Baumgartner 2021 Abortos General

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665

Pregnancy Wastage
667

56

Fetal Disease and Abortion: Diagnosis and Causes


Wes Baumgartner
Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Illinois, Urbana, IL, USA

I­ ntroduction progressive decrease over time in the risk of abortion, with a


slight increase in the last month [8]. Although losses during
Reproductive failure is a significant problem in breeding this time are a minority of overall wastage, the cost of invest-
management that arises from physiological, anatomical, ment by the cow and the manager is substantial. A mid-term
inherited, and infectious causes. The inability to achieve or abortion represents a loss of at least USD $600–1000 [8]. For
maintain a pregnancy may be divided into four main stages: practical purposes, unavoidable losses of 3% after pregnancy
failure to ovulate after estrus, failure of fertilization, embry- confirmation (six weeks’ gestation), with 1–2% loss in the
onic death (prior to gestation day 42), and fetal death [1]. periparturient period, may be considered acceptable or
Pregnancy wastage, which probably comprises the largest typical, although opinion in this area varies [8–10].
portion of these losses, encompasses the combined embry- This discussion will concentrate on fetal death and the
onic, fetal, and neonatal deaths that achieve nothing. It has approach to diagnosis, but will necessarily include some
been estimated that about 75% of pregnancy wastage occurs aspects of embryonic death, congenital abnormalities, and
in the embryonic stage [2, 3]. The majority of reproductive common gross findings. Additionally, a brief overview of
failure occurs in the first two weeks, at the time of develop- anatomy and development are included to familiarize the
ment from a morula to blastocyst where the conceptus reader with general concepts. A glossary of terms appears
begins enhanced protein synthesis and placental develop- at the end of this chapter.
ment [3–6]. Despite the importance of wastage at this time The investigation of abortion is a vital part of herd manage-
of development, the mechanisms contributing to embryonic ment and its importance is hard to overemphasize. Accurate
death are poorly understood and in most cases the cause is diagnosis is the only path to the effective control of disease. It
never established [1]. Factors typically thought to contribute should go without saying that a focused, efficient, and thor-
to embryonic death include heat stress, infections of the ough investigation technique with a definite purpose by pre-
uterus/gametes/embryo, local trauma, genetic factors, heavy pared veterinarians is the only relevant way to identify and
lactation in dairy cattle causing energy imbalances, mater- understand the etiologies of abortion. The necropsy itself con-
nal illness, aged oocytes from persistent follicles, small folli- tributes to this in several ways: by establishing definitive causes
cles, fetal–maternal incompatibilities, twinning, postpartum of death, identifying unsuspected findings, providing informa-
breeding intervals, and abnormal progesterone levels due to tion concerning zoonotic disease, contributing to discovering
estrus synchronization [1, 3, 6, 7]. Investigation into the new diseases and pathogenic mechanisms, and providing a
causes of early loss are hampered by the rarity of available means to test new diagnostic and treatment techniques [11].
early conceptuses that are either expelled or resorbed and go
unnoticed, only to result in a cow that returns to estrus or
fails to deliver a calf. P
­ athology
Abortion typically refers to pregnancy loss in the fetal stage,
between days 42 and 260. It is in this stage of gestation that the The expression of disease in the conceptus is remarkably
tissues of conception cannot be resorbed and, when expelled, varied in a general sense, in that it gives rise to bizarre
are more easily noticed. During the fetal period there is a developmental defects of potentially every sort. This is due

Bovine Reproduction, Second Edition. Edited by Richard M. Hopper.


© 2021 John Wiley & Sons, Inc. Published 2021 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/hopper/bovine
668 Fetal Disease and Abortion: Diagnosis and Causes

to the intricate physiology and morphology of fertilization Table 56.1 Disease-causing agents associated with endemic
and gestation that is shared between the dam and fetus. fetal losses.
The sequential stages of organ system development in
utero provide unique opportunities for infectious and non- Histophilus somni, Listeria monocytogenes, Trueperella pyogenes,
Leptospira spp., Ureaplasma diversum
infectious etiologies to manifest themselves at the gross
level, if pregnancy is maintained. In addition, the placenta, Bluetongue virus, bovine viral diarrhea virus (BVDV)
a unique organ of gestational necessity, is a target of many Neospora caninum, fungi, epizootic bovine abortion
disease-causing agents and can itself develop anomalous Inbreeding, sire-derived lethal traits, chromosomal abnormalities
defects that in turn directly affect the fetus. Feed estrogens (silage, poultry litter), progesterone aberrations
Despite this, in many cases, aborted tissues from infec- (high pasture protein)
tious and non-infectious causes exhibit little if any recog- Protein, vitamin A, iodine, selenium deficiency
nizable changes of significance. This is partly due to Protein/urea, copper, iodine excess
autolysis in utero masking subtle changes; the relative ease Endotoxins due to Gram-negative bacterial sepsis in dam
and rapidity by which fetuses succumb to disease, allowing
Endotoxin in Gram-negative bacterial vaccines, especially given
only a brief window for gross changes to manifest; and a during the first or last two months
rudimentary inflammatory response to injury [12]. Not Pine needle, broomweed, locoweed, narrow leaf sumpweed
only does the conceptus vary in its susceptibility to particu- toxicosis
lar insults across the gestational period, but also the degree High plant estrogens
and duration of insult determine the outcome, whether it Aflatoxin, ergotamine, fusarium (zearalenone), nitrate fertilizer,
be life, death, malformation, or inflammation [9]. organophosphate toxicosis
The physiology of pregnancy is well studied and dealt
Source: [15].
with in detail in preceding chapters. Despite our under-
standing of normal pregnancy, the physiology of abortion
and the mechanisms involved are poorly understood. In herd. If these bacteria are only seen in isolated cases, the
many cases, abortion may be mediated through the same significance to the herd is minimal [14]. However, if these
pathways that occur in normal parturition, but different organisms are consistently associated with abortions, then
mechanisms and pathways are also possible [8]. further investigation is warranted.
Non-infectious causes of abortion are similar to those
known to cause embryonic loss, including nutritional imbal-
­Categories of Reproductive Loss ances, malnutrition, stress, environmental toxins, teratogenic
compounds, hormone imbalances, and genetic abnormali-
The cause of abortion is often not known, which is a con- ties. An expanded list of etiologic agents is shown in
sistent source of frustration for managers and clinicians Table 56.1 and in the following chapters.
alike. In all species, abortion may be caused by infectious
and non-infectious etiologies. Specific causes and agents
are dealt with in detail later in this and subsequent chap- ­ athophysiology of Injury to the
P
ters. Of these, infectious causes of abortion (bacteria, Conceptus
viruses, fungi, protozoa) are probably the best understood
and characterized. It is common to see reports where the Maintenance of the first half of gestation (the first 200 days) in
percentage of cases with a specific diagnosis is less than cattle requires a persistent corpus luteum (CL), which is main-
50% [13]. Of these, at least half are due to infectious agents, tained by the fetus [9, 16]. Luteolysis may occur in pregnant
with the majority of these due to bacterial infection [8]. cows due to excess prostaglandins (PGs) (exogenous adminis-
Bacteria involved in abortions can be broadly grouped tration or secondary to heat stress) or Gram-negative bacterial
into those that are contagious and those that are opportun- septicemia [17]. If the CL is destroyed at an early stage, death
istic. The majority of bacterial abortions are caused by and rapid loss of the embryo with minimal degeneration may
opportunists, and these may be further divided into those be seen [18]. If there is fetal death prior to luteolysis, the CL
that are part of the natural flora, such as Trueperella pyo- may regress, with eventual expulsion of autolyzed fetal tissues.
genes (formerly Arcanobacterium pyogenes) and Histophilus However, in some cases the CL is maintained after fetal
somni, and those from the environment, such as Bacillus death, which can result in expulsion, resorption, or mummifi-
spp. and Escherichia coli [14]. The significance attached to cation [19]. Early abortions are typically not recognized; most
abortion by opportunists depends on the situation in the are occultly expelled, severely autolyzed, or mummified.
­Route from the Placenta to the Fetu  669

The maintenance of late-stage pregnancy requires both ­Effects of Maternal Disease


the fetus and placenta. At this stage in development, suffi-
cient fetal stress can induce parturition through natural Infectious pathogens may cause abortion either by
endocrine mechanisms. In this way, chronically diseased directly infecting the conceptus or by affecting the dam
fetuses can initiate their own premature delivery. such that severe physiological disturbance leads to abor-
Fetal death often leads to abortion within a few days tion. Uterine disease has significant effects on the con-
rather than immediately, allowing sufficient time for auto- ceptus and potential future fertility; ovarian and uterine
lytic changes to occur. The mechanism for expulsion of effects can be lasting despite resolution of the signs of
dead fetuses is unknown but may share many similarities active disease [22]. The dam is predisposed to infection
with normal parturition [19]. Autolytic changes include through non-specific immunosuppression that occurs
generalized edema, pallor, and hemoglobin-stained fluids during pregnancy [23]. Fever (mastitis, pneumonia), cir-
in the body cavities. Visceral tissues become pulpy or semi- culatory disease (myocarditis, severe anemia), hypoxia,
liquid [19]. In some cases, the time between fetal death and and endotoxemia (Gram-negative sepsis) are possible
expulsion may be characteristic for a pathogen, and may conditions that may cause abortion indirectly [21]. PGs
therefore be useful to the clinician. Fetal infections due to may be elevated in febrile states, which can lead to lute-
Listeria monocytogenes, T. pyogenes, non-septate fungi olysis and abortion [24]. The likelihood of abortion prob-
(Absidia spp., Mucor spp., Rhizopus spp.), and bovine her- ably increases with the number of pregnancies or previous
pesvirus (BHV)-1 may lead to fetal death with expulsion abortions by the dam [8].
days later. Fetuses infected by Campylobacter fetus and
Aspergillus spp. may be delivered alive [20].
It is important to recognize that infection of the conceptus
does not necessarily lead to fetal death. The ability of a patho- ­Routes of Infection to the Conceptus
gen to injure the conceptus is influenced by the dam (general
health, previous exposure), the stage of fetal development, In cases where infectious organisms invade the conceptus,
and the virulence of the infectious agent. Fetal development four routes are likely [21]. Hematogenous spread from the
is a continuum of organogenesis, physiological development, dam to the placenta is commonly suspected in cases of
and immune development. Early stages of gestation are more infectious abortion, particularly due to L. monocytogenes,
prone to infection and severe disease, as the capabilities of Leptospira interrogans, Salmonella enterica, Brucella abor-
the fetus are underdeveloped. The closer the fetus is to partu- tus, fungus, BHV-1, or BVDV infection. Ascending infection
rition, the stronger and more capable it is of defending itself from the vagina through the cervix can occur from primary
from pathogens. Thus, infection at different stages of devel- vaginitis (characteristic of Tritrichomonas foetus) or con-
opment will produce different outcomes in the fetus. tamination at insemination. The presence of pathogens
Bovine viral diarrhea virus (BVDV) infection is a good within the uterus (endometritis due to C. fetus, T. pyogenes)
example of this. Infection in the first trimester often leads to and descent from the abdomen via the uterine tubes (myco-
fetal death and resorption, while infection in the second tri- bacteriosis) are also possible pathways for organisms to
mester may lead to developmental anomalies. The charac- reach the conceptus.
ter of the developmental defects depends on which cells or
tissues are susceptible to the virus at the time of infection.
In the second trimester, cerebellar growth is maximal and ­Route from the Placenta to the Fetus
BVDV infection at this time may lead to cerebellar necrosis
and cerebellar hypoplasia. Also at this time, hair growth is Once a pathogen reaches the placenta, it may proceed to
highly active and BVDV infection may damage follicles, the fetus through the blood, via the umbilical veins, or by
resulting in hypotrichia. By the third trimester, the immu- contamination of the amniotic fluid [21] (Figure 56.1). For
nocompetent fetus may react to BVDV infection by mount- example, BVDV primarily infects the fetus hematoge-
ing a sufficient immune response with antibody production nously, whereas BHV-1 may first infect the placenta and
and virus elimination. The only evidence for such an infec- then proceed to the fetus. Primary placental infection with
tion would be fetal-specific antibody titers [21]. subsequent amniotic fluid contamination is characteristic
Other viruses, such as BHV-1, cause extensive cell necro- of fungal infections. In some cases, a pathogen need not
sis and hemorrhage, leading to rapid fetal death. Neospora infect the fetus, such as with S. enterica infection, where
caninum infection in the third trimester may cause only severe infection of the placenta may lead to generalized
mild inflammation, with the birth of asymptomatic calves. fetal hypoxia and subsequent death.
670 Fetal Disease and Abortion: Diagnosis and Causes

Figure 56.1 Fetus, omphalitis, and ascending bacterial


infection from the placenta. Purulent material is easily
expressed from the cord. Source: Photo courtesy of J. Edwards. Figure 56.2 Chorioallantois and placentitis. The cotyledons are
thickened with yellow discoloration due to fibrin and necrosis.
Intercotyledonary tissues are relatively unaffected. Source: Photo
­Lesions of the Placenta courtesy of J. Cooley.

Placentitis most commonly develops by one of three ways:


hematogenous spread, extension from a diseased uterus, or
an ascending vaginal infection. Gross placental lesions are
characteristic of chronic bacterial and fungal disease, while
viral infections generally produce no lesions [25]. Changes
of significance may occur in both the cotyledons and/or
intercotyledonary spaces. The presence of fibrin (yellow,
stringy, friable material) on cotyledons is an indication of
inflammation (Figure 56.2). Fibrin must be distinguished
from necrotic inflammatory exudate or entrapped caruncle
fragments (necrotic uninfected endometrial tissue). The
presence of ecchymosis and extension of the changes to the
intercotyledonary space are suggestive of an infectious
inflammatory process. With chronicity, stereotypical
Figure 56.3 Chorioallantois and fungal placentitis; maternal
changes of placentitis include (i) placental fibrosis and aspect on right, fetal aspect on left. Cotyledons are thick,
edema; (ii) cupping of cotyledons; (iii) exudate on chori- irregular, and tan to hemorrhagic. Intercotyledonary areas are
onic surfaces; and (iv) necrosis of the cotyledons [12]. thickened. The fetal side shows yellow discoloration and
Fungal and bacterial inflammation of the cotyledons is multiple discrete infarcts (arrows) due to vascular thrombosis.
Source: Photo courtesy of J. Edwards.
often associated with necrosis, which imparts a firm to fri-
able, tan, irregular or nodular consistency to the tissues
are thickened, opaque, and ecchymotic with fibrin, necro-
with interspersed ecchymoses. Fungal organisms prefer to
sis, and fibrosis [27].
grow along and within blood vessels; this often leads to
thrombosis, hemorrhage, and necrosis (Figure 56.3). Fungal
organisms may be particularly abundant at the periphery of
lesions rather than in the centers. A useful feature for inter- ­Lesions of the Fetus
pretation is the extension of the pathologic process into the
pericotyledonary chorioallantois. Such infiltrates may Gross lesions of the fetus, aside from malformations, are
bridge cotyledons and often impart a leathery thickened generally uncommonly noticed. They may be inapparent
texture. Another differential for such a change would be for four reasons: (i) the fetal immune system is not of suffi-
adventitial placentation (discussed in the section cient robustness to mount a response that is easily observed
“Pathology”). Leptospirosis and BHV-1 infections may also at the gross level; (ii) fetuses often die before lesions appear;
produce a placentitis and appear similar to one another [26]. (iii) lesions are masked by autolysis; and (iv) fetal pathology
Ureaplasma diversum is known to produce a rather char- may manifest itself in ways that are difficult to recog-
acteristic hemorrhagic amnionitis, where the membranes nize [15]. Table 56.2 lists some causes for commonly
­Lesions of the Fetu  671

Table 56.2 Possible causes for gross and microscopic lesions in bovine fetuses.

Lesion Possible causes

Gross lesion
Mummification BVDV, Neospora
Ascites/anasarca Congenital heart defect, nutritional myopathy/cardiac dilation, BVDV, Neospora
Arthrogryposis, musculoskeletal deformities Akabane/Schmallenberg/bunyaviruses, reduced in utero motility, genetic
Fibrinous peritonitis/pleuritis Bacteria (Trueperella, Campylobacter, Bacillus, Brucella, Chlamydia), fungi, EBA
Fibrinous pericarditis Bacillus, Campylobacter
Icterus Leptospira
Cerebellar hypoplasia BVDV, Schmallenberg, BTV
Hydrocephalus, hydranencephaly, BTV, BVDV, SBV, other bunyaviruses, genetic anomaly, toxins (lupines), genetic
porencephaly
Microphthalmia BVDV
Pulmonary/renal hypoplasia BVDV
Dermatitis/hyperkeratosis Fungi, EBA
Multifocal liver necrosis Listeria, BHV-1, Yersinia, Salmonella
Splenomegaly/lymphadenopathy EBA, HoBi-like pestivirus
Hepatomegaly Chronic passive congestion, EBA, lipodystrophy
Placentitis, infarctions Fungi
Placental exudate Bacteria (Trueperella, Campylobacter, Brucella, Leptospira, Mollicutes, Coxiella),
Trichomonas, BHV-1
Generalized petechiation/hemorrhage BVDV, anthrax, HoBi-like pestivirus
Microscopic lesion
Encephalitis Neospora, BHV-1, BVDV
Meningitis EBA, Leptospira, Brucella, other bacteria
Myocarditis Neospora, BVDV
Suppurative bronchopneumonia Bacteria
Bronchointerstitial pneumonia Ureaplasma, Brucella
Multifocal hepatic necrosis BHV-1, Listeria, Salmonella, Yersinia
Interstitial nephritis Neospora, Leptospira
Abomasitis/enterocolitis Bacteria, fungi
Conjunctivitis Bacteria, Ureaplasma, fungi
Placentitis Bacteria, fungi
Oxalate crystals, renal Congenital metabolic defect, associated with anomalies, ingestion of oxalate-
producing plants by dam
Liver: (1) Lipid; (2) fibrosis; (3) iron (1) Lipid-toxin exposure, lipodystrophy; (2) fibrosis-aflatoxin, passive congestion;
(3) iron-weak calf syndrome

Source: Based on [28].


BVDV, Bovine viral diarrhea virus; BTV, bluetongue virus; EBA, epizootic bovine abortion; BHV-1, bovine herpesvirus 1; SBV, Schmallenberg
bunyavirus.

encountered lesions in aborted fetuses. Other conditions ovine fetuses, changes associated strictly with autolysis
are listed further in the text. included (i) lack of odor, (ii) subcutaneous blood‑tinged
The most common finding in abortion is autolysis, the gelatinous edema, (iii) blood-tinged fluids in body cavities,
degree of which depends on the cause of death, the time (iv) renal cortex softening, (v) liver softening, (vi) abomasal
from death to abortion, and the time from abortion to content that was cloudy yellow to red, and (vii) uniform
examination [26]. In experimentally induced, sterile, dead color (pink/red) of tissues [29] (Figures 56.4 and 56.5). By
672 Fetal Disease and Abortion: Diagnosis and Causes

Figure 56.4 Aborted fetus; opened chest and abdomen. The Figure 56.6 Aborted fetus with Trueperella pyogenes infection;
lungs are uninflated (congenital atelectasis) and red with a shiny opened chest and abdomen. Fibrin strands are present on the
smooth pleura. Autolytic change is present (generalized reddening pleural surfaces. Autolytic change (generalized reddening of
of tissues, friable liver). Source: Photo courtesy of J. Edwards. tissues) is evident. Source: Photo courtesy of J. Cooley.

Figure 56.5 Fetus and placenta. The fetus exhibits generalized


red discoloration due to autolysis. Source: Photo courtesy of J.
Cooley.

