Small Animal Neonatology: They Look Normal When They Are Born and Then They Die
Sadly, it is inevitable that some kittens will die, and a low level of loss is to be expected, even in the best run breeding cattery. It is generally found that pedigree cats have higher levels of neonatal mortality than non-pedigree. In one study, pedigree cats had an average kitten mortality of 34.5% from birth to one year of age (range of 8-40%), compared to 10-17% in non-pedigree cats. These higher levels of mortality may reflect inbreeding within pedigree cats. However, there may also be bias in the non-pedigree data as it is difficult to get accurate figures for pet cats.
Kitten deaths can be divided into those occurring in the pre-weaning period (stillbirths and deaths in the first 4 weeks of life), and those occurring in the post-weaning period (deaths occurring from weaning to ~6 months of age). Overall, pre-weaning mortality is commonly 15-30%, and stillbirths typically account for <10% of all kittens born; although, the prevalence can vary considerably; from 6-22% in pedigree cats.
Kitten mortality is highest in the first week of life (typically >90% of all kitten mortality), after which it declines, only to rises again just after weaning. Pre-weaning losses usually result from non-infectious causes while infectious causes are more prevalent post-weaning. This is because prior to weaning the kittens are relatively protected from infectious disease by maternally derived antibody (MDA) (see section on infectious disease for more information on MDA). Kittens dying between birth and weaning are frequently called 'fading kittens'.
Neonatal kittens may die suddenly, or present as 'poor doers' and 'fade' within a few days. Unfortunately, the clinical signs of many neonatal diseases are very similar and vague. While normal kittens tend to cuddle together and sleep contentedly between feeds, sick kittens tend to lie separately, are generally more restless, are not keen to suckle, and cry frequently (if still strong enough to do so).
Neonates are vulnerable because their thermoregulatory mechanisms are poorly developed, they are at increased risk of dehydration and hypoglycaemia, and they are immunologically immature. Therefore, regardless of the initiating cause, neonates rapidly become hypothermic, hypoglycaemic, dehydrated, hypoxic, and die. They are predisposed to hypothermia because they cannot thermoregulate, lack insulating fat and thermogenic brown, cannot induce peripheral vasoconstriction, cannot react to cold by shivering, and have a large surface area to volume ratio over which to loose body heat. Hypothermia then triggers ileus and reduced intestinal absorption, increases susceptibility to infection, and eventually leads to cardiopulmonary failure. Neonates are predisposed to hypoglycaemia because they have high energy requirements (2-3x the metabolic rate of adults/kg body weight), but have no energy reserves and their immature livers are inefficient at generating energy. This can then be exacerbated by hypothermia-induced reduction of intestinal absorption. The neonatal risk of dehydration is because they have a higher percentage of body water (82%) than adults, while incurring greater loses through their immature kidneys, lungs and skin.
Causes of 'fading' or sick kittens:
Birth / queen-related factors (kitten hypoxia, trauma, hypothermia)
Low birth weight
Inappropriate environment (temperature, humidity, hygiene, overcrowding, over-handling)
Neonatal isoerythrolysis (NI)
Infection (viral, bacterial, parasitic)
1. Birth / Queen-Related Factors
Kittens that suffer dystocia have a significantly increased risk of death within the first few weeks of life. In fact, prolonged labour or dystocia are probably the most significant causes of neonatal death. This results from the effects of hypoxia and/or trauma. Dystocia occurs in ~6% of pregnancies (range 0-18%). Studies have shown that cats with extremes of conformation, such as the Siamese and Persians, experience much higher levels of dystocia (7-10%; see FAB Manual) than cats with normal conformation (generally <5%). Hypoxia during birth can result in stillbirth, or the birth of weak, slow, kittens that fail to suckle. These kittens usually die within the first week of life or, due to failing to ingest sufficient colostrum, have an increased risk of infectious disease.
Kitten mortality is usually highest in the first litter born to a particular queen and after her fifth litter. The high death rates in kittens from first-time queens probably relates to inexperience, trauma and cannibalism. Older queens tend to have smaller litters and tend to produce more kittens with congenital defects. The negative effect of extremes of litter size is seen as reduced survival of single kittens, and of kittens from litters of 7 or more. Kitten mortality also increases with increasing maternal obesity, and with other queen-related causes, including a lack of milk, mastitis, or maternal neglect.
2. Congenital Abnormalities
Obvious physical defects may be seen in 10-20% of stillborn kittens. However, the prevalence varies considerably; from 1-10% of kittens born to research cats, to 1-31% of kittens born to pedigree cats. Congenital disorders are present from birth, and can affect any body system. They may result from genetic disorders (see refs.) or teratogenic factors. Because inbreeding increases the risk of genetic disease, congenital disorders are seen more frequently in pedigree cats. In addition, certain defects are seen more frequently in some breeds than others (see FAB Manual and refs.).
