Time of Embryonic and Foetal Death

Embryonic death may occur very early, such as during the passage of the embryo through the oviduct, or during the early pre-implantation or free-floating phase of embryonic life. The early embryo may die either because of infection, which directly influences its developing cells, because of a hostile environment in the genital tract, or due to an abnormality in the embryo. Embryonic deaths then typically occur before or at days 15-17 when implantation occurs. Embryonic death goes unnoticed when the embryos are reabsorbed before pregnancy can be detected by transabdominal ultrasonography, i.e., in the bitch prior to day 22-25 of pregnancy. Foetal deaths occur after day 30 when organogenesis is complete, and at this stage ultrasonographic monitoring may reveal foetal death and the commencement of abortion.

Types of Pregnancy Loss in the Dog

Abortion

Abortion is defined as the expulsion of foetuses before full term pregnancy, i.e., before the conceptus is capable of independent life. Abortion is uncommon in the bitch; foetal reabsorption or mummification is more common.

Foetal Reabsorption

Foetuses will normally only be reabsorbed if they die during the first half of pregnancy. Incomplete reabsorption is possible as well as reabsorption of a few foetuses, while others develop to term. The most common causes are inadequate hormonal support, endometrial or placental disorders or intoxications, and infections, such as canine herpesvirus or brucellosis.

Mummification

The death of foetuses after the calcification of the skeleton, i.e., by day 50 in the dog, may often lead to the mummification of foetuses. The foetuses are maintained within the uterus, and degradation occurs to a certain extent, but the skin dries around the foetus forming a membrane that may delay complete foetal decay and reabsorption for prolonged periods of time. Mummified foetuses may be retained in non-infected uteri, and the general health of the dam is usually not affected. The skull and skeletal parts are also intact, and the foetus remains more or less recognisable in the uterus by ultrasonography and radiography. Infections often lead to complete foetal dissolution and decay, and may affect the health of the dam.

Premature Birth and Stillborn Puppies

The expulsion of foetuses after the foetus is capable of independent life. Stillborn puppies are full-term foetuses that are born dead. Death may occur a few days, hours or minutes before parturition. Infections, intoxications, dysfunctional placentas, inadequate uterine space, dystocia, malformations and luteal failure represent some causes.

Symptoms

Bitches diagnosed pregnant by either ultrasonography, relaxin test (<30 days) or radiography (>50 days) that have abnormal pregnancies, or do not give birth to pups at term, should be examined on the suspicion of foetal death or abortion. A history of abnormal discharge from vulva during pregnancy or fever or colic in pregnant bitches may also be noted. Vaginal discharge normally occurs in pregnant bitches from day 30-35 and is clear to mucoid or pink-tinged and odourless. If the discharge contains blood or pus, is brown, greenish or black-tinged or has a foul odour, this could imply serious pregnancy complications. Often, the pregnancy loss proceeds without any clinical symptoms.

Causes of Embryonic and Foetal Death

Infections

Infectious causes include common opportunistic bacteria that occasionally may cause infertility, embryonic or foetal death in the bitch, Brucella canis, virus infections and occasionally parasites. The normal flora, i.e., bacteria isolated from clinically healthy bitches, includes species such as staphylococci, streptococci (alpha or beta haemolytic and non-haemolytic), Escherichia coli, Pasteurella spp., Proteus spp., Pseudomonas aeruginosa, Klebsiella pneumoniae, Moraxella spp. and Haemophilus spp., all of which may be opportunistic pathogens. E. coli is most certainly involved as an ascending infection and a sequel to hormonal disturbances in pyometra, urinary tract infections and endometritis in bitches. Endotoxin production by certain strains of E. coli and exotoxins produced by toxin-producing Staphylococcus spp. may also cause more systemic effects such as septicaemia, as well as abortion in bitches, possibly due to increased prostaglandin synthesis and release caused by cell and tissue damage inflicted by the toxins.

Brucella canis is a gram-negative rod that causes late abortion in otherwise clinically healthy bitches. This is the only bacterium that is known to be a specific cause of infertility in dogs. This Brucella species as a rule infects only canines, but human infections have been reported. Brucellosis in dogs is endemic in South America and parts of North America, and has been reported once during later years in France, but it is not endemic in Europe.

Abortions following infection with parasites have been described for Toxoplasma gondii and Neospora caninum, but since few reports on parasite-related abortions have been found in the veterinary literature, abortions resulting from parasitic infections seem uncommon in dogs.