12 hours after death, the fetal corneas were cloudy, the liver Figure 56.7 Fetal liver section with hepatitis. Multiple tan foci
of necrosis are surrounded by hyperemic parenchyma. Source:
and kidneys were friable, and abomasal content became Photo courtesy of J. Cooley.
cloudy with brown flecks. After 36 hours, the subcutis con-
tained edema and the skin would slough. By 144 hours,
progressive dehydration was obvious (mummifica-
tion) [29]. Signs of fetal infection include fibrinous exu-
dates in body cavities, white to tan foci in the liver or lungs,
and evidence of abnormal development [26] (Figure 56.6).
Pathogens that invade the fetus via umbilical veins may
produce lesions in the liver, as it is the first organ encoun-
tered (Figure 56.7). L. monocytogenes, BHV-1, Yersinia
pseudotuberculosis, and S. enterica infections are often
associated with liver necrosis. For pathogens that infect
the amniotic fluid, exposure of the skin, lung, and intes-
tines may occur. Skin lesions are particularly well known
in cases of fungal infection, where pale patches of thick-
ened skin are evident (Figure 56.8). Lung and pleural dis-
ease may be manifestations of hematogenous systemic
Figure 56.8 Fetus with fungal dermatitis. Coalescing, mildly
spread or inhalation of infected amniotic fluid during fetal bulging, gray/tan foci are present in the skin of the neck. Source:
distress [21]. Photo courtesy of J. Edwards.
­Teratolog  673

arthrogryposis, ankylosis, scoliosis, torticollis, and similar


defects that lead to dystocia, stillbirth, or death in the peri-
natal period.

T
­ eratology

Abnormal development (congenital defects) in the fetus


may be caused by teratogens: toxic substances, infectious
disease agents (particularly viruses), nutritional imbal-
ances, endocrine imbalances, hypoxia, extreme tempera-
tures, and inherited or spontaneous genetic mutations [33,
34]. The manifestation of these defects includes resorp-
Figure 56.9 Fetal liver. The surface is tan and coarsely tion/abortion, malformation, alteration of growth, and
irregular. This change may be seen with chronic passive functional deficits (Figure 56.10). The late embryonic
congestion (heart anomalies) or epizootic bovine abortion.
period and early fetal periods are the times of greatest sus-
Source: Photo courtesy of J. Edwards.
ceptibility for the conceptus. During this time, each organ
system is established in an orderly fashion with morpho-
Epizootic bovine abortion (EBA) causes distinctive genesis occurring in “critical periods.” During these peri-
lesions in the fetal liver, lymph nodes, and spleen. The liver ods organs are at their most sensitive to teratogens.
is irregular and nodular; however, this change may also be In many cases congenital defects have no defined cause.
seen in cases of congenital heart disease where chronic Seasonal occurrence, history of stress, or maternal disease
passive congestion occurs (Figure 56.9). The spleen and are often noted, with or without a familial component [35].
lymph nodes are characteristically enlarged due to lym- The genetic composition of the fetus as well as the nature
phoid and mononuclear cell hyperplasia [19]. Yellow/fatty, and degree of insult figure largely in the outcome [13].
enlarged, and even fibrotic/cirrhotic livers may be seen in Genetic considerations are discussed in greater detail in
hepatic lipodystrophy, a poorly understood condition that Chapter 70.
may be related to selenium deficiency, toxin exposure (pyr- In cattle, viral infections are well-known causes of
rolizidine alkaloid, aflatoxin), or other genetic causes [30, defects. BVDV, infectious bovine rhinotracheitis (IBR),
31]. Iron in the liver was reported in association with weak (BHV-1), Wesselsbron, bluetongue, Akabane (bunyavi-
calf syndrome (possibly due to selenium deficiency) [32]. ruses including Schmallenberg), and Rift Valley fever
(RVF) viruses are commonly associated with embryonic
loss and neuromuscular defects [36, 37]. In addition, toxic
­ utcome of Exposure
O plants such as lupines, Conium maculatum, and locoweeds
to Abortifacient Agents are associated with defects [35]. Further discussion of such
toxins is presented in Chapter 69.
Fetuses exposed to abortifacient agents or conditions may
die (resorption/abortion/stillbirth), they may be infected
(with or without disease), they may be malformed (live/
dead), or they may be normal [23].
Death in the embryonic stage leads to resorption. In the
fetal stage the presence of skin and musculoskeletal struc-
tures, in addition to placental endocrine activity, prevents
resorption. Instead fetal death leads to autolysis and expul-
sion, or retention with mummification/maceration. In late
gestation, a sick or stressed fetus may precipitate its own
premature delivery with one of three results: the fetus may
be born and then die, it may be born and fail to thrive, or it
may be born and thrive even if infected [21].
Disease may impair fetal motion, a necessary require-
ment for proper musculoskeletal development. In such Figure 56.10 Fetal monster. A thoracopagus with shared
cases, the calves may exhibit severe changes, including viscera and four forelimbs.
674 Fetal Disease and Abortion: Diagnosis and Causes

­Anatomy

(See Figure 56.13 for identification of some anatomical


terms.) The placenta is a transient metabolic organ derived
from the fetal chorion and maternal endometrium to pro-
vide nutrition and metabolic exchange between mother
and calf. Gestation can be divided into the embryonic stage
with organogenesis and the fetal stage with fetal growth.
The embryonic stage extends to around day 45; the fetal
stage continues until delivery. Together, the chorioallantois
and amnion form the extraembryonic fetal membranes.
After fertilization, the zygote undergoes cleavage to form
a ball of cells (morula). With further division the morula
develops into the blastocyst, which is an inner cell mass (the
Figure 56.11 Palatocheiloschisis; cleft palate and lip embryo proper) and a blastocoele (fluid-filled cavity) lined
(mandible removed). by the trophoblast cell layer. The blastocyst, now about
1.5 mm wide, hatches from the zona pellucida at 9–11 days
after ovulation in order to attach to the endometrium of the
uterus [38]. By 19 days, the bovine blastocyst trophoblast
enlarges as a threadlike emanation/sac along the entire
length of the uterine horn [37, 39]. At this time, defective
embryos will die and be resorbed or expelled. Also, the CL is
developing and producing progesterone [13].
The primitive endoderm from the inner cell mass
migrates along the inner aspect of the trophoblast, lining
the cavity that will become the yolk sac. The yolk sac pro-
vides nourishment to the conceptus and has developed on
about day 20, but will quickly regress to an inapparent
rudiment by day 30 [39–41]. At this time, prior to uterine
attachment, the conceptus derives nourishment from the
Figure 56.12 Chondrodysplasia; Dexter “bulldog” calf. secretions of the uterine mucosal glands, known as histo-
trophe. This material is a yellow/white, opaque, thick
Calves with congenital defects often die during parturi- secretion sometimes mistaken for purulent exudate [13].
tion or soon thereafter. In many cases the anomalies are Once the fetomaternal placental circulation develops, fetal
grossly obvious, often affecting the neural and musculo- nutrition is supplied by diffusion of nutrients from the
skeletal systems (Figure 56.11). A wide range of malforma- blood across the placentome (hemotrophe) [37].
tions have been described, some of which have been The primitive mesoderm migrates between the endoderm
intensively studied and a genetic component has been and trophoblast (now a trophectoderm), fusing with the lat-
found (Figure 56.12). For the purposes of this chapter, rel- ter to form the chorion (somatopleure). The chorion then
evant anomalies are generally discussed for those that are rapidly expands as a transparent sac to fill the uterine
caused by infectious agents (BVDV, Akabane virus) or lumen [42]. Around this time, dorsomedially migrating
those that are not known to be inherited but are particu- folds composed of mesoderm/trophectoderm surround the
larly puzzling when encountered (acardiac twins, moles). embryo between days 13 and 16, providing complete envel-
Reviews are available [13]. opment of the embryo in an amniotic cavity (vesicle) by day
35 [43]. The site where these folds meet, the raphe or mesa-
mnion, persists as a broad attachment of the dorsum of the
­Neoplasia amnion to the chorioallantois in Bovidae. The amnion is
therefore composed of an inner trophectoderm and subja-
Congenital tumors and neoplasms are rare in calves and cent mesoderm with extensive attachment to the allantois.
are most often diagnosed as lymphomas, mesotheliomas, Between days 14 and 21, a diverticulum of the hindgut
embryonic tumors, and hamartomas. They have been extends from the embryo into the mesoderm of the umbili-
reviewed [31]. cus to form the allantois (allantoic vesicle) and, along with
­Anatom  675

Allantois
Uterine wall
Fetal cotyledon

Chorion Amnion

Necrotic tip
of chorion
Umbilical
artery

Umbilical vein

Umbilical cord

Allantoamnion

Fetal
bladder

Amniotic
Placentome cavity
Amniochorion
Uterine wall

Allantoic cavity Chorion


Urachus

Chorionic cavity Urachus-allantoic


junction

Figure 56.13 Schematic representations of the fetus in-situ during mid-gestation. Source: Images redrawn by Kirstin Cook from K.
June Mullins and Richard Saacke Illustrated Anatomy of the Bovine Male and Female Reproductive Tract. Germinal Dimensions Inc.,
Cadmus Professional Communications, Science Press Division, Ephrata, PA, 2003.

it, the vasculature supplying the chorion and amnion [25]. fusely or in multiple, 5- to 10-mm-wide, regularly spaced
The allantois continues to expand within the exocoelom to foci. Such proliferation may cover non-gravid horns that
fill both uterine horns, with widespread apposition and contain no cotyledons.
eventual fusion to the chorion (chorioallantois). It is thus Placentomes are usually arranged in two dorsal and two
T-shaped, with the stem of the T as the allantoic stalk of the ventral rows along both horns, although an extra row or
umbilicus and the other ends of the T as extensions of the reduced rows may be seen (see Figure 56.13). They become
chorioallantois into both uterine horns [37]. The chorioal- progressively larger the closer they are to the fetus and the
lantois attaches at four weeks’ gestation to the uterus, majority of cotyledons are present in the gravid horn. The
forming irregular villous projections over the uterine largest placentomes are closest to the main arteries and
caruncles, with eventual development into placentomes. become progressively smaller toward the periphery. In
By days 30–35, three to four fragile attachments (early some cases all cotyledons are present in the gravid horn
placentomes) are present in the pregnant horn; by day 40 a with few to no cotyledons on the non-gravid side. The coty-
maximum of 20 attachments are present in both horns. At ledonary rows may be interrupted by a circular bare area
day 70, 80–90 placentomes are present, which will number associated with the junction of the horns, near the
75–140 by mid gestation. Placentome size may vary widely, cervix [45].
from 5 to 15 cm in diameter. The fetal cotyledon has a vel- As development progresses, there is fusion of mem-
vety red surface (Figures 56.14 and 56.15). Both the weight branes to one another in the areas where they come into
and size of placentomes increase during gestation, particu- contact (see Figure 56.13). These attachments may be tran-
larly in the pregnant horn [44]. Between placentomes, sient, but fusion of the allantois and chorion occurs around
there is minimal chorioallantoic villous proliferation, days 50–60 [43]. In early gestation, the amnion is relatively
which may be seen as fine red velvety spots occurring dif- large and compresses the allantois laterally. As the amnion
676 Fetal Disease and Abortion: Diagnosis and Causes

reported [25, 37]. Amniotic fluid in full-term cattle varies


from 2 to 8 l, with reported averages at 2.2 or 5–6 l. Allantoic
fluid at term ranges from 4 to 15 l, with an average of 9.5–
10 l [13, 46].
The umbilicus is relatively short, being about one-quar-
ter the length of the fetus, or about 30–40 cm [13]. As such,
rupture of the cord occurs during parturition when the
fetal pelvis passes through the dam’s pelvis [47]. The
umbilicus is exclusively within the amnion and is com-
posed of two arteries, two veins (which merge into one
prior to entering the fetus), the allantoic stalk, and rarely
yolk sac remnants. The umbilical arteries and veins are
sheathed in smooth muscle, which contracts during partu-
Figure 56.14 Normal placenta. Cotyledon has a red velvety rition due to stretching, stopping blood flow after birth [37].
surface. The intercotyledonary spaces are smooth, shiny, opaque, The umbilical arteries arise from the caudal aortae, run-
and white. ning cranioventrally along the urachus, exiting with the
allantoic stalk to supply the chorioallantois. In necropsied
neonates, it is common to see swollen, purple, thrombosed
umbilical arteries at the level of the urachus; this is a nor-
mal inflammatory reaction to the severing of fetomaternal
circulation (Figure 56.16). Thrombosis of umbilical arter-
ies will be absent in stillborn calves [48].
By day 45, fetal organogenesis is complete and the fetal
growth stage then begins. Average weights, crown–rump
lengths, and external characteristics achieved during
growth are summarized in Table 56.3.

­Approach to the Problem


Figure 56.15 Normal fetus and placenta after 2 months’ Fetal loss in a herd may be divided into four epidemiologic
gestation. The calf is suspended in the amnion (white arrows), presentations, which may simplify and better direct inves-
which is further surrounded by the chorioallantois. Cotyledons
are evident (black arrow). White flecking in the intercotyledonary tigations. These four include (i) baseline losses, (ii) endemic
placenta is calcium deposition (circle), an incidental finding (see losses that exceed baseline and occur consistently and
section “Mineralization”).

grows and contacts the chorion, the amniochorion is


formed; on the opposite side of the calf where the amnion
contacts the allantois, the allantoamnion is formed. With
maturity, the allantois increases in volume to almost
entirely surround the amnion.Thus the fetus is immedi-
ately surrounded by the amniotic fluid, which is produced
by transamniotic fluid fluxation, fluid from the fetal lungs,
oral glands, and urination. Initially the amniotic fluid is
watery, slightly yellow and clear; later in development it
becomes viscous, translucent, opaque, and white or yellow.
Urine throughout early development is excreted through
the urachus and umbilicus to the allantois, but it may also
be excreted through the urethra. The contribution of urine
Figure 56.16 Calf with umbilical artery thrombosis. Bilaterally
to the amniotic fluid after 240 days’ gestation in cattle has
the arteries alongside the urinary bladder (asterisk) are focally
not been conclusively decided; both increasing and swollen and red due to the tearing and thrombosis associated
decreasing late-term transurethral urination has been with parturition.
­History/Background Investigatio  677

Table 56.3 Gestational age estimates of bovine fetuses.

Crown–rump
Age (months) Relative size length (cm) Weight External characteristics

2 Mouse 6–8 8–30 g Claw buds and scrotum present


3 Rat 13–17 200–400 g Hair on lips, chin, and eyelids
4 Small cat 22–32 1–2 kg Fine hair on eyebrows, claws developed
5 Large cat 30–45 3–4 kg Hair on eyebrows and lips, testes in scrotum,
teats developing
6 Small dog, beagle 40–60 5–10 kg Hair on inside of ear and around horn pits, tip
of tail, and muzzle
7 Dog 55–75 8–18 kg Hair of metatarsal, metacarpal, and phalangeal
region of extremities and beginning on back,
long hair on tail tip
8 Large dog 60–85 15–25 kg Fine short hair all over body, incisor teeth not
erupted

Source: [28]. John Wiley & Sons, Inc. Original content from [13].

chronically, (iii) epidemic losses characterized by high Finally, managers should be encouraged to document
losses in a specific time frame, and (iv) fetal losses that are and report all abortions, stillbirths, premature births, dys-
confused with conception failure or neonatal losses [15]. mature calves, and abnormal calves.
Baseline losses, as mentioned in the Introduction, are
considered largely unavoidable and may be due to illness in
the dam, lethal genetic make-up of the fetus, trauma, or ­History/Background Investigation
physiological abnormalities. It is important to monitor
such losses from a management standpoint as it will aid The importance of a thorough history cannot be overstated;
the discovery of endemic problems. While it is prudent to essential information is found in a systematic query of farm
thoroughly investigate all abortions, it is also costly. details. Abortion is both an individual and potential herd
However, with continued monitoring and testing, the man- problem, and lack of investigation in both will severely ham-
ager and veterinarian have a clearer picture of herd health per efforts to alleviate unacceptably high losses. Differentiating
and are better prepared to identify endemic problems. stillbirths from abortions will help clarify if more than one
Furthermore, upcoming epidemics may be identified at a problem is present [48]. It is important to keep in mind that
stage where losses can be minimized [15]. more than one agent may be involved in abortion. Similarly,
Endemic abortions significantly affect herd productivity due although more than one infectious agent may be present in an
to chronic excessive losses. It may be difficult to realize that aborted fetus, only one may be the cause of death. Organisms
there is a problem, but equally difficult to identify the source of regarded as low virulence may be the cause of abortion, but
the losses. Accurate record-keeping and routine pregnancy are also commonly present as contaminants [20].
diagnosis are therefore vitally important in order to recognize Sporadic abortions may be a manifestation of an ongoing
these issues [15]. Table 56.1 lists many disease-causing agents herd problem or they may be the beginning of an outbreak;
that are associated with endemic losses in cattle. BVDV, N. in either case investigation is warranted. Standard forms are
caninum, and Leptospira spp. are of particular importance. used to reliably collect important cow and herd information
Epidemic abortion storms may be due to many of the (see Appendix); systematic evaluation of management
same agents that cause endemic losses. BHV-1, B. abortus, practices will help direct investigations. Pertinent questions
and Leptospira spp. are well-known causes [23]. Herd are listed below [49]. These questions and other informa-
health status, vaccination history, pathogen virulence, tion are incorporated into the investigation form provided.
access to toxic agents, and clustering of pregnancies all have An expanded questionnaire has been published [50].
relevance in determining the likelihood of epidemic loss.
Herds with tight pregnancy patterns are more susceptible to
Aborted Calf
this type of outbreak. Investigations should make note of
the particular time/season and area where the losses are ●● When was it due? Is this a stillbirth (after day 260) or
occurring as this will aid in determining differentials [15]. abortion?
678 Fetal Disease and Abortion: Diagnosis and Causes

