Periparturient Diseases

Chapter 21 PERIPARTURIENT DISEASES






CLINICAL PSEUDOPREGNANCY (PSEUDOCYESIS)



Definition and Signs


All normal bitches enter a luteal phase (diestrus) of progesterone dominance following estrus (standing heat). Progesterone assays do not demonstrate any clear biochemical distinction between nonpregnant and pregnant bitches. Physiologically, all nonpregnant bitches in diestrus are pseudopregnant. However, this reference to a normal physiologic process needs to be differentiated from clinical pseudopregnancy, a syndrome recognized by breeders and veterinarians.


Signs of clinical pseudopregnancy are those commonly associated with pregnancy. They can be so convincing that owners have been known to insist that their bitch is pregnant, that she is about to whelp, or that she is suffering from dystocia. These clinical signs usually begin 6 to 12 weeks after estrus. They may be subtle, such as a change in appetite, weight gain, or abdominal enlargement. Sometimes the signs are suggestive of impending parturition: restlessness, decreased activity, nesting behavior, anorexia, vomiting, and/or mothering inanimate objects.


Less commonly, the signs may be quite overt and confusing, such as lactation or abdominal contractions. Certainly, some of these signs in a diestrual bitch would make an owner suspicious that his or her dog is pregnant. Bitches have been examined for delayed parturition, uterine inertia, or dystocia that have subsequently been demonstrated to be pseudopregnant! The phenomenon of nonpregnant bitches lactating could have had functional importance in evolution, when nonbred mature bitches (such as the wolf) have had to nurse and tend the litter of the pack-leading she-wolf (Voith, 1980).




Diagnosis/Interpretation


The diagnosis of clinical pseudopregnancy is established in any bitch that exhibits the typical signs of this condition but is demonstrated not to be pregnant. Assuming abdominal radiography or ultrasonography is negative for pregnancy, no blood, urine, or other tests are required to confirm the diagnosis. It is not usually possible to determine whether a bitch was pregnant, subsequently aborted, or resorbed a litter only to later appear pseudopregnant. Although such a sequence of events is possible, uncomplicated clinical pseudopregnancy is much more common than a scenario involving abortion/resorption.


Perhaps the most important message that veterinarians are encouraged to discuss with owners is the concept that clinical pseudopregnancy is an exaggeration of normal and that the condition, left untreated, always resolves. A bitch that failed to ovulate, one with abnormal ovaries, or one with an abnormal pituitary would not be able to exhibit clinical pseudopregnancy. The condition can only occur in a bitch with normally functioning corpora lutea that begin to regress. Decreasing progesterone concentrations then stimulate prolactin secretion. Therefore the condition suggests that the bitch must also have ovulated in order to have developed corpora lutea. In this sense, clinical pseudopregnancy demonstrates that a bitch is normal.


One differential diagnosis for galactorrhea is hypothyroidism. It has been suggested that increases in thyrotrophin-releasing hormone (TRH) promotes prolactin secretion and then lactation. One dog has been described with hypothyroidism, increased serum prolactin concentration, and galactorrhea (Cortese et al, 1997).



Treatment





CONSERVATIVE THERAPY.

Persistent lactation is a response to continuing stimuli for milk letdown. Some owners warm- or cold-pack the bitch’s mammary glands or run water over the glands to relieve discomfort. However, most bitches stimulate themselves by licking, by mothering inanimate objects, or by having an unrelated litter of puppies in close proximity. Therefore measures by owners to create stimulation are discouraged. Placing an Elizabethan collar around the neck of the bitch and removing any objects she may be mothering should hasten the resolution of pseudopregnancy.


If these measures do not succeed or if a more aggressive strategy is deemed necessary, one or both of the following are helpful. We recommend that water be removed from the bitch for a 6- to 10-hour period each night for 3 to 7 nights. This water deprivation forces fluid conservation, and lactation quickly ceases. Alternatively, a bitch can be treated with furosemide (Lasix) at an oral dosage of 0.25 to 0.5 mg/kg TID until lactation ceases (usually less than 7 days). Water restriction should not be implemented if furosemide is used.


Light sedation with a tranquilizer for several days may be helpful. The use of phenothiazines has been discouraged in the management of pseudopregnancy because they may inhibit or antagonize dopamine, which is a prolactin-inhibiting factor; that is, they may stimulate synthesis and/or secretion of prolactin. Therefore other forms of sedative or tranquilization medication are recommended (Voith, 1983). An alternative to tranquilization is to exercise a bitch in an attempt to interrupt unwanted behavior.



AGGRESSIVE THERAPY.




