FAILURE of PREGNANCY in DOGS

Expectations

There is very little written about failure of pregnancy in dogs.

A breeder survey about pregnancy failure and stillbirth in puppies in France was reported by Chastant-Maillard et al (2016). Abortion rate was reported as 6.8% or 37,946 litters. Stillbirths were 7.4% of 204,537 puppies from 37,946 litters. No specific disease statistics were provided.

Chastant-Maillard S, Guillemot C, Feugier A, Mariani C, Grellet A, Mila H. Reproductive performance and pre-weaning mortality: Preliminary analysis of 27,221 purebred female dogs and 204,537 puppies in France. Reprod Dom Anim 2016;

 

General considerations

 

 

Schlafer DH. Canine and feline abortion diagnostics. Theriogenology. 2008; 70: 327-331.

Non infectious disease

 

Anomalies - malformations

There are myriad congenital abnormalities that can result in failure of pregnancy. I could spend my whole life trying to document each and every one of them. The following are some highlights!

In a study of 97 puppies (from a total of 103) from 24 bitches, 3 were stillborn and 11 died within 48hrs - 5 for malformations. There were a total of 8 malformations.

Ortega-Pacheco et al (2020) published a report on congenital abnormalities in three dog letters. The abnormalities included gastroschisis, amelia and anencephaly. A cause was not known.

Hydrops fetalis is reported in a litter of Bulldog pups. (Ladds et al 1971)

Groppetti D, Martino PA, Ravasio G, Bronzo V, Pecile A. Prognostic potential of amniotic fluid analysis at birth on canine neonatal outcomes. Vet J. 2015; 206: 423-425.

Ladds PW, Dennis SM, Leipold HW. Lethal congenital edema in Bulldog pups. J Am Vet Med Assoc 1971; 159: 81-86.

Ortega-Pacheco A, Lezama-García MA, Colín-Flores R, Jiménez-Coello M, Acevedo-Arcique C, Gutiérrez-Blanco E. Presence of congenital anomalies in three dog litters. Reprod Domest Anim. 2020; 55: 652-655

Fetal Maternal incompatability

Dystocia

Dystocia appears to be the major cause of noninfectious death of puppies. In a study of 103 puppies from 24 bitches, 3 were stillborn and 11 died within 48hrs - 5 were euthanased for malformations.

 

Groppetti D, Martino PA, Ravasio G, Bronzo V, Pecile A. Prognostic potential of amniotic fluid analysis at birth on canine neonatal outcomes. Vet J. 2015; 206: 423-425.

 

Endocrine failure

Hypoluteoidism

Maintainance of pregnancy requires a myriad of interactions between fetus, placenta and maternal systems. For dogs, maintainance of the corpus luteum (CL) and progesterone concentration is critical. A lack of progesterone is hypoluteism, hypoluteiodism or luteal insufficiency.

The history of failure of the CL is suggested by the dog failing the pregnancy at the same stage of different pregnancies. A declining progesterone concentration at that stage and subsequent treatment with progesterone is highly suggestive.

Bitches that short cycle are more likely to have lower progesterone and potentially fail their pregnancies.

Control of the corpus luteum of dogs is not well understood, but there cell death of the CL that is part of regulated cell death (and usually programmed cell death). Premature activation of cell death subroutines is possible in some instances.

 

Görlinger S, Galac S, Kooistra HS, Okkens AC. Hypoluteoidism in a bitch. Theriogenology. 2005; 64: 213-219

Günzel-Apel AR, Zabel S, Bunck CF, Dieleman SJ, Einspanier A, Hoppen HO. Concentrations of progesterone, prolactin and relaxin in the luteal phase and pregnancy in normal and short-cycling German Shepherd dogs. Theriogenology. 2006; 66: 1431-1435.

Luz MR, Cesário MD, Binelli M, Lopes MD. Canine corpus luteum regression: apoptosis and caspase-3 activity. Theriogenology. 2006; 66: 1448-1453.

Purswell BJ. Management of apparent luteal insufficiency in a bitch. J Am Vet Med Assoc. 1991; 199: 902-903.

Hypothyroidism

Dogs that are hypothyroid are less likely to become pregnant (about 50%), and are more likely to have lower fetal birth weight and greater fetal death and periparturient disorders.

 

Panciera DL, Purswell BJ, Kolster KA, Werre SR, Trout SW. Reproductive effects of prolonged experimentally induced hypothyroidism in bitches. J Vet Intern Med. 2012; 26: 326-333.

Endometrial disease

Excessive number of fetuses

There is little written about excessive numbers of fetuses being a cause of Failure of Pregnancy. Identical monozygous twinning is reported, but not as a cause of fetal loss.

