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Basics ⬇

Outline

BASICS

Definition!!navigator!!

Fetal loss after 40 days of gestation (term stillbirth may apply >300 days) involving maternal, placental, and/or fetal invasion by microorganisms.

Pathophysiology!!navigator!!

  • Approximately 5–15% of abortions are infectious.
  • Abortion storms can occur, especially with EHV or MRLS when caterpillar populations are greatly increased.
  • Can involve viruses, bacteria, rickettsia, protozoa, fungi, or, with MRLS, ingestion of ETC. Some of the specific microorganisms associated with spontaneous, infectious equine abortions are listed below

Viruses

  • EHV-1 (1P and 1B strains); EHV-4; rarely EHV-2. EHV abortions generally occur late in gestation; >7 months.
  • EVA (>3 months of gestation).
  • Equine infectious anemia (direct causal relationship not yet established).
  • Vesivirus: recent correlation between its antibodies and equine abortions

Bacteria

  • Placentitis and possible, subsequent fetal infection by Streptococcus spp., Actinobacillus spp., Escherichia coli, Pseudomonas spp., Klebsiella spp., Staphylococcus spp., nocardioform actinomycetes, such as Amycolatopsis spp., Cellulosimicrobium spp., Crossiella spp., and Rhodococcus spp., Taylorella equigenitalis (rare, reportable), and Leptospira serovars.
  • Endotoxemia causes release of prostaglandin F2 alpha (especially <80 days of gestation (day 60 in many mares)); may be factor later in gestation, if repeated exposure.
  • MRLS is closely associated with ETC, or, potentially, other species of caterpillars, the setae of which cause microscopic bowel puncture and subsequent bacteremic spread to the fetus and/or placenta; species of Actinobacillus and nonhemolytic Streptococcus are cultured approximately 65% of the time

Rickettsiae

Ehrlichia risticii (Potomac horse fever).

Fungi

Placentitis caused by Aspergillus spp., Candida spp., or Histoplasma capsulatum.

Protozoa

Sarcocystis neurona or, possibly, Neospora spp. in aborted fetuses from EPM-affected mares.

MRLS

  1. A major concern in years when caterpillar populations are greatly increased; the geographic distribution, financial impact, and unusual pathogenesis of this syndrome make it a topic worthy of separate discussion.
  2. Early (≈40–150 days of gestation) and late (>269 days of gestation) abortion syndromes.
  3. Associated with greatly increased populations of ETCs.
  4. Oral exposure to ETC setae in conjunction with MRLS; currently theorized to be associated with microscopic bowel puncture and bacteremic spread to fetus and/or placenta

Depending on the specific infectious cause, the pathophysiologic mechanisms of spontaneous infectious abortions can involve the following sequence of events:

  • Fetal death by microorganisms.
  • Fetal expulsion after placental infection, insufficiency, or separation.
  • Premature parturition induced by microbial toxins, fetal stress, or a combination of mechanisms.
  • Final result—fetal death followed by absorption, maceration, or autolysis; fetal death during the stress of delivery (stillbirth) or birth of a live fetus incapable of extrauterine survival.
  • Some have suggested a caterpillar toxin-associated cause for the 2001–2002 outbreak of MRLS in central Kentucky and surrounding areas.
  • It is currently thought ingestion of ETC by pregnant mares is associated with penetration of intestinal mucosa by bacteria-contaminated, barbed caterpillar setae and their fragments. These migrate in blood vessels as septic setal emboli, deposited in vascular, immunologically susceptible targets, such as the early and late-term fetus and placenta

Systems Affected!!navigator!!

  • Reproductive.
  • Other organ systems can be affected if there is maternal systemic disease

Signs!!navigator!!