●● Was it born alive? Collecting serum from ten other herdmates (or 10% of the
●● Are fetuses mostly male or female? herd) will make serological assessment more meaning-
ful [8]. Whole blood in ethylenediaminetetraacetic acid
(EDTA) is useful for blood smear and serum chemistry
Aborting Cow
analysis of the dam. Gloves are to be worn during all exam-
●● Breed, age, lactation/parity number, source, dam/sire, inations, as zoonotic agents may be present. Samples for
bred naturally or artificial insemination (AI), conception blood culture should be taken as well.
date/last service, date of last normal parturition, previ-
ous abortions, and any work-up done.
Examination of Tissues
●● Vaccination history, vaccine brand/lot number, vaccine
handling, and storage. A necropsy is an examination with a definite purpose in
●● Deworming history. order to yield the maximum amount of information. As
●● Any clinical signs? such, it is vitally important to be systematic so that a full
●● Parturient period – cow movement, calving location, complement of tissues is taken during each examination.
observation, assistance rendered? Optimally one should send the entire fetus and membranes
to a diagnostic laboratory for evaluation. It is of primary
importance to send fetal membranes as these may be diag-
Herd
nostic. If this is not convenient, then a standard approach
●● Number of animals, number that are immature, number should be adopted, as described here.
purchased in last year, health problems/body condition. Examinations should be directed toward suspected eti-
●● Herd abortion history (sporadic/recurrent/recent, how ologies, but keep in mind that more than one pathogen
many in last week/month/year, which trimester affected, may be present. Typical findings in aborted calves that died
affects older/younger/all cows, any particular time of in utero include edematous red tissues that lack normal
year), problems with term calves (congenital defects). tinctorial distinction, clear red fluids in body cavities, pale
●● Are postpartum examinations performed routinely? soft livers, and friable autolytic kidneys. Digital photo-
graphs are an excellent way to document lesions and may
be useful in communications with diagnostic laboratories.
Nutrition
●● Feeding regime, types of forage, concentrates, minerals,
Examination of the Fetus
selenium.
●● Any changes in management, housing, pasture? It is important to verify the approximate time of death,
●● What is the quality of the forage? which can be done based on gross findings. In antepartum
●● Water source/quality? fetal death, tissues are autolyzed or mummified and
include the findings described above. Partum death is char-
acterized by signs of life (localized head or limb edema,
Environment
partial lung aeration, limb/rib fractures, subcutaneous
●● Access of herd to other cattle, animals, predators. shoulder hemorrhage, liver fractures with hemorrhage) in
●● Nature and quality of pasture. addition to appropriate fetal maturation/formation.
●● Any toxic plants on pasture? Neonatal deaths are characterized by aeration of the lungs,
●● Nutrient deficiencies in area pasture? umbilical artery thrombosis (swollen purple/red nodules
along the arteries that run lateral to the urinary bladder),
loss of the eponychium (soft fetal hoof keratin), and milk
Examination of the Cow
in the stomachs [51].
In some cases, the health condition of the cow has direct The method of necropsy for aborted fetuses is basically
implications as to the cause of abortion (plane of nutrition, the same as for any animal. The degree of autolysis and
respiratory/intestinal disease, Anaplasma sp., Babesia sp. weight of the fetus and placenta are noted. Even if
infection). Any vaginal discharge or cervical mucus should severely autolyzed, fetal tissues may be of use for poly-
be collected and sent to the diagnostic laboratory for micro- merase chain reaction (PCR) screening for pathogens.
biological analysis. Blood samples for serology should be Estimation of gestational age can be accomplished by the
taken from the dam as well as unaffected cows and those following formula: x = 2.5(y + 21), where x is gestation
that have recently aborted. Serum should be acquired two age in days and y is crown–rump length in centime-
to three weeks later in order to provide paired samples. ters [9]. The crown is a point midway between the orbits
­History/Background Investigatio  679

on a line traversing the frontal eminence; the rump is the


base of the tail or first coccygeal vertebra [52]. In
embryos, the greatest total length may be used instead of
crown to rump. For stillbirths, fetal weight is useful in
the diagnosis of dystocia due to fetal–maternal dispro-
portion. Also, comparison of calf weight to thyroid
weight in cases of suspect hyperthyroidism (goiter) may
be useful. Reports of normal thyroid weight in calves
vary from 6.5 to over 18 g [53]. Further discussion on this
subject can be found in the section “Non-Infectious
Causes of Abortion.”
Most aborted calves have no gross lesions. Small white/
tan foci in the lungs, liver, and kidneys may be present and
indicate necrosis or inflammation. The presence of fibrin
on organ surfaces is helpful for confirming inflammation.
Figure 56.18 Fetus with white mineral grit present over the
Meconium on the perineum or in airways/stomach indi- shoulder. Not to be confused with fungal dermatitis. Source:
cates fetal stress and anoxia, typically associated with pla- Photo courtesy of J. Edwards.
centitis or dystocia (Figures 56.17). Hemorrhage and
fractures of shoulder and hip joints are most often seen as Necropsy Method
a result of dystocia.
It is best to have an abortion kit prepared beforehand;
Slightly raised, white skin plaques that are firmly adher-
Table 56.4 enumerates materials to have in a kit [54].
ent, particularly around the eyes and face, indicate fungal
Zoonotic pathogens may be present, so always wear gloves,
infection. Sometimes calves will have scattered white min-
protective clothing, and eye/face protection, and use careful
eral on the hair, which is easily removed; this finding is
technique when examining dams and fetal tissues. In addi-
not significant but must be distinguished from adherent
tion, materials used in standard field necropsies are needed:
fungal plaques (Figure 56.18). In abortion/stillbirth, the
clean water, bucket, brush, scale, and disinfectant. Make
lungs are uninflated; they are uniformly dull red/plum
sure to disinfect contaminated sites and equipment. If there
colored, heavy, and sink in formalin (see Figure 56.4). In
are questions as to which samples are best to take, contact
cases of dystocia where fetuses may have taken a partial
the diagnostic laboratory to confirm which samples will be
breath, there may be incompletely inflated lungs; assess
lung aeration in sections of cranial and caudal lobes by
degree of flotation in fixative/fluid. Make note of any milk Table 56.4 Contents for abortion kit.
in the stomachs, as this indicates colostrum consumption,
which will interfere with bacteriological and serological Knife (15-cm boning) and steel
findings [9]. Nitrile/rubber gloves
String and ruler for measurements
Shears (small tree limb variety works well)
Culturette swabs
Overalls, washable apron, rubber boots
Alcohol swabs, syringes, needles to draw blood/fluids
Scalpel blades and handle
Lighter
Red-top glass vacutainer tubes, purple-top EDTA tubes
Hatchet/cleaver and hacksaw
Sterile rat-tooth forceps and scissors
Styrofoam box/cooler for temporary specimen storage
Sterile containers/whirltop bags/ziplock bags, permanent pen
Fixative (10% neutral buffered formalin), at least 500 ml in plastic
Figure 56.17 Fetus and amnion (opened). The amniotic fluid sealable container/jar
and skin are stained yellow/brown due to meconium. Source: Bucket, brush, disinfectant
Photo courtesy of J. Cooley.
680 Fetal Disease and Abortion: Diagnosis and Causes

submitted for advice. Taking photographs of lesions is a any fractures. Slice multiple lung lobes, examining the
relatively simple and excellent practice which will aid cut sections for changes in the lobules and airways.
diagnosis. Examine the thyroid gland. Collect tissues, especially
lesions (see numbers 18 and 19).
1) Measure crown–rump length along the vertebral ridge
12) Examine the heart, making sure to inspect all four
(see section “Examination of the Fetus”) and weigh
main valves and four chambers. Look for ventricular
fetus and placenta separately. Examine skin for exu-
septal defects or other anomalies. Heart blood may be
date and abnormalities, around the eyes and face in
used for serology testing.
particular for signs of fungal infection. If skin lesions
13) Collect visceral organs, examining gastrointestinal
are present, perform scrapes for fungal culture/wet
tract last. Identify the kidneys, ureters, and urinary
mount examination.
bladder. Remove the gastrointestinal tract by incising
2) Note hair development/whiskers and muscle tone.
the root of the mesentery and continuing the cut to the
3) Examine the body for congenital abnormalities, umbil-
diaphragm along the dorsum, avoiding the urinary
ical hernias, cleft palates, facial anomalies, etc.
tract. The tract may then be lifted out of the abdomen,
4) Examine for hemorrhages, fractures, hypopyon/
leaving the colon attached and uncut. Collect tissues,
hyphema, and lingual edema.
especially lesions (see numbers 16–18).
5) Wash the surface of the fetus with water to remove
14) Remove the adrenal glands.
gross contaminants.
15) Remove the urinary tract, making multiple slices
6) With the left side down, reflect right legs with a knife
through the kidneys. Identify genital organs.
and continue the skin incision from cranial to caudal,
16) Serially section the liver and spleen.
reflecting the skin to the dorsal and ventral midlines.
17) Open the forestomachs and abomasum and examine for
Collect any pooled blood between incised tissue planes
content. Continue into the intestine, making several
with a syringe if available (for serology).
incisions along each major section (duodenum, jeju-
7) Open abdomen at the highest point along the caudal
num, ileum, cecum, colon). Examine content and the
aspect of the ribs, being careful not to contaminate any
mucosa.
peritoneal fluid or tissues. Aspirate any abdominal flu-
18) Collect organs (kidney, liver, lung, spleen, thymus,
ids with a sterile syringe, place in sterile tube, label,
adrenal) in sterile bags (placenta kept in separate bag),
and refrigerate. Such fluids may be used as fetal sera.
and refrigerate.
Continue the cut along the caudal aspect of the ribs,
19) Collect in formalin for histopathology: lung, liver, kidney,
along the lumbar area, and cranial to the pelvis to
spleen, heart, adrenal glands, skeletal muscle (three to four
expose the abdominal viscera. Note any lesions, and
sections including tongue, diaphragm), thyroid, ileum,
volume, character, and color of fluids.
skin (including eyelid), thymus, and mesenteric lymph
8) Incise the diaphragm (noting if negative pressure is
node in 5-mm sections.
present) and cut the ribs at the costal angles and along
20) Remove the head from the body at the atlanto-occipi-
the sternum; remove the chest wall. Aspirate any tho-
tal joint. Harvest the entire brain (can be done at the
racic fluids with a sterile syringe, place in sterile tube,
clinic), even if severely autolyzed, and place whole in
label, and refrigerate. Such fluids may be used as fetal
formalin. If the fetus is severely autolyzed, take a swab
sera. Note any lesions, and volume, character, and
culture of the brain tissue prior to fixation. The skull is
color of fluids. Pleural surface of the removed chest
relatively soft and can be easily opened with a saw,
wall may be used as a makeshift cutting board/sterile
making two cuts along the inner aspects of the occipi-
field for dissection.
tal condyles, cranially (and somewhat laterally along
9) Aspirate fluids from the unopened abomasum with
the curve of the calvaria) toward the inner aspects of
sterile syringe, place in sterile tube, label, and refriger-
the orbital rims. Make a third incision across the
ate. Note the character of the abomasal fluid. Take
orbital ridge, connecting the first two cuts. Pry the cra-
samples of any other suspicious fluids at this time.
nium from the skull in one piece. Flip the head over,
10) Examine the body cavities and organs in situ, making note
placing the dorsum of the brain in the palm of your
of fibrin, hemorrhages, or abnormally situated organs.
hand and, with a scalpel, gently cut the nervous attach-
11) Remove thoracic viscera from tongue to lung (pluck).
ments of the base of the brain, allowing the brain to
Examine the mouth; one may split the mandibular
fall into your hand.
symphysis with a knife. Incise the esophagus along the
21) Collect ocular fluid with a needle/syringe for nitrate/
entire length; incise the dorsal tracheal membrane
nitrite levels if needed, and freeze. Collect eyelid and
from the larynx to the bronchi. Examine the chest for
ear notch for histopathology.
­History/Background Investigatio  681

22) Open several joints, looking for purulent exudate,


fibrin, and hemorrhage.
23) Examine fetal membranes for exudates, lesions, and
abnormalities (see next section for detailed instruc-
tion). Remove dirt/debris from the membranes prior to
sampling.
24) Place two to three sections with cotyledons in a sterile
bag, and refrigerate; make impression smears of any
lesions.
Figure 56.19 Placental membrane examination method. (Left)
25) Harvest the placenta for histopathology (at least three
The long axis of the chorioallantois is arranged perpendicular to
to four sections including cotyledons and intercotyle- the umbilical stalk. (Right) An incision is made along the dotted
donary areas). white line, allowing the chorioallantoic sac to be opened
26) Collect amniotic fluid if available, refrigerate, and (direction of white arrow) and laid flat. In this way, the vascular
axis, cotyledons, and membranes can be thoroughly examined.
culture.
Source: Courtesy of Rachael Fishman.
27) Collect dam blood in red-top tube for serology (herd-
mate blood samples may be collected as well; ten cows
or 10% of the herd has been suggested). Blood in EDTA horn being much larger. In this way, vessels and cotyledon
can be used for PCR. rows (normally four) may be examined thoroughly. Fresh
cotyledons have a red velvety texture with a mildly irregu-
lar surface. The size variation, shape, color, consistency,
Examination of the Membranes
and degree of cotyledon mottling should be noted, as well
Collect as much of the membranes as possible and care- as degree of autolysis. Occasional small tags of attached
fully examine the chorioallantois and amnion, as lesions caruncular tissue may be seen. Cotyledon margins are typi-
may be subtle, focal, and easily overlooked. In many cases, cally sharply defined, and the intercotyledonary chorion is
little if any placenta can be examined. It is important to try white, translucent, and smooth. Adventitial placentation is
to verify if all membranes have been expelled. Because of a frequent finding that appears as small cotyledons or
the attachments of the amnion to the chorion, as well as villous tuft formations adjacent to the placentomes that
the short umbilicus, calves will rupture and escape both may cover the entire placenta. Abnormalities in the pla-
the amnion and chorioallantois at delivery. Typically, centa are described in the following sections.
membranes are found with cotyledons on the outside.
The fetal membranes may be laid out lengthwise to iden-
Sample Collection
tify the umbilicus which is continuous with the internal
aspect of the amnion. Examination of amniotic mem- A complete set of tissues should be collected in every
branes and fluids is best done at this time. The umbilicus is case [55]. Depending on the etiologic agent (particularly
composed of four muscular turgid vessels (arteries and bacterial), different organs may have significantly different
veins) loosely enmeshed in slippery membranes. The recovery rates; lung, liver, and abomasal fluid should all be
gravid horn is easily identified as the larger half of the tis- submitted for culture/examination to maximize suc-
sue and should have larger placentomes. Avascular chori- cess [56]. Biological specimens must be properly collected,
onic tips (necrotic tips) should be identified and inspected prepared, stored, and transported, otherwise diagnostic
carefully, as true placental lesions may be present in the accuracy will suffer. It is important to maintain aseptic
gravid horn near the tip [19]. The umbilicus contains the technique despite apparent tissue contamination; this is
umbilical arteries and veins, which form a useful longitudi- necessary to maximize chances for diagnosis as well as for
nal axis by which to orient the placenta. From there the prevention of zoonotic infection. Microbiology samples
internal aspect of the allantoic cavity may be examined, should be kept chilled and sent to the diagnostic laboratory
with attention to the nature of any fluids present, thickness as soon as possible in a Styrofoam cooler with ice packs for
and color of membranes, and peculiar odors. Allantoic cal- overnight courier shipping. If fresh tissue samples cannot
culi are typically found at this time. be sent within two to three days, freezing at −70 °C and
By placing the umbilical vessels at one side of the tissue, delivering on dry ice is ideal [55]. If necessary, specimens
a lengthwise incision along the opposite side of the pla- can be placed at −20 °C until dry ice can be obtained.
centa will allow the placenta to be opened and laid flat, Conventionally frozen tissues (−20 °C) are often acceptable
with the umbilical vessels forming the central axis for PCR testing of many pathogens. Abomasal and tho-
(Figure 56.19). The horns are unequal in size, the gravid racic/pericardial fluid samples should be sent in sterile
682 Fetal Disease and Abortion: Diagnosis and Causes

tubes without additives. Frozen fetal liver, lung, and kid- Fungal sampling should at least include affected cotyle-
ney (2.5–5 cm chunks, −20 °C) should be kept for testing in dons; however, it is best to send the entire placenta. Fetal
case nutritional or toxicologic disease is suspected after ini- infection is inconsistent, but lung, skin, and abomasal con-
tial examinations [49]. tents are useful.
Chilled or frozen tissues should be placed in sealed bags For histopathology, sections approximately 5 mm wide in
(whirlpack-type bags often leak), preferably with a second- 10% neutral buffered formalin are best. The brain, however,
ary bag around them. Fluids shipped in glass tubes require should be immersed whole in formalin, without dissection.
ample padding in tight-fitting containers. Absorbent mate- If the brain is liquefied, fix separately. For small lesions,
rials should also be included in the package to prevent several foci should be submitted. For large lesions, a few
soaking of the exterior, which complicates and may delay sections including the margin with normal and abnormal
the shipping process. Disposable diapers are an effective tissues should be collected. Identify clearly any lesions
option [49]. Contact your diagnostic laboratory for proper seen in order to alert the diagnostician.
packaging and shipping requirements for abortion sam- Tissue smears from abomasal content or placenta may
ples, as they may contain infectious and/or zoonotic agents. assist diagnosis; wet mount examination and preservation
Viruses may have very specific tissue tropisms and there- of air-dried smears can prove valuable for detecting bacte-
fore require certain tissues for isolation. Specimens need to ria, fungi, and protozoa.
be collected as soon as possible as autolysis can be very At least 10 volumes of formalin per volume of tissue are
damaging to virions. Virology samples for abortions are needed for proper fixation. Tissues should be allowed to fix
typically pooled, although placing tissues in separate bags for at least 24 hours, preferably 3 days. The brain in particu-
is ideal. Placental tissues should be bagged separately from lar requires ample fixative over 3–4 days. Addition of 1 part
fetal tissues. Do not pool samples from multiple abortions. ethanol to 9 parts formalin (10% ethanol, 90% formalin)
Tissues should be kept cool but not frozen until arrival at may be used to prevent freezing in cold climates [57]. If for-
the diagnostic laboratory. If tissues will not be immediately malin is not available, 70% ethanol may be used. Tissues
used, freezing at −70 °C is better than at −20 °C [49]. If live may be sent in formalin, otherwise fix tissues for 24 hours,
viruses are sent packed in dry ice for virus isolation, be sure drain, and send in bags with formalin-moistened gauze. Be
to place samples in airtight containers as the gaseous phase sure to double-bag samples as containers may rupture in
of dry ice is carbon dioxide, which can lower sample pH transit. Contact your diagnostic laboratory for instructions.
and inactivate some viruses. Certain laboratories may have For blood samples, blood from the dam as well as the
preferences for virological samples, particularly if a certain fetus is ideal. Fresh blood smears are particularly useful if
pathogen is highly suspected. anaplasmosis is suspected. Blood in EDTA is preferred for
Bacteriology tissue samples should be 2.5–5 cm per side in PCR testing. For serum samples, draw 8–10 ml of serum
order that surfaces may be heat seared for proper culture. into tubes without additives, allow to sit for one to two
External and gut samples should not be bagged with internal hours until the clot begins to retract, then place in the
organs. If samples are contaminated, sending a swab culture refrigerator overnight. Centrifuge at 1000×g for 10 minutes
(Culturette™) in addition to tissues may be helpful. For and decant serum; send in a separate sterile tube. One may
severely decomposed specimens, aseptically collected brain freeze the serum (do not freeze whole blood) until needed.
tissue may be useful for isolating pertinent organisms [26]. Table 56.5 lists typical sample storage conditions.

Table 56.5 Fresh specimens collected for fetal and neonatal diagnostics.

Test Storage Specimens Notes

Bacteriology/mycology Keep refrigerated not Stomach contents, Collect stomach contents or pericardial
(culture, PCR) frozen unless PCR only pericardial fluid, liver, fluid in a syringe with a large-gauge needle
lung, brain, placenta Package each specimen in separate
containers. Placental culture results are
often contaminated – evaluate critically
Virology (virus isolation, May be frozen (at Lung, liver, kidney, heart, Package each specimen in separate
fluorescent antibody test, −70 °C if necessary) blood, placenta containers
PCR)
Nutrition, toxicology May be frozen Liver, kidney, ocular fluid
Fetal/maternal fluids Keep refrigerated Dam serum/fetal fluids Paired (acute and convalescent) if possible
­History/Background Investigatio  683

Diagnosis be erroneously blamed, depending on what is found in the


submitted fetus [8]. A positive result for a pathogen using
Arrival at an accurate diagnosis is the result of the coopera-
only one test modality may lead to error; serology, tissue
tive efforts of the attending veterinarian and the diagnosti-
smears, PCR, and histopathology should all be utilized in
cians at the laboratory. Even with the submission of proper
order to reach a confirmatory diagnosis [58]. PCR is an
samples, the establishment of a definitive diagnosis is
optimal first-line approach.
problematic. Expulsion of a dead fetus often occurs hours
It is important to realize that more than one disease or
to days after death; the resulting autolysis makes the diffi-
management problem may be at work in a herd, complicat-
cult task of fetal lesion identification even more so. Fetal
ing the resolution of endemic problems. Multiple patho-
membranes, which may have the only significant lesions to
gens may be present; some may not be obvious, while those
be found, are often not present for examination. Also, in
that are readily evident may not be directly contributing to
many cases examined tissues are severely contaminated,
abortion. In these cases, determining the actual cause of
whether due to incomplete expulsion or from the environ-
abortion is challenging.
ment. Finally, diagnostic laboratories run routine tests to
Serology results must be cautiously interpreted. A positive
identify well-known causes of abortion in a timely manner.
sample from a cow indicates exposure, which may or may
As such, investigation of unusual or poorly understood eti-
not be relevant in light of vaccination status. Twofold to
ologies is beyond their purview [20].
fourfold increases in titer over two weeks may be significant,
Keep in mind that the majority of pregnancy wastage
particularly with herdmate samples for comparison [8].
occurs at earlier stages of development, when expelled tis-
However, it is likely that dam serum antibody levels have
sues are least likely to be noticed. Early gestation abortions
reached their peak by the time abortion occurs, so it is not
are often detected only weeks after the fact, making inves-
unexpected to see a lack of rise in titer two to three weeks
tigation and diagnosis all but impossible. The majority of
later [15]. Serology may be particularly useful in diagnosing
tissues examined by clinicians and diagnostic laboratories
BVDV, leptospirosis, anaplasmosis, and abortions where the
are of large fetuses, which may bias the interpretation of a
agent is difficult to demonstrate by other methods [20]. The
herd problem where losses occur at various gestation
presence of a specific antibody in fetal serum does not mean
stages. Late-stage abortions may be the result of injury
that particular agent is the cause of abortion; BVDV and N.
many weeks prior to expulsion; they may not exhibit
caninum are two examples. Serology results must be care-
important or telling changes that could be present in ear-
fully weighed with microbiology, histopathology, molecular
lier aborted fetuses, preventing accurate diagnosis. Worse
testing, and herd history data. Table 56.6 lists common diag-
yet, in an effort to find a cause, other coincident agents may
nostic tests for specific pathogens.

