Prolonged Gestation

Bruce W. Christensen

Many factors influence the duration of gestation in horses and ruminants. Normal variations in length of gestation have been attributed to genetic, nutritional, and environmental factors.¹⁸⁰,¹⁸' The species, breed, and sex of the fetus; ambient temperature; and length of photoperiod are among factors that, within normal variations, affect the duration of gestation.²⁰,^180-188 The duration of pregnancy in Thoroughbred mares ranges from 310 to 374 days,¹⁸⁸ in dairy cows from 275 to 292 days, in beef cows from 271 to 310 days, in ewes from 143 to 155 days, and in does from 140 to 155 days.¹⁸⁹ Prolonged gestation periods are those that exceed the normal gestational variation attributable to genetic, nutritional, and environmental factors.

Of the several forms of prolonged gestation with genetic causes in cattle, the best described forms have been observed in Guernsey and Holstein cattle.^{20,187,190,193} In each the fetus fails to initiate parturition at term because of fetal adrenal hypoplasia. Prolonged gestation, from 3 weeks to 3 months beyond normal term, has been observed in a number of dairy cattle breeds.¹⁹⁴ Graves, Hansel, and Krook¹⁹³ described a Holstein fetus of 441 days’ gestation in which the pituitary pars distalis was aplastic and the adrenal and thyroid glands were severely hypoplastic. Two different types of fetuses have been associated with prolonged gestation in cattle.¹⁸⁰ In the first type, fetuses had a large skeleton and excessive growth of epidermal organ structures such as hair and hooves but no obvious deformities.

Several infectious agents have been incriminated in prolonged gestation in ruminants. Bluetongue virus, bovine diarrhea virus, and border disease virus may cause severe cerebral lesions in the fetus, resulting in the absence of a hypothalamus and pituitary stalk. Again, by virtue of the lack of adrenocorticotropic hormone, the sequence of events necessary for parturition does not occur.¹⁹⁰

The use of assisted reproductive techniques in cattle in the form of in vitro procedures and somatic cell nuclear transfer (“cloning”) offers advantages for reproducing important genetic lines, but they have many accompanying complications that have yet to be overcome. Besides increased pregnancy loss, increased birthweight of calves, and increased incidence of dystocia and perinatal losses, another complication is prolonged gestation in recipient cows compared with embryo transfer recipient and artificially inseminated cows.¹⁹¹ This technology has great potential for manipulating and preserving superior genetic potential.¹⁹⁵ The cow has been the most successfully cloned animal to date, but such cloning still has a low success rate.^190-198 This is an active area of research, and it is still hopeful that with further understanding the current pitfalls surrounding in vitro procedures and nuclear transfer will be overcome and use of the techniques will become more commonplace.¹⁹⁷

Veratrum californicum contains the teratogenic agent cyclo- pamine. When pregnant ewes ingest cyclopamine on the 14th day of gestation, their fetuses lack a pituitary gland or have a malformed hypothalamic stalk. These defects result in prolonged gestation by virtue of secondary adrenal hypoplasia.¹⁹⁰

Prolonged gestation in mares has been cited as an indication 199200

for induction of parturition.¹⁹⁹,²⁰⁰ However, the clinical sig­nificance of prolonged gestation in mares is undetermined because there is no apparent correlation between duration of gestation and readiness for birth.

Approach to Diagnosis of Prolonged Gestation

Approach to the diagnosis of prolonged gestation in mares and ruminants is essentially similar (Boxes 12.14 and 12.15). If the client is concerned about what is apparently prolonged gestation in an otherwise normal dam, an accurate breeding history should be obtained. Because no pathognomonic clinical or laboratory findings are associated with prolonged gestation, the diagnosis is predicated on the history and a general physical

■ BOX 12.14

■ BOX 12.16

Causes of Prolonged Gestation in Mares

Fescue toxicity

Fetal mummification

Delayed embryonic development

■ BOX 12.15

Causes of Prolonged Gestation in Ruminants

Fetal mummification

Fetal hypothalamic-hypophysial-adrenal axis disorder Autosomal recessive genetic disorder affecting Holstein and

Guernsey cattle (B)

Vitamin A deficiency (B)

Veratrum album toxicity (B)

Veratrum californicum toxicity (cyclopamine) (O) High environmental temperature (B)

Fescue toxicity Hydrops amnii (B, O)

Bluetongue (B, O) Bovine virus diarrhea (B)

Border disease (O)

Salsola tuberculata toxicity (Grootlamsiekte [exotic]) (O) Akabane virus (exotic) (B, O)

Somatic cell nuclear transfer (B)

B, Bovine; O, ovine; C, caprine.

examination of the dam. The overall condition of the dam should be determined. In addition to the reproductive history, exposure to infectious agents and toxic plants should be determined.

