Neonatal Isoerythrolysis: Is Your Foal At Risk?

by Melba S. Ketchum, D.V.M.
© Voice, August 1996

WHAT IS NEONATAL ISOERYTHROLYSIS (NI)?
Probably the best comparison is with the human condition erythroblastosis fetalis or Rh disease of newborn infants. What basically happens is that the dam develops an immunity against a blood group or blood type carried by her unborn foal. In horses, when the foal nurses its dam for the first time after birth, it receives the first milk or colostrum, which carries protective (passive) immunity or antibodies to help the foal maintain its health in its new environment which is laden with bacteria and viruses. The antibodies are formed by the dam’s immune system to fight against anything foreign or harmful to the body and are concentrated in the colostrum immediately prior to foaling. However, the colostrum can also carry antibodies against the foal’s blood type if its dam has been sensitized to that blood type. That means that the dam’s body has recognized a blood type different than her own, deems it foreign, and has made antibodies against it. If the foal ingests colostrum that contains antibodies against its blood type, it will absorb these antibodies into its blood stream. When this happens, the antibodies from the dam’s colostrum attach to the foal’s red blood cells and cause them to break apart. This is called cell lysis. The red blood cells of the foal are what carries oxygen to body, and as more and more red blood cells are destroyed, the foal grows weaker and eventually dies within the first forty-eight hours of life. Death is due to anemia and the resulting hypoxia (lack of oxygen). As the red blood cells are lysed, hemoglobin (which is the oxygen carrying component within the red blood cell) is released into the bloodstream. Hemoglobin is red to orange in color and causes the foal to appear jaundiced or orange colored as it seeps out of the blood vessels and into the tissues of the foal’s body. The most common areas of the body to observe jaundice are the gums and the whites of the eyes. In severe cases, the urine will also turn bright orange to blood red. Though some normal foals exhibit a very mild jaundice, any foal that becomes depressed and is obviously jaundiced, should be considered a potential case of NI. Emergency treatment by a veterinarian must be considered if the foal is to be saved, as they can die within a very few hours in severe cases.

HOW CAN MY FOAL SURVIVE IF IT HAS NI?
Once the veterinarian has determined a foal has NI, a blood transfusion can save it’s life, if administered in a timely manner. The best possible blood donor is the affected foal’s dam. The dam will not make antibodies against her own blood type, therefore when her blood is administered to the foal, the antibodies that her body made will not affect her blood, and the foal’s body will use her blood to carry oxygen insuring the foal’s survival. It is a gamble to use any blood donor other than the dam, as a blood donor of unknown type might possess the blood group that the antibodies have been formed against.
It might be pointed out that NI is probably more common than one might think because oftentimes, the death of a newborn foal is chalked up to some unknown congenital (inborn) abnormality and post-mortem examination by a veterinarian is not performed.

IS MY MARE AT RISK TO HAVE A FOAL AFFECTED WITH NI?
The probability of a mare having a foal affected with NI can be determined with great accuracy when the mare has been blood typed. The cause of NI is that the dam has produced antibodies against a certain blood group factor that is carried on the surface of red blood cells. That factor must be different from her own. These blood group factors are called red blood cell antigens and they are routinely tested for when a horse is blood typed. Two particular factors are responsible for more than ninety percent of the cases of NI. Those factors are Aa and Qa. (See figure 1 below). When the mare is negative for one or both of these factors, (see figure 2 below) she runs the risk of having a foal affected with NI, if that foal has inherited Aa and/or Qa from its sire. Other factors such as Ab, Pa, Dc, and Ua have also been reported to have caused a case of NI, however, only about one in two thousand mares will produce antibodies to factors other than Aa and Qa. Additionally, cases of NI due to antibodies to factors other than Aa and Qa oftentimes are not as severe. For example, in the case of antibodies against the blood group Ca, clinical NI is not seen and these antibodies can actually help protect against NI due to antibodies formed against another blood factor such as Aa. This is called antibody mediated immunosuppression. In this case, having a mare that is Ca negative is definitely a plus.