Historical Findings

One or more of the following:

  • Vaginal discharge, which can potentially be mucopurulent, hemorrhagic, or serosanguineous.
  • Premature udder development with dripping milk.
  • Anorexia or colic; GI disease.
  • Failure to deliver on expected due date.
  • Recent (1–16 weeks before presentation) systemic infectious disease or, similarly, recent introduction of infected carrier horses to the premises.
  • Other, recently aborting mares.
  • Inadequate EHV-1 prophylaxis.
  • History of placentitis.
  • Previous history of dystocia, especially with perineal and/or cervical trauma.
  • Previous endometrial biopsy with moderate/severe endometritis or fibrosis.
  • None or excessive abdominal distention consistent with gestation length.
  • Behavioral estrus in a pregnant mare, which might be normal, depending on gestation length, time of year, gestation length at time of loss.
  • Climatic and environmental conditions favoring increased populations of ETC (Malacosoma americanum) or, possibly, other caterpillar species with setae and development of MRLS in early and late pregnant mares.
  • Possibly geographic location if suspect MRLS and nocardioform placentitis

Physical Examination Findings

  • Early pregnancy loss is frequently unobserved and is described as asymptomatic.
  • Unless complications occur, abortion may occur rapidly, with the sole sign being a relatively normal, previously pregnant mare later found open.
  • Signs range from none to multisystemic and life-threatening disease, especially if dystocia occurs during delivery or if maternal organs are infected.
  • Depending on microorganisms involved, multiple animals can be affected.
  • Most symptomatic spontaneous infectious abortions occur during the second half of gestation; characterized by one or more of the following findings on physical examination:
    • Fetal parts/placental structures protruding through vulvar lips; abdominal straining or discomfort.
    • Premature placental separation (red bag).
    • Vulvar discharge (variable appearance), premature udder development, dripping milk.
    • A previously documented pregnancy is not detected at the next examination.
    • Evidence of fetal death by TRP, transrectal or transabdominal US.
    • Anorexia, fever, signs of concurrent systemic disease, especially with endotoxemia, dystocia, RFM.
    • Evidence of placental separation or echogenic allantoic fluid, especially in association with MRLS, as observed using transrectal or transabdominal US

Risk Factors!!navigator!!

  • Pregnant mares intermixed with young horses or horses in training are susceptible to EHV-1, EVA, or E. risticii.
  • Immunologically naive mares brought to premises with enzootic EHV-1, EVA, E. risticii, or Leptospira infections.
  • Pregnant mares traveling to horse shows or competitions.
  • Poor perineal conformation or dystocia with perineal lacerations or cervical trauma predisposes mares to ascending bacterial or fungal placentitis and, possibly, subsequent fetal infection.
  • Concurrent maternal GI disease or EPM.
  • Large numbers of ETCs in pastures with pregnant mares.
  • Geographic location with respect to MRLS and nocardioform placentitis

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

Other Causes of Abortion

  • Abortion, spontaneous, noninfectious.
  • Twinning.
  • Fetal abnormalities/teratogenesis.
  • Umbilical cord abnormalities with excessive twisting and thrombosis.
  • Placental pathology.
  • Maternal malnutrition or other noninfectious systemic disease.
  • Old mare, history of early embryonic death or abortion.
  • Old mare, poor endometrial biopsy.
  • Maternal exposure to:
    • Endophyte-infected tall fescue pasture, exposure to ergotized grasses, small cereal grains during last month of gestation; little or no mammary development (agalactia, if term is reached).
    • Phytoestrogens.
    • Other xenobiotics.
  • Iatrogenic or inappropriately timed induction of labor

Other Causes of Labor or Abdominal Discomfort

  • Normal parturition.
  • Dystocia unassociated with abortion.
  • Prepartum uterine artery rupture.
  • Colic associated with uterine torsion.
  • Discomfort associated with hydrops of fetal membranes or prepubic tendon rupture.
  • Colic unassociated with reproductive disease

Other Causes of Vulvar Discharge

  • Normal parturition.
  • Dystocia unassociated with abortion.
  • Normal estrus.
  • Endometritis.
  • Metritis or partial RFM.
  • Mucometra or pyometra

Imaging!!navigator!!

Transrectal and transabdominal US can evaluate fetal viability, placentitis, and alterations in appearance of amniotic and/or allantoic fluids, as well as other gestational abnormalities.