Dystocia

Causes of Dystocia in Mares

Common Causes

Malpresentation Malposition Malposture

Abortion Arthrogryposis

Twinning

Less Common Causes

Fescue toxicity Preterm parturition

Torticollis

Vaginal, vulvar obstructions (hematoma, callus, abscess, tumor) Pelvic injury, fracture

Uncommon Causes

Fetopelvic disproportion Congenital defects Hydrocephalus

Uterine dorsoretroflexion

Uterine torsion Hydrops of fetal membranes Rupture of prepubic tendon Fetal mummification, maceration

Vaginal prolapse Abdominal, inguinal hernia

Uterine inertia

Induction of parturition

Premature separation of chorioallantois from endometrium Uterine laceration

goats.⁹⁵ Dystocia represents an emergency situation that com­mands prompt resolution to afford the optimum prognosis for dam and fetus. Reposition, traction, fetotomy, and cesarean section are the obstetric procedures available for the manage­ment of dystocia. The economics of large animal practice often play a significant role in determining which course to pursue in resolving dystocia. The lives of the dam and the fetus may be at risk.

Although parturition has been divided into three distinct stages for descriptive purposes, the stages overlap clinically and normal parturition is observed as a continuous process. The equine fetus is lying in a ventral or ventrolateral posi­tion with head and forelimbs flexed during late gestation. During the first stage of parturition the fetus plays an active role, along with myometrial contractions, in assuming correct extremity posture as it positions itself for delivery through the birth canal. The second stage of parturition commences with rupture of the chorioallantois and culminates in delivery of the fetus. Myometrial contractions continue during third-stage parturition, which ends with the expulsion of the placenta. In the mare, parturition is a forceful, explosive act. The time between rupture of the chorioallantoic membrane and delivery of the fetus is normally about 20 minutes.²⁰ Separation of the fetal membranes from the endometrium may occur within 1 to 2 hours after the second stage of parturition commences; therefore the retained fetus must be delivered quickly or it will asphyxiate. Fetal expulsion in the ruminant is not quite as explosive as in the mare; second-stage parturition in the bovine usually requires 12 hour to 4 hours.²⁰ Ewes and does require a range of ^l∕₂ hour to 2 hours to complete the second stage, or

■ BOX 12.17

Causes of Dystocia in Ruminants

Common Causes

Fetopelvic disproportion (B, common; C, O, uncommon) Malpresentation

Malposition

Malposture

Twins, triplets (B) Uterine torsion

Periparturient hypocalcemia (B)

Failure of cervix to dilate (B, O; rare in C) Lymphedema

Less Common Causes

Preterm parturition Abortion

Congenital defects (fetal monsters)

Hydrops of fetal membranes (B, O)

Emphysematous fetus

Hydrocephalus (more common in B than O, C) Extremity ankylosis (more common in B than O, C) Breeding immature, young, small-for-age females Obesity (B)

Pregnancy toxemia (O, C) Uterine inertia

Fetal mummification, maceration

Uterine, cervical, vaginal obstruction Retained fetus

Pelvic fracture

Vaginal prolapse

Uncommon Causes

Phytoestrogen toxicity (B, O)

Rectovaginal constriction of Jersey cattle (B)

Uterine rupture

Abdominal, inguinal hernias

Lipomatosis (B)

Lupine poisoning, arthrogryposis (B)

Polybrominated biphenyl toxicity

Bovine fetal tumors

Rupture of prepubic tendon (B)

Hereditary edema, lymphedema in Ayrshire calves Prolonged gestation (B, O)

Chlorinated naphthalene toxicity

B, Bovine; C, caprine; O, ovine.

slightly longer if twins or triplets are present.²⁰ Primiparous animals generally require a longer time to expel the fetus than do multiparous dams.

Dystocia in large animals is often accompanied by force­ful straining. The dam may attempt to lie down and stand repeatedly. This is characteristic of dams with dystocia that is caused by fetopelvic disproportion, malposture, or fetal impaction. Alternatively, the dam may stand quietly with minimal or no straining, as in cases of uterine inertia, uterine rupture, or exhaustion associated with prolonged dystocia of any cause. Whatever the presentation of the dam, the attending veterinarian must be prepared for unexpected behavior when attempting to perform obstetric examinations and procedures. General anesthesia followed by elevation of the hindquarter will facilitate safe manipulation and vaginal delivery of a foal in mares with dystocia. This technique, if applied correctly, will likely result in less damage to the mare's reproductive tract. If general anesthesia is not an option, the dam, fetus, attendants, and veterinarians must be protected from injury. The dam should be placed in open-ended stocks with movable sides or a straw-bedded box stall. During obstetric examination and manipulation, mares and cows may attempt to get up and lie down, or they may suddenly collapse. Such sudden move­ments may injure the dam and veterinarian if rigid, closed-end stocks are used. Minimum physical restraint should be used; however, restraint should be sufficient to permit completion of the obstetric examination and procedures with efficiency and safety.

