Chapter 15 The Peripartum Period
THE PERIPARTUM EQUINE
ASSESSMENT OF THE MARE DURING LATE GESTATION
It has been estimated that between 25% and 40% of mares that are bred do not produce a live foal.1-4 Many factors contribute to this poor outcome, including infertility, early fetal loss, abortion, stillbirth, and perinatal death.2 During late gestation, two of the most important causes of reproductive loss are fetoplacental infection and complications of delivery including dystocia and perinatal asphyxia.2,5 As mares age, their pregnancy and foaling rates decline and their foals experience higher morbidity and mortality rates and decreased athletic ability.1,3
A 1997 National Animal Health Monitoring System (NAHMS) study of 7320 foals estimated a mortality rate of 1.7% within the first 48 hours of a live birth.6 This includes an estimate of euthanasia and spontaneous deaths. Sepsis, asphyxia, and dysmaturity, including prematurity and postmaturity syndromes, are the leading causes of neonatal foal mortality during the first two weeks of life. Despite dramatic advances in neonatal intensive care, many foals still die, not because their primary problem is untreatable, but because veterinary intervention was delayed, delivery was unattended, neonatal compromise was not recognized in a timely fashion, or critical care was unavailable or not economically feasible. Foals surviving severe peripartum illness often experience increased morbidity associated with chronic infections, suboptimal growth, or developmental orthopedic disease. Therefore the focus of equine neonatology has shifted from a strictly therapeutic approach to a preventative one. This new direction emphasizes assessment of fetoplacental well-being during late pregnancy. The three periparturient events that have the most devastating effect on neonatal survival are hypoxia, infection, and derangement of in utero development. These events can result in behavioral abnormalities, multiorgan system failure, neonatal death, abnormal fetal development, or premature delivery.
Many of the periparturient events associated with increased fetal and neonatal morbidity and mortality have been identified in the mare (Box 15-1). In human obstetrics, prepartum detection of placental dysfunction and fetal distress has become an important factor influencing the management of the last stages of pregnancy and the newborn infant. Following the lead in human perinatology, clinicians are developing biochemical and biophysical techniques for monitoring fetoplacental well-being in the pregnant mare.7-10 Mares with high-risk pregnancies should be identified early, treated appropriately, and monitored carefully through the birth process. Accurate assessment of fetal well-being is complicated and difficult in the human being. Fetal monitoring in the equine species is less developed and is handicapped by the size of the dam and fetus.
Box 15-1 Common Causes of Abortion, Stillbirth, and Perinatal Death in Horses
From Giles RC, Donahue JM, Hong CB, et al: Causes of abortion, stillbirth, and perinatal death in horses: 3527 cases (1986-1991), J Am Vet Med Assoc 203:1170, 1993.
Vaala has suggested that mares experiencing problem pregnancies be assigned to one of three categories: (1) mares with histories of abnormal pregnancies, deliveries, or newborn foals; (2) mares at risk for a problem with the current pregnancy because of systemic illness or reproductive abnormality; (3) mares that have no apparent risk factor but that experience an abnormal periparturient event.10 A list of important perinatal risk factors is presented in Box 15-2. Ideally, mares with high-risk pregnancies should receive some type of late gestation fetal monitoring or at least be carefully watched during late gestation and attended at the delivery. Personnel attending the delivery of a high-risk foal should be trained in resuscitation techniques.
A variety of biochemical and biophysical parameters can be measured in the late-term mare or fetus. Measurement of maternal progestagen concentrations in plasma may provide an indicator of fetal well-being. Maternal progestagen concentrations are relatively stable between days 150 and 315 of gestation, rising sharply over the remainder of the pregnancy before a large fall in the last 1 to 2 days before parturition. Progestagens are synthesized by the fetus and by the uteroplacental tissues. Two abnormal progestagen patterns have been described.11-14 In acute maternal illnesses, such as colic or torsion of the uterus, the progestagen concentration declines hours to days before abortion. In these mares progestagen concentration may fall to less than 2 ng/mL.14 In chronic disease states, such as laminitis or placentitis, there is a premature rise in the plasma progestagen concentration that can persist for weeks before abortion or premature delivery.11 It has been suggested that a premature increase in maternal progestagens could reflect hastened or precocious fetal maturation. Removal of the stressful event can lead to normalization in progestagen concentrations and the subsequent delivery of a normal-term foal. Progesterone radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) can be used to quantitate progestagens. Measurement of progestagens may be indicated to determine the need for progestin supplementation.15
An ELISA has been developed to measure equine fetal protein, and elevated concentrations were associated with twinning, placentitis, premature placental separation, uterine trauma, and fetal death.10,16 Additional studies are required before this test can be applied accurately in a clinical setting. Another reproductive hormone that holds promise as a marker of fetoplacental well-being and periparturient complications in the mare is relaxin. The placenta is the primary source of relaxin in horses.17 In healthy pregnant mares relaxin concentrations increase from about day 80 to a peak of 80 to 100 ng/mL at day 175, which persists until birth.18,19 In mares with problematic pregnancies, low relaxin levels during late pregnancy have been indicative of placental insufficiency associated with a variety of causes including fescue toxicosis,20 oligohydramnios, placentitis, and pituitary neoplasia.21
Several studies have demonstrated that ultrasound-guided transabdominal amniocentesis and allantocentesis can be performed relatively safely in the late-gestation mare as long as the procedure is performed aseptically and multiple attempts are not made.10,22 However, the clinical usefulness of fetal fluid analysis in the horse remains to be determined. Studies attempting to relate the phospholipid profile in amniotic fluid with equine fetal lung maturation have been inconclusive to date.10,22,23 Transabdominal-guided ultrasound amniocentesis has been used to detect experimentally induced equine herpesvirus 1 (EHV-1) fetal infection in utero.24 This technique holds promise as a diagnostic aid to detect specific fetal diseases and as a potential therapeutic avenue to deliver medication in utero.