Prolactin Inhibitors.

Ergot alkaloids (ergolines) and their derivatives have been identified as potent prolactin inhibitors (Krulich et al, 1981; Ferrari et al, 1982). They act via direct dopamine receptor stimulation at the level of the pituitary gland. Bromocriptine, an ergoline compound and dopamine agonist, inhibits pituitary secretion of prolactin. Bromocriptine, administered orally at 0.01 to 0.1 mg/kg/day in divided doses, does inhibit lactation and should be given until lactation ceases (Mialot et al, 1981, 1982; Janssens, 1986). Side effects to bromocriptine are common and include vomiting, anorexia, depression, and behavioral changes (Peterson and Drucker, 1981). Vomiting can be reduced by administering an antiemetic drug at the time bromocriptine is given. This is our drug of choice if aggressive treatment of a bitch is necessary; however, we have never needed to use it.


An equally effective but better-tolerated ergoline compound (cabergoline) was identified and evaluated. Cabergoline, administered at a dose of 5 μg/kg once daily for 5 to 10 days, was effective at sharply dropping prolactin concentrations and suppressing lactation in more than 95% of the bitches treated (Di Salle et al, 1984; Jochle et al, 1987; Arbeiter et al 1988). Side effects were considered mild and included lethargy (25% of dogs), inappetence, and vomiting (<5% of dogs). Success was slightly lower (21 of 26 dogs) in a more recent study (Harvey et al, 1997). Furthermore, the conclusion of the most recent study was that cabergoline is effective in suppressing prolactin release from the pituitary gland, but that this suppression may only be transient.


The drug has also been used to induce abortion in the second half of pregnancy in the bitch (Post et al, 1988). In a comparison between cabergoline and bromocriptine use in women, cabergoline was more effective and better-tolerated when used for hyperprolactinemic amenorrhea (Webster et al, 1994).






SPONTANEOUS ABORTION AND RESORPTION OF FETUSES




Causes






ABNORMAL MATERNAL ENVIRONMENT.




Hypoluteoidism.

Pregnancy is maintained by progesterone derived from ovarian corpora lutea. Failure to maintain progesterone concentrations above a critical level (1.0 to 2.0 ng/ml) is likely to result in expulsion of the fetus. A luteal phase defect has been associated with pregnancy failure in women, but the diagnosis is considered controversial (Meis et al, 2003). The syndrome has not been well documented in dogs (Olson, 1988), although one case has been described (Purswell, 1991). Progesterone insufficiency is possible, and progesterone concentrations may be low at the time of an abortion. The decreases, however, may be secondary to fetal death rather than representing the primary cause. It has been demonstrated that fetal death will result, within days, in subsequent decreases in serum progesterone concentration (Concannon et al, 1990). Furthermore, fetal distress secondary to virtually any cause may result in decreased serum progesterone concentrations (Johnston et al, 2001). Subnormal progesterone concentrations in a bitch that has already aborted is not proof of hypoluteoidism.


If progesterone is administered to a bitch with impending abortion, delivery may be interrupted even if the cause of the disorder is an infectious disease. Therefore it is advisable to educate owners regarding the potential adverse effects of preventing delivery: continued fetal growth and subsequent dystocia; and potential teratogenic effects, especially masculinization of female fetuses. Maintaining the inciting cause of abortion (e.g., infected fetus) could further harm or threaten the life of other fetuses or the bitch.


The diagnosis of hypoluteoidism is difficult, explaining the controversial nature of the diagnosis. It is imperative that pregnancy be confirmed with ultrasonography and closely monitored. Serum progesterone concentrations should be assessed at least twice weekly. If a known pregnant bitch aborts a litter following documented premature decreases in progesterone concentration in the serum, and no cause for the abortion is identified despite thorough necropsy, culture, and other testing of fetal and placental tissue, the diagnosis of hypoluteoidism can be considered.


It is accepted that serum progesterone concentrations must be in excess of 2 ng/ml for maintenance of pregnancy. However, such concentrations are at the detection limits of ELISA kits, which usually estimate concentrations as less than 1 ng/ml, 1 to 5 ng/ml, and greater than 5 ng/ml. Precise determination of progesterone concentration is critical in the diagnosis. The veterinarian cannot be completely confident using in-hospital assay systems. The bitch described in the Purswell report may not have had hypoluteoidism, because the laboratory progesterone value at the time of diagnosis with the kit was rechecked and documented to be 6.5 ng/ml (Purswell, 1991). One value should be considered inadequate to confirm a diagnosis. Laboratory progesterone concentrations should be used to confirm or deny borderline results. Does the syndrome exist? Possibly.