Joonè CJ, De Cramer KGM, Nöthling JO. The first case of genetically confirmed monozygotic twinning in the dog (pages 835–839). Reprod Dom Anim 2016; 51: 836-

Gestational / Placental disease

Abnormally invasive (Aggressive) trophoblasts - hyperplasia?

The normal placenta of the dog is a thing of beauty. Trophoblasts normally do not invade very far - just below the endometrium. On some occasions, trophoblasts are more aggressive then usual, They can invade the myometrium, and even go to the serosa. In some dogs, the uterus will rupture at this site as the wall of the uterus becomes very thin with this process.

Very rarely, and in my opinion, trophoblasts will invade extensively and replace the wall. This is not truely a neoplastic condition - the trophoblasts are not dysplastic and there is no mass. One case was virutally circumferential around the placenta, and the wall of the uterus was about 1mm thick!

In humans there is a name for abnormally invasive trophoblasts -

There is a report of placenta percreta in a dog. The trophoblasts were in the serosa. (Rosenberg et al 2020).

 

Rosenberg LM, Marinoff J, Crouch EE, Valenzano DM, Peters-Kennedy J, Cheong SH, Diel de Amorim MD. Uterine perforation secondary to metritis and placenta percreta in a postpartum bitch. Can Vet J. 2020; 61: 584-588.

 

Neoplasia and masses

Cushing et al (2011) reported on an allantoic cavity mass considered a trophoblastic/placental hamartoma or chorioepithelioma of allantoic cavity.

Cushing TL, Lopate C, Schlafer DH (2011) Benign Placental Mass with Fetal Growth Retardation in a Bull Mastiff. J Comp Path 2011 145: 352-354

Nutritional deficiencies

Toxicoses

Infectious disease

Givens and Marley (2008) list the following as infectious causes of reproductive loss

 

Givens MD, Marley MS. Infectious causes of embryonic and fetal mortality. Theriogenology. 2008; 70: 270-285

Bacteria

Domain: Bacteria

There are myriad cases where different bacteria are recovered from cases of failure of pregnancy. Many of them are not well described from a pathology point of view.

 

Pretzer SD. Bacterial and protozoal causes of pregnancy loss in the bitch and queen. Theriogenology. 2008 Aug;70(3):320-6. doi: 10.1016/j.theriogenology.2008.04.035. Epub 2008 May 20. PMID: 18495236.

Brucella canis

Phylum Proteobacteria, Class Alphaproteobacteria, Order Rhizobiales, Family Brucellaceae, Genus Brucella

 

Brucella canis is acquired by the dog either through oral (ingestion) nasal, conjunctival, or venereal routes. Dogs acquiring the bacterium by ingestion initially develop lymphadenitis of the head and neck and bacteremia. Epididymitis and testicular degeneration are the lesions in male dogs, and pregnant females develop placentitis and fetal endocarditis, pneumonia, and hepatitis.

Microscopically, there may be multifocal regions of coagulative necrosis of the placenta and adjacent to these are neutrophils and macrophages (Gyuranecz et al 2011). Trophoblasts of the marginal hematoma and zonary placenta are packed with Brucella organisms and there may be neutrophils within the chorion. Other possible lesions include a lymphocyte and macrophage rich portal hepatitis of the fetus (Gyuranecz et al 2011), multifocal renal hemorrhage, and lymphadenitis.

Bitches can abort several times.

Brucella abortus, Brucella melitensis and Brucella suis are reported in dogs and produce a similar disease to that of Brucella canis. Brucella canis is by far the most common.

 

Brennan SJ, Ngeleka M, Philibert HM, Forbes LB, Allen AL. Canine brucellosis in a Saskatchewan kennel. Can Vet J. 2008; 49: 703-708.

Carmichael LE, Kenney RM. Canine abortion caused by Brucella canis. J Am Vet Med Assoc 1968; 152: 605-616. 

Gyuranecz M, Szeredi L, Ronai Z, Denes B, Dencso L, Dan A, Palmai N, Hauser Z, Lami E, Makrai L, Erdelyi K, Janosi S. (2011) Detection of Brucella canis–induced reproductive diseases in a kennel. J Vet Diagn Invest 2011, 23:143–147

 

 

Campylobacter

Phylum Proteobacteria, Class Epsilonproteobacteria, Order Campylobacterales, Family Campylobacteraceae, Genus Campylobacter

 

There are a couple individual case reports of Campylobacter jejuni as a cause of reproductive failure with abortion and perinatal mortality.

Bulgin et al (1984) reported culturing Campylobacter jejuni from a Wheaton Terrier bitch which aborted and from aborted Poodle pups. Campylobacter spp are then on the list of bacteria that cause failure of pregnancy in dogs.