Electrolyte concentrations in prepartum mammary secretions may be monitored to predict impending parturition in the mare. As parturition approaches, the mammary concentration of sodium decreases and concentrations of potassium and calcium increase. An elevation in calcium concentration to over 40 mg/dL (10 mmol/L) is considered the most reliable indicator of readiness for birth and may be used to help determine whether elective induction or cesarean section should be performed. The increase in calcium occurs over the last 72 hours of gestation.25,26 Test strips are commercially available to measure calcium and magnesium concentrations in a field setting (Predict-a-Foal test, Animal Health Care Products, Vernon, CA; FoalWatch kit, Chemetrics, Calverton, VA). The mammary concentration of potassium increases and the mammary sodium concentration decreases over the final 7 days of the gestational period. The mammary concentration of potassium typically exceeds that of sodium between 1 and 5 days before foaling. This has been used by some as a predictor of birth, although a recent study concluded that the use of mammary electrolyte concentrations was not reliable because of individual variability both in raw concentrations and in percent changes.27
An arbitrary scoring system using calcium, sodium, and potassium concentration in the mammary secretions to assess fetal maturity has been described.26 False-positive results—that is, values that inaccurately predict imminent foaling—have been associated with vaginal discharge, placentitis, and premature lactation. False-negative results occur commonly in mares with systemic illness or in animals that have undergone general anesthesia. In many mares the changes in the electrolytes occur only within hours of delivery, so if monitoring is not performed frequently, the changes will be missed.10,27,28 The decision on whether or not to induce parturition in a mare should not be based on the results of this type of testing alone.
Fetal heart rate (FHR) monitoring is routinely used in the human fetus to detect fetal distress, particularly hypoxia, during late gestation and labor and delivery. Doppler ultrasound is the most common technique used for FHR monitoring; this technology has been adapted for use in the mare.29 First the fetal heart is located using an ultrasound transducer, then the Doppler transducer is placed on the mare’s abdominal wall directly over the fetal heart. Fetal movement is detected by a pressure transducer or by a hand placed on the mare’s abdomen. Continuous FHR monitoring for at least 10 minutes is preferred to better detect abnormalities in heart rate and rhythm. Use of M-mode echocardiography makes it easier to obtain an FHR measurement because of the rapid motion of the normal equine fetus. Heart rate is normally regular and decreases from greater than 120 beats per minute (bpm) before day 160 of gestation to between 60 and 90 in late gestation.8,29-31 An average of 10 heart rate accelerations (25 to 40 bpm) was observed in a 10-minute period; 95% of these were associated with fetal movement.29 Cardiac accelerations in response to fetal movement are an indicator of fetal well-being. Cardiac rhythm should be regular. Persistent bradycardia is associated with fetal distress and is mediated by a vagal response to hypoxemia. Severe tachycardia and arrhythmias have been associated with impending fetal demise. Although persistent fetal tachycardia and bradycardia suggest fetal compromise, normal heart rate alone does not guarantee that the fetus is healthy. Prolonged periods of fetal inactivity in the absence of maternal sedation are also suggestive of fetal compromise.
A fetal electrocardiogram (ECG) may also be used to assess FHR and fetal heart rhythm after day 150 of gestation.30,31 The procedure is relatively easy to perform. The left arm electrode is placed on the dorsal midline of the mare at the lumbar region, and the left leg electrode is placed 15 to 20 cm cranial to the mare’s udder on the ventral midline. The hair should be clipped, and ample gel or alcohol should be placed to ensure good contact of the electrodes. Poor fetal signals may result from poor electrode contact or placement, fetal movement, or electrical interference.10
Transabdominal ultrasonography allows noninvasive evaluation of the intrauterine environment and fetal well-being. A biophysical profile (BPP) using five parameters is used in women to evaluate fetal distress late in pregnancy.32,33 The BPP evaluates the following: fetal tone, fetal movement, fetal breathing, FHR reactivity (i.e., increased FHR during fetal activity), and amniotic fluid volume. The BPP was predicated on the theory that during asphyxia the most complex activity, FHR reactivity, disappears first, followed sequentially by fetal breathing, fetal movements, and fetal tone. Decreases in fetal fluids are associated with chronic intrauterine stress and hypoxia, dysmaturity, and placental insufficiency.34
Transabdominal ultrasonography can be used in the mare to evaluate the equine fetus after day 90 when the gravid uterus contacts the ventral abdominal wall. This technique is used more commonly during the second and third trimesters. Recent studies have focused on the development of a modified BPP using FHR reactivity, fetal activity, fetal breathing movements, qualitative and quantitative fetal fluid assessment, evaluation of placental integrity, and measurement of fetal size. Transducers with lower frequencies (2 to 4 MHz) are required because of the deep tissue penetration needed. The mare’s ventral midline must be cleaned and clipped from the level of the umbilicus caudally to the mammary gland, and a viscous coupling gel applied. Minimal maternal restraint is usually required. Chemical sedation should be avoided because drugs such as xylazine and detomidine induce fetal bradycardia and retard fetal movement.