If treatment is attempted for hypoluteoidism, several strategies can be employed. It is important to know the first day of diestrus, as defined with vaginal cytology (see Chapter 19). Exogenous progesterone should be discontinued after 50 to 53 days of diestrus (whelping typically occurs 55 to 58 days into diestrus). A recent study demonstrated that 3 mg/kg of progesterone in oil, intramuscularly, once daily (Progesterone Injection; Steris Laboratories Inc, Phoenix, AZ) is adequate to maintain serum concentrations above 10 ng/ml. Serum progesterone concentrations decreased below 2 ng/ml 48 to 72 hours after the final injection (Scott-Moncrieff et al, 1990). As little as 2 mg/kg every 48 hours may be sufficient to maintain pregnancy (Eilts, 1992). Alternatively, synthetic progesterone (17α-ethyl-19-nor-testosterone [Steraloids Inc, Denville, NJ]), 1 mg/kg SC daily, has been used successfully in maintaining pregnancy in ovariectomized bitches (Steinetz et al, 1989). The use of Ovaban (Schering, Union City, NJ) for preventing hypoluteoidism has not been described, although undocumented reports of 5 mg/day until day 55 of diestrus have been suggested.


An oral progestogen, allytrenbolone (Regumate, Hoechst RA), has been evaluated for maintaining pregnancy in ovariectomized bitches. Bitches were treated following ovariectomy on day 30 to 32 of pregnancy. Treatment was continued through day 54 of cytologic diestrus. The use of 0.044 mg/kg daily maintained pregnancy in only two of six pregnant bitches. The use of 0.088 mg/kg (0.2 cc/10 pounds) resulted in three of three bitches carrying their litters to term, with parturition beginning on the expected date in each. However, although two bitches had normal parturition, one had dystocia and death of all puppies. None of the bitches receiving the Regumate at either dosage had optimal milk production. Several litters were said to have been nursed by untreated controls, one bitch was able to nurse most of her litter 3 days after whelping, and one was able to nurse her entire litter beginning 3 days after whelping. Prolactin secretion was assumed to be suppressed by the drug in all bitches. If use of the drug is contemplated, clients must be warned that milk supplementation may be needed. In addition, the drug should not be used unless whelping dates have been reliably estimated, with serial progesterone concentrations obtained during proestrus and early estrus or with vaginal smears used for identifying day one of diestrus (Eilts, 1992).





INFECTIOUS AGENTS.

Numerous agents have been implicated in causing uterine infection, fetal death, and resorption or expulsion of litters from the bitch (see Table 21-1). These agents include Brucella, Escherichia coli, Streptococcus, herpesvirus, canine parvovirus, distemper virus, mycoplasma, Campylobacter species, Toxoplasma, and others. In our experience, confirming that a litter has been lost and that the cause was an infectious agent is quite difficult. If infection is to be pursued, it is recommended that fetal/placental or neonatal tissue, stomach and stomach contents, and vaginal swabs of the bitch be submitted for culture. Infectious agents, such as Campylobacter, may require special handling (Bulgin et al, 1984).




Canine Herpesvirus Infection.

Canine herpesvirus (CHV) is fairly ubiquitous in dogs, with 80% to 100% of certain populations having been exposed. Dogs in contact with many other dogs, via shows or in kennels with a great deal of turnover, are at greatest risk. Lifelong states of latent infection can occur, and immune responses are characterized as minimal and/or short-lived. Therefore, any serum-neutralizing antibody titer is significant, especially if coupled with clinical signs. Recrudescent canine herpes with virus shedding may be stimulated by the stress of pregnancy and parturition.


CHV infection in neonatal pups is an acute fatal infectious disease characterized by generalized focal necrosis and hemorrhage. The disease in adult dogs is usually subclinical or mild, such as conjunctivitis, serous or mucopurulent ocular and/or nasal discharges, and vaginal/vestibular/vulvar lesions that are vesicular early in the course of the disease and later become circular and pock-like. Genital lesions usually disappear shortly after infection, but they may reappear with the onset of proestrus. Canine herpes virus infection can result in fetal resorption and/or mummification if the bitch is infected early in gestation, abortion if the bitch is infected in mid-gestation, or premature birth if infection occurs in late pregnancy (England, 1998). A bitch may have dead and/or mummified fetuses in the same litter with unaffected live pups. Abortion has occurred between 44 to 51 days of gestation following infection on day 30. It is also possible for an infected bitch to be infertile or to have litters that are small in number. The fetal placenta from a bitch with canine herpesvirus infection is typically underdeveloped and congested. Several grayish white foci ranging in size from miliary to “rice grain” in size can be observed in the placental labyrinth. Sometimes the lesions form zonal structures 2 to 3 mm wide. Typical changes are also seen histologically.