IF MY MARE IS AT RISK, HOW CAN I BE ASSURED THE FOAL WILL NOT BE AFFECTED WITH NI?
First, the mare has to be exposed to another horse’s blood red blood cell antigens to develop the antibodies that cause NI in the foal. This exposure occurs when the mare delivers her first foal and a small amount of the foal’s blood leaks into the mare’s bloodstream. Therefore, maiden mares are at very low risk for having a foal affected with NI. Any mare having had a blood or plasma transfusion is at risk, though, even if the transfusion was administered as a foal. Even plasma substituted for colostrum contains enough red blood cell antigens suspended in it to cause the recipient to develop antibodies.
Multiparous mares (mares having already foaled at least once) who are Aa and/or Qa negative are definitely at risk. With this in mind, there are three ways to assure the mare will not have a foal affected with NI. First, a stallion can be selected that is Aa and/or Qa negative to match the mare. With the lack of the same blood factors, any antibodies the mare might have produced as a result of a previous pregnancy will not affect the foal because the foal will not have inherited Aa and/or Qa from the sire. Of course even though this method is almost foolproof in preventing NI, it requires planning ahead, limits the choice of stallions, and requires knowledge of the potential sire and dam’s blood types.

In the alternative that the owner chooses to breed his “at risk” mare to an Aa and/or Qa positive stallion, there are tests available that will show if the mare is producing antibodies. If she is not producing antibodies against blood factors, then the foal can be allowed to nurse normally. To test a mare, a serum or colostrum sample is taken within a month of foaling. That is the time when antibodies are at maximum levels. The serum or colostrum sample is then sent to an equine blood typing laboratory where it is diluted (titered) and mixed with a panel of known blood typed horses. If the mare’s serum or colostrum lyses any of the known samples, then the laboratory recommends the foal be withheld from nursing the dam for a minimum of forty-eight hours and that colostrum from another mare be substituted. The mare should always be thoroughly stripped of antibody laden colostrum prior to allowing the foal to nurse after the forty-eight hour withdrawal. In one experimental case, a foal still became affected with NI after being withheld from its dam for forty-eight hours, so perhaps seventy-two hours is the safest withdrawal period. During this time the foal should remain muzzled when it is with its dam to prevent nursing.

Probably the most fail safe test for mares at risk that are bred to stallions with reactive blood factors is a method called crossmatching. If blood from the sire is available, it is mixed with the mare’s serum or colostrum instead of using a panel of known horses. If there is no cell lysis, it can be assured the foal can safely nurse. However, if lysis occurs, then the dam’s colostrum must be withheld or the foal must be crossmatched with its dam immediately after birth and prior to nursing to see if it has inherited an affected factor from its sire. Since time is of the essence, a test known as the jaundiced foal agglutination test (JFA) can be performed by most veterinarians with a minimal amount of time and equipment. The results of the JFA test are almost as accurate as a true crossmatch, so one should not hesitate to use this test if the need arises.

JUST HOW COMMON IS NI IN TENNESSEE WALKING HORSES?
Approximately 78% of Tennessee Walking Horses have the blood factor Aa. That means that 22% of the mares are at risk. Of that 22%, not every mare will develop antibodies during her broodmare career. However, if the loss of even one valuable foal can be prevented, then testing or selective breeding is justified.

Only 6% of Tennessee Walking Horses have the Qa blood factor. Therefore, 94% of the mares are at risk for developing anti-Qa antibodies. However, since only 6% of the stallions have the Qa factor, the risk of NI as a result of antibodies against Qa is minimal as most foals will not inherit Qa because of the low frequency in this breed.

CAN I TELL IF MY MARE IS AT RISK BY LOOKING AT MY BLOOD TYPING CARD?
An owner can determine if their mare has the blood factor Aa or Qa by simply looking at the mare’s blood typing card. The examples below illustrate examples of mares at risk and not at risk. For the mares at risk, corresponding stallions are shown as examples to aid in proper selection of a sire.

REFERENCES: Bailey, Ernest, et al; Neonatal Isoerythrolysis of Foals; An Update on Testing