In the pregnant mare, transabdominal ultrasonography has been used to detect twins, document fetal position, estimate fetal size using fetal aortic diameter, evaluate fetal activity, evaluate placental integrity, determine fetal fluid clarity and volume, and monitor FHR and fetal breathing. After 9 months of gestation most fetuses are in an anterior presentation and are unlikely to change that presentation before delivery.35 The mean fetal thoracic aortic diameter averages between 2.2 and 2.5 cm in horse fetuses.8 Fetal activity increases with advancing gestational age, and FHR decreases. During late gestation the equine fetus should demonstrate good tone and moderate activity with only brief episodes of inactivity (<20 min). During the last month of gestation the FHR averages between 60 and 90 bpm with transient bouts of tachycardia (25 to 40 bpm above baseline) observed during or immediately after fetal activity. Fetal breathing is characterized by excursion of the diaphragm between the thorax and the abdomen, with accompanying ribcage expansion. Regular breathing movements are observed intermittently in most late-term fetuses. It is difficult to differentiate fetal from maternal breathing movements. The maximum ventral fetal fluid pocket depths average 8 cm for amniotic fluid and 13 cm for allantoic fluid.8 Excessive fetal fluid accumulation is observed in cases of hydrops. Markedly decreased amounts of fetal fluids have been associated with placental dysfunction and the birth of a dysmature, hypoxic foal. As gestation advances, fetal fluids increase in turbidity. Sudden increases in turbidity may be associated with meconium passage, hemorrhage, or inflammatory debris. Average uteroplacental thickness viewed transabdominally ranges between 8 and 15 mm.8 Thicker uteroplacental units may indicate placental edema, placental separation, or placentitis. Areas of separation between the uterus and chorion appear as black anechoic areas.
Transabdominal real-time ultrasonography can provide both structural and functional information about the health and environment of the fetus. Because of the depth of penetration required, 2- to 4-MHz transducers should be used. As in other procedures involving ultrasonography, familiarity with the normal appearance of the placenta and fetus is essential to detect abnormalities. Details on how to perform the evaluation can be found in other texts.29,36-38 In the mare this procedure has been used in late gestation to determine fetal position, estimate fetal size, evaluate the placenta and fetal fluids, detect premature placental separation, and assess fetal movement and viability.10,37 Overall, fetal activity tends to increase with advancing gestational age; periods of inactivity longer than 15 minutes may indicate the need for further evaluation. A BPP has been developed that uses several parameters to establish an idea of the size and overall health of the equine fetus.9,29,39 The parameters include fetal weight, as estimated by the fetal aortic diameter (mean 2.1 cm at 300 days’ gestation to 2.7 cm at term), heart rate, movement, uteroplacental thickness (mean 1.26 ± 0.33 cm), qualitative allantoic fluid appearance, and allantoic volume estimation. Additional studies are needed to establish the validity of this profile in predicting fetal health or compromise in a larger group of mares.
EFFECTS OF PLACENTAL INSUFFICIENCY
The effects of uteroplacental vascular insufficiency on the newborn depend on the severity of placental compromise and the severity and duration of prenatal and perinatal asphyxia. Conditions associated with chronic asphyxia in the large animal fetus include chronic placentitis, villous atrophy, twin and postterm pregnancies, ingestion of endophyte-infected fescue grass by the pregnant mare,40 and ingestion of ponderosa pine by pregnant cattle.41
If decreased uteroplacental blood flow is long-standing, growth is concomitantly inhibited in the fetus. The pattern of growth retardation associated with chronic placental insufficiency is usually asymmetric. This type of growth retardation is characterized by visceral wasting with relative preservation of fetal length and head circumference. Affected human infants are expected to be long and thin, with loss of subcutaneous fat and a large head relative to the body size. The same is probably true in the large animal neonate. It has long been recognized that twin equine neonates and other abnormally small foals tend to have heads that are disproportionately large for their small, wasted bodies.42
In placental vascular insufficiency the fetus has the ability to avoid overgrowing its nutrient supply and to maximize organ growth. Under metabolic stress there is a fetal antiinsulin response, with loss of fat and glycogen stores and muscle mass. Associated with the decrease in uteroplacental blood flow is an increase in uterine and fetal vascular resistance, and redistribution of cardiac output, with a greater percentage of blood flow going to organs such as the brain and heart. Unless uteroplacental insufficiency is very severe, brain growth continues at a relatively normal rate. In the human fetus the redistribution of cardiac output also results in decreased blood flow to the lung and kidney and decreased production of fetal urine and lung liquid, two major components of amniotic fluid. A decrease in amniotic fluid volume is therefore associated with chronic fetal asphyxia. The regulation of these adaptations is not completely understood, but corticosteroids, catecholamines, and vasopressin, among others, play a role.43,44
It is thought that repeated episodes of hypoxemia during gestation slowly deplete cardiac glycogen stores and impair the ability of the heart to effectively pump blood during subsequent hypoxemic episodes, such as during labor. The newborn with depleted glycogen stores may also be at increased risk of developing hypoglycemia and hypothermia. Meconium aspiration and persistent arterial hypertension in the newborn period are secondary to chronic fetal hypoxia. Immature skeletal ossification, particularly of the carpal and tarsal bones, has also been associated with growth retardation in the foal.42
There are certain advantages associated with fetal adaptation to chronic placental insufficiency. Growth-retarded premature human infants have a lower incidence of hyaline membrane disease than babies of the same gestational age who are appropriately sized.45 Presumably, fetal hormones, such as the corticosteroids and catecholamines that are released in response to nutrient deprivation, stimulate the early maturation of the lung and surfactant system. Accelerated neurologic maturity has also been documented, along with accelerated pulmonary maturity.46 Therefore the fetus that has been chronically exposed to an adverse in utero environment may be in some ways more tolerant of premature delivery and independent life outside the uterus than the “normal” fetus that is abruptly displaced through induction of labor or cesarean section. The low-birthweight fetus therefore represents a successful adaptation to a nutrient-deprived environment. Its smaller size, decreased metabolic needs, and early organ maturation actually place it at lower risk for hypoxic injury at birth and aid its transition to independent life after delivery.44 Further discussion of the characteristics, treatment, and prognosis of growth-retarded premature foals may be found in Chapter 19.
