Failure of Passive Transfer in Horses

Infectious disease is a major cause of death in neonatal foals. The foal is born immunocompetent, meaning it probably is able to initiate an immune response to organisms to which it is exposed. However, a newborn foal lacks protective immunoglobulins at birth, and that lack of protection can allow organisms to overwhelm the foal before it can mount a suitable defense. The most important host defense in the newborn horse is the passive transfer of antibodies in the form of immunoglobulins from the mare to the neonate through colostrum.

Mare and Foal

Approximately 25 percent of newborn foals will experience some level of failure of passive transfer. Barbara D. Livingston Photo

Unlike humans, in horses there is no natural transfer of antibodies through the mother's placenta. It therefore is necessary for the newborn foal to obtain antibodies through the mother's milk shortly after birth. The early milk (colostrum) is rich in immunoglobulins provided by the mother. The ingestion of colostrum by the newborn allows for passive transfer of immunoglobulins, which provide almost immediate immunity to the foal. Foals which do not receive these antibodies are at high risk and are diagnosed as having a condition known as failure of passive transfer (FPT). Approximately 25% of newborn foals will experience some level of FPT.

Under normal conditions, the foal receives sufficient colostrum in the first 12 hours after birth to provide adequate protection against the "bad bugs" in his environment.

The immunoglobulins circulating in the mare's serum--essentially all of which are immunoglobulin G (IgG)--are concentrated in the colostrum. The mare generally starts producing colostrum in the last two weeks of her pregnancy. A foal will suckle shortly after birth, and during its first few meals will receive colostrum containing large quantities of IgG. The newborn foal has specialized cells in its intestinal tract at birth that are capable of readily absorbing the large molecules of IgG. This absorptive capacity, however, is short-lived and generally is gone when the foal is 24 hours of age. This "closure" of the gut is the result of natural shedding of those cells and replacement with more mature cells. If sufficient colostrum is ingested, the immunoglobulin levels in the foal's blood will rise rapidly.

In certain situations, the foal does not obtain sufficient immunoglobulin to increase the blood level to "protective" levels, and this foal is diagnosed as suffering from FPT. A variety of situations can contribute to FPT. These include the following: 1) The mare's inability to produce colostrum or the production of low quantities of antibodies in the colostrum; 2) loss of colostrum prior to parturition through premature lactation; 3) maternal infection; 4) neglect or rejection of the foal by the mare; 5) death of the mare; 6) premature birth; 7) inability of the foal to ingest the colostrum; 8) inability of the foal to absorb IgG; and/or 9) effects of toxic substances such as is seen with fescue toxicosis.

The failure of passive transfer does not produce clinical signs in the foal in and of itself. Frequently, the signs of FPT will be demonstrated in the foal's health in the first few weeks of life. Signs that suggest FPT are the onset of bacterial infection, arthritis, pneumonia, and enteritis.

Due to the delay in determining a systemic problem, an attempt to diagnose FPT is done by checking serum IgG in the foal within 24 hours after birth and during the first few weeks after birth. There are several immunoglobulin assays available. The two most convenient for field use are the CITE test and Zinc Turbidity IgG Quantitative Analysis. The CITE test provides an estimate of the milligrams (mg) of IgG present per deciliter (dl) of blood. The consensus is that low or no circulating levels of IgG indicate partial failure or failure of passive transfer.

There have been no prospective studies done that demonstrate what quantitative blood level of IgG can assure protection against neonatal foal diseases. Many studies have been carried out to pinpoint a value of IgG above which adequate passive transfer can be assumed. A variety of levels has been proposed as cutoff points, and these are being used today as reasonable guidelines.

It is generally accepted that blood levels below 200 mg of IgG per deciliter constitute a complete failure of passive transfer. Foals having 200-400 mg/dl are considered to be in partial failure of passive transfer. Adequate levels of IgG range from 400-800 mg/dl. A level of 400 mg/dl is usually adequate for a foal which has had a normal birth, is generally in good health, and is kept in a relatively clean environment.

It should be noted that a sick foal might have an IgG level that is not reflective of the foal's IgG prior to onset of disease. A dehydrated foal might have a high concentration of IgG, yet the level might be inadequate for protection. On the other hand, a foal might have an antigen burden of infection that will markedly lower the IgG level, yet this foal might be coping well. It is therefore important that the practitioner determine the range of IgG for the circumstances under which he/she observes the foal and provide treatment accordingly.

Treatment Options

The treatment of FPT depends on a number of conditions, including conditions surrounding the birth, IgG level, age of the foal, the environment to which the foal is exposed, and the presence of secondary infection. Treatment is focused toward supplying immunoglobulins and managing infections that might exist. Treatment should begin immediately if FPT can be anticipated early after birth due to premature birth, lactation problems of the mare, lack of nursing, mares which have grazed on fescue grass, a weak or orphaned foal, general concern due to the history of previous foals from the same mare, or general medical issues such as infection or birth abnormalities. Prophylactic treatment with IgG might be beneficial in stopping an infection at the outset.