Other Diagnostic Procedures!!navigator!!

  • Except for placentitis, abortions secondary to endotoxemia, and fetal expulsion associated with dystocia, most abortions are asymptomatic. The expelled fetus and fetal membranes vary in condition from intact to autolytic in appearance.
  • Definitive diagnosis of equine abortion in ≈50–60% of all cases.
  • Excluding twins and EHV-1, the diagnostic rate may only be 30%, especially if limited samples are submitted and are accompanied by moderate to severe fetal and placental autolysis with environmental contamination.
  • Laboratory testing to determine the cause of a spontaneous, potentially infectious abortion includes the following procedures:
    • CBC, serum biochemistry for inflammatory or stress leukocyte response, or evidence of other organ system involvement.
    • Suspected endotoxemia—maternal P4 assay is indicated if the pregnancy is at risk prior to determining an infectious cause of an impending abortion. ELISA or RIA analyses for P4 may be useful at <80 days of gestation (normal levels vary from >1 to >4 ng/mL, depending on reference laboratory). At >100 days, RIA detects both P4 (very low > day 150) and cross-reacting 5α-pregnanes of uterofetoplacental origin. Acceptable levels of 5α-pregnanes vary with stage of gestation and the laboratory used.
    • To aid in establishing a diagnosis of abortions caused by placentitis, a maternal uterine swab/uterine lavage sample or, as advocated by some, a uterine biopsy can provide samples for culture and cytology (swab or lavage) or histopathology (biopsy).
    • Analyses for other maternal hormones can be performed.
    • Maternal serologic testing can be useful in diagnosing infectious abortions (diagnostic for abortions by Leptospira serovars; confirms EVA abortion). Serum samples should be collected in all cases of abortion in which cause is unknown (a paired sample collected 21 days later might be indicated).
  • The following samples should be collected from the fetus and the fetal membranes for histopathologic and cytologic evaluations, as well as microbiologic, serologic, and molecular testing procedures:
    • Fresh/chilled fetal thoracic or abdominal fluid and serum from the fetal heart or cord blood.
    • Fetal stomach contents.
    • 10% neutral-buffered formalin-fixed and chilled/frozen fetal membranes (chorioallantois or allantochorion; amnion or allantoamnion), as well as fixed and chilled/frozen samples of fetal heart, lung, thymus, liver, kidney, lymph nodes, spleen, adrenal, skeletal muscle, and brain.
    • Stained cytologic smears collected from fetal membranes

Pathologic Findings!!navigator!!

Viruses

  • EHV
    • Gross pleural effusion, ascites, fetal icterus, pulmonary congestion, and edema; 1 mm, yellowish-white spots on enlarged liver; relatively fresh fetus.
    • Histopathologic findings for EHV-1 and -4 include areas of necrosis, prominent, eosinophilic, intranuclear inclusion bodies in lymphoid tissue, liver, adrenal cortex, lung, as well as a hyperplastic, necrotizing bronchiolitis.
    • Fluorescent antibody staining of fetal tissues.
    • Virus isolation from aborted fetus.
    • PCR can be used for EHV-1/EHV-4, as well as, possibly, other viruses and microorganisms listed below, depending on the diagnostic laboratory.
  • EVA
    • Few gross lesions.
    • Autolyzed fetus.
    • Placental/fetal vascular lesions.
  • Vesivirus
    • Nonspecific lesions

Bacteria and Fungi

  • Fetal infection and placentitis
    • Gross pleural effusion, ascites with enlarged liver; rare plaques of mycotic dermatitis; placental edema and thickening with fibronecrotic exudate on the chorionic surface, especially at the cervical star in fungal infections.
    • Histopathologic evidence of inflammatory disease; autolysis may make interpretation difficult.
  • Leptospirosis
    • Gross fetal icterus and autolysis.
    • Nonspecific histologic changes; mild, diffuse placentitis

Endotoxemia

Fetus minimally autolyzed.

