An estimated 25% to 40% of mares that are bred do not produce a live foal.^1–3 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.^2,4 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.⁵ 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 2 weeks of life.⁶ 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. 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, multi-organ system failure, neonatal death, abnormal fetal development, or premature delivery.

Many of the periparturient events associated with increased fetal/neonatal morbidity and mortality have been identified in the mare (Box 15-1). Biochemical and biophysical techniques for monitoring fetoplacental well-being have been developed for use 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 handicapped by the size of the dam and fetus.

Mares experiencing problem pregnancies can 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; and (3) mares with no apparent risk factor, which 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 watched carefully during late gestation and attended at the delivery. Personnel attending the delivery of a high-risk foal should be trained in resuscitation techniques (see later).

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 falling greatly in the last 1 to 2 days prior to parturition. Progestagens are synthesized by the uteroplacental tissues from pregnenolone (P5) derived from the fetus.¹¹ Two abnormal progestagen patterns have been described.^12–15 In acute maternal illnesses, such as colic or torsion of the uterus, the progestagen concentration declines hours to days prior to abortion. In these mares the concentration may fall to less than 2 ng/mL.¹⁵ 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.¹² 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 full-term foal. Progesterone RIAs and ELISA assays can be used to quantitate progestagens because of significant cross-reactivity. Measurement of progestagens may therefore be indicated to determine the need for progestin supplementation.¹⁶

Relaxin is a marker of fetoplacental well-being and periparturient complications in the mare.¹⁷ The placenta is the sole source of circulating relaxin in mares.¹⁸ In healthy pregnant mares, relaxin concentrations increase from about day 80 to a peak of 80 to 100 ng/mL at day 175, a value that persists until birth.^19,20 A recent study of mares with normal pregnancies reported slightly lower values over the final 7 weeks of gestation, with a mean weekly value of 63 ng/mL.¹⁷ Plasma values drop at delivery and are cleared within 48 hours of passage of the fetal membranes. In mares with problematic pregnancies, low relaxin levels during late pregnancy have been indicative of placental insufficiency associated with a variety of causes including twinning, fescue toxicosis, oligohydramnios, placentitis, and pituitary neoplasia.¹⁷ The variability in values make it difficult to rely on relaxin concentration as a marker of treatment efficacy in problem pregnancies.¹⁷ Elevated concentrations of equine fetal protein were associated with twinning, placentitis, premature placental separation, uterine trauma, and fetal death, but further studies are required before this test can be applied accurately in a clinical setting.¹⁰

Several studies have demonstrated that ultrasound-guided transabdominal 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.^10,21,22 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.^10,23,24 Transabdominal-guided ultrasound amniocentesis has also been used to detect experimentally induced equine herpes-virus (EHV-1) fetal infection in utero.²⁵ The technique holds promise as a diagnostic aid to detect specific fetal diseases and as a potential therapeutic avenue to deliver medication in utero. Preliminary data demonstrated that mares that delivered healthy foals had a significantly higher amniotic fluid lactate concentration at the time of delivery than mares that delivered sick foals.²⁶ The significance of this finding is unknown.

Electrolyte concentrations in pre-partum 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 (400 µg/mL; 10 mmol/L) is a reliable indicator of readiness for birth and can 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.^27,28 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, CA). The milk calcium test better predicts mares that are not likely to foal rather than accurately determining the timing of foaling.

There are increases in the mammary concentration of potassium and a decrease in the mammary sodium concentration over the final 7 days of the gestational period. The mammary concentration of potassium typically exceeds that of sodium between 1 and 5 days prior to foaling. This has been used by some practitioners as a predictor of birth, although one study concluded that the use of mammary electrolyte concentrations was not reliable because of individual variability both in raw concentrations and in percent changes.²⁹ The reversal of the milk sodium to potassium ratio was more accurate at predicting the day of birth than the milk calcium concentration in Martina Franc jennies, a breed that has longer mean gestational length.³⁰ The ratio reliably reversed 24 to 48 hours before parturition.