Odendaal et al (1994) reported the culture of Campylobacter jejuni from the vaginal discharge of 3 German Shepherd bitches that aborted in late gestation.

Sahin et al (2014) described a case were an aborted fetus had low numbers of neutrophils within the lungs. Campylobacter jejuni was cultured from the placenta and lung and liver.

 

Bulgin MS, Ward AC, Sriranganathan N, Saras P. Abortion in the dog due to Campylobacter species. Am J Vet Res 1984; 45: 555-556.

Odendaal MW, de Cramer KG, van der Walt ML, Botha AD, Pieterson PM. First isolation of Campylobacter jejuni from the vaginal discharge of three bitches after abortion in South Africa. Onderstepoort J Vet Res. 1994; 61: 193-195.

Sahin O, Burrough ER, Pavlovic N, Frana TS, Madson DM, Zhang Q. Campylobacter jejuni as a cause of canine abortions in the United States. J Vet Diagn Invest. 2014; 26: 699-704.

Coxiella burnettii

Phylum Protobacteria, Class Gammaproteobacteria, Order Legionellales, Family Coxiellaceae, Genus Coxiella

 

Dogs seroconvert to Coxiella burnettii and human disease is linked to exposure to canine placenta and fluids. The overall prevalence is low, however. its role in failure of pregnancy is not known.

Stefanetti et al (2018) examined tissues from abortions, stillbirths and neonatal mortality in 94 dogs by PCR and no Coxiella burnetii was detected.

 

Shapiro AJ, Norris JM, Heller J, Brown G, Malik R, Bosward KL. Seroprevalence of Coxiella burnetii in Australian dogs. Zoonoses Public Health. 2016 Sep;63(6):458-466

Stefanetti V, Compagnone A, Sordini C, Passamonti F, Rampacci E, Moscati L, Marenzoni ML. Retrospective Biomolecular Investigation of Coxiella burnetii and Leptospira spp. DNA in Cases of Abortion, Stillbirth and Neonatal Mortality in Dogs and Cats. Top Companion Anim Med. 2018; 33: 122-125.

Leptospira

Phylum: Spirochaetes, Class Spirochaetes, Order Leptospirales, Family Leptospiraceae, Genus Leptospira

 

Stefanetti et al (2018) examined tissues from abortions, stillbirths and neonatal mortality in 94 dogs by PCR and no Leptospira was detected.

 

Stefanetti V, Compagnone A, Sordini C, Passamonti F, Rampacci E, Moscati L, Marenzoni ML. Retrospective Biomolecular Investigation of Coxiella burnetii and Leptospira spp. DNA in Cases of Abortion, Stillbirth and Neonatal Mortality in Dogs and Cats. Top Companion Anim Med. 2018; 33: 122-125.

 

Salmonella

Phylum Proteobacteria, Class Gammaproteobacteria, Order Enterobacterales, Family Enterobacteriaceae, Genus Salmonella

 

Salmonella sp is a recognised cause of abortion in dogs.

 

Morse EV, Duncan MA. Canine salmonellosis: prevalence, epizootiology, signs, and public health significance. J Am Vet Med Assoc. 1975; 67: 817-820.

Pretzer SD. Bacterial and protozoal causes of pregnancy loss in the bitch and queen. Theriogenology. 2008; 70: 320-326.

Streptococcus

 

Placentitis is reported in dogs infected with Streptococci. Lamm et al (2010) reported on 2 cases of placentitis and 15 of 25 fetal and neonatal dogs had streptococcal septicemia.

Lamm CG, Ferguson AC, Lehenbauer TW, Love BC. Streptococcal infection in dogs: a retrospective study of 393 cases. Vet Pathol. 2010; 47: 387-395.

Viruses

Canid herpesvirus 1 (CaHV 1)

Phylum Peploviricota, Class Herviviricetes, Order Herpesvirales, Family Herpesviridae, Genus Varicellovirus

Pratelli et al (2014) examined serum from 865 bitches and found a seroprevalence of 15-18% (depending on method).

It is possible for CaHV 1 to produce a typical herpes type failure of pregnancy however the majority of animals with disease are newborn puppies usually within the first two weeks of life but occasionally up to 12 weeks of life.

Pratelli A,  Colao V, Losurdo M. (2014) Serological and virological detection of canine herpesvirus-1 in adult dogs with and without reproductive disorders. The Vet J 2014; 200: 257-260

Carnivore bocaparvovirus 1 (Canine minute virus)

Phylum Cossaviricota, Class Quintoviricetes, Order Piccovirales, Family Parvoviridae, Genus Bocaparvovirus, Species Carnivore bocaparvovirus 1

CnMV is of the Order Unassigned, Family Parvoviridae, Subfamily Parvovirinae, Genus Bocavirus

CnMV, formally called Canine parvovirus 1 or minute virus of dogs, is a cause of early embryonic mortality, stillbirth and perinatal mortality, and neonatal mortality in the first weeks of life. Single cases are often missed. Whole litters can be affected and there may be myocardial necrosis and pneumonia, and enteritis. The age of affected puppies reflects when the pup was infected.

