Joni L. Freshman, DVM, MS, DACVIM
Chances are that you have been presented with puppies or kittens that have failed to thrive, some of which have eventually died.
Chances are that you have been presented with puppies or kittens that have failed to thrive, some of which have eventually died. The causes of neonatal illness, commonly referred to as fading puppy and kitten syndrome, are many. Overall neonatal mortality in puppies varies from 12% to 36% in both closed breeding colonies and in breeders' homes, while in kittens in purebred catteries it is 15% to 27%.1,2
Various maternal and litter factors affect mortality in neonates. For example, in laboratory beagle breeding colonies, as a bitch ages the neonatal mortality rate of her offspring increases.3 And in queens in a large domestic shorthaired breeding colony, the smallest neonatal loss was at the fifth parity, with the greatest loss at the seventh parity.4 While other factors likely play a role, the dam's age is an important element in neonatal mortality, although the precise reasons for this have not been defined.
Causes of fading puppy and kitten syndrome can be divided into three groups: environmental, genetic, and infectious.
Environmental causes include factors affecting the dam as well as those due to poor mothering.
Hypothermia is a primary or contributing cause of many neonatal deaths. In their first week of life, puppies and kittens are essentially poikilothermic (their body temperatures vary with environmental temperature). The ability to shiver develops after Day 6. In the first week of life, normal body temperature in neonates is 95 to 98 F (35 to 36.7 C).5 In the second and third week, normal body temperature rises to 97 to 100 F (36.1 to 37.8 C), and by the fourth week neonate body temperatures are the same as those in adults.6 Hypothermia results in a decreased heart rate and circulatory collapse. In addition, hypothermic neonates do not nurse, are unable to digest food, and develop ileus. Hypothermia quickly results in a deterioration of cardiovascular, respiratory, and gastrointestinal function, which can rapidly cause death.7
In hot climates or with inappropriate supplemental heat, hyperthermia can occur. While hyperthermia is less common than hypothermia, a body temperature higher than normal for the neonate's age should alert you to this possibility. Neonates in the first week of life can pant in response to overheating and may cry relentlessly.
Maternal factors can affect neonatal survival. Overweight queens have increased neonatal mortality compared with normal-weight queens.4 Maternal obesity is also a contributing factor to neonatal loss in bitches.8
In bitches, the dam's age has a significant effect on neonatal mortality. Beagle colony bitches from puberty to 4 years of age had a neonatal mortality rate of 18.5%.3 This rate increased to 38.9% in bitches at 7 years of age and to 79.3% at 9 years of age.3
Maternal neglect is another common environmental cause of fading puppy and kitten syndrome. Primigravida dams and dams that deliver by caesarean section are at increased risk for poor mothering. In one study, bitches with normal vaginal delivery had a 2.2% neonatal mortality rate at birth and an 8% mortality rate at Day 1, while bitches that delivered by caesarean section had an 8% neonatal mortality rate at birth and a 13% neonatal mortality rate two hours postpartum.2 While causes for this difference were not delineated in this study, possibilities include the effect of anesthetic drugs on pups, postoperative pain in the dam, and inadequate mothering due to lack of exposure to dog attachment pheromone in the amniotic fluid.
In my clinical experience, mothering ability has a genetic aspect, so breeding bitches and queens should be selected with this in mind. Clinical reports indicate that poor mothering may sometimes be associated with hypocalcemia.9,10 Maternal neglect can be exhibited by a dam's reluctance to lie with and warm the neonates, refusal to permit nursing, or lack of sufficient milk production or letdown. Large-breed or barrel-bodied bitches may also step on or clumsily crush puppies. Trauma is a common cause of neonatal death during the first week of life—16.7% in one study.5 Queens may exhibit cannibalism, especially inexperienced dams or dams in a stressful or crowded environment.
Environmental toxins can cause fading puppy and kitten syndrome. Bedding materials and products used to clean the whelping or queening box should be evaluated for safety in neonates. Neonatal skin is thin, and chemicals can be more readily absorbed transcutaneously in a neonate than in an adult.11 Respiratory tract exposure to chemicals can also be a concern. Avoid pine oils and phenols as well as direct contact with bleach or quaternary ammonium residue.12 Use gentle cleaners with little odor, and remove all residue before contact with the neonates.