Table 56.6 Summary of diagnostic tests for bovine abortion.

Agent Preferred fetal tissues Preferred fetal diagnostic test Additional diagnostics

Bovine herpesvirus 1 Kidney, adrenal, liver, FA (frozen tissue), IHC, VI IHC of placenta if placentitis is present
lung
Bovine viral diarrhea Lung, heart, kidney, FA, IHC, VI, PCR Antigen-capture ELISA, RT-PCR
virus placenta, skin
Bluetongue virus Brain, spleen PCR, VI Fetal serology
Bunyaviruses (including Brain PCR Fetal/precolostral serology; congenital
Schmallenberg) abnormalities
Brucella Placenta, lung, Bacterial culture Culture of milk from dam; dam and fetal
abomasal contents, serology
uterine fluid
Listeria Placenta, lung, brain, Bacterial culture, IHC Gram’s stain of freshly aborted tissues, PCR
abomasal contents
Salmonella Placenta, liver, lung, Bacterial culture
abomasal contents

(Continued)
684 Fetal Disease and Abortion: Diagnosis and Causes

Table 56.6 (Continued)

Agent Preferred fetal tissues Preferred fetal diagnostic test Additional diagnostics

Yersinia Placenta, liver, lung, Bacterial culture


pseudotuberculosis abomasal contents,
intestines
Leptospira Kidney, placenta FA (fetal kidney smear), IHC, PCR of fetal urine; fetal and maternal
PCR serology
Ureaplasma Lung, abomasal Ureaplasma culture, PCR
contents, placenta
Campylobacter Lung, abomasal Campylobacter culture, IHC, Silver staining of histology tissues, PCR
contents, placenta darkfield microscopy
Epizootic bovine Thymus, spleen, Modified Steiner’s silver stain Elevated fetal serum immunoglobulins
abortion lymph nodes of histology slides, IHC
Chlamydia Placenta PCR, IHC, FA Macchiavello’s, Gimenez, or modified
acid-fast stains of histology slides
Coxiella burnetii Placenta PCR, IHC Macchiavello’s, Gimenez, or modified
acid-fast stains of histology slides
Fungi Placenta, abomasal Fungal culture, H&E Direct identification by KOH wet mounts of
contents, lung, skin skin or placenta or GMS and PAS stained
lesions histology slides
Tritrichomonas Placenta, abomasal Tritrichomonas culture, Darkfield microscopy of abomasal contents,
contents, lung Bodian’s silver stain of PCR. Examination of maternal uterine
histology slides, IHC, H&E discharge
Neospora Brain, lung, kidney, IHC, PCR Fetal serology (IFA, microagglutination
skeletal muscle, liver, titer, ELISA). Maternal serology
placenta
Sarcocystis Brain, lung, liver, IHC Genomic probe; ribosomal RNA assays
kidney, skeletal
muscle, placenta
Nutrient deficiency Liver, heart, thyroid Thyroid iodine assay Maternal blood-selenium, other
Liver mineral (selenium)
Congenital defects Fetal hair Fetal muscle Teratogenic virus testing
Toxicosis Liver, kidney, fat, Gas chromatography mass
urine, brain spectrometry
Abomasal/amniotic
fluid, thoracic fluid

Source: Based on [28].


ELISA, Enzyme-linked immunosorbent assay; FA, fluorescent antibody test; GMS, Gomori–methenamine silver stain; H&E, standard
histopathology stains; IFA, indirect fluorescence test; IHC, immunohistochemistry (usually formalin-fixed tissues); KOH, potassium hydroxide
test; PAS, periodic acid–Schiff stain; PCR, polymerase chain reaction; RT-PCR, reverse transcription PCR; VI, virus isolation.

­ pecific Manifestations of the


S must be present. The time course, which may take months,
Conceptus Relating to Pathology depends on the size of the fetus. This process generally
occurs in the second and third trimesters, when fetal bones
Mummification are sufficiently developed to resist resorption. As fetal fluids
are absorbed, tissues become compressed, shrunken, red/
Mummification is an uncommon event in which there is brown, and sticky to dry, without odor. As the membranes
often no certain cause. It is the process of progressive dehy- atrophy and the uterus involutes, hemorrhage occurs
dration and compaction of a sufficiently mature dead fetus between the uterus and fetal tissues, imparting the red
in utero. In order for this to occur, bacterial infection (tissue “hematic” sticky material onto the tissues (Figures 56.20
lytic organisms) of the dead fetus must be absent, no air can and 56.21). This hematic type of mummification apparently
be present in the uterus (closed cervix), and a functional CL is distinctly bovine [13, 36].
­Specific Manifestations of the Conceptus Relating to Patholog  685

Figure 56.20 Opened uterus with mummified fetuses. Friable,


non-odorous, hematic material obscures the fetuses. Source: Figure 56.22 Opened uterine horn with a macerated fetus.
Photo courtesy of J. Edwards. Bone fragments in purulent fluid remain. The ovary has a
retained corpus luteum. Source: Photo courtesy of J. Cooley.

(Figure 56.22). In cattle this is due to exposure of the


retained fetal tissues to bacteria. This occurs when there is
failure of fetal expulsion after death with retention of the
carcass partially or entirely within the uterus. The bacteria
may be those that caused fetal death or those that arrive
through an open cervix [12]. Maceration is distinct from
autolysis, which is digestion of tissues by endogenous
enzymes and requires no bacteria. When bacteria gain
access to a dead fetus in the reproductive tract, they are able
to multiply rapidly at body temperature and are relatively
insulated from the dam’s immune system. Bacterial diges-
tion of tissues and gas formation (emphysema) ensues. The
uterus surrounds the fetus and there is an intense metritis.
Figure 56.21 Fetal mummy. The carcass is shrunken and
In early gestation, macerated embryos are resorbed or
contracted with diffuse red/brown discoloration, dry tissues, and expelled with little exudate. After the first trimester, the
sunken eyes. Tissues lack odor and emphysema. Source: Photo fetal skeleton is sufficiently formed to resist disintegration,
courtesy of J. Edwards. and skeletal fragments may be retained. Bone fragments
may become embedded in the uterus or may perforate the
The uterus tightly wraps around the fetal materials, com- wall and remain free in the abdomen [60]. CL regression
pacting the mummy. The longer this proceeds, the drier and cervical dilation may be found on palpation. Cows may
and firmer the fetus becomes, remaining in utero for as display vague signs of illness due to a persistent and severe
long as two years. In the cow, mummification is most com- uterine infection [19].
mon at the end of the first and beginning of the second Emphysema usually occurs when incomplete abortion or
trimesters [60]. Various infectious and non-infectious eti- near-term dystocia allow putrefactive vaginal flora to invade
ologies have been implicated in their occurrence (BVDV, the dead fetus. Incomplete abortion occurs when there is
tritrichomoniasis), but the cause is usually unknown [12, partial cervical dilation and insufficient expulsion of the
19]. Mummification may be associated with certain breeds fetus, which is partly or totally retained in the uterus [19].
(Guernsey, Jersey) or certain breeding/genetic combina-
tions [13]. In cases of uncomplicated mummification,
Embryonic Death with Persistent Membranes
prognosis is good for return to fertility [36].
(Moles)
Moles are not neoplasms, but are masses of hyperplastic or
Maceration
edematous immature placental tissue [61]. Once fertilization
Maceration describes the effect of dead fetal tissue soften- occurs, the blastocyst divides into embryonic and extraem-
ing due to fluid soaking and saprophytic digestion in utero bryonic tissues; the latter becomes the trophoblast, which is
686 Fetal Disease and Abortion: Diagnosis and Causes

the forerunner of the placenta. Later in development, cardiac tissue remnants. Despite this, a functional heart is
endodermal and mesodermal tissues from the embryo absent. They develop in association with a twin that has
migrate along the inner aspect of the trophoblast to form the sufficiently normal cardiovascular function to support the
chorion, which is the outermost fetal tissue that is in contact monster through placental vascular anastomoses [69].
with the uterus. Thus, embryonic mesenchyme contributes Various theories as to their development have been pro-
to the stroma of the placenta. This is an important point, for posed [70]. In cattle, such twins often manifest as globoid,
in order to form placental tissues, embryonic tissue must hair-covered masses of soft tissue attached to an umbilicus
have been present [61, 62]. Thus it is not surprising to find (Figure 56.23). Other monsters have rudimentary limbs,
fetal tissues in moles, even though it is rare. faces, and teeth. In rare cases multiple monstrous anoma-
Hydatidiform moles are defined in humans by macro- lies may be present [13].
scopic features and are termed (complete and partial)
based on the degree of fluid accumulation. They are
Adventitial Placentation
named hydatidiform for their abundant, bulbous, botry-
oid to polypoid villi, which are edematous with watery In some cases, particularly in older multiparous cows and
fluid-filled cisterns. Villous edema and trophoblastic those with a history of metritis, there is inadequate placen-
hyperplasia are constant and characteristic features [61, tomal development due to uterine damage. To compensate,
63]. The hydropic swelling seen in moles may also occur the intercotyledonary chorion develops bright-red to tan,
in unrelated gestational disorders, such as maldevelop- fine, villous structures and small accessory cotyledons
ment of the placental vasculature or edema following (adventitial placentation) (Figures 56.24 and 56.25). In some
early fetal death [64]. cases proliferation may be abundant [13]. Rarely, villous pro-
In humans, complete moles are derived from an anucle- liferation may appear as a diffuse process with few or no
ate egg fertilized by one or two sperm, leading to a pater- obvious placentomes due to destruction of caruncles [71,
nally derived (androgenetic) tissue, most often 46XX. 72]. This process may be incidental, but excessive adventitial
Conversely, partial moles arise from the fertilization of an placentation may be associated with pathologic conditions
ovum by two sperm, generating a triploid conceptus [61]. such as hydrallantois [19, 73]. This condition indicates sub-
Such anomalies lead to fetal loss, but membranes survive normal placental capacity and such cows, particularly if
and proliferate (mole). other stressors are involved, may not be able to maintain
Moles in cattle are rare and have been reported as hyda- full-term calves, resulting in late-term abortions/stillbirth.
tidiform or cystic [19, 65–67]. Bovine placental masses simi-
lar to hydatidiform moles in humans have been reported to
Dropsy of the Fetal Sacs (Hydramnios/
be between 40 and 60 cm wide and weighing up to 48 kg [66].
Hydrallantois)
The masses are smooth, soft/firm, ovoid/irregular, and pale
gray/tan with multiple pendulous nodules that appear fatty. Hydramnios and hydrallantois refer to excessive accumulation
They are often associated with twinning [66, 67]. Microscopic of fluids in the amnion and allantois cavities, respectively;
descriptions resemble descriptions in the human litera-
ture [67, 68]. Recently, a mole of androgenetic origin (60XX)
was reported in association with a stillborn male calf [66].
More commonly, moles in cattle have been termed “cystic
placental moles.” They are thought to arise after fetal death,
with or without resorption, where membranes persist as an
empty cystic structure of a size similar to normal membranes
at three to four months’ gestation [19, 65]. The cyst is filled
with clear gel-fluid and stroma. In some cases, the tissues
become infected, leading to pyometra and expulsion [19].

Acardiac Twins
Acardiac twins (acardiac monster, amorphous globosus,
holoacardius acephalus, holoacardius amorphous) are the
most bizarre and severely malformed fetuses imaginable.
They represent a twin whose development is completely Figure 56.23 Acardiac monster with umbilicus. A hair-covered
disturbed and, unlike the name, may indeed have some soft tissue globe. Source: Photo courtesy of J. Cooley.
­Specific Manifestations of the Conceptus Relating to Patholog  687

grossly normal. Fluid accumulation may reach 250 l. [74]


Fetuses are usually born dead or are small and may have
ascites or anasarca (Figure 56.26) [19, 73]. A heritable con-
dition was identified in Japanese Black cattle in which fetal
polyuria led to hydrallantois and secondary pressure-
induced hydronephrosis, a correlation which has been
reported in other breeds [76, 77].
Hydramnios is much less common than hydrallantois. It
is associated with fetal malformations that may be congen-
ital or inherited. Congenital defects include any severe
anomaly, such as schistosomus reflexus, that impairs nor-
mal swallowing. Inherited defects include Dexter bulldog
fetuses (see Figure 56.12), hydrocephalic Hereford fetuses,
Figure 56.24 Chorioallantois, maternal aspect, with adventitial Angus fetuses with osteopetrosis, and Guernsey fetuses
placentation. Placenta (top) has been partially pulled away from with pituitary hypoplasia [13].
the endometrium (bottom). Cotyledon proliferation is irregular
but tissues are shiny, without fibrin, intercotyledonary
hemorrhage, or necrosis. Source: Photo courtesy of J. Cooley. Fetal Dropsy
Fetal dropsy encompasses three main presentations: ana-
sarca, ascites, and hydrocephalus. Fetal anasarca may be
seen with dropsy of fetal sacs (Figures 56.26 and 56.27). It
is sometimes associated with genetic defects such as pul-
monary hypoplasia. Fluid accumulates in soft tissues, often
enlarging the fetus such that cesarean section is
required [78]. Fetal ascites may be commonly seen in cases
of infectious abortion or developmental defects. Ascites or
placental edema may occur as a rare accompaniment to B.
abortus infection [13, 36].

Hydrocephalus

Figure 56.25 Chorioallantois, fetal aspect, with adventitial Hydrocephalus refers to an absolute increase in cerebrospinal
placentation. Arteries and veins (white) arborize onto the fluid (CSF) within the brain ventricular system, within the
coalescing placentomes. Source: Photo courtesy of J. Cooley. meninges, or both (Figure 56.28). Congenital hydrocephalus

edema of the chorioallantoic membrane may also be present.


In most cases, aside from Dexter bulldog calves, fluid accumu-
lation occurs in the last trimester [36]. Fetal swallowing partly
regulates amniotic fluid volume in the second half of gesta-
tion; conditions that prevent or slow fetal swallowing may lead
to fluid retention [45]. Allantoic fluid is a watery fluid gener-
ated by the fetal kidney. It is excreted through the urachus,
reaching 8–20 l at term. Amniotic fluid is more viscous and
glairy (albuminous), due in part to fetal salivary secretions.
Hydrallantois is associated with placental dysfunction
and is seen with uterine or placental disease. It is generally
considered a maternal placentation problem and adventi-
tial placentation is commonly present [74]. This condition
is seen sporadically in dairy and beef cattle and has been
reported with Sida carpinifolia toxicosis in Brazil [75]. It is Figure 56.26 Fetus and placenta. The fetus is edematous
(anasarca) with yellow/brown skin due to meconium staining.
more common in twin pregnancies. Membranes may be The allantois is markedly expanded by edema (hydrallantois).
more fibrous than normal, but the character of the fluid is Source: Photo courtesy of J. Cooley.
688 Fetal Disease and Abortion: Diagnosis and Causes

infection. The brainstem, cerebellum, hippocampus, and


olfactory regions may be spared. The bones of the skull cav-
ity are generally normal [79]. Other causes of congenital
hydrocephalus include Veratrum californicum ingestion by
pregnant cows and vitamin A deficiency [82]. The cause of
hydrocephalus may be difficult or impossible to determine
in some cases.

Amniotic Plaques
Amniotic plaques are normal, discrete, flat, white, 2–20 mm
wide, round to irregular foci of squamous epithelium on
the internal surface of the amnion (Figures 56.29
Figure 56.27 Fetus with anasarca. Source: Photo courtesy of J. and 56.30). Immediately around the umbilicus they may
Edwards. become papillary or villous. They often resolve by six
months’ gestation, occur most often around the umbilicus,
and are not found on the fetus. Plaques are not considered
to be of pathologic significance and are not associated with

Figure 56.28 Brain, dorsolateral aspect. Hydrocephalus, with


collapse of cerebral hemispheres and cerebellar coning.

occurs in two main forms: obstructive (hypertensive) and


compensatory (normotensive). Obstructive hydrocephalus is Figure 56.29 Fetus and placenta (amniotic surface exposed).
The umbilicus and amnion are covered by amniotic plaques.
associated with an inherited malformation, the most common Source: Photo courtesy of J. Cooley.
of which is stenosis of the mesencephalic aqueduct [79]. Six
such heritable forms have been described in Holstein, Jersey,
Hereford, Charolais, Ayrshire, Dexter, and Whitebred
Shorthorn breeds. Affected calves often have many other
obvious defects [80]. Characteristically, there is marked dom-
ing of the skull with malformation of the bones of the
cranium [81].
Compensatory hydrocephalus, on the other hand, arises
as a result of CSF accumulation after severe brain necrosis.
It is often associated with in utero infections with BVDV
and Akabane, RVF, Wesselsbron, Schmallenberg, and blue-
tongue viruses. Hydranencephaly is a form of compensa-
tory hydrocephalus where the neopallium (outer cerebrum)
has been reduced to a very thin, almost translucent mem-
brane with little to no parenchyma (see section “Bovine
Figure 56.30 Placenta, umbilicus, and fetal aspect of amnion.
Viral Diarrhea Virus (BVDV) Infection”). Such lesions Numerous coalescing amniotic plaques cover the amnion.
result from the aplastic and necrotizing effects of viral Source: Photo courtesy of J. Cooley.
­Specific Manifestations of the Conceptus Relating to Patholog  689

signs of inflammation. They are to be distinguished from


fungal plaques. Their presence is useful for orientation of
tissues for examination as they occur on the internal (fetal)
side of the amnion [19].

Mineralization
Mineralization of the allantois or amnion appears as a net-
work of white spots or streaks, typically associated with
small vessels (see Figure 56.15). The material is not gritty
but is soft, occurring most often in the second trimes-
ter [19]. After this time the mineral disappears and is prob-
ably incorporated into fetal bone [13]. Mineral may also be
present on the coat of the calf which may be easily wiped Figure 56.32 Hippomane and avascular chorion tip. Source:
from the hair (see Figure 56.18). The origin and signifi- Photo courtesy of J. Edwards.
cance of this finding is uncertain, but it must be differenti-
ated from fungal dermatitis. Allantoic calculi are irregular, discoid, rubbery, tan masses
with tapering margins, 3–15 cm wide and up to 4 cm
thick [13]. They have been described in horses, donkeys,
Necrotic Tips
zebras, cattle, deer, goats, and ewes, among others [84]. In
Necrotic tips (Figure 56.31), or avascular chorion, is a nor- cattle they are common and may be multiple. They are not
mal area of necrosis occurring at the extreme tips of the known to be of significance.
chorioallantois of both horns. These areas are pale tan,
shrunken, up to a few centimeters long, and clearly demar-
Meconium
cated from the villous chorioallantois. Necrotic tips may be
unilateral, particularly in the non-gravid horn. In some Meconium is a combination of sloughed intestinal and epi-
cases, necrosis of the non-gravid horn may involve as much dermal cells, mucus, bile acids, and various other metabo-
as the entire horn [45]. lites of fetal development. These contributed materials
collect in the fetal colon, where water and electrolyte
absorption forms thick, brown, tenacious feces that may
Allantoic Calculi (Hippomanes in Horses)
develop into pellets. Calves will also shed hair into the
Known since the time of Aristotle (hippomane means amniotic fluid, which is then swallowed by the fetus and
“horse madness”), these allantoic aggregates are composed collected in the colon to be expelled as part of the meco-
of mineral and mucoprotein that deposit in progressive nium. As such, meconium pellets may be composed of
laminations around a nidus of cell debris (Figure 56.32) [83]. abundant matted hair, which may be expelled into the
amniotic fluid or may be ingested and found in the alimen-
tary tract of the fetus [39, 85]. In cases of fetal stress/
hypoxia, meconium may be prematurely expelled and aspi-
rated, causing discolored amniotic fluid, smearing of meco-
nium on the fetus, and meconium in airways (Figures 56.26
and 56.33).