An arbitrary scoring system using calcium, sodium, and potassium concentration in the mammary secretions to assess fetal maturity has been described.²⁸ False-positive results (i.e., a value that inaccurately predicts imminent foaling) have been associated with vaginal discharge, placentitis, and premature lactation. False negatives 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; thus, if monitoring is not performed frequently, the changes will be missed.^29,31 Recently, a comparison was made among milk calcium carbonate concentration, refractometry index, and pH with respect to prediction of foaling in healthy Thoroughbred mares.³² Milk pH declines from a mean of approximately 7.4 to 6.4 over the final week of parturition. The positive predictive value (PPV) of foaling within 72 hours and the negative predictive value (NPV) of foaling within 24 hours for calcium carbonate concentration (using a water hardness test kit) were 93.8% and 98.3%, respectively. The PPV within 72 hours and NPV within 24 hours for mammary secretion pH (using pH paper 6.2-7.6) were 97.9% and 99.4%, respectively. Both techniques were superior to handheld refractometry. The authors used cutoff values of 400 µg/g for calcium and 6.4 for pH. The decision on whether or not to induce parturition in a mare should not be based solely on the results of this type of testing.

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.⁷ 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. Fetal electrocardiogram (ECG), a procedure that is relatively easy to perform, may also be used to assess fetal heart rate and rhythm after day 150 of gestation.^33–36 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. An alternative method involves placement of the left leg lead on the left neck, the left arm lead in the left flank at the height of the hip, the neutral lead on the mare’s croup, and the right arm lead over the linea alba cranial to the udder, and connecting the lead to a Televet 100 recording system (Kruuse, Marvel, Denmark). This configuration allows for simultaneous determination of the maternal and fetal ECG. 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/min before day 160 of gestation to between 60 and 90 beats/min in late gestation.^9,33–35 In normal mares the FHR and heart rate variability are relatively constant over the final 10 days of gestation, and are therefore not useful indicators of foaling.³⁵ Cardiac accelerations in response to fetal movement are an indicator of fetal well-being. An early study reported an average of 10 heart rate accelerations (25 to 40 beats/min) in a 10-minute period; 95% of these were associated with fetal movement.³⁷ A more recent study reported that the number and duration of cardiac accelerations and decelerations remained relatively constant over the last 2 months of pregnancy. There were approximately 22 accelerations per hour lasting around 29 to 42 heartbeats, and around 24 decelerations per hour lasting 24 to 60 heartbeats.³⁵

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 or 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, also suggest fetal compromise.

Transabdominal ultrasonography allows noninvasive evaluation of the intrauterine environment and fetal well-being. In the mare transabdominal ultrasonography can be used 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. 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 since 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 prior to delivery.³⁸

A biophysical profile has been developed that uses several parameters to establish an idea of the size and overall health of the equine fetus.^7,8,37 The parameters include fetal weight, as estimated by the fetal aortic diameter (mean, 2.1 cm at 300-d gestation to 2.7 cm at full term), FHR (decreases with advancing gestational age), movement (increases with advancing age), uteroplacental thickness, qualitative allantoic fluid appearance, and allantoic volume estimation. During late gestation the equine fetus should demonstrate good tone and moderate activity with only brief episodes of inactivity (<20 min). Fetal breathing is characterized by excursion of the diaphragm between the thorax and the abdomen with accompanying rib cage expansion. Regular breathing movements are observed intermittently in most late-term fetuses. It is difficult to differentiate fetal from maternal breathing movements. The average uteroplacental thickness viewed transabdominally ranges from 8 to 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. 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 can be associated with meconium passage, hemorrhage, or inflammatory debris.

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, and ingestion of endophyte-infected fescue grass by the pregnant mare.

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 asymmetrical. 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 equine 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 bodies.³⁹

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 anti-insulin 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.^40,41

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 a result of chronic fetal hypoxia. Immature skeletal ossification, particularly of the carpal and tarsal bones, has also been associated with growth retardation in the foal.³⁹

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 that are appropriately sized.⁴² 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.⁴³ 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-birth-weight 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 of hypoxic injury at birth and aid its transition to independent life after delivery.⁴¹ Further discussion of the characteristics, treatment, and prognosis of growth-retarded premature foals may be found in Chapter 17.

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 resulting from 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 or accompanied by severe perinatal asphyxia or hypoglycemia, or unless growth retardation is very severe.⁴⁴ 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 following discharge from the hospital and have grown to a normal size. Problems resulting from 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.