Detailed pedigree analysis, including the coefficient of inbreeding (COI), can often lend insight into the cause of neonatal losses. Deleterious homozygous genes can result not only in decreased litter size because of early embryonic loss but also in increased neonatal mortality. In research colonies of purebred dogs, litters with a low COI (0 to 0.25) had a 10-day mortality rate of 26.5%.13 Highly inbred litters, with a COI of 0.734 to 0.785, had a 10-day mortality rate of 73%.13 Breeding of siblings or continued line breeding results in increased mortality rates when the COI is greater than 0.375.13 Pedigree software programs to determine the COI are readily available with databases for a variety of breeds.*
Gross abnormalities can be found in many ill or deceased neonates. Cleft palates and lips, atresia ani, portosystemic shunts, open fontanelles, and cardiovascular abnormalities are relatively common. In one study, 20% of kittens that were stillborn or died within three days of birth had gross anatomical abnormalities.4 Inborn errors of metabolism are likely even more common but are difficult to diagnose. Swimmer (flat) puppies and kittens can be identified by dorsoventral flattening and lateral widening of the thorax. The cause is unknown but probably relates to both genetic and environmental factors. Pectus excavatum is a more severe deformity resulting from intrusion of the sternum into the thoracic cavity.
Thymic dysfunction and atrophy can result in a fatal wasting syndrome in neonates.14 The critical period for this appears to be 3 to 6 weeks of age, as experimental removal of the thymus during this time is fatal.14 Thymic atrophy can result from stress, corticosteroid administration, toxins, malnutrition, viral diseases, and zinc deficiency.14 Evaluating the thymus is an important part of necropsy in any deceased neonate.
Low birth weight is an important risk factor for neonatal mortality.1,15,16 Kittens have a normal birth weight of 100 ± 10 g (3.5 ± 0.35 oz). Kittens with a birth weight of less than 90 g (3.2 oz) have poor survival rates.15 In one study, 59% of kittens that were stillborn or had early neonatal deaths had low birth weights.1
While puppy birth weight varies with breed, there are estimates for a variety of breed sizes. Pomeranian birth weights average 120 g (4.2 oz), beagles 250 g (8.8 oz), greyhounds 490 g (17.3 oz), and Great Danes 625 g (22 oz).17 Average birth weights may vary within breeds according to family lines; breeders often have records helpful for comparison and assessment.
Pups and kittens may lose a small amount of weight (< 10%) during the first 24 hours of life, but after that, weight gain should be steady. Pups should gain 5% to 10% of their birth weight daily, while kittens should gain 7 to 10 g (0.25 to 0.35 oz) a day.18,19 Failure to gain is a clear early sign of potential problems in a neonate and should be addressed immediately.
Transient juvenile hypoglycemia syndrome is associated with low weight, particularly in toy-breed dogs.7 Because of limited glycogen stores, poor gluconeogenesis, and high metabolic rates, failure to maintain frequent feedings can result in hypoglycemia. This can occur for several weeks to months in toy breeds and often arises when the pups are transferred to a new home where feeding schedules are not rigidly followed.20
Because of endotheliochorial placentation, almost no placental transfer of antibodies occurs in bitches or queens. Essentially all passive antibody transfer occurs through absorption of colostrum in the first 12 to 24 hours postpartum.21,22 In cats, this also presents the risk of early death due to neonatal alloimmune hemolytic anemia. Cats have two main blood types, A and B, with a rare occurrence of AB. In North America, most domestic shorthaired cats are type A, with only 1.7% to 4.7% exhibiting type B.1 Various purebred cats have a higher prevalence (19% to 59%) of blood type B (Table 1).1,7
Table 1. Prevalence of Blood Type B in Selected North American Cat Breeds*
Heterozygous type B queens bred to type A toms can produce type A kittens. Since all type B cats have circulating anti-A antibodies, ingestion of colostrum by these kittens will result in acute alloimmune hemolytic anemia and severe illness or death. Clinical signs and laboratory findings include failure to thrive, dark-red-brown urine, and anemia; acute death also occurs.1
Bacteria, viruses, and intestinal parasites can all cause or contribute to fading puppy or kitten syndrome (Table 2).