Little is known about the pharmacokinetics of drugs in pregnant domestic animals. Accordingly, it must be assumed that sedative and anesthetic drugs will depress neonatal and fetal functions at least as much as those of the mare. The effects on myometrial activity of drugs administered to dams experiencing dystocia must also be considered. Acepromazine has little effect on the fetus and is generally considered safe for use in the pregnant mare. However, acepromazine was shown to have a suppressive effect on myometrial activity in cycling mares.²¹² Xylazine causes significant fetal cardiovascular compromise in horses and has been reported to stimulate myometrial activity in cows and mares.^212-214 The fetal and myometrial effects of detomidine are similar but of longer duration compared with those of xylazine.^212,213 The effects of detomidine on myoelectrical activity in the uteri of cows and mares treated during the last trimester of pregnancy were dose dependent.^215,216

As equipment is being organized and the process of evaluat­ing the dam begins, a pertinent reproductive history should be obtained, including the dam's age, her previous breeding history, and the outcomes of previous pregnancies (i.e., abortion, normal parturition, dystocia). Her present gestational status should be determined; has parturition commenced at term, or is it a preterm or postterm delivery? Her udder should be examined to determine the stage of development. Information about the progress of the current parturition should be obtained. The time since rupture of the chorioallantoic membrane, the duration and intensity of labor, whether fetal membranes or parts have appeared at the vulva, and previous attempts to assist in delivery should be noted. If the dam is recumbent, the veterinarian should determine if she has attempted to or been able to rise. Although a complete examination of the dam is optimum, it should be postponed until after the delivery of the fetus. However, in obtaining the dam's reproductive history, questions about her current physical condition should be included. Such predisposing factors as recent weight loss, systemic disease, and trauma should be considered. She should be assessed for signs of hemorrhage, dehydration, and shock.

After the tail has been wrapped, the perineal area should be thoroughly and gently washed and rinsed. Examination of the dam's reproductive tract may cause some discomfort or pain. Caudal epidural anesthesia (1 to 1.25 mL/100 kg of 2% lidocaine or other anesthetic) is often an excellent means of facilitating examination and resolution of dystocia and at the same time minimizing trauma to the dam, fetus, and operator. Lidocaine epidural anesthesia, however, may cause hindlimb weakness and ataxia. Safe and effective analgesia can also be induced by epidural administration of xylazine (0.17 mg/kg diluted in 10 mL physiologic saline). A combination of lidocaine (0.22 mg/kg) and xylazine (0.17 mg/kg) resulted in an onset of analgesia within a few minutes and a duration of over 5∕₂ hours.²¹⁷ Although both vaginal sensitivity and the Ferguson reflex are reduced by epidural anesthesia, myometrial contrac­tions and abdominal press are not totally eliminated unless the dam is put under general anesthesia. This approach has to be combined with an elevation of the hindquarter of the dam, in order to provide sufficient space for safe manipulation of the fetus. Great care must be taken during the examination of the genitalia and fetus. In addition to the viability of fetus and dam, the dam's future reproductive potential is at risk and must be preserved. The vulva, vestibule, vagina, and cervix should be carefully examined. The location of the fetus in the birth canal, as well as its viability, presentation, position, and posture, should be determined. Schuijt and Ball²¹⁸ described a procedure to manually dilate the bovine birth canal before forced extraction is attempted. In the management of dystocia in any species, forced extraction should proceed only after maximal dilation of the caudal reproductive tract in order to minimize the potential for injuries to the dam during parturition (i.e., cervical, vaginal, and vulvar lacerations; hematomas; postparturient vaginal necrosis; and obturator, perineal, and gluteal paralyses).^20,219 Mares are especially susceptible to cervical lacerations, which may have detrimental consequences on the dam's future reproductive performance. Slow traction with continuous palpation of cervical stretching by the attending obstetrician is therefore recommended in equine dystocias.

The integrity of the birth canal, fluids, and fetal membranes serves as an indicator of the length of time the dystocia has persisted and the well-being of the fetus. Generous lubrication is required in all cases of dystocia and should be applied continu­ously during the management of dystocia to prevent damage to the dam's birth canal. Lubricating preparations consisting of methyl cellulose are superior to those consisting of mineral oil or soaps. Several liters of lubricants should be infused into the bovine and equine uterus by the use of a nasogastric tube.

Traction or forced extraction can usually be successfully implemented after correction of malpresentation, malposition, or malposture. Because of the length of the extremities of the foal, manipulation is more difficult in the mare than in the cow and requires extensive repulsion to provide adequate room for manipulation. Examination and manipulation can be greatly facilitated by elevating the mare's hindquarters under general anesthesia, enabling the fetus and viscera to recede cranially into the mare's abdominal cavity, thereby allowing more room for the operator.²²⁰ If a nonviable fetus cannot be delivered by traction or forced extraction or if the owner is unwilling to select cesarean section, fetotomy can be performed.^210,220 Beyond the delivery of the nonviable fetus, fetotomy is indicated to save the mare and her subsequent fertility.²¹⁰ The advantages of fetotomy include avoiding major abdominal surgery (cesarean section) and its complications and preserving the birth canal because excessively large parts are not forced through it.^20,219-221 At the same time, the primary disadvantage of fetotomy, particularly if not properly performed by an experienced obstetrician, is trauma to the birth canal by instruments, wire, or bone.²⁰ The indications, equipment, procedures, and complications of fetotomy have been reviewed in several publications.^{20,210,219-221}