Arthrogryposis
Arthrogryposis describes a condition where congenital
joint contractures occur in one or many limbs and may be
associated with scoliosis, kyphosis, lordosis, and torticollis.
The limbs are rigidly fixed and variably bent in every sort of
unnatural position. These changes occur as a result of
decreased limb movement due to myogenic or neurologic
Figure 56.31 Chorioallantois with uterine horn tips. The horn
at the top is avascular and shrunken. The lower horn tip is abnormalities. As a result of neurologic disease in utero,
relatively normal. Source: Photo courtesy of J. Edwards. muscles are underdeveloped and articular surfaces are
690 Fetal Disease and Abortion: Diagnosis and Causes

Figure 56.33 Meconium aspiration; stillbirth due to severe Figure 56.34 Spina bifida; failure of proper development of
neurologic malformation (Chiari-like). vertebra, spinal cord, and skin over lumbosacral area.

misshapen due to lack of proper stimuli. It may occur spo-


radically, in association with viral infection (bluetongue,
Akabane, BVDV, Schmallenberg), or due to maternal toxin
ingestion (lupines, poison hemlock, some types of tobacco).
Breed-associated syndromes in cattle have been described.
Arthrogrypotic fetuses are associated with stillbirth,
hydramnios, and dystocia for obvious reasons [86].

Congenital Skin/External Lesions


A variety of abnormal conditions may present in the skin Figure 56.35 Hypospadia; failure of the ventral urethal fold to
and can be hereditary, but not necessarily so. Hypotrichosis/ close from anus (far right) to prepuce (left).
alopecia, a less than normal amount of hair, is one of the
best described and many heritable forms are known [87]. Hypospadias are the failure of the urethral folds to join,
Non-genetic causes include iodine deficiency (fetal goiter), and in severe forms may present as linear fissures from
pituitary hypoplasia, maternal ingestion of Veratrum album, the perineum to the prepuce (Figure 56.35).
BVDV infection, and autoimmunity [88]. Calves may lack Epitheliogenesis imperfecta, an inherited absence of skin
hair entirely or have thin, soft, and even curly hair. Affected formation, presents as large red defects in the distal limb
areas are usually symmetric and the skin itself appears nor- skin/hooves and additional oral lesions [89, 90].
mal. The distribution can be patchy and calves may also Non-symmetrical skin defects can occur as a result of
have dental anomalies. A rare and distinctive condition is fragile skin collagen (asthenia/dermatosparaxis) or
ichthyosis fetalis, in which generalized alopecia is combined vesicobullous disease (epidermolysis bullosa, familial
with marked hyperkeratosis, resulting in fissures or plate- acantholysis of Angus calves, mechanobullous disease
like folding of the skin over the entire body. Calves may be of Brangus calves). These conditions are hereditary
stillborn or die soon after birth; it is hereditary [87]. and rare; definitive diagnosis requires histopathology
Defects, tears, and ulcers in the skin at birth can be due and electron microscopy [87, 89].
to various conditions. One of the more common is spina
bifida (spinal dysraphism), a congenital defect in spinal
development. In its most mild form calves have small areas
­Causes of Abortion
of alopecic or glabrous skin on the dorsal lumbar midline
(Figure 56.34). The underlying muscle, bone, and spinal
Embryonic Death
cord have varying degrees of malformation, with a lack of
the fusion normally seen in neuraxial folding. Lesions may The early part of gestation is a time when fetal organ systems
bulge due to meningomyelocele formation. In some cases and extraembryonic membranes develop to achieve placen-
the spinal canal is continuous with the skin and in severe tation, which is the point at which the chorion and endome-
cases there are anomalies of the head as well. trium attach. Prior to this, the uterus must be presented with
­Fetal Death (Days 42–260  691

an embryo by days 15–17 in order to prevent luteolysis and Abortion may be observed in association with severe
maintain pregnancy [91]. Failure to do so leads to early abdominal trauma or stress, starvation, fetal hyperthermia
embryonic death. Late embryonic death occurs after mater- or hypoxia, genetic abnormalities, and environmental
nal recognition but prior to the fetal stage (days 42–260). causes (toxic plants, phytotoxins, mycotoxins, pharmaceu-
A variety of factors contribute to embryonic death, ticals), and from iatrogenic intervention.
including heat stress, metritis, maternal endocrine abnor- Toxic causes of abortion may be particularly difficult to
malities (progesterone), aged gametes, trauma, genetic diagnose, especially if they are not one of the better-known
abnormalities, nutritional deficiencies, and maternal–fetal varieties. Specific lesions associated with certain toxins
incompatibilities [1]. Infectious disease is able to cause may be poorly described and therefore not easily recog-
embryonic loss in three major ways: (i) the uterine environ- nized. Subclinical toxin exposure may lead to fetal death
ment of a febrile cow is also hyperthermic and may lead to and abortion in an otherwise normal-appearing cow.
loss; (ii) infectious organisms may directly infect the Diagnosis in such cases is unlikely to be recognized by rou-
embryo or may interfere with the uterine environment; tine examination [20]. For specifics the reader is referred to
and (iii) endotoxin from Gram-negative bacterial infection Chapter 69 on the subject.
may lead to premature luteolysis [1]. Therapeutic estrogenic compounds, PGs, or glucocorti-
coids may induce abortion [13]. Vitamin A is teratogenic,
whether in deficiency or excess, and is associated with
defective musculoskeletal and neural development which
­Fetal Death (Days 42–260)
may lead to abortion [95].
Iodine deficiency has been reported in cases of fetal
Non-Infectious Causes of Abortion
hyperplastic goiter in association with weak, alopecic, still-
Twinning is associated with higher rates (three to seven born, and aborted calves [96]. Causes for hypothyroidism
times normal) of stillbirth and abortion as well as retained in cattle include forage/water low in iodine, selenium defi-
membranes [92]. Abortion may occur at any time during ciency, ingestion of goitrogenic plants, or genetic reasons
gestation; rates of 30–40% have been reported for twin (Afrikaner cattle) [97, 98]. The thyroid gland in such cases
pregnancies [13]. In bovine twins, placental vessel anasto- is large and may weigh more than 30 g. Both iodine-defi-
moses are almost always present, leading to fetal chimer- cient diets and high calcium intake have been impli-
ism and freemartins. cated [99]. For suspected cases, removal of the entire
Umbilical cord constriction is a rarely reported cause of thyroid gland is advised. Weigh the entire gland, fix half in
abortion. This is largely due to three factors. Firstly, in the formalin, and submit the rest fresh for iodine analysis.
calf the umbilicus remains entirely within the amnion and Gland weight above 30 g in addition to thyroid iodine con-
is relatively short near term, such that rotation about the centrations below 1000 mg/kg (or thyroid iodine wet
long axis (rolling over) is rarely possible. Secondly, the weight 0.03% or dry weight 0.01%) and consistent histologi-
amnion is extensively fused to the chorioallantois, prevent- cal changes are necessary for diagnosis [98, 99].
ing rotation of the amnion within the chorioallantois, Excessive dietary selenium has been associated with
unlike the mare. Thirdly, at five to six months’ gestation, abortion or weak calves, with accumulation in the
the length of the calf exceeds the amnion width. By this liver [100]. Conversely, selenium/vitamin A/E deficiency
stage, 95% of calves adopt an anterior presentation and has been associated with poor fertility, cardiac mineraliza-
cannot rotate around their transverse axes, preventing tion, ascites, stillbirth, and abortion [101–104].
umbilical twisting and compression. In the mare, fetal Finally, allergies or assumed anaphylactic reactions due
anterior presentation is not firmly adopted until the ninth to vaccines have been associated with abortion [13].
month [93]. If these assumptions are valid, then any con-
striction, twist, or entanglement should have occurred
Infectious Causes of Abortion
before the third trimester. Development would then pro-
ceed with relative normalcy until near term, when progres- The remainder of this chapter deals with contagious and
sive umbilical constriction could impair venous and non-contagious abortion-related pathogens. In Table 56.7
allantoic outflow. The result would be placental edema and the approximate gestational stage of abortion is listed for
possible abortion. Such a situation was suggested in a various agents [105]. For each broad category of pathogen
report of term abortion with placental edema in a Belgian (bacteria, virus, protozoa, fungi), sequential preference is
White Blue calf, a breed in which it may be more common. often given in order of perceived importance. Many patho-
Calves have had their cords wrapped around the abdomen, gens are included in this section, partly due to their custom-
legs, or neck [94]. ary inclusion in other references concerning abortion, but
692 Fetal Disease and Abortion: Diagnosis and Causes

Table 56.7 Approximate stages of development when abortion occurs for specific pathogens.

Agent Embryo Early Mid Late

Anaplasma marginale L
Trueperella pyogenes L L
Aspergillus fumigatus L L
Bluetongue virus L L L
Bovine herpesvirus 1 (IBR) V V V
Bovine viral diarrhea virus V V V
Brucella abortus H
Campylobacter fetus L L L
Chlamydia spp. L
Coxiella burnetii L
Epizootic bovine abortion L V
Histophilus somni L
Leptospira spp. V
Listeria monocytogenes L
Mortierella wolfii L L
Mucor spp. L L
Neospora caninum V L
Salmonella spp. V V
Tritrichomonas foetus L L
Ureaplasma spp. L

Source: Adapted from [56, 105].


L, Low herd abortion rate; V, variable herd abortion rate; H, high herd abortion rate.

also for the sake of completeness and utility as a reference. tion of pregnancy, leading to prolonged estrus in cows. If
Several of these organisms are discussed in other chapters bacterial replication in the uterus is slower, mid-gestation
and detailed information can be found therein. For those abortions are seen [14]. Non-venereally transmitted C. fetus
pathogens that are only mentioned in this chapter, further subsp. fetus or Campylobacter jejuni infections are associated
discussion is included in the following text. with sporadic abortion due to ingestion of infected material/
Zoonotic pathogens include B. abortus, Campylobacter tissues [106].
spp., Mycobacterium bovis, L. monocytogenes, Coxiella bur- In infected herds, low fertility rates and abortion (<10%)
netii, Leptospira spp., and Salmonella spp. are typical. Abortions are uncommon and occur most often
at four to six months’ gestation, but may occur in the last
trimester; fetuses may be autolyzed, freshly dead, or even
Bacteria
delivered alive [20, 27]. Gross fetal lesions are non-specific
Campylobacter fetus subsp. venerealis Infection and include fibrinous pleuritis, pericarditis, and peritoni-
C. fetus is the cause of widespread venereal disease in cattle tis [27, 107]. Membranes are not typically retained and may
associated with infertility, embryonic mortality, and, uncom- have lesions that resemble Brucella sp. infection, such as
monly, abortion [106]. C. fetus is an obligate pathogen of the thickened leathery intercotyledonary spaces and variably
female reproductive tract, causing a mild transient endome- necrotic cotyledons [19]. However, placental lesions are
tritis [14]. After coitus, bacteria spread from the vagina to the variable and often subtle or inapparent.
uterus within two weeks. However, infection does not seem Darkfield examination of abomasal contents will reveal
to impair fertilization and early embryonic development. motile bacteria with rapid darting movements; this is charac-
Subsequent rapid bacterial replication in the uterus incites teristic of C. fetus or C. jejuni [14]. Organisms can be cultured
inflammation, leading to embryonic death between 30 and from aborted tissues (lung, placenta, abomasal fluid), but iso-
70 days’ gestation. This often occurs after maternal recogni- lation may be problematic as drying is highly detrimental to
­Fetal Death (Days 42–260  693

viability. Several types of transport enrichment media are fluid with diffuse cotyledonary necrosis (tan, uniformly
available; contact your local laboratory for preferred meth- affected) [26]. These changes are similar to those seen in
ods. Amies transport medium with or without charcoal is BHV-1 infection.
particularly useful for cultures [27, 106]. Fresh specimens are essential for isolating the bacteria, as
bacterial competition, desiccation, and acid pH are detrimen-
Leptospirosis tal to leptospiral survival [109]. Pericardial fluid, abomasal
Leptospirosis is a worldwide infectious disease of many fluid, and kidney are particularly good samples for finding
species (including humans), with highest prevalence in bacteria. Bacterial lability and autolysis of samples makes
tropical areas [108]. Antigenically distinct serovars of isolation difficult and inefficient [27, 113]. Opportunistic bac-
Leptospira spp. (Icterohaemorrhagiae, Hardjo, Pomona, teria (T. pyogenes, Bacillus spp.) may also be present in
Grippotyphosa, etc.) may belong to more than one genomic aborted specimens, obscuring leptospiral involvement [19].
species (L. interrogans sensu stricto and Leptospira borg- One of the best methods for diagnosis is by serology
petersenii), since bacteria are classified into serogroups as using the microscopic agglutination test (MAT).
well as genomic species [108, 109]. In cattle, L. interrogans Immunohistochemical tests are used for identifying bacte-
serovar Hardjo type hardjoprajitno and L. borgpetersenii ria in fixed tissues and fluorescent antibody (FA) tests may
serovar Hardjo type hardjo-bovis are the most important be used on frozen material. The kidney, lung, placenta, and
causes of abortion, stillbirth, and reproductive failure [19]. adrenal glands are most useful for finding antigen [14, 19].
These Hardjo types (hardjoprajitno and hardjo-bovis) are Refrigerated samples should be sent to the diagnostic labo-
of particular importance in cattle; both are adapted/main- ratory promptly. PCR testing is available. For detailed dis-
tained in cattle (cattle are incidental hosts for Pomona and cussion concerning diagnosis see Chapter 59.
Grippotyphosa). Infection in maintenance hosts is charac-
terized by efficient transmission, high incidence of infec- Brucellosis
tion, chronic disease, persistence in the urinary tract, poor Brucella abortus is a highly contagious, zoonotic, intracel-
antibody response, and few organisms in tissues [14]. The lular bacterium that is an important cause of abortion and
Hardjo strain important in the USA and found throughout infertility in cattle. Cattle are the primary host of B. abor-
the world is L. borgpetersenii serovar Hardjo type hardjo- tus, which is widespread in Africa, Asia, Europe, and Latin
bovis. The other, L. interrogans serovar Hardjo type hardjo- America [114]. In areas where cattle are housed with sheep
prajitno, is a highly virulent organism found primarily in or goats (western Asia, southern Europe), Brucella meliten-
Europe [19]. The Pomona serovar is maintained in swine; sis may infect cattle and cause abortions [115].
cattle are incidental hosts. Serovar Pomona infections are The cow is the source of infection, and the bacterium is
associated with severe acute disease in adults, with hemo- mainly spread by placental tissue and uterine discharge,
lytic anemia, hemoglobinuria, mastitis, and abortion dur- but spread via milk, contaminated feed, and in utero does
ing the septicemic stage [110]. occur. Uterine discharge may contain B. abortus for two
Bacteria are effectively shed in urine and may spread weeks prior to and two to three weeks after calving or abor-
transplacentally, venereally, orally, via inhalation, and tion [14]. Acute infection is characterized by abortion,
across conjunctiva [109]. Bacteremia follows a 4- to 10-day delivery of weak or premature calves, retained fetal mem-
incubation phase, resulting in localization to the kidney branes, metritis, infertility, and sterility in cows and
and reproductive tracts. This in turn results in persistent bulls [114]. Carpal hygromas can be common in certain
shedding in urine and reproductive fluids. Maintenance of areas and may be the only obvious sign of infection [115].
Leptospira spp. in the uterus may lead to fetal infection and In managed vaccinated herds infection may be subclinical,
abortion [14]. whereas in fully susceptible herds abortion rates may be as
Pregnant cows generally abort in the last trimester or high as 70% [116].
deliver weak infected calves; often abortion may be the Bacteria penetrate the nasal/oral mucosa and incite a
only sign of infection in the herd [27, 109]. They may be local or regional lymphadenitis, with enlarged lymph
sporadic or epidemic, occurring most often in the second nodes that may be hemorrhagic. In time, bacteria spread
and third trimesters [27, 111]. Abortion rates vary accord- hematogenously, with a bacteremia that may be recurrent
ing to serotype; serovars Pomona and Grippotyphosa can and persistent. B. abortus has an affinity for the placental
approach 50%, while serovar Hardjo typically ranges from trophoblasts, in which they grow to large numbers, and is
3 to 10% [19]. Fetuses are often autolyzed and may be associated with persistent inflammation and necrosis.
icteric [27]. In some cases the liver may have a green tinge Infection then spreads to the fetus [19].
due to cholestasis. Membranes may have intercotyledonary Abortion is the principal sign, occurring in the second
edema, and less commonly will have yellow/brown viscous half of gestation, after the fifth month. Infected cows may
694 Fetal Disease and Abortion: Diagnosis and Causes

abort only once, thereafter delivering term calves that may and polyarthritis may also be seen [20, 51]. Placentas are
or may not be infected [116]. often retained; changes include multifocal cotyledonary
Placentitis is a consistent feature. Fetal membranes are necrosis and intercotyledonary placentitis with gray/white
often retained and contain yellow slimy exudate with gray/ to red/brown exudate [19, 119]. Aborting cows exhibit dis-
yellow flocculent debris between and especially surround- ease before, during, and after abortion, including weight
ing the cotyledons [19]. Cotyledons are variably necrotic loss, metritis, and septicemia [14, 19]. Recurrent abortion
with thickening and fissures, or are soft to leathery, from year to year and in the same cow may be seen.
sometimes with sticky, brown, odorless exudate [19]. Organisms can be isolated from numerous fetal tissues;
Intercotyledonary tissues may be similarly affected. in some cases refrigerating specimens can aid in recovery
Fetuses are expelled one to three days after death; they of Listeria spp. [19]. Highly selective media are available.
are often autolyzed and may not have gross lesions [27, Gram staining of fetal fluids or tissue impressions reveal
116]. They may be edematous with serosanguineous cavity Gram-positive short rod bacteria in large numbers [14].
fluids and fibrinous pleuritis/pericarditis/peritonitis,
pneumonia, and multiorgan hemorrhage [19, 114, 117]. Histophilus somni (Formerly Haemophilus somnus)
Abomasal fluids may have yellow flocculent material [116]. Infection
Pneumonia in aborted calves is an important and outstand- H. somni is a Gram-negative bacterial pathogen in cattle
ing feature; tissues are firm, sometimes presenting with a best known for causing pneumonia, arthritis, myocarditis,
cobblestoned surface or small white foci [19, 116]. and thrombotic meningoencephalitis. It is a normal inhab-
The gold standard for diagnosis is the isolation of itant of the male and female bovine genital tracts and is
B. abortus from the fetus or placenta (abomasal contents, associated with infertility, abortion, and endometritis.
spleen, lung), but this may be difficult. Serology is the best Orchitis and epididymitis have been reported in bulls.
method to detect infection, using the milk ring test and card Natural breeding spreads the bacterium. Transmission by
agglutination test. PCR methods are used to differentiate AI is unlikely, as many strains are sensitive to the antimi-
vaccine strains from wild-type bacteria. Organisms are plentiful crobials used to preserve frozen semen [19].
in aborted tissues. Vaccination of pregnant cattle with strain The association of H. somni with infertility is controver-
RB51 is associated with abortion and should be avoided [115, sial; this bacterium is a normal inhabitant of the reproduc-
118]. For detailed discussion refer to Chapter 60. tive tract and research results are mixed [14]. As a cause of
abortion, H. somni is not common; abortions are sporadic
Listeria Infection and infection rarely results in outbreaks. Typically, abortions
L. monocytogenes and Listeria ivanovii are associated with occur in the second half of gestation. Placental lesions con-
disease in cattle, which takes the form of meningoencepha- centrate on cotyledons, where there is necrosis due to vascu-
litis, neonatal septicemia, and abortion [119]. Listeria spp. litis and thrombosis. Such lesions are characteristic of this
are common in the environment, particularly in colder organism and indicate hematogenous spread from the
temperate climates. Disease in cattle is often associated vagina or respiratory tract. Fetal death is rapid and autolyzed
with feeding spoiled silage where bacteria grow to large carcasses are characteristic. Gross fetal lesions are uncom-
numbers. Hematogenous spread to the placenta 5–12 days mon; fibrinous bronchopneumonia may be seen [19].
later with subsequent fetal sepsis occurs. If infection occurs Organisms may be cultured from abomasal contents and
early in the last trimester, rapid fetal septicemia and death membranes. However, light bacterial growth from the pla-
occurs. Abortion occurs a few days later, with partial mask- centa may be due to contamination from the birth canal.
ing of lesions due to autolysis [19]. Infections near term are Culture must be interpreted in conjunction with necropsy
associated with significant metritis and septicemia in the findings [14].
dam, with dystocia and retained membranes. In these
cases, autolysis may be less severe, allowing better visuali- Salmonella Infection
zation of fetal lesions [19]. Salmonella spp. cause infectious and contagious disease in
Abortions are sporadic and rarely exceed 15% [119]. They humans and livestock around the world. S. enterica subsp.
typically occur in the third trimester but may occur in the enterica is divided into hundreds of serovars, of which
second. Fetuses die in utero and exhibit varying degrees of Dublin is best associated with cattle abortion, although
autolysis. Even if fetuses are well preserved, lesions may be other serotypes may be involved, like typhimurium [121].
few; the most commonly seen are pinpoint white/tan foci of Salmonella Dublin is regionally distributed around the
liver necrosis that may mimic herpesvirus infection [120]. world and is known to persist on farms due to periodic fecal
Small abomasal erosions, fibrinous serositis, pneumonia, shedding, particularly around the time of parturition [121].
­Fetal Death (Days 42–260  695