Table 2. Infectious Causes of Fading Puppy and Kitten Syndrome*
Neonatal septicemia results from systemic bacterial infection. Because of their immature immune systems, puppies and kittens are at risk for infection through the placenta, umbilicus, or gastrointestinal or respiratory tract from contaminated environments. Dams with postpartum metritis or other bacterial infections may act as a source.18 Gram-negative organisms are most commonly isolated, but Streptococcus and Staphylococcus species can be involved, particularly in kittens.18,23 Group B streptococcus has been identified as a cause of death in neonatal puppies.24 Brucella canis can cause neonatal puppy death as well as fetal loss. Clinical signs of sepsis vary but include vomiting, diarrhea, constant crying, fever, failure to nurse, and sloughing of the ear and tail tips and toes. Hypoglycemia often occurs with septicemia.18,25
Viral infections are a common infectious cause of neonatal losses in dogs and cats.1,4
In puppies, canine herpesvirus infection is a frequent cause of neonatal morbidity and mortality.26 Herpesvirus is a mild endemic respiratory virus in adult dogs, but it causes abortion and early neonatal death when contracted by a bitch during the last three weeks of gestation and neonatal illness and death when pups are exposed in the birth canal or during the first three weeks of life.23 Clinical signs include constant crying and abdominal pain; acute death also occurs. Necropsy reveals petechiation of the kidneys, liver, and intestines, and infection is confirmed with virus isolation.27 Nested polymerase chain reaction testing has also been used to document canine herpesvirus infection and is available from a number of sources.28**
A canine herpesvirus vaccine is available in Europe but not in the United States. In a challenge study with six vaccinated and six control bitches, the vaccinated bitches developed high titers to canine herpesvirus, lost no pups to canine herpesvirus infection, and had higher pregnancy rates and lower neonatal mortality than did control bitches.29 Control bitches lost 62% of pups to canine herpesvirus infection.29
Infection with canine parvovirus type 1, also known as minute canine virus, presents a similar picture, with rapid onset of crying, failure to nurse, vomiting, diarrhea, dyspnea, weakness, and sudden death at 5 to 21 days of age.30 Diagnosis depends on isolating the virus, which must be done with a particular cultured cell line that may not be available at all laboratories.***
While less common because of vaccination programs, canine parvovirus type 2 infection, canine distemper, and infectious canine hepatitis are all capable of causing neonatal illness and death in puppies.4 As routine vaccinations perhaps become less common, these diseases should be kept in mind and considered as differential diagnoses at necropsy.
Kittens are susceptible to a multitude of viruses (Table 2) that can cause neonatal illness and death. Feline herpesvirus type I and calicivirus are most common.1 These infections may be transient, but failure to control hypoglycemia and hypothermia or secondary bacterial infection can result in rapid decline. Feline leukemia virus, transmitted by the dam or other in-contact cats, results in thymic atrophy and slow wasting of kittens.1 Coronavirus infections are also common in ill kittens, causing diarrhea and feline infectious peritonitis. Panleukopenia, while uncommon because of vaccination programs, can also result in kitten deaths. The most common time frame for viral infections in kittens is from 3 to 4 weeks of age, but kittens can be affected in their first week of life.1
Intestinal parasitism is a frequent complicating factor in fading puppy and kitten syndrome. Because roundworms and hookworms are transmitted transplacentally, most pups are born with these parasites.31,32 Roundworm larvae are also transmitted in the milk during nursing in both kittens and puppies. Marked illness can occur before the patent period. In pups, the pulmonary migration phase of the larvae shortly after birth may prove fatal. Hookworm larvae are also transmitted transplacentally and through the dam's milk in kittens and puppies.31,32 Marked infestation can result in deterioration and fatal anemia at as early as 2 to 3 weeks of age.1,23 Death can occur before a patent infection develops, so do not rely on fecal examination for diagnosis.23
Protozoan parasites, primarily Giardia species, Coccidia species, and, in kittens, Tritrichomonas foetus, are major causes of diarrhea in the young. While rarely fatal, they can contribute to illness and can put a neonate at higher risk of additional infection. Toxoplasma gondii infection is an uncommon cause of illness in kittens, resulting in fever, neurologic and respiratory signs, and death in three to 12 days.18
Clearly, the causes of fading puppy and kitten syndrome are many. In clinical cases, multiple factors often play a role, so a complete evaluation and thorough support of the neonate are important in determining a cause and in effecting a successful outcome. Evaluating and treating affected neonates are covered in the next two symposium articles.
Joni L. Freshman, DVM, MS, DACVIM
3060 Woodview Court
Colorado Springs, CO 80918
*Breeders Assitant-Tenset Technologies, Cambridge, UK, www.tenset.co.uk; WinCanis Pedigree-Willowind, www.geocities.com/willowind_dals/pedigree; BreedMate-Wild Systems P/L, New South Wales, Australia, www.breedmate.com.
**The veterinary diagnostic laboratories at Colorado State University, University of California-Davis, and University of Florida-Gainesville.
***Canine parvovirus isolation is available at the Animal Health Diagnostic Center, College of Veterinary Medicine, Cornell University.
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