Rickettsiae

  • Ehrlichia risticii
    • Gross placentitis.
    • Typical histopathologic findings include colitis, periportal hepatitis, lymphoid hyperplasia, and necrosis

Protozoa

There are reports of Sarcocystis neurona-associated abortions in EPM-positive mares.

MRLS

Histopathologic findings similar to bacterial infections.

Treatment ⬆ ⬇

Outline

TREATMENT

Appropriate Health Care!!navigator!!

  • Except late-gestational placentitis (>270 days) and endotoxemia, no therapy indicated to preserve fetal viability with spontaneous, infectious abortion.
  • For mares that abort, there is only prophylactic therapy for metritis or endometritis.
  • Therapy is generally limited to intrauterine lavage with or without antibacterial therapy but might include a systemic component consisting of antibiotics, NSAIDs, and/or IV fluids, especially if septicemia, endotoxemia, and/or laminitis are suspected.
  • Preexisting GI disease and complications, such as laminitis, may warrant hospitalization and intensive care

Nursing Care!!navigator!!

Most affected horses require limited nursing care, except in instances of endotoxemia and Gram-negative septicemia, dystocia, RFM, metritis, laminitis.

Activity!!navigator!!

There should be paddock exercise to permit observation, but this recommendation is subject to change if the mare exhibits clinical signs of laminitis.

Diet!!navigator!!

Feed and water intake, as well defecation and urination, should be monitored, but no particular dietary changes should take place in the absence of GI disease or laminitis.

Client Education!!navigator!!

Inform owners of:

  • Availability of vaccines to prevent some types of viral abortion.
  • Increased risk for abortion in mares with a previous history of dystocia (especially those mares with perineal or cervical trauma) or placentitis.
  • Possible complications of abortion

Surgical Considerations!!navigator!!

Indicated in instances of dystocia or GI disease requiring surgical intervention or repair of previous perineal lacerations, cervical trauma, or other structural abnormalities.

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Altrenogest administered 0.044–0.088 mg/kg PO daily can be started later during gestation, continued longer, or used only for short periods of time, depending on serum P4 levels during the first 80 days of gestation, clinical circumstances, risk factors, clinician preference. Note that serum levels reflect only endogenous P4, not exogenous, oral product.
  • If near term, altrenogest frequently is discontinued 7–14 days before the foaling date unless indicated otherwise by fetal maturity/viability, or actual gestational age is in question

Precautions, Possible Interactions!!navigator!!

  • Altrenogest is only used to prevent abortion in cases of endotoxemia or placentitis (>270 days of gestation) if the fetus is viable.
  • Altrenogest is absorbed through skin; wear gloves and wash hands

Alternative Drugs!!navigator!!

  • Injectable P4 (150–500 mg oil base) IM.
  • Newer, repository forms of P4 are occasionally introduced; however, some evidence of efficacy should be provided prior to use

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • 7–10 days post abortion, TRP and US to monitor uterine involution.
  • Observation for signs of systemic disease, laminitis.
  • Assess genital tract health using vaginal speculum, hysteroscopy, uterine culture and cytology, and/or endometrial biopsy.
  • Base treatment on results of these testing procedures. Uterine culture <14 days postpartum or post abortion can be affected by contamination at the time of parturition (abortion)

Prevention/Avoidance!!navigator!!

Vaccines

  • A killed-virus EHV-1 vaccine at 5, 7, and 9 months of gestation (some recommend vaccination at 3 months of gestation, as well); approved for abortion prevention in pregnant mares; 2 month interval due to short-lived vaccinal immunity.
  • Other EHV vaccines, including combinations of EHV-1 and -4, have been used off-label for abortion prevention, with some anecdotal reports of their efficacy for this purpose.
  • EVA vaccine not specifically labeled for abortion prevention; a modified live vaccine only to be administered to open mares 3 weeks before anticipated exposure to infected semen or in enzootic conditions. First-time vaccinated mares should be isolated for 3 weeks after exposure to infected semen. Note that some countries forbid importation of horses with titers to EVA