Transmission of herpesvirus can occur venereally, transplacentally, via fetal contact with virus-filled vesicles that rupture during birth, or through respiratory routes of infection. Diagnosis depends on viral isolation. Viral isolation requires fastidious sampling and culture techniques from refrigerated but not frozen tissue. A negative culture for this virus may be due to inadequate methodology. Separation of infected animals from noninfected animals is advisable, especially in the final 3 weeks of gestation and the first 3 weeks of life. Because no vaccine is available for prevention, veterinarians can only recommend careful physical examination and review of the history from dogs to be used in a breeding program (Hashimoto and Hirai, 1986; Evermann, 1989).






Diagnosis (Fig. 21-1)


Abdominal ultrasonography is a highly sensitive and reliable means of diagnosing pregnancy (as early as 16 days of gestation) and detecting viable fetuses by recognition of functioning hearts (as early as 24 days of gestation). Confirmation of pregnancy early in gestation using ultrasonography allows a veterinarian the opportunity to recognize loss of a few fetuses or an entire litter.



Abdominal radiography can also serve as a tool in recognition of pregnancy and, therefore, of abortion or resorption. This tool is not as reliable as abdominal ultrasonography because pregnancy cannot be confirmed radiographically until skeletal development is complete; after 42 to 45 days of gestation. Thereafter, collapse or decalcification of the skeleton, intrafetal gas, or an abnormal fetal position can be helpful in assessing viability of fetuses (Fig. 21-2).



If a pregnant bitch is brought to the clinic exhibiting signs consistent with illness or abortion, the veterinarian must focus on completing a thorough history and physical examination. The reproductive history should include the results of previous matings and any previous problems possibly related to the reproductive tract. A careful accounting of this breeding and information regarding the male is imperative. Results of Brucella testing of the bitch and dog, as well as previous mates, are critical. Additional information to obtain includes vaccination and worming protocols; travel, contact, or exposure data; diets and supplements; environmental conditions; and medications (see Chapter 20). The physical examination should include careful and gentle abdominal palpation. Vaginal examination must be performed and culture and cytology obtained. Radiography and/or ultrasonography should be strongly considered. Blood and urine tests can be chosen as dictated by the history and physical examination. Titers for the various infectious agents may be diagnostic. Hormone assay for progesterone concentrations may be helpful in determining the likelihood of ovarian failure during the course of pregnancy. Low plasma progesterone concentrations (<2 ng/ml) indicate that corpora luteal function has failed as a primary defect or secondary to some other disorder.


If abortion/resorption is known to have taken place, a Brucella titer should be determined. Thorough necropsy of any fetus also may be informative. Bacterial or viral cultures of fetal and placental material are valuable, but results may be altered by contamination. The veterinarian must remember the long list of causes for abortion/resorption that cannot be detected using the few studies described here.


Any bitch undergoing cesarean section should also undergo complete inspection of her uterus and abdomen. Regardless of the number of ova released at ovulation or the ovary from which they arise, fetuses are normally implanted with equal and consistent spacing in both uterine horns. If obvious unequal spacing is recognized (i.e., four fetuses in one horn and one fetus in the other horn), the veterinarian should strongly suspect abortion or resorption of a portion of the litter during gestation. Close inspection with biopsy and culture of the uterus is strongly recommended in an effort to confirm suspicions of local or diffuse uterine abnormalities.



Treatment







DYSTOCIA




Practical Description






THE FETUS.

Occasionally the fetus is too large for the birth canal. The most common explanation for fetal oversize is conception of a single fetus, potentially resulting in a fetus too large for the pelvic canal (Fig. 21-3). Normal “presentation” (posture of the fetus as it enters the pelvic canal) usually results in normal delivery (Fig 21-4, A, B). However, abnormal fetal presentation causes relative oversize. Examples of relative fetal oversize include headfirst presentation with retention of the forelegs, resulting in significantly increased shoulder width (Fig 21-4, C); breech presentation with retention of the rear legs (Fig 21-4, D); presentation of one foreleg and retention of the other; lateral or ventriflexion of the head (Fig 21-4, E, F); or transverse presentation (Fig 21-4, G; Johnston et al, 2001). These problems usually require surgical intervention. Fetal oversize typically does not result from breeding a large male to a small bitch. The bitch usually “dictates” the size of the newborn, whereas both bitch and stud determine adult size of their offspring.


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Jul 10, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on Periparturient Diseases
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