blood type that lacks certain antigens, making its blood compatible with the majority of the equine population. This minimizes the risk of adverse reactions when the blood is transfused into recipient horses.

In mule foals, it appears that blood donation from any horse other than the mare is an effective treatment, since most horses do not have antibodies against donkey factor. ^[1][4]

Considerations

Note that the red blood cells introduced from a donor horse will likely be rapidly removed by the foal’s immune system, since they are of a different blood type than their own. Typically this process takes around one week. ^[2]

As part of this process, the foal will begin producing its own antibodies against that blood type. Receiving additional blood transfusions may trigger another red blood cell destruction event. ^[1][4]

To prevent this from occurring, usually only one blood transfusion is given, with the goal that the foal’s own production of red blood cells will restore normal cell levels before the donor’s red blood cells are completely eliminated by the immune system. ^[1][4]

Foals that receive a blood transfusion as part of their NI treatment will require careful blood donor selection in future emergency scenarios. Females will also be predisposed to producing an NI foal in the future themselves if their foal’s blood type matches the donor blood type. ^[1]

Plasma Exchange

Plasma exchange involves drawing blood from the foal, removing the antibody-containing plasma from the blood, and replacing with donor plasma. ^[8]

This technique is common in human medicine to remove toxins from the bloodstream, and there is some evidence to support its use as a treatment for NI in foals. ^[8] Plasma exchange may become more common in NI management in the future.

Polymerized Hemoglobin

Polymerized hemoglobin is a potential alternative to blood transfusion that has been successfully used in an NI foal. ^[9] This product is ultra-purified bovine hemoglobin, which is the main oxygen-carrying component of red blood cells.

One of the major benefits of hemoglobin versus blood transfusion is that the product does not require matching of blood types since it does not contain complete red blood cells. This means that the foal can benefit from improved oxygen-carrying capacity in the bloodstream without the risk of further red blood cell destruction. ^[9]

Polymerized hemoglobin is uncommon in equine medicine, so your veterinarian may not have the product available for use. ^[9]

Other Treatments

When red blood cell destruction occurs levels of free hemoglobin in the blood may increase. However, hemoglobin is highly toxic to the kidneys. Intravenous fluids help “wash out” the hemoglobin from the kidneys, reducing the risk of kidney failure. ^[1][4]

Foals with NI may also benefit from supplemental oxygen, as reduced red blood cell count lowers the oxygen-carrying capacity of the blood. ^[1][4]

Prognosis

The overall prognosis of NI is poor, with many foals dying before symptoms are identified. ^[1][4] In cases that are caught early and receive prompt treatment, the prognosis is good. ^[6]

Liver failure is a potential complication that can result in death or euthanasia, particularly in foals that receive large volumes of donor blood or multiple transfusions. ^{[1][2][6][10]}

Prevention

Neonatal isoerythrolysis is entirely preventable with appropriate management of breeding stock.

A straightforward way to prevent this condition is to identify mares with the highest risk of producing affected foals and ensure the foal is tested before it consumes colostrum.

Mares are considered at risk if they have previously had an NI foal or if they do not have Qa or Aa factors as part of their blood type. ^[1][3]

Breeding these mares to stallions that also do not carry Qa and Aa factors is one way to prevent NI. However, many stallions do not have their blood type tested. ^[1][3]

Preventing Colostrum Intake

Most breeders with at-risk mares choose strategies that prevent the foal from consuming colostrum after birth. Preventative measures include: ^[1][2][3]

• Muzzling the foal shortly after birth to prevent consumption of the mare’s colostrum
• Performing a JFA test using the mare’s colostrum and the foal’s blood to assess the risk of NI

If the JFA test suggests that NI is likely to occur, management of the mare and foal includes: ^[1][2][7]

• Tubing an alternative source of colostrum into the foal, such as donor colostrum from a colostrum bank
• Testing the foal’s antibody levels to determine whether failure of passive transfer (FPT) has occurred, and administering a plasma transfusion if FPT is present
• Milking out the mare regularly and discarding the colostrum

Once the mare’s colostrum is depleted and they produce regular milk, the foal can be unmuzzled and allowed to nurse from the mare. Repeating the JFA test can identify when antibodies in the milk are fully depleted. ^[1][7]

Summary

• Neonatal isoerythrolysis is a potentially fatal, but entirely preventable, disease affecting neonatal foals
• Identifying at-risk mares early and stopping the foal from nursing colostrum is the best preventative strategy available
• Foals that develop NI require intensive treatment, including blood transfusions
• If caught early and treated promptly, the prognosis for affected foals is good