Premature lactation, purulent vaginal discharge, previous history of growth-retarded foals, advanced maternal age, and prolonged gestation are problems that should raise the suspicion of chronic uteroplacental insufficiency. The labor and delivery should be attended to minimize the chances of acute asphyxia. The newborn animal should be examined for evidence of growth retardation, infection (particularly in utero acquired pneumonia secondary to placentitis), and metabolic and acid-base derangements. Ample colostrum should be administered, and body temperature and blood glucose should be monitored closely.
One author has suggested that intrauterine growth retardation is unlikely to pose any substantial additional threat to the neurodevelopment of premature human infants unless it is accompanied by chromosome abnormalities, severe perinatal asphyxia, or hypoglycemia, or unless growth retardation is very severe.47 Human infants that display characteristics of asymmetric growth retardation commonly “catch up” by late infancy or early childhood. Similar observations have been made in the foal. Many mildly to moderately growth-retarded newborn foals have also done well after discharge from the hospital and have grown to a normal size. Problems secondary to an immature musculoskeletal system, such as angular limb deformities, have been the most common complications noted in these individuals, but careful orthopedic management can result in a successful outcome.
PLACENTITIS
Placentitis is a common cause of reproductive losses in horses in the United States. During the 1998-1999 foaling season in Kentucky, 24.7% of cases of aborted, stillborn, and premature foals were associated with placentitis.48 The most common cause of placentitis is ascending infection from the lower urogenital tract via a relaxing cervix. A far less common route of infection is the hematogenous avenue, resulting in a diffuse or multifocal placentitis. Most cases of placentitis are the result of bacterial infection caused by typical equine pathogens including Streptococcus equi subsp. zooepidemicus, Enterobacter agglomerans, Klebsiella pneumoniae, and Pseudomonas aeruginosa. In Kentucky and some other regions a slightly different form of placentitis has been recognized and is characterized by focally extensive placentitis located predominantly at the base of the placental horns at the junction of the horns and the body of the placenta. The affected area is covered with thick, tenacious, brown mucoid exudate, and the underlying chorionic villi are necrotic and absent or reduced in size. This form is associated with infection with a group of gram-positive, branching, filamentous Nocardioform-like organisms.48
Clinical signs of placentitis include vaginal discharge that may be evident on the mare’s vulva, tail, or inner thighs, premature udder development, and precocious lactation. Premature udder development is the result of placental compromise, fetal stress, a precocious increase in maternal progestagen concentration, and enhanced fetal adrenocortical activity. Despite even voluminous vaginal discharge, most mares with placentitis do not become febrile and do maintain a normal appetite. The dam’s hemogram and fibrinogen concentration usually remain within normal limits. Transrectal ultrasound can be used to identify placental separation and uteroplacental thickening of the caudal uterine body. This region is most commonly involved in mares with ascending placental infection. Measurement of the combined thickness of the uterus and placenta (CTUP) is established. This measurement increases from approximately 6 mm at 7 months of gestation to 10 to 12 mm at term.49,50 A measurement greater than 12 mm at 11 months or greater than 15 mm at 12 months is consistent with placental pathology.49 Measurement of CTUP alone can be misleading, and a recent recommendation involved monitoring of the CTUP by ultrasound along with determination of the maternal progestagen concentrations to give a more accurate assessment of fetal well-being.11 Transabdominal ultrasonography can be used to evaluate other areas of the placenta to detect loss of placental integrity or increased uteroplacental thickening. Measured using transabdominal ultrasound, the uteroplacental unit should be <16 mm during late gestation. Other signs suggestive of placentitis include increased fetal fluid echogenicity, which may be the result of hemorrhage, purulent exudate of the brown mucoid material associated with Nocardioform placentitis.51 If placentitis is severe enough to alter placental function, reduced fetal movement, loss of heart rate variability, and absolute fetal bradycardia indicate fetal compromise.