Canine herpesvirus 1 (alpha-herpesvirus), the minute virus of canines (parvovirus) and the blue-tongue virus (one report) have been shown to cause abortions in dogs. Canine herpesvirus 1 (CHV I) was first described from the USA, the disease later spreading worldwide. Herpesvirus causes different clinical symptoms depending on the age and immune status of the infected dog. CHV1 is an inhabitant of the upper respiratory tract of adult dogs. Male-to-female venereal contact is not a significant means of viral transmission. Infection in pregnant bitches may affect the litter during gestation by causing necrosis of the placentas. If the pregnant bitch is infected early, before day 30, reabsorption or occasionally abortion may result later. If the bitch is infected during the last 3 weeks of pregnancy the infection is most likely to result in late foetal deaths resulting in abortion, mummification or stillborn puppies.

The minute virus of canines or canine parvo-virus 1 (CPV1) was initially believed to be non-pathogenic, but it can cause mild to severe illness in spontaneously infected puppies (respiratory and intestinal illness). The symptoms are usually milder than with canine parvovirus 2 (CPV2) infections. The infection may occur transplacentally to the foetus or via the oronasal route in pups and adult dogs. Infection in utero can cause embryo reabsorption and abortion, especially when the dam is infected prior to day 30 of gestation.

Non-Infectious Causes

The embryo is dependent on progesterone throughout gestation. Peripheral progesterone concentrations must remain >6 nmol/l for pregnancy maintenance. Progesterone antagonists mifepristone or aglepristone, however, cause abortion by blocking the action of progesterone in the uterus without affecting peripheral progesterone concentrations. The canine pregnancy is dependent on normal corpus luteum function throughout pregnancy, since progesterone is mainly of ovarian origin in dogs. Any toxic or hormonal substance that may induce endogenous release of prostaglandins and subsequent luteolysis can result in abortion. Luteolysis is accompanied by decreasing peripheral progesterone concentrations. In cases of pending abortion progesterone levels often drop to less than 3 nmol/l.

The existence of idiopathic luteal insufficiency (hypoluteoidism) is controversial, but the condition has been described in the veterinary literature. Pituitary prolactin is essential for maintaining the corpus luteum after days 30-35, and antiprolactin drugs, such as cabergoline and bromocryptine, alone or in combination with luteolytic substances (prostaglandins), have been used to terminate pregnancy in cases of unwanted mating. Normal placental function and production of placental relaxin is essential for foetal survival. Pathogens that influence placental function (i.e., herpesvirus placentitis) may cause abortion.

Diagnosis

Serology of dam and virus isolation from aborted foetuses or placentas, combined with foetal autopsy, are used to help diagnosis. Herpesvirus isolation is possible for 2-3 weeks after primary infection. For serology, paired samples should be taken 14 days apart and kept refrigerated until analysed. Serum progesterone analysis and ultrasound monitoring are useful if abortion has commenced.

Therapy

If the dam has a fever, fluid therapy and appropriate antibiotics should be given. Antibiotics include pregnancy safe compounds, such as cephalosporins (20-30 mg/kg i.m, s.c. or orally q8-12h) or ampicillin (30 mg/kg i.v., i.m. or orally q6-8h). Prognosis for maintaining the current pregnancy is often poor, but there are usually no problems in later pregnancies, except for Brucella-infected patients. Brucella spp. vaccines have not been developed, but a herpesvirus vaccine is commercially available (Eurican®, Merial Animal Health). In cases of luteal insufficiency gestagen supplementation (altrenogest, 0.088 mg/kg orally q24h) may be used after day 30 of pregnancy only if the mating date is known, and treatment must be terminated 2 days prior to the expected whelping date to allow opening of the cervix. The pregnancy should be monitored by ultrasonography. Prognosis is optimistic with regard to carrying a dysmature foetus to term with gestagen supplementation, but bitches may experience recurrent abortions.

References

1.  Concannon PW, Tsutsui T, Scille V. Embryo development, hormonal requirements and maternal responses during canine pregnancy. In: Concannon, PW; England, GCW; et al. eds. Advances in reproduction in dogs cats and exotic carnivores. Essex: Journals of Reproduction and Fertility Ltd, Cambridge University Press, 2001; 169-179.

2.  Gunzel-Apel A-R. Non infectious causes of pregnancy loss/ abnormal pregnancy in the bitch. In: Pathology of canine and feline reproduction, physiology and pathology of the neonate. The 2nd Course in Reproduction in Companion, Exotic and Laboratory Animals of the European School of Advanced Veterinary Studies, Hannover, Germany, 2003; 2: 17.1-17.11.