Cesarean section is indicated for a dam with dystocia when attempts to deliver the fetus by reposition, traction, and fetotomy are unsuccessful or contraindicated, and continued attempts may compromise the fetus, the dam, or her subsequent fertil­ity.^{20,95,201,205,208,222-227} Cesarean section may be the only rational procedure for delivery of some fetuses (e.g., emphysematous fetuses, deformed fetuses, bicornuate fetuses). In addition, high- risk pregnancies caused by maternal conditions can be effectively and efficiently managed by cesarean section.²⁰⁵ The specific indications, procedures, and complications of cesarean section have been reviewed in a number of publications.^{20,201,205,208,222-227}

Management of a case of dystocia is not complete until a systematic examination, focusing on the dam's reproductive tract, has been conducted. Complications during dystocia involving the reproductive tract and other body systems can affect the outcome of the case.^{20,202,228,229} As much as possible, examination of the dam's reproductive tract should rule out the presence of another fetus in the uterus or abdominal cavity.²⁰ The most common reproductive injuries incurred by dams during parturition include cervical, vaginal, and vulvar lacerations; hematomas; postparturient vaginal necrosis; and uterine hemorrhage.²⁰⁶,²¹⁹,²²⁹ Gastrointestinal complications, such as constipation associated with unwillingness to defecate, postpartum perineal inflammation, and bruising or rupture of entrapped or compressed segments of the gastrointestinal tract, can follow parturition in the mare.²²⁹ Musculoskeletal and neurologic complications have been reported after parturition in cows and mares.²⁰ Retained placenta, delayed uterine involution, metritis, and laminitis may result from normal parturition but are more likely sequelae of dystocia.^20,229,230

The signs associated with normal progression of each of the stages of parturition must be explained carefully to clients and farm managers. It is only through understanding the clinical signs associated with events of normal parturition that clients become proficient at recognizing abnormal events and know when to seek professional assistance.

Retained Fetal Membranes

Mats H.T. Troedsson

Retained fetal membranes represent the failure of the entire or partial placenta to be expelled within physiologic time limits. Although variation exists among species regarding the duration of time that must pass before a placenta is considered retained, the condition is one of the most common complications occur­ring in animals after parturition.

Retained Fetal Membranes in Mares

The anatomic structure of the equine placenta is described as diffuse, epitheliochorial, and microcotyledonary. It is composed of the allantochorion, the allantoamnion, and the umbilical cord.²³¹ During most normal foalings, the separation of fetal membranes from the endometrium and their subsequent expulsion occur within 12 hour to 3 hours of the delivery.^210,232,233 The incidence of retained fetal membranes is 2% to 10% in the mare, with a higher incidence in draft horses than in lighter horse breeds.²³⁴ The cause of retained fetal membranes remains unclear, but it is believed that allantochorionic microcotyledons near the tip of the nongravid uterine horn have failed to separate as a result of an endocrine unbalance, a disturbance in normal myometrial contractions, or any swelling at the site of micro- cotyledons²³⁵ (Box 12.18). Diagnosis of retained fetal membranes in the mare is straightforward when it is based on the observa­tion of membranes hanging from the vulva beyond 3 hours after foaling. However, if the fetal membranes fall cranially over the pelvis, they remain within the uterus without being visible, and the diagnosis must be made using vaginoscopy or ultrasonography or by digital intrauterine examination. If an early diagnosis of complete or partial retention of fetal mem­branes has been missed, the diagnosis may be made 1 to 2 days after foaling. At this time, clinical signs indicative of metritis are often present (i.e., fever, depression, colic, and/or laminitis).

After their expulsion, the fetal membranes should be stored until they can be scrutinized to determine if they are complete. The clinician should rinse the fetal membranes with water and, on a flat surface, thoroughly examine them for complete- ness.²³⁶ Evidence that a part of the placenta is retained in the uterus or that an area of microvilli has been sheared off and retained in the endometrial crypts is an indication for digital endometrial examination or ultrasonographic examination and institution of appropriate therapy (see Chapter 43).

Approach to Diagnosis of Retained Fetal Membranes in Mares

HISTORY. Many cases of retained fetal membranes follow episodes of dystocia, cesarean section, and fetotomy. An increased incidence of retained fetal membranes has been reported in mares that abort after the seventh month of gesta­tion.²³⁴ However, no increase in the incidence of retained fetal membranes associated with abortion, stillbirth, twinning, and

■ BOX 12.18

■ BOX 12.19

Causes of Retained Fetal Membranes in Mares

Common Causes

Dystocia

Preterm parturition

Abortion

Endometritis, metritis

Twinning

Induced parturition

Stillbirth

Less Common Causes

Fetotomy

Cesarean section

Placental edema at uterine horn tip

Placentitis

Drugs

Prolonged gestation

Fescue toxicity

Poor condition, poor environment, fatigue, increasing age, and other debilitating conditions

Hypocalcemia

Dropsy of fetal membranes

Entrapped placenta

delivery of a weak or diseased foal was observed if it occurred 237

without dystocia.²³⁷

PHYSICAL EXAMINATION. Fetal membranes must be examined after their expulsion to determine their entirety and integrity. Tears, missing areas of tissue, and areas of chorionic surface devoid of microvilli should be considered evidence of partly retained fetal membranes, and immediate action should be taken to enhance expulsion of retained tissue and minimize complications.