Samples of vaginal discharge should be cultured, and Gram stains performed. The goal of maternal therapy is to treat the placental infection and maintain the pregnancy, provided there is no evidence of severe fetal distress or demise. In many cases, because the infection is of long duration, the fetus has been chronically stressed and therefore is relatively mature for its gestational age and better prepared to tolerate premature birth. If placentitis is suspected, after delivery the foal should be considered a high-risk individual. Commonly encountered problems in the newborn foal that was exposed to placentitis are pneumonia, uveitis, growth retardation, incompletely ossified bones, and, sometimes, systemic sepsis.
MANAGEMENT OF THE HIGH-RISK LATE-GESTATION MARE
Each mare should receive a complete physical examination, and a complete foaling history should be obtained. She should be evaluated regularly for clinical signs of impending parturition (sacroiliac ligament and perineal relaxation, mammary development, and mammary secretion electrolyte concentration). The reproductive tract may be evaluated by rectal palpation, and transabdominal ultrasonography may be performed at regular intervals to detect changes in the fetus, fetal fluids, or placenta. Prolonged periods of starvation are best avoided to prevent maternal hypoglycemia.10 Estimation of progestin concentrations in the maternal circulation, using a commercial progesterone assay, is recommended.11
When treating the pregnant mare for any medical or surgical condition, there are two patients to consider: the dam and the fetus. Any illness or disease that affects the mare’s cardiovascular system has the potential to affect placental perfusion and the integrity of the fetoplacental unit. Hypotension, endotoxemia, and hypoxemia are examples of conditions that can alter uteroplacental blood flow and jeopardize the pregnancy. Diseases that stimulate prostaglandin production have the potential to initiate labor and delivery. Illnesses that produce prolonged periods of anorexia in the late-term mare can also lead to premature delivery. The effect of various drugs on the placenta and fetus should be considered when treating the pregnant mare. If delivery is not imminent, then many drugs will pass through the placental and fetal circulation and be cleared by the maternal liver and kidneys. Because of the epitheliochorial nature of the mare’s placenta, some drugs will not cross the placental barrier at all. If drugs are administered to the mare and the fetus is delivered shortly thereafter, then the neonate must rely on its renal and hepatic function to process, degrade, and excrete those drugs. In most instances, as long as fetal well being and placental integrity are closely monitored, the goal of most therapies is to treat the maternal condition and maintain the pregnancy as long as possible to achieve an acceptable degree of fetal maturation. Early data derived from late pregnant mares indicated that penicillin and gentamicin did not readily cross the fetal membranes.52,53 However, recent studies using microdialysis probes inserted into the allantoic fluid of normal mares reported therapeutic concentrations of penicillin and gentamicin in the allantoic fluid after 22,000 IU/kg of potassium penicillin G (intravenous [IV] administration q6h) and 6.6 mg/kg gentamicin (IV q24h).54 Studies in two mares with experimentally induced bacterial placentitis again confirmed passage of both drugs across the placenta. The combination of trimethoprim-sulfadiazine (30 mg/kg orally [PO] bid) and the phosphodiesterase inhibitor pentoxifylline (8.5 mg/kg PO bid) also readily crosses the fetal membranes in both healthy mares and in animals with experimental placentitis.53,55 In many cases medical treatment of the placental infection and prolongation of pregnancy is associated with a good outcome. Maternal treatment includes systemic antibiotics, flunixin meglumine, and altrenogest.10 Because of the usual presence of mixed gram-positive and gram-negative placental and fetal infections, a broad-spectrum antibiotic that reaches therapeutic levels in the fetus and fetal fluids should be selected. Therapeutic options include penicillin and gentamicin, trimethoprim-sulfonamide, and ceftiofur. Low doses of flunixin can be administered to decrease inflammation and prevent prostaglandin-mediated induction of delivery. Regumate (altrenogest) (10 to 20 mL PO q24h) is given to help maintain the pregnancy. If there are large areas of placental thickening, IV dimethyl sulfoxide (DMSO) (0.5 to 1 g/kg) can be administered to decrease placental edema. Pentoxifylline has also been administered in attempts to improve placental perfusion.
If premature delivery appears unavoidable, then one or two doses of maternal steroids can be used with the hope of stimulating and accelerating fetal lung maturation through enhanced surfactant production. In the high-risk mare, it is very important that the delivery be attended by knowledgeable personnel and that all supplies, drugs, and equipment required for diagnosing and correcting a dystocia and stabilizing the mare and foal be organized and close at hand. A spontaneous, vaginal delivery is generally preferred in the high-risk mare, because of both the profound problems associated with the untimely delivery of a premature foal and the complications sometimes associated with induced labor or cesarean section.56,57 (See Chapter 19, Prematurity.) There are instances, however, when an induced birth or cesarean section is indicated or preferred.