It is a cattle-adapted pathogen that causes enteric disease/ associated with discharge and pyometra, although the cow
dysentery, pneumonia, or polyarthritis in adults, but may may appear normal [126].
also present with abortion as the principal sign [121]. Abortion can occur at any time throughout gestation, but
Organisms survive in the environment for months to years the cow is often in the second half of gestation. Abortions
and may be transported from farm to farm [122]. Bacterial are generally sporadic but may occur in clusters. Retained
infection in the dam leads to hematogenous spread to the membranes are common; cotyledons are covered with yel-
placenta and subsequent placental failure and abortion, low/brown exudate and intercotyledonary tissues are
with or without fetal infection [19]. Abortion may be due to thick, opaque, and covered with similar exudate [27, 126].
infection of the fetus, but as abortion may also occur in Fetuses exhibit variable degrees of autolysis with fibrinous
association with stressful events, pyrexia, and maternal exudates on serosal surfaces; sometimes lungs are dark
enteritis may precipitate expulsion [19]. Abortions are red with yellow foci or there is a characteristic hemor-
typically sporadic to epizootic, occurring most often in rhagic tracheal cast consistent with suppurative broncho-
the second half of gestation, often with retained pneumonia [19, 51] (see Figure 56.6).
membranes [121]. T. pyogenes is readily isolated from fetal lung, abomasal
Aborted calves are often autolyzed and may be emphyse- contents, or membranes.
matous. Pale foci of necrosis may be seen in the liver. Fetal
fluids are fibrinous and amber colored; membranes are thick- Various Opportunistic Bacterial Infections
ened and red/gray with yellow exudate and caruncular frag- Sporadic abortions in cattle may be caused by environmen-
ments on the cotyledons [19, 27]. Organisms can be recovered tal and endogenous opportunistic bacteria, including
from placental tissues and abomasal contents [19]. Bacillus spp., E. coli, Acinetobacter spp., Mannheimia
haemolytica, Nocardia spp., Aliarcobacter spp., Pasteurella
Yersinia pseudotuberculosis Infection spp., Pseudomonas spp., Staphylococcus spp., Streptococcus
This Gram-negative bacterium is associated with entero- spp., Helcococcus, and Serratia marcescens [13, 127–129].
colitis, caseous mesenteric lymphadenitis, and septicemia Almost any bacterium that can gain access to the dam’s
in calves. Apparently healthy cattle may carry the bacteria bloodstream has the potential to infect the conceptus.
subclinically [123]. Sporadic abortion (often in the second Abortions occur most often in the second half of gestation.
half of gestation) has been reported, possibly due to uterine Fetal membrane retention and autolysis vary. Membranes
infection via transient bacteremia from the gut flora [124]. are thickened with yellow/brown exudate (Figure 56.36).
Fetuses typically have minimal autolysis; body cavities Fibrinous exudates may be found in body cavities. Fetal
contain abundant fluid with fibrin tags, and livers may bronchopneumonia (white spotted lungs) is sometimes
have multiple pale tan foci of necrosis [19, 27, 124]. Lungs present [27].
may be firm due to bronchopneumonia [124, 125]. Bacillus licheniformis is considered an important isolate
Microscopic lesions are characterized by abundant necro- associated with abortion, particularly in Europe. Outbreaks
sis, vasculitis, and large bacterial colonies. Cotyledons are may be common. B. licheniformis apparently has little
thickened, red/tan, with little exudate and caruncular tis-
sue tags; intercotyledonary areas have fibrosis [19, 27].
Bacteria may be cultured from various tissues.

Trueperella (Arcanobacterium) pyogenes Infection


A common cause of suppurative inflammation in cattle that
may act as a primary pathogen or a secondary invader,
Trueperella pyogenes is a Gram-positive commensal organ-
ism in the respiratory, gastrointestinal, and urogenital tracts
in healthy cattle. Tissue invasion leads to abscessation in
any organ, causing a wide variety of clinical signs [126]. T.
pyogenes is often isolated from aborted tissues and is consid-
ered to be a primary pathogen in cattle abortion [19].
Uterine infection occurs hematogenously or via ascend-
ing infection, which is often acquired in the postpartum
Figure 56.36 Chorioallantois with bacterial placentitis.
period, in part due to retained membranes. Fetal infections Hemorrhage and fibrinous exudate cover the cotyledons and
are not consistently present. The ensuing endometritis is intercotyledonary spaces. Source: Photo courtesy of J. Edwards.
696 Fetal Disease and Abortion: Diagnosis and Causes

inherent pathogenic potential, and reports of disease often have been reported lasting up to six months, with conception
implicate coinfection, such as with N. caninum and rates as low as 20% [14]. Fetal membrane retention is com-
BVDV [9, 130]. Fetal edema, fibrinous pericarditis, granu- mon. Since few diagnostic laboratories attempt to culture this
lomatous hepatitis, bronchopneumonia, and placentitis organism, there is wide regional variability in diagnosis fre-
have been reported [130]. Infected silage is implicated as a quency. In the USA many cases are reported from Canada [27].
cause of cow infection, with a resulting bacteremia that Grossly, the amnion is often severely affected with thick-
may infect the cotyledons and spread to the fetus. ening/fibrosis, mineralization, necrosis, hemorrhage,
Cattle can develop subacute anthrax (Bacillus anthracis), fibrin, and meconium staining [19, 139]. The chorioallan-
with localized disease in the respiratory, gastrointestinal, tois may be similarly affected with white to brown exudate.
and subcutaneous tissues. Pregnant cattle that survive Aborted fetuses are commonly fresh [120]. Fetuses and
infection may have fetoplacental infections as a result of newborn calves may have firm poorly aerated lungs. The
bacteremia; gross fetoplacental lesions may be absent [131]. constellation of amnion, chorioallantois, and lung lesions
More severely affected cattle may present with protracted is characteristic of U. diversum infection [19].
fever, subcutaneous edema, hemorrhagic vaginal dis- Definitive diagnosis requires culture of organisms from
charge, an edematous fetus, bloody amniotic fluid, placen- stomach contents, placental tissues, liver, or lung in addi-
tomal hemorrhage, and lack of typical lesions in the tion to consistent lesions [140]. These organisms preferen-
maternal liver, spleen, and kidneys [132, 133]. tially localize to the fetal–maternal interface (placentome).
Specific media are required for culture; consult the diag-
Mollicute Infection nostic laboratory for preferred methods. Samples should be
The Mollicutes are bacteria that lack cell walls and have a refrigerated and transported immediately. Deliver samples
preference for mucosal and serosal surfaces. They are known in frozen media (Stuart broth, Amies without charcoal),
causes of chronic respiratory, urogenital, mammary, muscu- preferably in liquid nitrogen or dry ice rather than wet
loskeletal, and ocular disease in ruminants. Coinfection ice [141]. PCR methods for M. bovis and general Mycoplasma
with other pathogens is common. Mycoplasmopsis (prev. spp. are available.
Mycoplasma), Metamycoplasma (prev. Mycoplasma),
Mycoplasma, Ureaplasma, and Acholeplasma spp. have been Chlamydia-Like Organism Infection
associated with male and female reproductive disease in cat- Bacteria of the order Chlamydiales are obligate intracellu-
tle, including abortion [134]. These species, including those lar parasites, ubiquitous, infect a wide range of vertebrate
known to cause disease, are often found in the mucous species, and cause a wide variety of diseases [142, 143].
membranes and reproductive tracts of normal animals. Chlamydia abortus, Chlamydia pecorum, Chlamydia psit-
Endometritis, granular vulvovaginitis, salpingitis, infer- taci, Waddlia spp., and Parachlamydia spp. are of interest
tility, seminal vesiculitis, epididymitis, and granular bala- in cattle production. Abortion in cattle is usually caused by
noposthitis occur with infection. Transmission may occur C. abortus, but C. psittaci abortion has been reported [144].
venereally, mechanically (including AI as they can with- Chlamydia spp. have also been associated with mastitis
stand freezing), and by respiratory routes [134]. Disease is and infertility [14]. C. pecorum is associated with enteritis,
multifactorial and associated with intensive husbandry. pneumonia, neurologic disease, polyarthritis, and conjunc-
Mycoplasmopsis (Mycoplasma) bovis, Mycoplasmopsis tivitis. Infectious forms may be shed in feces, urine, semen,
(Mycoplasma) bovigenitalium, Metamycoplasma uterine fluids, and ocular/nasal discharges [145]. Ingestion
(Mycoplasma) canadense, Mycoplasma leachii (type 7), and or inhalation of the organism leads to infection.
U. diversum have been reported causes of abortion in cattle, Parachlamydia spp. and Waddlia chondrophila have been
but M. bovis and U. diversum abortions are the best known isolated from aborted calves in Europe and in the USA [146–
and characterized [134–138]. The association of these 148]. The overall contribution of Waddlia and Parachlamydia
organisms with abortion in general is controversial and is spp. to cattle reproductive disease is uncertain.
not well understood. However, M. bovis is not a normal C. abortus is an uncommonly diagnosed cause of abor-
inhabitant of the reproductive tract and thus its presence in tion in cattle [27, 149, 150]. Fetal loss is more sporadic than
an abortion is significant. Mycoplasmal abortion is uncom- in sheep, but abortion rates of up to 20% can occur [149].
mon. Reported lesions include placentitis, fetal broncho- Although the prevalence of occult chlamydial infections
pneumonia, and myocarditis [14]. may be high in some areas, currently the contribution of
U. diversum is the most important abortion-related patho- such infections to fetal losses is unclear [149, 151, 152]. The
gen in this group, causing embryonic death, abortion (often method of natural transmission of infection in cattle has
in the last trimester), stillbirth, weak calves, and neonatal not been verified but is probably through contact with
pneumonia [19, 134]. Outbreaks of U. diversum infertility contaminated fetal fluids and tissues, as in sheep [153].
­Fetal Death (Days 42–260  697

Affected cows may show little sign of disease, delivering splenomegaly, dermatitis, large and coarsely nodular livers,
aborted, stillborn, or weak calves, sometimes with retained and small thymuses surrounded by edema and hemor-
membranes [154, 155]. C. abortus abortions typically occur rhages [27, 159]. The presentation and lesions are character-
during six to eight months of gestation, often presenting istic. Diagnosis requires compatible lesions and herd history
with necrotizing placentitis, with or without vasculitis [146]. in addition to elimination of other causes [159].
Tissues have leathery, reddish, opaque intercotyledonary
patches and multifocal cotyledonary necrosis. Fetuses may Coxiella burnetii Infection
have pink/red subcutaneous edema, ascites, thymic and The cause of Q fever in humans, C. burnetii is a Gram-
subcuticular petechiae, and serofibrinous pleuritis/peritoni- negative, obligate intracellular rod bacterium that repli-
tis, which in some cases may be severe [154, 155]. Chronically cates within macrophages [161]. Organisms are hardy and
infected calves may have nodular mottled livers and enlarged resist desiccation, pH change, ultraviolet radiation, and
lymph nodes [155]. Parachlamydia and Waddlia related disinfectants. Found worldwide except in New Zealand, C.
abortions also exhibit necrotizing placentitis, but vasculitis burnetii is present in a wide variety of rodents, birds, wild
is uncommon [146]. Experimental W. chondrophila infec- and domestic animals (including reptiles, dogs, cats, pigs,
tion led to placentitis but not abortion [156]. horses), ticks, and domestic ruminants, the latter serving
Diagnosis of chlamydial abortion requires examination as reservoirs for human infections [161]. Prevalence is vari-
of the placenta, where organisms multiply in cotyle- able worldwide; in the USA prevalence in 316 bulk milk
dons [153]. Cotyledons and uterine discharges contain samples was greater than 90% [162]. Routine pasteuriza-
abundant organisms [14]. Isolation is the gold standard for tion kills the organism [110].
diagnosis, which is necessary to identify species and In endemic areas infected calves may clear the infection or
strains/serotypes/subtypes; such methods require special- become latently infected. During late pregnancy hormonal
ized media and special expertise [157]. It is important to changes are thought to trigger C. burnetii replication in the
recognize that many cattle harbor chlamydiae in their uterus, fetus, and mammary gland [161]. Infected sheep,
intestinal tracts, which may contaminate aborted tissues goats, and cattle are typically asymptomatic when they pre-
and confound complement fixation tests and PCR, leading sent for late-term abortion, stillbirths, and weak neo-
to false-positive results [153]. Exposure of cows may be nates [161, 163]. Abortion in cattle is uncommon to rare. The
common and single titers are of questionable worth, organisms are shed in feces, milk, urine, fetal fluids, and
although a rise in titer is suggestive of significant infection fetal membranes in large numbers [161]. Infection usually
as delivery of an infected fetus leads to a rise in titer two to occurs through inhalation of infected aerosols, but spread
three weeks after parturition [14]. Specific antibody in fetal through infected equipment, manure, and ticks is possible.
thoracic fluid or tissues is confirmative [19]. The presence Approximately half of seropositive heifers shed C. bur-
of placentitis with identification of organisms within netii at calving; there is reduced shedding with age.
lesions by immunohistochemistry (IHC) as well as PCR is Chronically infected cows may shed organisms in milk,
diagnostic. Placental smears stained with Giemsa, feces, and vaginal mucus intermittently for several months
Gimenez, or modified Ziehl–Neelsen acid-fast methods are to years [164]. Gross lesions are confined to the placenta,
useful for diagnosis [19, 155]. Chlamydial organisms where the intercotyledonary zones are covered by abun-
should be considered as serious zoonotic agents and may dant, white, inspissated exudate, giving the tissue a thick
cause abortion in humans [158]. leathery appearance [19]. Multifocal mineralization and
pericotyledonary necrosis may develop [161].
Epizootic Bovine Abortion (EBA) Placental exudate smears stained with Gimenez or Ziehl–
EBA is a regionally important and specific disease confined Neelsen acid-fast staining methods show numerous organ-
to the western USA. It is associated with certain pine ranges isms, but these may be easily confused with Chlamydia spp.
that sustain the argasid tick Ornithodoros coriaceus [159]. PCR and enzyme-linked immunosorbent assay (ELISA) are
The etiologic agent, Pajaroellobacter abortibovis, is transmit- effective in diagnosis. The mere presence of C. burnetii in
ted by the tick [159, 160]. Disease is typified by premature aborted tissues is not sufficient evidence for diagnosis; cows
calving and abortion in otherwise normal cattle [27]. The may carry the organism long term and they may be in
disease in the fetus is a chronic one, developing over three placentas of subsequent pregnancies [19, 164].
months or more prior to abortion. Abortions occur sporadi-
cally or in severe outbreaks, often in the last trimester. Tuberculosis
Fetuses are expelled fresh; retained membranes are not typi- Mycobacterium tuberculosis (syn. M. bovis and Mycobacterium
cal. Lesions include petechiae in the mouth (particularly the caprae) has beenlargely eliminated from many countries
ventral tongue), enlarged peripheral lymph nodes, ascites, around the world, yet remains enzootically or in limited
698 Fetal Disease and Abortion: Diagnosis and Causes