Vital signs may be normal early in cases of retained fetal membranes. A rectal examination should be performed to determine the degree of uterine involution. Aseptic intrauterine palpation can be performed to determine the area and extent of retention and the integrity of involved tissues and fluid.²³⁶ Systemic signs of dehydration, septicemia, toxemia, and laminitis may accompany fetal membranes retained for 24 to 36 hours.²²⁹ Occasionally mares with retained fetal membranes show signs of colic. Therapeutic approaches for retained fetal membranes in mares are discussed in Chapter 43.

Retained Fetal Membranes in Ruminants

The anatomic structure of the ruminant placenta is described as cotyledonary and epitheliochorial.²³³ It is composed of the allantochorion, allantoamnion, and umbilical cord. Fetal membranes are considered pathologically retained in the cow if they are not expelled by 8 to 12 hours after calving.^232,233 The incidence of retained fetal membranes in dairy cattle is 3% to 12% after normal parturition.²³⁸ Dairy cows are more commonly affected than beef cows.²³⁸ The incidence of retained fetal membranes may exceed 50% after abnormal parturition or abortion and in brucellosis-infected herds.²³⁸ The retained placenta itself is relatively innocuous, but the condition is important because cows with retained fetal membranes experi­ence an increased incidence of postpartum complications such as metritis, pyometra, ketosis, mastitis, delayed conception, and abortion.^214,239 The principal cause of retained placenta in cattle is a disturbance in the loosening process between the fetal cotyledons and maternal caruncles²⁴⁰ (Box 12.19). The processes that lead to successful loosening and separation of

Causes of Retained Fetal Membranes in Ruminants

Common Causes

Multiple births Induced parturition

Placentitis (bacterial, fungal infection) Hypocalcemia

Abortion Stillbirth

Dystocia Abnormal gestation length

Less Common Causes

Injury, inflammation, or edema of placentome Cesarean section

Uterine torsion

Necrotic placentome secondary to uterine and systemic disease Excessive weight gain during dry period

Uterine atony

Dropsy of fetal membranes Entrapment of separated placenta Prostaglandin F_2α deficiency

Trace mineral deficiencies (selenium and iodine) Vitamin deficiencies (carotene, vitamins A and E) Mineral deficiencies, imbalances (calcium and phosphorus) Heat stress

Increasing age Nitrate toxicity

High milk production

the placentome occur during the months preceding parturition. Many infectious and noninfectious factors are believed to disrupt the separation and expulsion processes. An endocrine causal relationship does not appear to exist.²⁴¹

Clinical signs of retained fetal membranes in the doe and ewe are similar to those in the cow. The placenta of the ewe and doe is considered retained if it is not expelled within 24 hours after parturition.⁹⁵ The incidence of retained placentas in does is 6.4%.²⁴² Placental retention for longer than 24 hours may cause metritis in ewes and does. Inadequate dietary selenium and inadequate nutrition and exercise during gestation have been seen as factors predisposing does to retained pla- centas.²⁴² There have been several reports on factors that predispose to retained fetal membranes.^{210,232,233,238,240,243,244} Many infectious and noninfectious factors apparently contribute to the disruption of the process of loosening and separation of the placentome. Accordingly, it has been suggested that a retained placenta should be considered to be a sign of an underlying disease.²⁴⁵

Approach to Diagnosis of Retained Fetal Membranes in Ruminants

HISTORY. A review of accurate breeding records correlates retention of fetal membranes with the duration of pregnancy. Gestational periods of abnormal lengths result in a higher incidence of retained placenta than do normal-term parturitions. Induced parturition, twinning, and late-term abortions have been associated with retained fetal membranes in cows. Many periparturient diseases and conditions affect the incidence of _retain_ed f_etal memW_es 210,232,233,238,240,243,244

Ietaineetamemianes.

PHYSICAL EXAMINATION. In cows that have calved spontane­ously and without problem after a normal gestation period, little illness tends to be associated with retained fetal membranes, and treatment may be unnecessary. Transient decreases in appetite and milk production may be observed.²³⁸ However, metritis, toxemia, and septicemia may be observed when retention of fetal membranes is associated with gestation of abnormal length, dystocia, nutritional deficiencies, or certain infectious diseases. Metritis affects up to 90% of cows with retained fetal membranes.²⁴³ For considerations for the treat­ment of retained fetal membranes in cows, see Chapter 43.