Administration of two to three liters of colostrum in the first six to 12 hours after birth is desirable. Colostrum, however, is not generally available, thus a supplement supplying adequate IgG is important. Sufficient IgG must be administered to raise the blood levels within the first 24 hours, prior to gut closure.

A purified, freeze-dried immunoglobulin recently has been brought to market that can be used orally and intravenously. The product, called Lyphomune, is the only purified product available and is appropriate for use in these cases. Plasma has been used as an oral treatment, but requires relatively large volumes to provide sufficient IgG levels in the blood. Another product on the market is a form of concentrated serum called Seramune.

Each dose of Lyphomune will consistently provide 10 grams of IgG, and in recent clinical trials was shown to raise the foal's circulating IgG to much the same efficacy levels as colostrum. It is important to give the foal supplemental oral IgG within the first few hours of life, preferably before 12 hours have elapsed. The earlier you provide IgG, the greater the absorption rate.

It takes approximately 50-70 grams of IgG orally, either in colostrum or purified IgG, to raise a foal from no detectable IgG in its blood to a level of 400-800 mg/dl or approximately 1.2-1.6 grams per kilogram of body weight. Smaller amounts might be sufficient if the foal already has some level of IgG.

After a foal is 12 hours old, alternate treatment for FPT should be considered. In recent studies, it was demonstrated that foals were able to absorb significant amounts of IgG given orally after 24 hours (although the 12-hour mark is the best target and the most widely accepted). If IgG levels are below 400mg/dl after 24 hours, intravenous therapy should be considered. Some animals below this cutoff can do well without supplemental therapy, but they should be carefully monitored.

Plasma transfusion has been the classic treatment for foals with FPT discovered after gut closure. Care must be taken to check the plasma prior to administration for anti-erythrocyte antibodies and to make sure it is free of bacterial contamination. Twenty milliliters of plasma per kilogram of body weight administered to a foal intravenously has been shown to raise IgG levels into the minimum "protective" range of 400-800 mg/dl. In a neonatal foal of 45 kg, two to four liters of plasma might be needed.

Purified IgG (Lyphomune) can be used for intravenous treatment and is commercially provided with a transfusion setup. Approximately 10 grams of this product, dissolved in 400 milliliters of 5% dextrose per 20 kilograms of body weight, is required to raise the blood level to 400 mg/dl. Therefore, two to four 10-gram doses with a total volume of 0.8-1.6 liters will raise levels to the protective range of 400-800 mg/dl. This product is certified free of anti-erythrocyte antibodies and bacterial contamination.

Transfusion with plasma occasionally will induce mild reactions, usually consisting of trembling and hyperventilation. Milder reactions occur with the purified IgG product. If transfusion is stopped for ten minutes and resumed at a slow rate, treatment can continue and be completed. Levels of IgG should be checked after treatment to determine if the desired protective levels have been reached. A period of time should be allowed prior to this test for tissue distribution of the IgG. Clinical trials have shown that IgG levels peak three or four hours after treatment, whether orally or intravenously, then gradually decline.

FPT is a treatable condition. The appropriate treatment course for FPT is dependent upon the time it is discovered after foaling. Conditions of the mare and those surrounding the foaling are important considerations in determining treatment. Prophylactic treatment is safe and easy, allowing a level of comfort if close monitoring and appropriate emergency treatment are not readily available. Colostrum, plasma, and purified IgG are suitable treatment for FPT. In each case, it is important that the IgG level of the product is known. Colostrum generally has a highly concentrated IgG level, but colostrum is variable, and some colostrum might have insufficient levels of IgG to properly boost the foal's circulating IgG levels.

Although colostrum is the source of choice for IgG, it must be given orally and preferably within 12 hours after birth. Plasma has varying amounts of IgG and, depending on the source, the difference might be considerable. Commercially prepared plasma will have more consistent IgG content than that collected randomly. Plasma can be given either orally or intravenously, but the quantity needed for oral treatment might exceed the foal's physical capacity. The purified product Lyphomune has consistent batch-to-batch levels of IgG and provides 8-10 grams of IgG per 10-gram dose. The purified IgG also can be given orally or intravenously at volumes much lower than plasma.

About the Author

E.L. Squires, MS, PhD

Edward Squires, BS, MS, PhD, is a professor at University of Kentucky and the Director of Industry Relations for The Gluck Equine Research Center. Squires authored Understanding The Stallion, published by Eclipse Press and available at or by calling 800/582-5604.

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