Induction of parturition should be considered with the following:
Evidence of premature placental separation or a history of premature placental separation associated with dead or asphyxiated foalsIndications for cesarean section may include the following:
If induction of parturition or cesarean section is elected, every effort should be made to ensure that the fetus is mature and is ready to be born; the usual result of induction at an inappropriate time is a nonviable newborn. Three essential criteria are a gestation of longer than 330 days, good-quality colostrum in the udder, and softening of the cervix.56 The scheduling needs of the veterinarian or owner should never be the only criterion used for determining the timing of delivery. A slow continuous oxytocin infusion administered at a rate of 1 unit/minute usually results in delivery within 20 to 40 minutes.10 Alternatively, multiple IV or intramuscular injections of 10 to 20 units of oxytocin every 10 minutes have been recommended.56,58 Other investigators have shown that smaller IV doses of oxytocin (2.5 IU administered every 15 to 20 minutes until rupture of the chorioallantois or a total of 20 IU of oxytocin has been administered) is an effective, and perhaps more physiologic, method of induction.59
Induction of parturition in the mare has been associated with more violent, painful contractions than spontaneous labor and a higher incidence of premature placental separation and neonatal asphyxiation. Cesarean section also predisposes to neonatal peripartum asphyxia. Maternal hypotension secondary to general anesthesia and the weight of the maternal abdominal contents on the aorta and vena cava may both compromise uteroplacental circulation. For further details concerning anesthesia of the late-term mare, the reader is referred to other texts.60,61 The management of a mare with hydrops amnion was recently described.62 Abdominal support was used along with nonsteroidal antiinflammatory drugs and altrenogest to maintain the pregnancy up until day 321, when spontaneous delivery occurred. The delivery was complicated by uterine inertia, maternal postpartum hypovolemic shock, and cardiac arrhythmias, but both mare and foal survived.
THE PERIPARTUM RUMINANT
The peripartum period is a high-risk period for the fetus and dam. Approximately 5% to 10% of the annual calf crop and 15% to 20% of the annual lamb crop in the United States dies before weaning.63,64 Between 50% and 70% of neonatal mortality occurs in the first 3 days of life, with dystocia, starvation, and hypothermia responsible for 50% to 60% of these losses.64,65
Reduced fetal viability often reflects mismanagement of maternal nutrition and/or the maternal environment during the last trimester of pregnancy and/or the prepartum and peripartum periods. Investigation of perinatal morbidity and mortality should begin with assessment of maternal management. Some of the more common causes of stillbirth and perinatal mortality are listed in Box 15-3.
Box 15-3 Common Causes of Stillbirth and Perinatal Death in Ruminants63,64,124,125
Forty percent to 60% of stillbirths are associated with dystocia. Calves that survive dystocia are more likely to have edema of the head and tongue, making suckling difficult. They are also weak and exhausted and likely to be recumbent for a longer period of time and expose themselves to more fecal pathogens.66 Dystocia affects the uptake of immunoglobulins by the calf, and calves that survive dystocia are more likely to become sick in the first 45 days of life.67 Maternal variables correlated with dystocia and consequently calf mortality at birth include parity and conformation. Dystocia and stillbirths in heifers are most commonly secondary to fetopelvic incompatibility. Fetopelvic incompatibility accounts for a lower proportion of dystocias in multiparous cows, but weak labor secondary to hypocalcemia, uterine torsion, and incomplete cervical dilation are more common in older cows.68 In a large study of Holstein calving records, 8.3% of calves born to heifers were stillborn compared with 3.6% of calves born to multiparous cows.69 Dam pelvic diameter is an important determinant of dystocia for heifers.70 Pelvic measurements can be used to identify abnormally small or abnormally shaped pelvises. Large frame size of the dam correlates with a reduced risk of dystocia; however, continued selection for large frame size tends to select for larger birthweight and dimensions of calves.71 Age at first calving for heifers is not correlated with risk of dystocia as long as heifers are fed and managed to achieve appropriate growth and stature before calving.72-74 The risk of dystocia in heifers is increased by poor nutrition in the last trimester.75 Appropriate nutrition and management of replacement heifers to achieve appropriate size and stature at parturition reduces maternal and neonatal losses by reducing the incidence of dystocias. Maternal consequences associated with calving difficulty and delivery of a stillborn calf include decreased milk production and reduced reproductive efficiency. Reductions in milk production ranging from 100 to 400 kg have been reported to be associated with the birth of a stillborn calf. If the stillborn calf is delivered by cesarean section, the reduction in milk yield is in the order of 300 to 500 kg.69 Delivery of a stillborn calf is also associated with depressed conception rates, increased services per conception, and delayed conception.
Use of calving ease bulls over primiparous cows helps to reduce the incidence of dystocia and subsequently mortality during parturition. The heritability of calving ease is relatively low; estimates of maternal calving ease range from 0.03 to 0.24,68,76,77 and paternal heritability is approximately 0.147. Despite the relatively low heritability of calving ease, selection for calving ease should not adversely affect other production parameters in dairy cattle, as the genetic correlation between calving ease and other dairy production traits are generally close to 0.68 Calving ease evaluations are intended to increase the use of artificial insemination (AI) for heifers. To facilitate sire selection most breed associations provide guidelines regarding calving ease or expected progeny difference for calf birthweights. An example of such a scheme is the calving ease and reliability values assigned to AI Holstein bulls. In this system the calving ease score is the expected percentage of difficult births predicted for calves delivered by primiparous cows.78 The reliability score provides an indication as to the number of births that were considered in deriving the calving ease score. The higher the reliability score, the larger the number of observations the calving ease score is based on and the more likely it is that the calving ease prediction will accurately reflect the outcome.