Alterations in Lactation

Bruce W. Christensen

The mammary glands are modified cutaneous glandular structures considered accessory reproductive organs that func­tion to secrete milk for the nourishment of the young.²⁴⁶ The mammary glands are located in the prepubic region in the mare, cow, ewe, and doe. The cow's udder is composed of four mammary glands, whereas in the doe, ewe, and mare the udder has two mammary glands. One teat serves each mammary gland, and in the cow, ewe, and doe each teat has one streak canal. The mare has two streak canals per teat.

The mammary glands are ectodermal in origin, and most of their fetal development occurs during the first half of gesta- tion.²⁴⁷ Except for growth that occurs in association with some of the anomalous conditions of the mammary gland or as a result of the deposition of fat, there is little growth of mammary tissue between birth and puberty. Further mammary gland development occurs with each estrous cycle after the onset of puberty. Development of the duct system is primarily attribut­able to estrogen. Progesterone is the principal stimulant to development of secretory tissue. However, neither estrogen nor progesterone alone or in combination can cause optimum mammary gland growth and development.²⁴⁸ Insulin, cortisol, thyroxine, prolactin, and growth hormone are necessary for full mammary gland development. During pregnancy the mammary gland attains maximum development under the control of pituitary, ovarian, adrenal, and placental hormones.²⁴⁹ During parturition a process of interrelated neuroendocrine processes initiates lactogenesis, the production of milk. The secretion of milk and its release from the mammary gland after parturition depend on the availability of appropriate amounts of the hormones named previously, especially prolactin and oxytocin.

In addition to mastitis, conditions that manifest themselves as alterations in the mammary gland and lactation are fairly common in ruminants and horses. Problems caused by condi­tions that affect the mammary gland are often multifactorial in that they compromise the well-being of the patient, the nutrition of the offspring, and ultimately the economics, especially in commercial dairies.

Enlarged Mammary Gland

Many conditions and diseases of the mammary gland cause swelling or enlarging of the gland²⁵⁰ (Boxes 12.20 and 12.21). Enlargement may involve one or more of the glands of the udder. However, the enlarged mammary gland is not necessarily inflamed. Several anomalies of the mammary gland cause noninflammatory enlargement of the gland (e.g., gynecomastia, precocious udder development).^250-252 It is important to deter­mine whether the enlargement of the gland is attributable to an infectious or a noninfectious cause. Trauma is probably the most likely cause of noninfectious inflammation of the mammary gland. Mastitis, with which a large number of organisms have been associated, is the most common cause of mammary gland inflammation (see Chapter 36).

Evaluation of a patient with an enlarged mammary gland should include the medical and reproductive histories. The age and sex of the animal may limit the considerations. Gyneco­mastia is seen in young bucks, rarely in rams and bulls, and

■ BOX 12.20

Causes of Enlarged Mammary Glands in Mares

Common Causes

Mastitis

Abscessation

Periparturient udder edema (physiologic)

Gland distention associated with weaning

Less Common Causes

Trauma (contusion, hematoma, seroma, laceration) Neoplasia (malignant melanoma, carcinoma)

Cutaneous histoplasmosis (Histoplasma farciminosus)

■ BOX 12.21

Causes of Enlarged Mammary Glands in Ruminants

Common Causes

Mastitis

Periparturient udder edema

Abscessation

Trauma (contusion, hematoma, seroma, laceration) Pendulous udder (B, C)

Blind quarters (aplastic duct) (B)

Less Common Causes

Eczema

Urticaria (irritants, caustic chemicals; contact dermatitis; insect bites)

Sarcoptic and psoroptic mange

Primordial mammarian tissue swelling (accompanies witch's milk)

Photosensitization

Sunburn

Frostbite

Cowpox (B)

Pseudocowpox (B)

Goat pox

Contagious ecthyma (orf) (C, O)

Furunculosis, abscesses Staphylococcal folliculitis

Papillomatosis, warts

Caprine arthritis-encephalitis (C, O)

Zearalenone toxicity

Neoplasia (lymphosarcoma, malignant melanoma [C], squamous cell carcinoma [C])

Milk allergy (B)

Tuberculosis (B)

Ovarian neoplasia

Caseous lymphadenitis (O, C)

Cutaneous lipomatosis

Enzootic mycobacterial nodular-ulcerative mammillitis (B) Bovine herpesvirus mammillitis (BHV-2) (B)

Precocious udder development (B, C)

Udder cysts (C) Gynecomastia (C)

Pseudopregnancy (C)

Foot-and-mouth disease (exotic)

B, Bovine; C, caprine; O, ovine.

never in stallions.^250,252 Congenital anomalies such as stenotic or absent teat canals are not determined until parturition occurs and lactation commences.²⁵⁰ The animal should be given a complete physical examination, with emphasis on the affected mammary gland. Examination of the gland should

■ BOX 12.22

■ BOX 12.23

Causes of Udder Edema

Mares

Peripartunent udder edema (physiologic)