geographic areas in Central and South America, North tropical and subtropical areas worldwide. A. marginale
America, Africa, Europe, Asia, and Oceania. Disease caused infects erythrocytes, leading to extravascular hemolysis,
by M. caprae is not significantly different from that caused by anemia, icterus, fever, and weakness [170]. Initial infec-
M. bovis. Mycobacterium infection occurs in a wide range of tions are the most severe, leading to chronic persistent
hosts, including domestic livestock, cats, and dogs. The bacte- infection that is often subclinical. A. centrale is a milder
rium is a major economic problem in terms of trade and pathogen, usually employed as an immunizing agent
industry as well as being a zoonotic pathogen. One of the against A. marginale [171].
major problems encountered in terms of eradication is the A. marginale is rarely implicated as a cause of abortion.
prevalence of M. tuberculosis in wildlife reservoirs such as Suggested causes of fetal loss include pyrexia, severe ane-
farmed and wild cervids, European badgers, buffalo, bison, mia, or stress in the dam. Aborted calves show variable liver
brushtail possums, and European wild boars [165, 166]. and lung petechiation with splenic enlargement [172].
Mycobacterium is typically spread by inhalation or inges- A. phagocytophilum is the cause of pasture fever in cattle
tion. With reference to theriogenology, bull carriers may and tick-borne fever of sheep and goats in northern Europe,
spread infection through coitus [13]. An initial site of although the bacterium is distributed worldwide. While
infection may develop into a persistent focus of bacterial currently considered to be one species, A. phagocytophilum
replication, with subsequent hematogenous spread to vari- strains causing ruminant disease differ in distribution, dis-
ous organs. Disease is characterized by the presence of ease, severity, and target hosts from those causing human
tubercles, which are discrete, pale tan granulomas of vari- granulocytic ehrlichiosis [173]. The organism infects circu-
ous sizes in virtually any organ. They may resemble lating granulocytes and large lymphocytes, which are best
abscesses, with abundant caseous necrosis. In adult cattle, seen during clinical illness [171]. Signs include fever,
tubercles are most common in the lungs and the lymph cough, nasal discharge, and leukopenia [170]. Although
nodes of the mesentery, pharynx, and thorax; generalized present in the USA, cases of clinical illness in cattle have
lesions are uncommon. Mycobacterium reaches the uterus not been reported. A. phagocytophilum has been known to
hematogenously or by peritoneal spread to the uterine cause abortions (and storms) during first exposure to
tubes. Uterine infection may primarily affect the serosa/ infected ticks during late pregnancy [9, 173].
muscularis or may concentrate in the endometrium. The Diagnosis of Anaplasma spp. can be made on Giemsa-
uterine tubes may be severely affected [167]. Abortion due stained blood smears during the acute phase in cattle, but
to endometritis often occurs late in gestation [168]. it is not useful for carrier states. Blood from live cattle
Retained placentas and purulent to caseous uterine exu- should be collected in anticoagulant and refrigerated to be
date may be seen [13]. sent to a diagnostic laboratory. Smears from the liver, kid-
Congenital tuberculosis occurs in about 1% of at-risk ney, heart, lungs, or peripheral blood vessels can be made
calves [168]. Transplacental transmission may occur hema- from dead animals and air dried for staining [174]. Serologic
togenously via tuberculous endometritis with umbilical tests and PCR methods are available.
spread to the fetal liver (hepatic primary complex) and
lymph nodes [166]. Alternatively, fetal swallowing or inha-
Viruses
lation of tuberculous amniotic fluid may result in enteric
or pulmonary lesions, respectively [168]. Mycobacterium Herpesvirus
avium has been reported as a cause of abortion in cattle Bovine Herpesvirus 1 (BHV-1, Infectious Bovine Rhinotracheitis
housed with infected chickens [13]. Virus, Infectious Pustular Culvovaginitis Virus) Infection BHV-1
At least 10 g of fat-free affected tissue should be submit- virus is an important worldwide alpha-herpesvirus
ted for culture. pathogen of cattle, known to cause abortion, genital
disease, respiratory disease, encephalomyelitis, and severe
Anaplasma Infection systemic disease in neonates [27]. Other ruminants,
There are currently three species of anaplasmal bacteria including deer, pigs, goats, wildebeest, and buffalo are
that infect cattle: Anaplasma marginale, Anaplasma cen- susceptible [175]. Infected cattle shed virus from oculonasal
trale, and Anaplasma phagocytophilum (previously and reproductive fluids. Like other herpesviruses, latency
Ehrlichia phagocytophila, Ehrlichia equi, and human gran- is established after infection through the genital or
ulocytic ehrlichiosis agent) [169]. A. marginale is the cause respiratory tract [175]. Respiratory infection in naive
of anaplasmosis in cattle and can infect buffalo, bison, pregnant females is likely to lead to fetal infection and
deer, and other hoofstock. This infectious but non-conta- abortion [176]. Clinical signs in adults are generally mild,
gious agent is spread by arthropod bites, mechanical with conjunctivitis or respiratory tract disease. However,
means, or transplacentally [169]. Anaplasmosis occurs in signs may be absent at the time of abortion, which typically
­Fetal Death (Days 42–260  699

occurs several weeks after initial infection [27, 175]. sporadically in Australia, Europe, and the USA
Abortion is typically seen in the second half of gestation, (Figure 56.37) [184]. Transmission may occur through the
anywhere from two weeks to two to three months after genital tract, with evidence suggesting possible negative
clinical disease; fetuses are expelled three to seven days embryological effects [185–187]. The virus has been
after death [13, 175]. Abortions may be sporadic in herds isolated from an aborted fetus [188].
with previous exposure, which includes modified live
vaccines [176]. If naive pregnant cattle are exposed, storms Bovine Viral Diarrhea Virus (BVDV) Infection BVDV is one of
affecting 25–60% may occur [27, 177]. the most important infectious causes of reproductive loss
The virus spreads hematogenously in the dam to the in cattle worldwide. It is a pestivirus that uses the
caruncle, where it invades the placenta and then the fetus. reproductive system for spread within herds. Negative
Herpesviruses induce widespread cell necrosis in multiple effects on herd reproduction range from genital tract
organs, leading to rapid fetal death [19]. Fetuses show inflammation, reduced reproductive efficiency, and
advanced autolysis with few lesions; tissues are red due to embryonic death to abortion storms, delivery of small
hemoglobin staining and abundant reddish fluid may be calves, persistently infected calves, and congenital
present in body cavities [175]. Pinpoint white foci of defects [19, 111].
hepatic necrosis may be present [27]. Less commonly, pul- Transplacental infection is likely in cattle [176]. Viremia
monary and renal hemorrhage with necrosis is seen [19, leads to fetal infection as it is a primary target for the
178]. Renal necrosis may be pronounced [179]. Diffuse pla- virus [189]. The manifestations of disease in pregnancy
centitis similar to that seen in leptospirosis may be found vary according to virus strain and stage of fetal develop-
and yellow/brown amniotic fluid may be evident. ment at the time of infection [176]. Fetal infection in the
Fetal lung, liver, spleen, kidney, adrenal gland, and pla- first and second trimesters often leads to embryonic death,
centa are good sources of virus; samples should be kept resorption, mummification, or abortion [27]. Fetal calves
cold. Freezing at −70 °C is acceptable, but standard freez- infected with non-cytopathic viral strains between one and
ing (−20 °C) will inactivate the virus [175]. Histopathology four months become persistently infected, immunotoler-
may give a presumptive diagnosis, which can be confirmed ant calves that produce no antibody to the virus [111].
by IHC, PCR, FA detection, immunoperoxidase tests, or Those infected after four months may successfully elimi-
virus isolation. Kidney and the adrenal gland are useful for nate the virus, but in some cases those infected between
FA testing [27]. Cows that abort typically have low titers at 100 and 150 days develop congenital anomalies [27, 111].
the time of abortion and fetuses die so rapidly that fetal Such anomalies are quite variable but include central nerv-
antibody production may be poor or non-existent [19]. ous system anomalies (hydranencephaly, hydrocephalus,
cerebellar hypoplasia, microphthalmia, retinal dysplasia,
Bovine Herpesvirus 4 (BHV-4) Infection A widespread cataracts), thymic hypoplasia, hypotrichosis, bone defects,
gammaherpesvirus in cattle considered minimally virulent brachygnathism, arthrogryposis, and pulmonary or renal
or avirulent in adults, BHV-4 may be an important cause of hypoplasia/dysplasia (Figure 56.38). Necrotizing myocar-
abortion [177, 180]. Presence of the virus in abortions is ditis leading to chronic passive hepatic congestion and
often associated with other pathogens [19]. Associated
disease includes pneumonia, keratoconjunctivitis, orchitis,
sudden death in neonates, digital dermatitis, mastitis,
encephalitis, diarrhea, vulvovaginitis, postpartum metritis,
and abortion [177, 181]. The contribution of BHV-4 as a
cattle pathogen at this point is mostly hypothetical, with the
exception of the latter three conditions [180]. The role of
BHV-4 in abortion is incompletely understood [182].
Abortion is reported to occur between five and nine months’
gestation. Descriptions of lesions in the literature are few,
with no gross fetal or placental lesions reported. Cytomegalic
intranuclear inclusions are seen microscopically in multiple
organs [183].

A pathogen typically
Bovine Herpesvirus 5 (BHV-5) Infection
associated with severe meningoencephalitis in young Figure 56.37 Brain, coronal section. BHV-5 necrotizing
calves, BHV-5 outbreaks are seen in South America and meningoencephalitis; severe tissue loss over the left cerebral gryi.
700 Fetal Disease and Abortion: Diagnosis and Causes

the virus can be identified [113]. Evidence for transplacen-


tal transmission includes detection of BVDV in fetal tissues
or precolostral antibodies in fetal serum or fetal fluids.
However, a persistently infected (non-cytopathic BVDV
infection) fetus will not produce antibody. Infected dams
that carry persistently infected calves may have high titers
that continue to increase until delivery [194]. Contaminated
modified live BVDV vaccines have been reported to cause
disease and congenital defects [176].
Recently, another pestivirus (HoBi-like, BVDV-3) has
been associated with abortion and respiratory disease in
cattle in Brazil, Southeast Asia, and Italy [195–197]. The
origins of this virus are poorly understood; hypotheses
include viral emergence from South America or transmis-
sion from water buffalo to cattle. Natural infection has not
Figure 56.38 Brain, dorsolateral aspect. Hydranencephaly and been reported in North America, Europe, Australia, India,
cerebellar hypoplasia, BVDV in utero infection. The caudal aspect and Africa so far [195].
of the cerebrum lacks gyri and is thin to the point of In natural cases, seromucous oculonasal discharge, tra-
translucency (arrowhead). The cerebellum is vestigial (arrow).
Source: Photo courtesy of J. Cooley.
cheitis, bronchopneumonia, and gastroenteritis have been
reported in infected calves. Abortions were seen in the sec-
ond trimester [198]. Experimentally, hyperthermia, oculo-
fibrosis with ascites as well as congenital diabetes mellitus nasal discharge, and lymphopenia were seen in calves.
have been reported (see Figure 56.9) [27, 190]. Individual Lambs also exhibit nasal discharge, while pigs show no
herds may have only a few calves with congenital defects; signs but will seroconvert. Peak seroconversion occurs in
consecutive calves may have the same defects [191]. More calves by 21 days after infection; nasal and fecal shedding
often, fully developed but small (50–66% normal size) occur [195]. HoBi-like virus has been isolated from bull
calves are delivered [192]. Infections in the last trimester semen. In utero infection may produce persistently infected
do not typically produce disease as calves are immunocom- calves, similar to BVDV. Current testing is complicated by
petent and produce anti-BVDV antibodies [189]. the similarity of the HoBi-like viruses to BVDV.
Fetal death and abortion typically occur in the first tri- Cattle are susceptible to border disease virus (BDV)
mester, but can occur at any time. The abortion rate varies infection, which is a pestivirus generally associated with
but is usually low [189]. There is a delay between fetal small ruminants. The virus can be transmitted between
death and expulsion (as much as 50 days), which often pro- sheep and cattle, and abortions have been reported in asso-
duces autolyzed specimens from which it is difficult to ciation with infection. Infected cattle have signs similar to
detect the virus. Additionally, dams often seroconvert dur- those of BVDV infection; they may develop diarrhea, and
ing this delay, making serum titers of little value [113]. persistent infection in calves can occur [199]. Experimental
Lesions aside from teratogenic changes are therefore diffi- infection caused growth retardation and hydrocephalus in
cult to appreciate and rarely noted. Enlarged spleens, calves [200]. Many antigen and antibody tests cannot dis-
lymph nodes, and nodular mottled livers may be seen [189]. criminate between BVDV and BDV; specific PCR assays,
Thrombocytopenia inducing strains (types 1b and 2) may with or without sequencing, are necessary for diagnosis.
cause widespread petechiation and hemorrhage [193].
Placental lesions are generally not seen [51].
Orbivirus
The virus is fairly resistant and can survive in moist tis-
sues for several days; preferred samples for virus isolation Bluetongue Virus (BTV) Infection
include lymphoid organs [189]. Various other diagnostic BTV is the cause of a widespread arthropod-borne orbiviral
methods are used including IHC, FA, and ELISA [27]. disease of domestic and wild ruminants, particularly of
BVDV is widespread, and molecular evidence of infection sheep [201]. Virus distribution is confined to areas where
in an aborted fetus does not prove it to be the etiologic susceptible hosts (wild game, sheep, and cattle) are found
agent. Herd history and fetal lesions consistent with BVDV and the Culicoides spp. biting midges are present for trans-
infection are necessary for diagnosis [27]. A history of mission [201]. BTV is generally considered non-contagious
ataxic, small, or blind calves in the herd is suggestive. Fresh and infected animals shed little virus, except possibly in the
specimens and often multiple fetuses are required before semen of viremic bulls [19]. However, novel serotypes with
­Fetal Death (Days 42–260  701

minimal virulence can be horizontally transmitted among PCR techniques use whole blood in EDTA. Live attenuated
sheep and goats [202]. BTV infection may be seasonal, and killed vaccines are available. Live vaccines are effective
depending on the climate and numbers of Culicoides; in tem- but are associated with abortion and congenital anomalies
perate zones, late summer/early autumn is common [203]. when used in pregnant females in the first period of preg-
The range of infection has increased since 2000, as a result of nancy [204]. Fetal BTV antibody from serum or cavity fluids
additional Culicoides spp. vectors, emergence of novel BTV indicates in utero exposure [27]. Complementary lesions are
serotypes, and changes in climate [202]. After infection, ani- needed for diagnosis.
mals may be viremic for several weeks, but this does not lead
to immunotolerance or persistent infection [176, 204]. Epizootic Hemorrhagic Disease Virus (EHDV)
Clinical signs in adult cattle are rare and mild, particularly in Infection
enzootic areas [177]. When clinical disease occurs, signs EHDV is an orbivirus transmitted by Culicoides midges
include the formation of ulcers in the mouth and tongue as that affects wild and domestic ruminants, particularly
well as on the muzzle. The coronary bands develop hypere- white-tailed deer [214]. Of the many serotypes found
mia and ulceration, and hoofs may slough [191]. worldwide, Ibaraki virus, an Asian strain of EHDV sero-
After introduction into the skin, the virus is transported type 2, has long been considered the only strain of signifi-
to local lymph nodes where it replicates. Subsequent hema- cance to cattle. However, recent outbreaks of severe disease
togenous spread to secondary organs then occurs. BTV rep- in cattle have been seen with serotypes 6 and 7 in Turkey
licates in macrophages, lymphocytes, and vascular and Israel [215, 216]. Disease in cattle mimics BTV; mortal-
endothelial cells, causing host cell death. This results in ity is often low and morbidity varies [214]. Abortions and
widespread injury to small blood vessels which leads to stillbirths have been reported in outbreaks of Ibaraki virus
vascular leakage, edema, subsequent thrombosis, and tis- infection in Japan [217, 218].
sue infarction [205].
Infections during pregnancy cause congenital abnormal- Palyam Serogroup Orbivirus Infection
ities more commonly than abortion; early embryonic This group includes at least 15 viruses that are primarily
death, mummification, and stillbirth also occur [19]. found in Africa, Asia, and Australia and are associated with
Congenital abnormalities due to BTV are sporadic and are abortion and teratology in cattle [219]. Culicoides midges
known to occur principally in the USA and South Africa, are natural vectors, but the virus has also been isolated from
where modified live vaccines are used. These vaccine mosquitoes and ticks. Of these, the Chuzan (Kasba) virus is
strains were considered largely responsible for fetal malfor- best known, causing hydranencephaly and cerebellar hypo-
mations [206]. Abortions associated with BTV2 and 9 vac- plasia in calves [220, 221]. The presence of infection in
cines have been reported in Europe [207]. Until recently, herds is usually found after abortion and malformations are
transplacental transmission was thought to occur only in seen. Abortions may occur at any stage of gestation, being
laboratory modified strains, although now serotype 8 sporadic or epidemic [219]. Antibodies in precolostral
(BTV8) in Europe has been shown to frequently cross the serum are helpful in establishing a diagnosis [219].
placenta [27, 208, 209]. BTV8 is unusual not only for its
virulence in cattle, but also for its wild-type transplacental
Bunyaviridae
transmission and oral transmission in field and experimen-
tal reports [210–212]. Rift Valley Fever Phlebovirus (RVF) Infection
Like BVDV, fetal disease is associated with gestational RVF is the cause of severe disease in domestic ruminants
age at infection. Fetal infection prior to day 70 may lead to and humans; the virus is largely confined to sub-Saharan
fetal death and absorption, while infection between 70 and Africa and Madagascar [222]. Mosquitoes are the main
130 days can cause stillbirth, weak calves, hydranenceph- route of transmission, with many capable species, including
aly, or abortion. If infection is just prior to fetal immuno- some found in the USA [19, 222]. Disease is most severe in
competence, hydrocephalus or porencephaly may result. young ruminants. In calves, severe hemorrhagic diarrhea
Fetal infection after 150 days can cause encephalitis or pre- and liver necrosis (with icterus) develop over a rapid course,
mature birth, but malformations do not occur [27, 206]. with mortalities ranging from 10 to 70%. Adult cattle may
Abortions occurring in the last trimester have been associ- show only abortion, which can occur at any gestational
ated with hydranencephaly [213]. stage and may reach 80–90% [177, 222]. Abortion is due to
Isolation of BTV is difficult and the virus is inactivated by fetal death; specimens are autolyzed and exhibit liver necro-
freezing at −20 °C [176]. Virus may be isolated from blood (in sis [223]. Fetal livers are enlarged, soft, friable, and yellow/
anticoagulant: EDTA, heparin), spleen, or lymph nodes if tis- red with hemorrhages or subcapsular hematomas [224].
sues are sent refrigerated to an appropriate laboratory [204]. Placental lesions have not been described. Aborted tissues
702 Fetal Disease and Abortion: Diagnosis and Causes

contain large amounts of virus [19]. Hepatic lesions are the details of horizontal transmission and its significance are
considered diagnostic; differentials include BTV and poorly understood [239, 240]. SBV has been found to be shed
Wesselsbron virus. The virus may be isolated from the liver, in semen, unlike Akabane virus, and vertical transmission
spleen, and brain; keep refrigerated or freeze and send on occurs [241]. The susceptibility of non-ruminant species to
dry ice. Serological tests are available [225]. SBV is unclear [239]. SBV is unlikely to pose a risk to
humans [242].
Akabane and Simbu Serogroup Orthobunyavirus Virus can be isolated from blood and various fetal tissues
Infection and fluids [19]. PCR and immunochemical methods are
This group includes about 25 viruses in the Bunyavirus available for detection in tissues. For SBV, brainstem tissue
genus that occur worldwide, including the Akabane, Aino, for PCR and pleural fluids for antibody testing have been
Tinaroo, Peaton, Shamonda, Shuni, and Schmallenberg reported as an optimal combination for diagnosis [243].
viruses (SBVs) [226–230]. The Akabane virus, which occurs Differentials for arthrogryposis/hydranencephaly include
in Australia, Japan, China, Korea, the Middle East, and BTV, BVDV, Chuzan, Wesselsbron, SBV, genetic causes,
Kenya, is possibly the most important pathogen of this and toxins such as lupines.
group, although SBV is now on the rise in Europe [19, 231]. Wesselsbron virus infection is caused by a mosquito-
Transmission is via Culicoides gnats and probably mosqui- borne flavivirus primarily found in Africa. Disease is most
toes [230, 232]. Clinical disease in adult cattle may be mild severe in young small ruminants. Infection in adult cattle is
or inapparent, with reduced milk yield, diarrhea, or inap- typically subclinical [244]. Pregnant cattle may sporadi-
petence [230, 233]. Clinical disease is more characteristic cally abort, deliver weak calves, or deliver apparently
of SBV than in other viruses of this group [234]. Certain healthy calves. Certain viral strains can produce encephali-
variants (genogroup Ia, Iriki strain) of Akabane virus are tis, porencephaly, and cerebellar hypoplasia [19].
known to cause neurologic disease outbreaks (bovine epi-
zootic encephalomyelitis) in calves and adult cattle in East Bovine Parvovirus (BPV) Infection
Asia [191]. The Shuni virus has recently emerged as a cause Bovine parvovirus (BPV) is widespread in the USA and
of neurologic disease in calves and abortion in Israel [235]. worldwide. Often associated with diarrhea in calves, it is an
Infection during pregnancy may produce abortions, mal- uncommonly diagnosed cause of abortion [19, 192, 245].
formations, mummies, and stillbirths [19]. Abortions occur Virus can be transplacentally transmitted to developing
in the third trimester and can occur as clusters or epidem- fetuses [246]. Experimental data indicate first and second tri-
ics [230, 232]. Viruses in this group are neurotropic and are mester fetuses are most susceptible [246]. If infected between
known to cause arthrogryposis, muscular hypoplasia, and days 107 and 150, fetal cerebellar hypoplasia may be seen [19].
hydranencephaly defects in domestic ruminants [233, 236– Fetuses infected in the last trimester can respond immuno-
238]. Hydrocephalus, cerebellar hypoplasia, porencephaly, logically, preventing death. BPV should be considered in
scoliosis, and cardiopulmonary defects are also herds with abortion and repeat breeding problems [245].
reported [177, 233]. The gestational stage at which infection BPV is present in multiple fetal visceral tissues and in
occurs determines the severity and outcome of infection, membranes [19, 246]. BPV can be grown in cell cultures,
with decreased severity seen in later infections [230, 232]. but care should be taken that supplemental sera do not
SBV was first noticed in the summer of 2011 in northern contain BPV antibodies. Serum from fetuses infected in the
Germany and the Netherlands as a febrile syndrome in third trimester will have specific antibody to BPV [247].
adult cattle; signs included fever, decreased milk produc-
tion, and diarrhea [234]. SBV is the first outbreak of a
Miscellaneous Viruses
Simbu serogroup virus in Europe and has now spread
across much of Western Europe [239]. The virus is associ- Bovine enterovirus (picornavirus), adenovirus, pseudora-
ated with abortion and congenital malformations in cattle, bies virus (Suid herpesvirus 1), parainfluenza virus 3
sheep, and goats. The losses in cattle due to decreased milk (PI3), lumpy skin capripoxvirus, malignant catarrhal
production and return to service may be more costly than fever (gammaherpesvirus), foot and mouth disease virus
losses due to malformed calves, which in the Netherlands’ (picornavirus), and bovine leukosis virus have been asso-
outbreak occurred in 1–3% of farms [239]. ciated with abortion [13, 192].
SBV antibody seroprevalence was 72% in cattle from the Bovine PI3, generally considered a common mild respira-
Netherlands between November 2011 and February 2012; a tory pathogen, has been diagnosed uncommonly in abortions.
high seroprevalence in red deer, roe deer, and mouflon was Abortion calves have red rubbery lungs [248]. Prevalence in
also found. Current evidence suggests that biting midges herds is high, and association with abortion may be incidental
(Culicoides spp.) are involved in horizontal transmission, but or contributory with other pathogens. Experimental infection
­Fetal Death (Days 42–260  703