Management variables that influence the risk of dystocia and perinatal mortality include stocking density of preparturient cows, timing of calving, and cow grouping. In a study of 123 beef herds the dystocia rate was highest for cows housed in a barn and decreased progressively through barn-and-yard, barn-and-pasture, and pasture-only calving location categories.79 The most common cause of dystocia in penned heifers was vulval constriction, whereas dystocias in paddocked heifers were most commonly associated with malpresentations.80 Calving beef heifers 6 weeks before cows has been recommended to allow the heifers longer to recover and conceive after calving than cows.81 In a herd level comparative study this practice was associated with a higher incidence of dystocia and stillborn calves.79 Presumably because of better nutritional management, heifer dystocia rate is reduced the longer heifers are maintained as a separate group from cows before calving.79
Fetal variables that influence the risk of mortality include sex, size, and number. Calves born to primiparous cows, twins, and bull calves are more likely to die at birth than calves born from multiparous cows, single calves, and heifer calves.82,83 Low and high birthweight calves are at greater risk of mortality than average birthweight calves.82 Small calves experience greatest mortality at parities greater than one, and large calves at first parity.72 Fetal viability may be compromised in utero by a number of infectious agents. Common infectious agents associated with abortion and or birth of weak calves are listed in Box 15-3. Manifestations of disease in the newborn are dependent on the time of exposure to the infectious agent.
Environmental stress before or around the time of parturition can compromise the fetus or neonate. Heat stress affects fetal viability by impeding calf growth in the last trimester of pregnancy84 and by depressing colostral quality85 and immunoglobulin transfer.86 Uterine blood flow and placental mass are reduced and endocrine profiles altered when cattle are heat stressed during the last trimester of pregnancy. Heat stress during the last 3 weeks of pregnancy lowers dry matter intake, contributing to a negative energy balance at this time, promoting mobilization of body fat and ketogenesis. Transfer of immunoglobulins to colostrum is impaired, and the concentration of protein, casein, lactalbumin, fat, and lactose in colostrum is reduced.85 Cold, windy, and wet conditions also adversely affect calf survival. The magnitude of the effect of climate on neonatal survival depends on the age of the dam, sex and size of the calf, and incidence of dystocia in the herd.82 Cold stress sufficient to cause hypothermia in calves leads to subcutaneous hemorrhages and delayed absorption of colostral immunoglobulins.87
Maintenance of adequate nutrition throughout pregnancy is essential to provide for the growing fetus and to maintain a healthy dam capable of delivering and nursing the fetus. Pregnancy toxemia, hypocalcemia, protein energy malnutrition, micronutrient deficiencies, and obesity may all impair the health of the fetus directly, or indirectly by affecting the health or capacity of the dam to deliver the fetus. Protein energy malnutrition and copper deficiency have been associated with impaired fertility, weak calves, and high calf mortality.88
Assessment of Fetal Viability
Fetal viability is rarely evaluated during the prepartum period in production animals, but it is a serious consideration when the prepartum dam is diseased or debilitated. Assessment of fetal viability is diagnostically challenging, but a number of methods are available to evaluate the fetus and fetal environment. During the physical examination of cattle, uterine blood flow, uterine tone, and presence of a vaginal discharge may be evaluated via rectal palpation and a vaginal speculum examination. Reduced fremitus in the uterine arteries and increased uterine tone may be appreciated by rectal palpation after fetal death. Abdominal ultrasound is useful for examining the uterus, placenta, and fetuses of small ruminants. The uterus and placenta of cattle can be examined by transrectal ultrasound, but examination of the fetal calf via transrectal or transabdominal ultrasound is often compromised by limited access. Fortnightly ultrasound of the uterus and placenta of recipient cows carrying cloned calves is conducted to detect evidence of hydroallantois and placental edema in these high-risk pregnancies.89 After fetal death, some of the following may be observed: thickening of the uterine wall, increased echogenicity of chorioallantoic and amniotic fluid, altered fetal posture, altered contour of the amnion, and reduced definition and ultimately reduced size of the caruncles.* Examination of the fetus may reveal gross congenital abnormalities, and ultrasound of the fetal chest allows visualization of a beating heart and determination of FHR. The normal heart rate of full-term lambs is 108 to 126 bpm.90 Measuring the heart rate of fetal calves is more difficult than in small ruminants but can be achieved via transabdominal Doppler using a 1.5-Mhz probe. The normal heart rate of full-term calves is 90 to 125 bpm.91 In human medicine FHR is used as a measure of fetal viability. FHR accelerations associated with fetal movement are considered a sign of fetal well-being, and persistent bradycardia or tachycardia a sign of fetal stress.92 Normal FHR patterns of ruminants need to be characterized in more detail before FHR measurements are used for prenatal clinical assessment of ruminant fetal well-being.93