Additional Prophylactic Steps

  • Segregate pregnant mares from horses susceptible/exposed to infections.
  • Isolate immunologically naive individuals until immunity to enzootic infections is established and/or enhanced. Depending on infectious agent, protection may only be accomplished postpartum.
  • Limit transport of pregnant mares to exhibitions or competitions.
  • Careful observation of pregnant mares and monitor mammary development.
  • Use appropriate biosecurity protocols and isolate aborting mares, with proper disposal of contaminated fetal tissues.
  • Proper diagnostics to identify an infectious cause of abortion.
  • Correct structural abnormalities, such as poor perineal conformation, perineal lacerations, or cervical trauma, in order to prevent ascending placentitis.
  • Manage preexisting endometritis before next breeding.
  • Prevent pregnant mare exposure to ETCs until 7–8 weeks after ETC death.
  • Insecticides to control ETCs; consider toxicity of insecticide

Possible Complications!!navigator!!

  • Abortion in late pregnancy can be associated with dystocia and other potentially life-threatening conditions.
  • Future fertility and reproductive value can be impaired by dystocia, RFM, endometritis, laminitis, septicemia, trauma to genital tract

Expected Course and Prognosis!!navigator!!

  • Most patients recover with appropriate treatment.
  • Complications can involve significant impact on mare's survivability and future fertility.
  • Prognosis is guarded for pregnancy maintenance with endotoxemia and placentitis.
  • Mares with placentitis, especially those with predisposing structural abnormalities, are more susceptible to future recurrence of this type of abortion

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Synonyms!!navigator!!

  • Abortion.
  • Spontaneous abortion.
  • Infectious abortion.
  • Bacterial abortion.
  • Viral abortion.
  • Fungal abortion.
  • Mycotic abortion.
  • Protozoal abortion.
  • Rickettsial abortion

Abbreviations!!navigator!!

  • EHV = equine herpesvirus
  • ELISA = enzyme-linked immunosorbent assay
  • EPM = equine protozoal encephalomyelitis
  • ETC = eastern tent caterpillar
  • EVA = equine viral arteritis
  • GI = gastrointestinal
  • MRLS = mare reproductive loss syndrome
  • NSAID = nonsteroidal anti-inflammatory drug
  • P4 = progesterone
  • PCR = polymerase chain reaction
  • RFM = retained fetal membranes/placenta
  • RIA = radioimmunoassay
  • TRP = transrectal palpation
  • US = ultrasonography, ultrasound

Suggested Reading ⬆ ⬇

Christensen BW, Roberts JF, Pozor MA, et al. Nocardioform placentitis with isolation of Amycolatopsis spp in Florida-bred mare. J Am Vet Med Assoc 2006;228:1234–1239.

McKinnon AO, Pycock JF. Maintenance of pregnancy. In: McKinnon AO, Squires EL, Vaala WE, Varner DD, eds. Equine Reproduction, 2e. Ames, IA: Wiley Blackwell, 2011:2410–2417.

Powell DG. Mare reproductive loss syndrome. In: McKinnon AO, Squires EL, Vaala WE, Varner DD, eds. Equine Reproduction, 2e. Ames, IA: Wiley Blackwell, 2011:2410–2417.

Timoney PJ. Equine herpes virus. In: McKinnon AO, Squires EL, Vaala WE, Varner DD, eds. Equine Reproduction, 2e. Ames, IA: Wiley Blackwell, 2011:2376–2390.

Troedsson MHT, Macpherson ML. Placentitis. In: McKinnon AO, Squires EL, Vaala WE, Varner DD, eds. Equine Reproduction, 2e. Ames, IA: Wiley Blackwell, 2011:2359–2367.

Webb BA, Barney WE, Dahlman DL, et al. Eastern tent caterpillars (Malacosoma americanum) cause mare reproductive loss syndrome. J Insect Physiol 2004;50:185–193.

Author(s) ⬆

Author: Tim J. Evans

Consulting Editor: Carla L. Carleton