may cause bronchiolitis and interstitial pneumonia. Abortion fluid accumulation. No consistent gross lesions are seen,
due to PI3 is rare [27, 249]. although pale streaking in skeletal or cardiac muscle may
Fetal antibodies to bovine enterovirus have been detected be present [267]. Cotyledons may be necrotic and areas of
in high percentages of aborted fetuses tested in two stud- malacia (soft, pitted, darker areas) may be seen in the brain
ies [250, 251]. This virus has been associated rarely with sig- or brainstem [19]. Submitting the entire fetus with pla-
nificant enteric disease in adult cattle, and experimental centa is optimal. Fetal brain is the most consistently
reproduction of illness in calves has been difficult [252, 253]. affected tissue for finding lesions. IHC is highly useful for
diagnosis since organisms may be few and difficult to find
in autolyzed tissues [254]. The results of such methods
Protozoa
should be viewed cautiously, as fetuses infected later in
Neospora caninum Infection gestation may only have a mild N. caninum infection but
N. caninum is a common worldwide infectious apicompl- die from a secondary pathogen [27]. Congenitally infected
exan parasite of domesticated livestock, dogs, and some calves often have high precolostral titers, but antibody
species of deer [254]. Dogs (including coyotes, dingoes, and levels vary and may even be undetectable [9, 19].
gray wolves) are definitive and intermediate hosts. Currently
there is no evidence for infection in foxes [255]. Livestock Tritrichomoniasis
are intermediate hosts that harbor tachyzoites that form tis- This is a worldwide venereal disease of bull-bred cattle due
sue cysts [256–258]. Tachyzoites may be found in a variety to T. foetus parasitism. Commercial AI services in the USA
of cell types, but tissue cysts are almost exclusively found in often screen for this pathogen, although custom-collected
the nervous tissues, including brain, spinal cord, eye, and semen may be contaminated. This flagellated protozoan is
nerves. Infection occurs in both beef and dairy herds and it an obligatory inhabitant of male and female genital tracts,
is a major cause of dairy cattle abortion in the USA and the occurring in both beef and dairy herds. Concurrent infec-
UK [259–261]. Vertical transmission is a common and tion with C. fetus subsp. venerealis may be common. Females
highly efficient route of infection in ruminants and can pro- of all ages exhibit equal susceptibility and present with a
gress through multiple generations in congenitally infected history of bull-bred infertility due to embryonic death.
heifers [256, 262]. Cattle may also become infected by inges- Infection typically causes vaginitis that may progress to
tion of sporulated oocysts from canid feces. endometritis; such infections may cause embryonic death
Maternal seroprevalence is highly variable; seropositive and abortion (5 to >20%) in the first half of gestation, with
cattle are more likely to abort than seronegative cattle [27, uncommon later-stage abortions. The majority of pregnan-
263]. Antibody titers in infected cows may fluctuate or cies are probably lost by day 17. Fetuses aborted in mid
decline over time and many may be persistently infected, pregnancy may be macerated and expelled with mem-
making interpretation of sample results difficult [27]. branes. Cows may develop pyometra due to retained
Serum samples from precolostral calves are useful for fetuses, which may present as multiple pyometras in a bull-
determining infection in suspect cows, due to the efficiency bred herd. Uterine fluids are copious with little odor and
of transplacental transmission [264]. For abortions, spe- can vary from watery and flocculent to red/brown and
cific antibodies in fetal serum (after 100 days’ gestation) or inspissated. Embryonic death after recognition of preg-
brain/spinal cord tissue are indicative of infection but do nancy (17 days) can lead to irregular cycling and return to
not prove N. caninum as the abortigenic agent. Similarly, estrus 60–90 days after breeding.
negative titers do not rule out neosporosis since fetal anti- Placentas show little evidence of pathology aside from
body formation depends on exposure level, gestational age, edema or the presence of white flocculent material and
and duration of infection [27, 254, 265, 266]. mild cotyledonary hemorrhage. Fetuses present in varying
Abortion is the only clinical sign in cattle, occurring from three stages of autolysis, from fresh to macerated, and in many
months’ gestation to term, but predominating at five to six cases show no gross pathologic changes. Mild rumenitis
months, a hallmark pattern of this pathogen [256, 259, 267, 268]. with plaque formation can be seen occasionally [107]. In
Abortions may be sporadic, endemic, or epidemic [269]. Calves late-stage abortions bronchopneumonia and necrotizing
may be stillborn, mummified, malformed, or born alive; calves enteritis have been seen.
may rarely show neurologic signs [73, 254]. They may also be Diagnosis depends on finding organisms in fresh fetal flu-
small for their age, ataxic, or have flexion/hyperextension of the ids/abomasal contents and pyometra fluids (directly from
limbs [19]. In most cases of infection, asymptomatic congenitally the uterus) where they are often plentiful. Tissues older
infected calves are produced [267]. than 48 hours are poor specimens. Commercial media are
For definitive diagnosis an examination of the fetus is preferred for transport and culture (In-Pouch TF Bovine,
necessary. Fetuses are typically autolyzed with serosanguineous Biomed Diagnostics, OR, USA) and samples should be
704 Fetal Disease and Abortion: Diagnosis and Causes

maintained between 22 and 37 °C. Buffered saline solutions not contagious. The degree of environmental contamina-
(physiologic saline, lactated Ringer’s) can be used, but sam- tion may increase the risk of fetal infection [27, 280].
ples should be kept cool (not frozen) and delivered as soon A variety of ubiquitous environmental fungi cause
as possible (<48 hours) to a diagnostic laboratory. Positive abortions in cattle worldwide. Prevalence of fungal types
identification of T. foetus may be complicated by other flag- and commonality of fungal abortion varies geographi-
ellated protozoan species. Immunohistochemical methods cally. Aspergillus spp., Zygomycetes (Absidia, Mucor,
are also available to detect organisms in fixed tissues. Rhizopus, Mortierella), Candida spp., and
T. foetus infections may mimic C. fetus subsp. venerealis Pseudallescheria boydii are among the more frequently
infections [9, 13, 19, 27, 269–272]. reported [19]. Aspergillus fumigatus and other Aspergillus
species are reported as the most common causes of
Sarcocystis Infection mycotic abortion, with Zygomycetes the second most
Sarcocystis cruzi, Sarcocystis hirsuta/Sarcocystis bovifelis, common [278]. It is thought that primary maternal dis-
and Sarcocystis hominis are coccidian protozoal parasites ease in the respiratory or gastrointestinal tract leads to
that commonly infect cattle. Carnivores are the definitive hematogenous spread to the placentomes, as lesions are
hosts while herbivores are the intermediate hosts. Cattle first seen there and are most severe. Clinical signs in the
are infected by ingesting sporulated oocysts in carnivore dam are typically not seen. However, fetal abortion with
feces. Once ingested, sporozoites are released into the gut, Mortierella wolfii is associated with a severe post-abor-
where they penetrate the mucosa and develop in arteries as tion pneumonia in the dam [27, 280].
meronts. The parasites are released from vessels as merozo- Abortions occur in the last trimester and they generally
ites that then infect capillaries throughout the body. After a do not exceed 10% incidence in a herd [280]. They may be
second round of replication, merozoites infect mononu- seasonal in association with increased environmental
clear cells and enter muscle and neural tissues to encyst. exposure. In the northern hemisphere, the winter and
Clinical disease is uncommon in adult cattle but is associ- spring are most often associated with abortion [280].
ated with hemorrhage and edema due to the effects of Retained membranes are common. Infection causes severe
intravascular maturation [273]. Signs include fever, ptyal- thickening of cotyledons with extension into the intercoty-
ism, lymphadenopathy, anemia, and abortion, with experi- ledonary areas, imparting a cracked or leathery appearance
mental oral infection [274]. to tissues. Cotyledons may have entrapped shreds of mater-
Abortion is rare and has been reported in the third trimes- nal caruncular tissue (see Figure 56.3). Fetuses may have
ter; fetal hypoxia due to dam anemia, premature parturition minimal autolysis.
due to PGF2α release, pyrexia, or direct infection of the fetus Placentitis develops slowly, interfering with fetal nutri-
are suggested etiologies [13, 19]. Parasitic cysts may be present tion and often leading to fetal death. However, normal
in the placenta or the fetus, but this is not typical. Gross lesions live calves may be born in cases of mild or even severe
may resemble N. caninum infection or be inapparent [19, 27]. placentitis [13]. Fungal infection then extends to the fetus
Microscopic lesions are typically plentiful, consisting of by infection of amniotic fluid. Fetuses may have numer-
necrosis in soft tissues and tissue cysts [27]. ous irregular tan epidermal plaques, particularly on the
face, back, and sides (see Figure 56.8) [19]. Infections due
Miscellaneous Parasites to septate fungi (Aspergillus spp.) often cause raised, dry,
Abortion in herds infected by Trypanosoma vivax has been and wrinkled skin lesions, while infections due to non-
reported, likely a result of anemia and overall ill-health in septate fungi (Mucor spp., Rhizopus spp.) may cause flat,
the cow [275]. Babesia bovis and Babesia bigemina are asso- moist, white/red foci [20]. Because of the chronicity and
ciated with abortions as a result of pyrexia and fetal infec- severity of infection in placentomes, incarceration of cot-
tion. Infected aborted fetuses are anemic and icteric, with yledons may prevent membrane detachment for up to
swollen icteric livers [276]. Theileria orientalis, a cause of 10 days. At this stage, complete placentomal necrosis may
benign/non-transforming theileriosis, is associated with ensue, with retention of necrotic tissues, maceration,
severe anemia and abortion in Australia, New Zealand, and/or pyometra [13].
and Japan [277]. Gross lesions are distinctive (see Figure 56.39). Placental
lesions may mimic B. abortus or Campylobacter sp. infec-
tion [280]. Organisms may be cultured from the placenta,
Fungi
abomasal fluid, or lung. Placentas or, less commonly, abo-
The incidence of mycotic abortion varies widely [278]. In masal fluids may have incidental fungal contamination.
some areas fungal abortion is the most common abortion Diagnosis requires compatible lesions in addition to the
diagnosis [279]. Losses are sporadic as these organisms are presence of fungi.
Definitions  705

Cotyledon Discrete, monomorphic, regularly placed


elevations of the chorioallantois that are directly
apposed and adhered to the uterine caruncles.
Embryo An animal in early development that does not
have a form recognizable as a particular species.
Embryonic death Death of the conceptus prior to day 42.
Endemic abortion Abortion in a continuous pattern, at
a rate greater than 5% throughout the year.
Epizootic/epidemic abortion A storm of abortions
where greater than 10% of at-risk cattle abort in a short
period of time, usually within two to three months.
Fetal death Death of a fetus prior to complete expulsion
from the dam, subdivided into antepartum and
intrapartum.*
Fetal period The stage of development between days 42
Figure 56.39 Placenta with fungal placentitis and Aspergillus and 260, divided into early (days 42–120), middle (days
sp. Placentomes are swollen with abundant fibrinous exudate.
Source: Courtesy University of Illinois Veterinary Diagnostic
120–180), and late (days 180–260).*
Laboratory. Fetus An animal in development that has identifiable
features of a given species.
Gestation The period of pregnancy; breeds typically vary
Definitions in length, from 278 to 293 days.
Hamartoma A focally excessive overgrowth of mature
Asterisk denotes definitions from an authoritative normal cells in an organ that typically contains those cells.
source [52]. IBR Infectious bovine rhinotracheitis virus (bovine
herpesvirus 1).
Abortion Expulsion of a conceptus incapable of Inner cell mass The group of cells in the blastocyst at
independent life.* Calves born after day 260 are one pole that develop into the embryo.*
generally thought to be able to survive Morula The early stage when eight or more cells are
independently. Expulsion of the entire conceptus arranged in a solid mass without organization.*
(complete abortion) or portions (incomplete Periparturient (peripartum) With reference to the
abortion) may occur. dam, the time span occurring during the last 10%
Allantois A secondary outgrowth of extraembryonic (30 days) of gestation to the first few weeks of calf life.
splanchnopleure from the ventral hindgut. The Placenta The fetal and maternal specialized organs of
mesoderm is vascular.* transfer between mother and offspring. The fetal
Amnion Extraembryonic somatopleure that is inverted placenta is the chorioallantois, while the general term
around the embryo such that the ectoderm lines a “fetal membranes” includes the amnion as well.
cavity filled with amniotic liquor. The mesoderm is Placentome The union of chorionic villi (cotyledon) and
avascular.* caruncle.
Birth Expulsion of a live fetus. Premature parturition Delivery of an immature viable
Blastocyst The stage in development after the morula, where calf prior to completion of normal gestation (about
the cells form a hollow sphere with an inner cell mass.* 260 days).
BVDV Bovine viral diarrhea virus (bovine pestivirus). Somatopleure The lateral and ventral body wall of the
Calf A live-born bovine. embryo composed of an outer ectoderm and an
Caruncle (plural carunculae) Discrete, monomorphic, underlying mesoderm.
regularly placed fleshy elevations of the inner uterine Splanchnopleure The embryonic layer formed by the
wall. fusion of the visceral mesoderm to the endoderm
Chorion Extraembryonic somatopleure that is composed (definitive yolk sac wall).
of an outer ectodermal trophoblast and is not part of Sporadic abortion Individual or small numbers of
the amnion. The mesoderm is avascular.* abortions occur at irregular intervals and typically do
Conceptus An inclusive term denoting the embryo or not exceed 3–5% annually.
fetus and membranes. Stillbirth Delivery of a dead fetus within the time of
Congenital Present at birth.* expected viability (after day 260).
706 Fetal Disease and Abortion: Diagnosis and Causes

Teratogen Anything, infectious or otherwise, that causes ­Acknowledgments


abnormal development in a conceptus.
Trophoblast The outer cellular layer composed of Dr. F. Austin contributed to portions of this chapter regard-
extraembryonic ectoderm through which all ing microbiology sampling of specific pathogens. The
physiological exchange takes place.* author wishes to thank Drs J. Cooley and J. Edwards for
Zona pellucida The non-cellular layer surrounding the ovum. their figure contributions and editorial comments.
Zygote A diploid cell formed from fusion of male and female
pronuclei lasting until the first cleavage is complete.

56.A Appendix

Abortion Diagnosis
Owner

Address

Phone/Fax/Email:

Veterinarian Name/Phone/Address:

Aborted calf: date aborted:___________Estimated due date: __________ Crown-rump length _________cm

Assistance needed for delivery? Y/N Vet involved? Y/N Calf alive when problem first noticed? Y/N

Gross fetal lesions:

Gross placental lesions:

Formalin fixed tissues: 10 parts fixative Fresh/chilled tissues: DO NOT Chilled samples: not in syringes
for each part tissue: Brain (whole) FREEZE
Abomasum contents (3 ml)-
Liver Ileum Placenta (3 cotyledons) bag
separately sterile tube
Heart ventricle Adrenal
Thoracic/abdomen fluid/heart blood
The following can be pooled if
Thymus (w/ trachea & esophagus) necessary: (3 ml)-sterile tube

Lung (2 sections) Eyelid Maternal serum, red top tube;


Kidney (whole organ)
Placenta (3–4 cotyledons) Thyroid at abortion 10–14 days later
Liver (2”x2”)
Lymph Node (mesenteric) Kidney Herdmate serum, red top tube
Lung (2”x2”)
Spleen Colon (several cows are preferable)
Spleen (1/2 organ)
Sk.muscle (limb,tongue & diaphragm) 10–14 days later
Thymus (1 cm slice)
T.foetus: TF pouch culture fetal fluids Fetal liver, kidney (frozen); bagged
Adrenal (whole)
keep at rec. temp. separately

Cow/Dam

Breed: Age/Tag#: Lactation#: Source/dam/sire:

Conception Date/Last Service: Date of last normal parturition:


AI Bull Hired bulls Y/N

Figure 56.A1 Abortion case submission form: abortion diagnosis.


  ­Reference 707

Vaccines/ date given/ brand/ lot #/booster intervals Previous Abortions: Y / N When?
Workup Done? Y/N Results?
IBR: __________________________________________
BVD:__________________________________________ (DairyFarm) Previous clinical disease
Neospora: ______________________________________ Avg. days to in cow: Y/ N (circle all
1st service:________ that apply): Present in last
Lepto 5way: ____________________________________
Lepto hardjobovis:_______________________________ Calving interval ________ Week Month
Tritrichomonas:_________________________________
Breedings per conception: 3 mo. 6 mo.
C.fetus:________________________________________
12 mo. 24 mo.
Chlamydophila:_________________________________ _________

Dam disease signs (circle all that apply): GI Respiratory Fever Mastitis

Retained placenta Anemia, dyspnea, emaciation (Anaplasmosis)

Changes in cow management/ pasture/ feeding regime:

Housing:

Forage: Grass hay ___________ Legume Hay __________ Pasture _________


Corn Silage ______ Other _________

Forage quality:

Concentrates/Minerals/Commodities/Selenium:

Any testing of feed/water for nutrients/toxins?

Feeding Program: Prepared or made on-farm Water source

# adults in herd/ body #immature in herd/ body # purchased in last: 6 mo.______ 12 mo. ______
condition: condition:
Source:
Number of herd abortions in last:
Health problems:
Week_____ Month_____ 6mo._____
Associated with cold/hot weather?

Affects which trimester: 1st 2nd 3rd Farm Abortion Frequency: Pregnancy exams
routinely done: Y / N
Affects which cows: old young mixed Sporadic
Problems with term calves: Postpartum exams
Recurrent routinely done: Y / N
Weak Ataxic Stillborn Malformed
_____ days after calving
Describe/how many: Recent problem

Herd reproductive problems? Y / N What %?:______ Circle all that apply: Anestrus Metritis

Repeat Breedings Irregular Cycles Retained Placentas Cystic Ovaries

Length of Breeding/calving season(beef):

Access to other cattle/ animals/ predators? Toxic plants on pasture?

Figure 56.A1 (Continued)

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