Etiology

True fading puppy syndrome

• Pups usually have:
  • No macroscopic lesions (except often a small liver without obvious morphological lesions).
  • No identifiable congenital defects.
  • No histological lesions.
  • Absence of contents within stomach and small intestine.
  • Some have evidence of aspiration of amniotic fluid during parturition.
• True fading puppies have significantly lower phosphatidylcholine components of lung surfactant than pups that died from known causes.
• Lung surfactant required for normal respiratory adaptation and maintenance following birth.
• In normal animal, increased respiratory effort tends to stimulate surfactant production and it may be that pups with true fading puppy syndrome are born marginally hypoxic, do not breathe deeply and therefore enter a fatal cycle of low surfactant → hypoxia → failure to thrive → failure to suck → hypothermia → ultimately death.
• May also be impacted by subclinical dystocia Dystocia.

Known causes of neonatal mortality

• Etiology can include:
  • Poor husbandry.
  • Maternal factors (including illness, poor nutrition etc which usually result in low birth weight pups).
  • Congenital defects.
  • Problems at parturition (usually dystocia resulting in anoxia or hypoxia).
  • Poor mothering behaviour.
  • Trauma.
  • Immune insufficiency.
  • Infection with viruses, bacteria or parasites.
• Infectious causes account for up to 20% of all cases depending upon country.
• Some infectious agents are specific pathogens, whilst others are opportunistic organisms which colonize a compromised neonate.
  • Specific agents include:
    • Canine herpes virus Canine herpesvirus.
    • Canine parvovirus Canine parvovirus.
    • Canine distemper virus Canine distemper disease.
    • Some protozoal diseases.
  • Exposure of an immunologically naive bitch to canine herpes virus Canine herpesvirus during late pregnancy can result in abortion or neonatal death, usually 7 to 21 days after birth. Earlier demise of the pups does not normally occur and on this ground alone herpes virus infection can be differentiated from true fading puppy syndrome.
  • Canine parvovirus type-1 Parvovirus disease associated with CPV-1 may cross placenta if bitch exposed in early pregnancy. Results in resorption or acute neonatal death 7 - 21 days after parturition, although rare.
  • Infection with canine parvovirus type-2 Parvovirus disease associated with CPV-2 may cause myocarditis Heart: myocarditis in neonates, although now very uncommon.
  • Congenital infection with canine distemper virus Canine distemper disease rarely seen.
• Number of bacteria have been isolated from dead pups with:
  • Peritonitis Peritonitis.
  • Pneumonia Lung: bacterial pneumonia.
  • Pleuritis Pleuritis.
  • Enteritis.
• Bacteria include:
  • Beta-hemolytic streptococci Streptococcus spp.
  • Staphylococci Staphylococcus spp.
  • Pasteurella spp Pasteurella multocida.
  • E coli Escherichia coli.
  • Campylobacter spp Campylobacter jejuni.
  • Salmonella spp Salmonella spp.
  • More rarely ureoplasmas and mycoplasmas Mycoplasmas and ureaplasmas.
• Most are part of commensal flora of genital tract and only cause disease when neonate is additionally challenged. Inherent vulnerability of neonate puts it at risk for colonization by these organisms.
• Transplacental infection with Toxoplasma gondii Toxoplasma gondii is uncommon although experimental infection may result in neonatal death.
• Incidence of natural transplacental transmission of Neospora caninum Neospora caninum is unknown; experimental infection results in stillbirth with evidence of myocarditis Heart: myocarditis.
• Toxocara canis Toxocara canis infection usually causes disease in pups over 2 weeks when worms are large and cause gastrointestinal obstruction or migrate up biliary tract and cause hepatitis. Migrating larvae in prepatent period can also cause disease.

Consequences of neonatal illness

• Whatever initial challenge, inherent susceptibility of newborn results in ultimate demise.
• Neonates have poor mechanisms of thermoregulation, are unable to shiver and have poor reserves of brown adipose tissue; therefore susceptible to hypothermia Hypothermia.
• Puppies are susceptible to dehydration and have immature liver enzyme systems and an immature ability to regulate glucose (relying almost entirely on hepatic glycogen reserves over first 24 hours). Prolonged parturition or a prolonged interval to feeding means that reserves may be exhausted; hypoglycemia Hypoglycemia may complicate hypothermia. When there is a neonatal challenge, common for pup to enter a fatal cycle hypoxia → failure to thrive → failure to suck → dehydration → hypothermia → ultimately death.

Predisposing factors

General

• Predisposing factors include:
  • Subclinical dystocia Dystocia.
  • Persistent hypoxia due to delay in removal of fetal membranes or fluid by dam.
  • Persistence of hypothermia associated with delay in drying neonate or a cold or draughty environment.
  • Poor mothering behaviour by inexperienced bitch may be primary cause of both hypoxia and hypothermia.
• Inadequate intake of fluid is a significant problem, not only because of requirement to absorb colostrum, but since adequate fluid maintenance is important for recovery from acidosis Acid base imbalance. Neonates have high percentage of fluid within extracellular space and relatively poor renal function. When combined with ability to lose fluid because of high surface area: body ratio and undeveloped urine concentrating ability, results in increased susceptibility to changes in fluid balance compared to adults.
• Neonates have incompletely developed immune system until at least 10 days after birth and are therefore susceptible to bacterial and viral infection. 80% antibodies must be absorbed across intestine 24-48 hours after birth. Failure to consume sufficient colostrum during time when intestinal wall is open to absorption of protein will seriously compromise neonate.
• Neonates have limited fat reserves and poor ability to generate energy from precursors. Glycogen reserves are depleted shortly after birth, leaving neonate requiring early intake of energy. Short period of time without food can result in significant hypoglycemia Hypoglycemia , particularly in neonates that have been hypoxic or hypothermic.

Pathophysiology

• Whilst initial cause may differ, namely unknown etiology (possibly due to inadequate production of surfactant for true fading puppy syndrome) or a known etiology, ultimate issue is:
  • Dehydration and hypoxia.
  • Resultant failure to thrive.
  • Failure to suck.
  • Hypothermia and ultimately death.

Timecourse

• Most pups die 3-5 days after onset of clinical signs.