Congenital defects resulting from exposure to teratogenic substances may be seen in cats of any breed. For example, cleft palates may result from treatment with griseofulvin, corticosteroids, or excessive amounts of vitamin A; skeletal deformities may result from the administration of organophosphate anti-flea products. It has also been suggested that overheating, in some pregnant cats, may result in an increased risk of skeletal deformity in their kittens. Severe defects usually result in stillbirth or early neonatal death. Milder disorders may result in fading kittens, or only become apparent later in life.
3. Low Birth Weight
Underweight kittens have a significantly increased risk of neonatal death. They are physiologically immature compared to normal-weight kittens, and they may be too weak to nurse adequately. In addition, they lack insulating fat and thermogenic brown fat, and they have weak thoracic muscles and immature lung development. They are particularly susceptible to hypothermia, dehydration, respiratory failure, and sepsis.
Kittens may be born underweight because of maternal malnutrition or ill-health; congenital disease; in utero infections; or any condition that results in poor placental blood supply. The average birth weight for most breeds of cat is 100g ± 10g. However, it is normal for some breeds to have significantly smaller kittens (Oriental; ave. 80g); while others (Maine Coon) have significantly larger kittens (ave.120g) (see FAB Manual). It is therefore very important to know what the average weight for kittens of a particular breed is when trying to decide whether or not a particular kitten is underweight. As a general guideline newborn kittens <75g are likely to have very high death rates.
4. Inappropriate Environment
Environmental factors, such as extremes of temperature and humidity, poor hygiene, overcrowding, or over-handling, all result in increased kitten mortality. Ideally, the kittening room should be well ventilated, draft free, and maintained at a fairly constant 18-24°C, 55-60% humidity. This will allow the dam to be comfortable, and she can supply any additional heat required by the offspring. Where kittens have to be hand-reared it is necessary to supply additional heating. Ideally the temperature in the box should be maintained at 29-32°C, but the box should be large enough for the kittens to move away from the heat if they become too hot. The temperature is gradually reduced to 27°C by 7-10 days and 22°C by the end of the first month. Overcrowding will lead to increased infectious disease and disease resulting from competition at the mother's nipples (which can in turn result in inadequate nutrition [see below]). Over-handling will not only limit the kitten's feeding time, but with nervous queens, may result in cannibalism of her kittens.
Providing kittens with a suitable environmental temperature is essential. A kitten that has ceased to suckle regularly will quickly become cold and hypoglycaemic. Since neonates cannot shiver and are unable to control their own body temperature hypothermia will result, and this will lead to a further reduction in activity and suckling. The rectal temperature of new-born kittens ranges from 35-37°C in the first week, to 36-38°C in the second and third weeks, and reaches normal adult levels of 38-39°C by the fourth week.
Hypothermia is particularly harmful as it can initiate a number of other problems. For example: a week-old kitten should have a temperature of 35-37°C and a heart rate of 200-250 bpm. However, if its temperature falls to 30°C, its heart rate will fall to 40-50 bpm. While this is initially a protective response, if sustained, it can lead to a decrease in respiratory rate, which may in turn lead to cardiopulmonary failure. Also, a hypothermic kitten will not suckle effectively, its gastrointestinal motility will become depressed, and it will have an increased susceptibility to infection. It is therefore important to check the temperature of any potentially weak or ill kittens. However, if their rectal temperature is <34°C the kitten is likely to die.
5. Inappropriate Nutrition
Care should be taken to feed the queen an appropriate diet. Incorrect nutrition of the queen can affect the quality of the milk she produces. Generally, when the queen is healthy and producing adequate milk the kittens should have no problems with inappropriate nutrition. Inadequate milk production may be associated with an inexperienced or overly nervous queen, old queens, sick or malnourished queens, dystocia, certain familial traits, systemic illness or mastitis. Inadequate milk uptake by the kitten can also result from anything causing kitten ill-heath or weakness, from competition and bullying by siblings, or any environmental factor that distracts or upsets the queen-kitten bond.
Normal kittens should suckle within 2 hours of birth as they can only adsorb colostrum in the first 16-24 hours of life. Since any kitten not gaining sufficient weight has an increased risk of neonatal death it is important to weigh kittens regularly (at birth, daily for the first week, then at least twice weekly until after weaning). A loss of <10% may be expected in the first 24h, but after that there should be daily weight gain (~10-15g/day; 5-10%); they should double their birth weight by 1-2 weeks of age and weight gain should be steady and progressive. Any weight loss (or lack of weight gain) should be investigated, and any kittens losing more than 10% body weight are unlikely to survive.