Ruminants

Periparturient udder edema (physiologic) Hereditary predisposition

Overfeeding of grain prepartum

Excess dietary protein

Obesity

Excess dietary sodium, potassium Hypomagnesemia (chronic udder edema) Disturbances in udder blood and lymph circulations Excessively long dry period

Anemia

include observation, palpation, and expression of its contents. Cytologic and bacteriologic examination of the secretion from the mammary gland may be helpful in determining the cause and establishing the prognosis of enlarged mammary glands. In postpartum cows the most common causes of enlarged mammary glands are periparturient udder edema and mastitis. Mastitis occurs most often in mares after weaning. Trauma to the udder is more likely to be problematic in cows and goats than in ewes and mares because the udder is more pendulous in the former.²⁵⁰ Undesirable udder traits of genetic origin occur in the goat (e.g., hanging or saclike udder, polythelia, blocked teat).²⁵³ Lacerations, superficial contusions, and seromas are detected by close examination of the affected gland. Diagno­ses of other injuries may rely on examination of the gland's secretion for evidence of increased cellularity and hemorrhage. Mammary gland neoplasia is rare in mares, cows, and small ruminants.^250,254-256

Udder Edema

Udder edema, one of the most common causes of enlarged mammary glands, results from the excessive accumulation of intercellular fluid in the mammary gland (Box 12.22). The disorder is observed during the late gestation and early post­partum periods and is common in both horses and ruminants, but it is probably more frequently seen in dairy cattle. One study reported an udder edema incidence of 18% in dairy cattle, of which less than 1% required veterinary treatment.²⁵⁷

Two forms of udder edema are seen in cattle.²⁵⁸ In the physiologic or acute form, there is edema of the mammary gland during the late gestation and early postpartum periods.²⁵⁸ The entire udder is usually symmetrically involved, and the edema may involve adjacent abdominal and perineal areas.²⁵⁸ The condition is usually not obviously painful but may cause the cow some difficulty in lying down and walking because of the mammarian swelling. Chronic bovine udder edema differs from the acute form in that affected cows develop udder edema within 6 weeks after calving, and the edema may persist for several months.²⁵⁸ The swelling may be localized in the form of plaques on the ventral aspect of the rear of the udder, or it may involve the ventral abdominal wall.²⁵⁸

Udder edema is a relatively common condition of dairy goats.²⁵⁹ Two-year-old does kidding for the first time are most commonly affected; however, all ages can be affected. Affected does usually have colostrum at parturition, but within a few hours the udder is warm, hard, and agalactic.

Broodmares affected with udder edema have generalized ventral edema during the last 1 to 2 weeks of gestation and for as long as 2 to 3 days after foaling. The extent of ventral Causes of Agalactia and Hypogalactia in Mares Common Causes

Mammary aplasia, hypoplasia

Abscessation

Mastitis

Abortion

Premature birth

Postpartum complication

Less Common Causes

Endocrine dysfunction

Nutritional deficiencies, malnutrition

Neoplasia

Squamous cell carcinoma

Malignant melanoma

Pituitary adenoma

Lymphosarcoma

Other tumors

Fescue toxicity

Trauma to mammary gland

Periparturient disease

Dystocia

Anemias

Severe toxicity

edema varies, ranging from local swelling of the udder and immediately adjacent subcutaneous tissues to a generalized swelling that may extend from posterior to the mammary glands forward, along the ventral abdomen and thorax, to the axillary or pectoral area. In the mare such edematous accumulations are referred to as plaques of edema. Affected broodmares seem to be uncomfortable and reluctant to move. Younger brood­mares, especially primiparous mares affected with udder edema, appear to be in more pain than older mares, and some of the mares so affected refuse to allow their foals to suckle.

Agalactia

Any disease or condition that adversely affects the dam has the potential to compromise lactation. Agalactia, the failure of lactation after parturition, may be attributable to a primary endocrinologic or mammary gland problem, or it may be secondary to any of a multitude of systemic conditions and diseases (Boxes 12.23 and 12.24). True agalactia may be attribut­able to mammary gland anomalies or inadequacies among the numerous endocrinologic factors of development and pregnancy. Agalactia may be a complication of many conditions. In some animals the conditions to which agalactia is secondary manifest as alterations in a specific system, whereas other animals with agalactia may demonstrate such signs as fever, weight loss, anorexia, and anemia. Inadequate nutrition is rarely the cause of clinically observed agalactia. Fescue grass toxicity, caused by ingestion of the ergot alkaloid-producing Acremonium coenophialum, is an important cause of agalactia and hypoga­lactia^260,261 (see Clinical Signs of Fescue Toxicosis earlier).

Agalactia should not be confused with failure of milk ejection (milk letdown). Administration of oxytocin may enhance milk letdown but does not affect milk production. Oxytocin stimulates a release phenomenon that acts on previously secreted and stored milk. Although somatotropin may increase milk produc­tion in a normally lactating cow, its effect on agalactia has not been adequately studied.