CnMV in experimental challenge causes fetal resorption and the birth of dead or weak pups. Spontaneous disease was not reported until 2012. Lesions in affected pups include anasarca and myocarditis. Intranuclear inclusion bodies are seen in duodenal epithelial cells and within bronchial epithelial cells.

Decaro et al (2012) reported on a litter of puppies where 5 of 6 died. One was stillborn and the others died within 3 weeks.

Decaro N, Amorisco F, Lenoci D, Lovero A, Colaianni ML, Losurdo M, Desario C, Martella V, Buonavoglia C. Molecular characterization of Canine minute virus associated with neonatal mortality in a litter of Jack Russell terrier dogs. J Vet Diagn Invest. 2012 Jul;24(4):755-758

Bluetongue virus

Phylum Duplornaviricota, Class Resentoviricetes, Order Reovirales, Family Reoviridae, Genus Orbivirus

BTV is usually a virus of ruminants spread by Culicoides insects.

Many years ago Evermann et al (1994) reported infection of dogs with BTV 11. The source of the infection was a contaminated vaccine. The bitches were vaccinated late in pregnancy with a modified live vaccine. An aborted fetus and placenta has placental vasculitis. The dams also died and had fibrin on the pleura and interstitial pneumonia. Some vasculitis was seen and also fibrin thrombi in glomerular capillaries. Virus was isolated from the dams, but not the puppy. Lesions suggest endothelial infection with the virus.

Howerth et al (1995) found 1 of 130 canine serum samples to have antibody to BTV 11. This study was in Georgia USA.

Dubovi et al (2013) reported isolating BTV 11 from 3 aborted puppies from Cornell. The pups were autolysed and no lesions were found.

Gaudreault et al (2015) reported on the sequences of BTV 11 recovered from 2 cases of abortion from Texas and Kansas. These were naturaly acquired and evidence suggests it was vector borne.

 

 

Dubovi EJ, Hawkins M, Griffin RA Jr, Johnson DJ, Ostlund EN. Isolation of Bluetongue virus from canine abortions. J Vet Diagn Invest. 2013; 25: 490-492.

Evermann JF, McKeirnan AJ, Wilbur LA, Levings RL, Trueblood ES, Baldwin TJ, Hughbanks FG. Canine fatalities associated with the use of a modified live vaccine administered during late stages of pregnancy.J Vet Diagn Invest. 1994; 6: 353-357.

Gaudreault NN, Jasperson DC, Dubovi EJ, Johnson DJ, Ostlund EN, Wilson WC. Whole genome sequence analysis of circulating Bluetongue virus serotype 11 strains from the United States including two domestic canine isolates. J Vet Diagn Invest. 2015; 27: 442-448.

Howerth EW, Dorminy M, Dreesen DW, Spires EA, Stallknecht DE. Low prevalence of antibodies to bluetongue and epizootic hemorrhagic disease viruses in dogs from southern Georgia. J Vet Diagn Invest. 1995; 7: 393-394

 

Canine distemper virus

Phylum , Class , Order Family Paramyxoviridae, Genus Morbillivirus, Canine distemper virus (CDV)

Canine distemper virus, by virtue of its multisystemic effects. Two scenarios are reported in experimental infection: abortion but no fetal infection, and birth of virus infected puppies.

 

Krakowka S, Hoover EA, Koestner A, Ketring K. Experimental and naturally occurring transplacental transmission of canine distemper virus. Am J Vet Res. 1977; 38: 919-922.


Protozoa

Toxoplasma gondii

Phylum Apicomplexa, Class Conoidasida, Order Eucoccidiorida, Family Sarcocystidae, Genus Toxoplasma

 

Neospora caninum

Phylum Apicomplexa, Class Conoidasida, Order Eucoccidiorida, Family Sarcocystidae, Genus Neosporum

Leishmania

Phylum Sarcomastigophora, Class Zoomastigophora, Order Kinetoplastea, Family Trypanosomatidae, Genus Leishmania

 

Leishmania amastigotes were found in the trophoblasts of a dog with placentitis.

 

Dubey JP, Rosypal AC, Pierce V, Scheinberg SN, Lindsay DS. Placentitis associated with leishmaniasis in a dog. J Am Vet Med Assoc. 2005; 227: 1266-1269.