It is essential that kittens gain adequate nutrition as they have a greater risk of developing hypoglycaemia than adults. This is because they are metabolically less able to generate glucose than adults, while having a much larger requirement for it. Any kitten that is ill or stressed may develop hypoglycaemia. This may be seen as weakness, hypothermia, crying, difficult breathing, seizures, coma and, eventually, death.
Neonatal kittens are also very susceptible to dehydration. This may result from inadequate consumption of milk, or excessive fluid losses (usually associated with overheating, excessively low humidity, or diarrhoea). Kittens contain relatively more body water than adults and their water turnover rate is twice that of adults. Neonatal kitten maintenance fluid requirements are ~130-220ml/kg/24h, compared to 50-65ml/kg/24h for a mature cat. This is because kittens have greater fluid losses through their skin, lungs and kidneys, which are all immature.
Since the kittens derive all of their food and water in the form of milk, when the supply is inadequate, supplemental feeding is needed. Where the kittens have been orphaned or the queen is unable to feed them they will need total replacement feeding (see FAB Manual). Weaning should begin at 3-4 weeks of age. It is important to ensure that all of the kittens gain sufficient food at this time. In large litters competition at the food bowl can lead to weaker kittens being bullied and so eat less.
6. Neonatal Isoerythrolysis (NI)
In certain cat breeds NI is a relatively common cause of fading kittens. It results from the immune-mediated destruction of a kitten's erythrocytes by its mother's antibodies. The maternal antibodies enter the kittens via the colostrum when the kittens first suckle. The kittens are born healthy. However, after suckling, affected kittens may die suddenly or stop feeding, become weak, and show haemoglobinuria (brown stained urine). These kittens may then develop jaundice, anaemia, tachypnoea, and tachycardia. In severe cases this leads to collapse and then death. Surviving kittens may develop necrosis of the tail-tip and other extremities, which may then slough between 3 days and 2 weeks of age.
Cats have 3 blood groups; Type A, B, and AB. Type A is genetically dominant to Type B. Genetically, a Type A cat may therefore be A/A or A/b. The rare blood type AB is inherited slightly differently, and is recessive to Type A but dominant to Type B. AB cats are only found in breeds in which the Type B has been identified, usually increasing in frequency as the percentage of Type B cats increases. The frequency of Type A, B and AB blood types varies between breeds (Table below), and also, to some extent, between countries. Generally, most domestic short and longhaired cats (DSH/DLH) are Type A (75-100% Type A; 0-25% Type B; 0-10% Type AB). Interestingly, the Bengal breed appears to have a particularly high number of AB cats, although actual prevalence data are not yet available.
Table. Breed prevalence of feline blood types.
100% Type A
~80% Type A
75-100% Type A
60% Type A
40% Type A
British Short Hair (BSH)
Norwegian Forest Cat
All Type B cats have high levels of naturally occurring antibody directed against Type A erythrocytes, while only a third of Type A cats have naturally occurring antibody directed against Type B erythrocytes (and the amounts of antibody are usually rather low). NI occurs when a Type B queen gives birth to a Type A kitten. When the kitten suckles colostrum the maternal anti-A antibodies enter the kitten's circulation and attack its erythrocytes, causing anaemia and jaundice. Since these antibodies occur naturally, the queen does not need to be sensitised by previous pregnancies or blood transfusions. Since the highest proportion of Type B cats are seen in BSH cats, NI is seen most frequently in this breed of cat.
Where NI is seen, all sexually active cats should be blood-typed to prevent further inappropriate mating. In addition, it is recommended that all BSH cats should be blood-typed prior to breeding. This can be done using a simple in-house test card (Rapid Vet-H, dms laboratories). It is important to ensure that Type B queens do not mate with Type A toms. Where an unknown mating has occurred, placental blood can be used to determine a kitten's blood type. If the queen's blood-type is known to be Type B, and a kitten is found to be a Type A, it can be prevented from suckling the queen, at least until it is >24h old. While this procedure will prevent the occurrence of NI, the lack of colostrum will leave the kitten at risk of infectious disease.
Kittens showing signs of NI, if <24h old, should be immediately removed from their mother to prevent further absorption of anti-A antibodies. In kittens, most colostral antibodies are absorbed by 12-24h of age. Once removed, the kittens can either be fostered to a Type-A queen, or fed milk replaced formula for 24 hours. After this time it is generally safe for them to be returned to their dam. If the anaemia is severe a blood transfusion will need to be performed (see separate notes). However, despite removing the kittens as soon as clinical signs are noted, most affected kittens that die within their first week of life.