Inexperienced or nervous mares with adequate milk are often reluctant to allow their offspring to nurse, in part because of the mare's inexperience. Such nervous mares need not necessarily be primiparous mares. Although not allowing their

■ BOX 12.24

■ BOX 12.25

Causes of Agalactia and Hypogalactia in Ruminants

Common Causes

Mammary aplasia, hypoplasia

Mastitis

Abscessation

Caseous lymphadenitis (udder involvement) (C, O) Caprine arthritis-encephalitis (CAE; hard udder) (C, O)

Less Common Causes

Endocrine dysfunction

Malnutrition

Water deprivation

Self-sucking (B, C)

Trauma

Chapped teats; teat dip irritation (B, C)

Milk allergy

Neoplasia

Malignant melanoma (C)

Lymphosarcoma

Squamous cell carcinoma

Carcinomas

Fescue toxicity

Papillomatosis

Mycoplasmal agalactia (C, O)

Anemias

Severe toxicity

B, Bovine; C, caprine; O, ovine.

offspring to nurse is usually a manageable behavior problem, the mare's udder should be examined for evidence of periparturi­ent edema, inflammation, and painful conditions.

APPROACH TO DIAGNOSIS OF AGALACTIA. An accurate reproductive history should be obtained. It should be determined whether the dam is primiparous or multiparous. If primiparous, is she manifesting anxiety in the presence of her offspring? If multiparous, has she been agalactic at previous parturitions? Has she sustained recent trauma, perhaps during parturition, or was there exposure during gestation to infectious diseases or toxic plants? After a history has been determined and the dam and neonate have been observed, attempts to facilitate the youngster's suckling might be indicated. Is the dam agalactic, or does she simply refuse to let the neonate suckle? Such measures as twitching or tranquilizing the nervous and inex­perienced mare may resolve that problem. If assessing the dam's behavior toward her offspring does not resolve the problem, a thorough physical examination should be initiated. The objective now should be to rule out or incriminate infec­tious and inflammatory conditions contributing to the agalactic state. The dam herself may be systemically affected, or the problem may be localized in the udder or a mammary gland.

In listing causes of agalactia and hypogalactia in Boxes 12.23 and 12.24, the authors included only those that have a direct effect on the anatomic integrity of the mammary gland or its function. Abnormalities involving any system may compromise lactation.

Galactorrhea and Precocious Mammary Gland Development

Galactorrhea, the abnormal manifestation of lactation (not the secretion of true milk), occurs occasionally from the Causes of Galactorrhea and Precocious Mammary Gland Development in Horses and Ruminants

Impending abortion

In utero death of one twin fetus

Spontaneous (inappropriate prolactin secretion) Placental separation

Zearalenone toxicity

Pregnancy (especially multiple fetuses)

Suckling

Pseudopregnancy (caprine)

Ascending infection during pregnancy, placentitis Ovarian tumors

primordial mammary gland of young foals and ruminants, including neonates.²⁵⁰ The secretion is popularly known as witch ' milk.

Precocious mammary gland development and galactorrhea occur in pregnant and nonpregnant mares and in some of the ruminant species (Box 12.25). Such premature udder development and subsequent lactation have been observed in nonpregnant and nonsuckled doelings and heifers.^250,262 Udder development and subsequent lactation have been observed in young nonpregnant heifers and does being suckled by other young animals.²⁵⁰ In addition to the continued stimulation of suckling, other causes of premature mammarian development and lactation may be trauma and diseases of the pituitary, ovarian, and adrenal glands.²⁵⁰ Zearalenone toxicity has been implicated in precocious mammary gland development and lactation in heifers.²⁶³ Milk production is nonphysiologic in that it is of insufficient quality and quantity and does not justify milking the affected animals. There is no evidence that such abnormal development compromises normal lactation after 250

parturition.²⁵⁰

Inappropriate lactation has been observed at various stages of pregnancy in most domestic species.²⁵⁰ The most common cause of galactorrhea is abortion. Lactation may commence before or even without expulsion of the dead fetus. Lactation during pregnancy has also been observed in association with multiple fetuses, placentitis, and ovarian tumors. Accordingly, premature mammary gland development during gestation should be considered a warning of impending abortion, and the dam should be examined. Occasionally, pregnant mares develop mammarian enlargement during middle to late gestation that spontaneously regresses.²⁶¹ Some of these mares begin to lactate before parturition. It must be kept in mind that pre­mature lactation and subsequent loss of colostrum is one of the most important causes of failure of passive transfer of immunoglobulins.²⁶⁴

Gynecomastia, the abnormal development of the male's mammary glands, has been observed in bucks in which rudi­mentary mammary glands and associated teats underwent development.^250,262 The aberrant structures, located on both sides of the buck's scrotum, can secrete up to 1 L daily of a substance that resembles milk. The cause is presumed to be endocrine imbalance but has not been determined. Lofstedt and colleagues²⁶⁵ reported adrenal neoplasia as a cause of lacta­tion in a wether.