Fetal loss associated with abnormal placentation occurs sporadically and is reflected by alterations in volume and composition of allantoic and amniotic fluid. In a study of 60 cases of bovine hydrops, 88% were hydroallantois, 5% hydramnios, and 7% a combination of both.94 Hydroallantois is often associated with disease of the uterus and hydramnios with genetic or congenital defects of the fetus (Dexter cattle with bulldog calves, Angus calves with osteopetrosis, Guernsey calves with pituitary hypoplasia or pituitary aplasia).95 The concentration of sodium and chloride in allantoic fluid of cattle during the last 12 weeks of gestation is normally low (Na = 52 ± 20 mmol/L and Cl = 17 ± 11 mEq/L) and concentration creatinine concentration is high (1224 μg/mL ± 458).96 With hydroallantois, allantoic fluid sodium and chloride concentrations rise toward extracellular fluid concentrations (Na = 116 ± 13 and Cl = 81 ± 12 mEq/L), and allantoic creatinine concentration decreases (193 ± 73 μg/mL).96 Normal amniotic fluid has electrolyte concentrations similar to those of plasma (Na = 132 ± 7 and Cl = 115 ± 8 mEq/L) and a lower creatinine concentration than allantoic fluid (70 ± 26 μg/mL).96 Cows with hydroallantois are also often hyponatremic and hyperglycemic.94,97
Estrone sulfate is a marker of a viable fetoplacental unit and has been used to assess fetal viability in cattle.98 Estrogen synthesized by embryonic tissue is converted to estrone sulfate by the endometrium, which contains the enzyme sulfotransferase. Estrone sulfate assays can be used to diagnose pregnancy in small ruminants after 50 days99 and in cattle after 100 days.100 Estrone sulfate may be measured in plasma or milk84,100; baseline values are low after fetal loss, regardless of the stage of pregnancy. Compromise of the fetoplacental unit reduces estrone sulfate production. In a study of the effects of heat stress on pregnant cattle, plasma estrone sulfate concentrations were significantly lower throughout pregnancy in cows that gave birth to low-birthweight calves.84 Plasma concentrations of estrone sulfate rise slowly during the second trimester of pregnancy from 0.74 ng/mL to 3.66 ng/mL from day 90 to day 210 of pregnancy. The last trimester of pregnancy is associated with a rapid rise in the concentration of estrone sulphate to 13.36 ng/mL at approximately 10 days before parturition.101
In human medicine, diagnosis of surfactant deficiency is based on the ratio of two phospholipids in amniotic fluid, lecithin (L) and sphingomyelin (S). If the L/S ratio is greater than 2, the surfactant system is mature and respiratory distress syndrome is rare.102 The L/S ratio in amniotic fluid collected from cattle may also be used to assess surfactant system maturity,103 providing a measure of readiness for birth, but is rarely employed in clinical veterinary medicine. Crude surfactant harvested from bovine lungs at a slaughterhouse has been used intratracheally with calves that appeared to be in respiratory distress shortly after birth.104
INDUCTION OF PARTURITION IN RUMINANTS
Manipulation of parturition may be considered for maternal, fetal, or management reasons. Fetal viability after induced parturition is variable among species. The viability of calves induced within 14 days of anticipated calving date is good.105 Viability of lambs and kids induced more than 5 days before anticipated parturition date is poor.95 Absorption of colostral immunoglobulins by premature calves is reduced, so colostral transfer should be monitored closely in induced neonates.106 Induction of parturition or cesarean section is often necessary to prevent mortality of small ruminants with pregnancy toxemia.107 Fetal viability is often improved by induction of parturition with dexamethasone; however, delivery of the fetuses via cesarean section is often necessary because of the debilitated state of the dam. Secretion of glucocorticoid hormones from the adrenal cortex increases markedly during the final days of gestation. The prenatal increase in fetal glucocorticoid secretion plays an important role in the cascade of endocrine events leading to parturition and stimulates maturational events in the lungs, liver, kidney, and gastrointestinal tract in preparation for postnatal life.108
Steroids stimulate production of surfactant phospholipids by alveolar type II cells, enhance the expression of surfactant-associated proteins, reduce microvascular permeability, and accelerate overall structural maturation of the lungs.109 Administration of 10 mg of flumethasone and 25 mg of dinoprost to pregnant cows 30 hours before elective cesarean section increases the L/S ratio, improving lung function and reducing complications associated with respiratory acidosis in the calf.110 Induction of parturition has been used to reduce the incidence of dystocia in herds or breeds experiencing a high incidence of dystocia associated with fetomaternal disproportion.111 Large birthweights are strongly correlated with fetomaternal disproportion.112,113 Induction of parturition within 14 days of anticipated calving date is associated with good calf viability and a 3.2-kg reduction in birthweight of beef calves.105
Exogenous glucocorticoids, prostaglandin F2α (PGF2α), or a combination may be used to induce parturition in cattle (dexamethasone 20 to 30 mg alone or in combination with 25 mg PGF2α) and in sheep and goats (10 to 20 mg dexamethasone and/or 15 mg PGF2α).95 Glucocorticoids are more effective than prostaglandin for inducing parturition in sheep.114 A lower incidence of dystocia and higher viability of calves has been reported in cattle induced with glucocorticoids compared with cows induced with prostaglandin.115 Cows treated with dexamethasone or prostaglandin within 14 days of anticipated calving date usually calve within 72 hours of treatment.105 Combination of dexamethasone with prostaglandin increases the efficacy and reduces the interval to parturition (36 hours).116,117 Retention of fetal membranes is a common complication of induced parturition in cattle.118 Retention of fetal membranes may be associated with reduced first service conception and subsequent pregnancy rates.119 Treatment of cows with prostaglandin at calving was reported to reduce the incidence of retained fetal membranes,120 but subsequent studies have failed to support this.116,121 Induction of cattle by administration of 25 mg of triamcinolone (Opticortinol) at day 270 followed by treatment with dexamethasone and prostaglandin 6 days later appears to reduce the incidence of retained fetal membranes associated with induction.118,122 Coliform mastitis is an uncommon complication observed after induced parturition.123
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