In general, infections are involved in relatively few early neonatal deaths. However, they can result in significant mortality from 3-4 weeks of age onwards. Since neonatal kittens have immature immune systems, and gain <5% of their MDA transplacentally, they need to gain protection from infectious disease via transfer of MDA in the colostrum. The passive protection of the intestines by MDA continues for the entire duration of suckling as IgA antibodies resist gastric degradation and can bind potential pathogens in the gut lumen, preventing them from attaching to or penetrating the intestinal mucosa. The ability of neonates to absorb MDA begins to decline 6h after birth, and is no longer possible after ~48h. The majority of neonatal infections are caused by agents to which vaccines are not available; it is therefore important that neonates are born into the same environment as their dam has been living since she will then have raised antibodies against its resident infectious organisms. The protective effect of systemically absorbed MDA usually begins to wane from 3-4 weeks of age. The kittens' natural immunity is still developing at this time, and since most vaccine regimens do not start until ~8 weeks of age, this can leave a period of time when the kittens are particularly at risk from these infectious diseases.
A healthy kitten should be able to cope with a low level of infectious organisms within its environment. It will generally experience no more than occasional mild and brief clinical signs. However, if the kitten's immune system becomes suppressed serious disease or fatal infections may occur. Factors which may contribute to an inadequate immune response include inadequate colostrum intake, inadequate nutrition, low birth weight, peri-natal hypoxia, congenital disorders (especially of the immune system), previous trauma or infection, a low environmental temperature, or an unhygienic environment leading to a build up of contamination with infectious agents.
Respiratory and gastrointestinal infections are seen most frequently. (See FAB Manual, refs and separate lecture for the treatment of sick neonates).
The cat flu viruses (feline calicivirus [FCV] and feline herpes virus [FHV-1]) are perhaps the most commonly seen viral infections of kittens. While in healthy kittens infection may be mild and brief, weak kittens may develop more severe clinical signs or secondary bacterial infections. FHV-1 infection may also be associated with abortion.
Feline coronavirus infection (FCoV), like the cat flu viruses, is hard to eliminate from breeding catteries. When present infection may be associated with an increased incidence of reproduction failure, abortions and stillbirths. Affected kittens may show signs of diarrhoea, malaise, or 'fading', and occasional cases of more classical effusive feline infectious peritonitis (FIP).
Feline panleukopenia virus (FPV) is usually seen in catteries that fail to vaccinate properly. It is occasionally seen in kittens from vaccinated queens, possibly resulting from severe environmental contamination. Infection may result in abortions, stillbirths, fading kittens, diarrhoea, panleukopenia, septicaemia, cerebellar ataxia, and/or death.
Feline leukaemia virus (FeLV) has been almost eliminated from the pedigree breeding population in many countries. Neonatal disease caused by this infection is therefore seen mainly in rescue catteries. In this situation it may result in reproductive failure, abortions, stillbirths, fading kittens, a panleukopenia-like syndrome, septicaemia or death.
(In puppies canine herpes virus is a common cause of puppy loss, and can result in abortion, or neonatal death associated with abdominal distension and pain at <3weeks of age. Other common viral infections of puppies include canine distemper virus, canine parvovirus, canine coronavirus [which appears to be changing in significance], canine adenovirus-2, and parainfluenza).
Where infectious disease is suspected it is important to ensure that the queens' vaccination programme is up to date. Since kittens gain some protection from infectious disease in the form of MDA passed in the colostrum, it may help to give booster vaccines prior to mating. In some cases it may be appropriate to instigate an isolation breeding and early weaning programme (see FAB Manual).
In kittens, bacterial infections are often seen secondary to viral infection (cat flu, FeLV, FIV, FPV, FIP). However, bacterial infections can also be seen without prior viral infection. In most cases the bacteria originate from the queen's birth canal (beta haemolytic Streptococcus sp. [Strep. G infection]), gastrointestinal tract (E. coli, Salmonella sp., Campylobacter sp., many normal enteric bacteria), or respiratory tract (Bordetella sp., Pasturella sp., Mycoplasma sp.). Clinical signs depend on the site, nature, and severity of the infection. They may include diarrhoea, coughing, dyspnoea, polyarthritis, omphalophlebitis, or dermatitis, as well as the less specific signs more typical of fading kittens.
Ultimately, many of these infections may result in septicaemia and death. The increased risk of sepsis in neonates results from the factors listed above, especially failure of passive transfer of MDA. In addition, neonatal propensity to develop hypoglycaemia and intestinal ileus (especially when cold), significantly increases the risk of translocation of enteric bacteria into the blood stream. This is exacerbated by sepsis further predisposing to hypothermia and hypoglycaemia (possibly resulting from impaired liver function, depletion of glycogen, and peripheral utilisation of glucose by bacteria and leucocytes). Disease may be very sudden or may run a more protracted course. While the clinical signs are varied, they frequently result in bradycardia, dyspnoea, dehydration, weakness, crying, seizures, coma and death. Sepsis often occurs as the final stage of other conditions, and is particularly associated with systemic viral infections. The most common cause of sepsis are gram-negative bacteria, but can include; Streptococcus, E. coli, Staphylococcus, Klebsiella, Enterobacter, Enterococcus, Pseudomonas, Clostridium, Bacteroides, Fusobacterium, Pasteurella and Salmonella.
In well-run catteries parasite infestation should not be a problem. Where queens are not wormed, heavy kitten infestations can result in a poor body condition, soft or bloody stools, lack of appetite, a pot-bellied appearance, weight loss, and occasionally death. A severe flea, tick or hookworm infestation can result in significant anaemia. Gut parasites, such as Giardia, Tritrichomonas foetus, Isospora or Cryptosporidia may cause diarrhoea and a failure to thrive. Toxoplasma infection may result in abortion, stillbirths and fading kittens.
Where specific infections keep recurring it may be necessary to try to detect carrier animals. However, since a number of infections can cross between species, affecting both cats and dogs, and even humans, it may be necessary to look for carriers amongst pet dogs, or even the owners. This is true for many of the bacterial and protozoal gut infections (e.g., Salmonella, Campylobacter, Giardia and Cryptosporidia), and can also occur with Bordetella bronchiseptica (which is one of the causes of 'Kennel Cough').
Table. Infectious agents which may cause disease in kittens.
Feline herpes virus (FHV)
(Also called feline rhinotracheitis virus)
Feline calicivirus (FCV)
Chlamydophila felis (formerly Chlamydia psittaci)
Feline coronavirus (FCoV)
Feline panleukopenia virus (FPV)
Bacterial sepsis (Streptococcus sp., E. coli, Salmonella sp. etc.)
Feline leukaemia virus (FeLV)
Feline immunodeficiency virus (FIV)
Staphylococcus and Streptococcus sp
(bacterial omphalitis, polyarthritis)
General Approach to Unraveling Causes of Kitten Mortality
Trying to find out what may be causing kittens to 'fade' can be very difficult. Firstly, it is hard to decide exactly when there is a significant level of neonatal mortality. Secondly, most cases are multifactorial, so a number of factors may need to be addressed in order to reduce mortality. Thirdly, clinical signs are generally non-specific and the small size of kittens makes collection of samples difficult. Generally, concern should be raised when pre-weaning losses exceed 20%, post-weaning losses exceed 10%, the number of losses suddenly increases, or a particular cause of death is seen more frequently than previously.
It is strongly advised that cattery owner's should keep detailed records of all animals within their premises; including details of matings, litter sizes and birth weights. All incidents of disease should be noted. It is by noting changes in the morbidity and mortality patterns that problems can be recognised early. Using this data it may be possible to track the spread of infectious disease or determine the breed-line of a genetic disorder.
Since there are usually no particular clinical signs that suggest a specific disease, investigation usually involves looking at the entire cattery. In most cases some aspect of the environment is not ideal, or aspects of the management and/or nutrition are unsound. A full investigation is often needed before any recommendations can be made. The investigator will need a background history of the cattery and want to examine all sick animals; looking for obvious signs of trauma, congenital defects or disease. Because it is difficult to collect blood samples from young kittens the most useful samples are often collected after a kitten has died. For this reason it can be very useful to have post mortem examinations performed on any kittens that die. The breeding queens, particularly the mothers of any fading kittens, should also be examined. Ideally, they should be observed interacting with the rest of the litter, then examined for signs of general ill health, metritis, mastitis, or aggression towards the kittens.
In order to determine if environmental factors are involved, the investigator may need to visit the cattery. They may want to look at the design and construction of the premises, consider the source of new stock, the genetic relationships between the cats, the total number of cats (and other animals) within the household, the size of any subgroups, and the day-to-day cleaning protocols. They may also want to discuss any recent changes in the management of the cats (feeding, vaccination, worming, flea treatment, use of isolation facilities, etc).
It is useful to remember that a single design defect or a particular bad practice rarely causes an outbreak of disease. More typically, disease outbreaks result from an 'event cascade', where a number of different confounding factors come into play.
(See separate lecture for specific treatment options for sick neonates. Techniques for Neonatal Resuscitation and Critical Care)
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