Pregnancy toxemia in ewes is a disease affecting sheep during late gestation, characterized by feed refusal and neurologic dysfunction progressing to recumbency and death. It is seen more often in older ewes and those carrying multiple fetuses. Pregnancy toxemia is almost never observed in replacement ewe-lambs or yearlings lambing for the first time.
Epidemiology and Pathogenesis
The primary predisposing cause of pregnancy toxemia is inadequate nutrition during late gestation, usually due to insufficient energy density of the ration and decreased rumen capacity as a result of fetal growth. In the last 4 wk of gestation, metabolizable energy requirements rise dramatically. For example, ewes pregnant with twin lambs need ∼1.8–1.9 times more energy and protein than maintenance requirements.
In late gestation, the liver increases gluconeogenesis to facilitate glucose availability to the fetuses. Each fetus requires 30–40 g of glucose/day in late gestation, which represents a significant percentage of the ewe's glucose production and which is preferentially directed to supporting the fetuses rather than the ewe. Mobilization of fat stores is increased in late gestation as a method of assuring adequate energy in the face of increased demands of the developing fetus(es) and impending lactation. However, in a negative energy balance, this increased mobilization may overwhelm the liver's capacity and result in hepatic lipidosis with subsequent impairment of function. Additionally, twin-bearing ewes appear to have more difficulty producing glucose and clearing ketone bodies, thus increasing their susceptibility to pregnancy toxemia.
Ewes with a poor body condition score (BCS ≤2.0) or that are overconditioned (BCS ≥4.0) and carrying >1 fetus are most at risk of developing pregnancy toxemia, although it can occur even in ideally conditioned ewes on an adequate ration. Susceptible thin ewes develop ketosis due to a chronically inadequate ration being offered and, in the face of increasingly insufficient energy to meet increasing fetal demands, the ewe mobilizes more body fat with resultant ketone body production and hepatic lipidosis. Overconditioned ewes may have depressed appetites, and adipose mobilization quickly overwhelms the liver's capacity, resulting again in hepatic lipidosis. In addition, there may be a population of sheep that are less responsive to insulin production in the face of inadequate nutrition. Ewes fitting these criteria may quickly shift from subclinical ketosis to clinical pregnancy toxemia if feed intake is acutely curtailed by such events as adverse weather, transport, handling for shearing or preventive medication, or other concomitant disease (footrot, pneumonia, etc). These variants of pregnancy toxemia have been termed primary pregnancy toxemia (thin ewes and inadequate nutrition), estate ketosis (fat ewes), and secondary pregnancy toxemia (ewes suffering from other disease).
Early clinical signs can be detected by an observant shepherd. Most cases develop 1–3 wk before lambing. Onset earlier than day 140 of gestation is associated with more severe disease and increased risk of mortality. Decreased aggressiveness at feeding, particularly with grain consumption, indicates a problem. Ewes may also show signs of listlessness, aimless walking, muscle twitching or fine muscle tremors, opisthotonos, grinding of the teeth, and as the disease progresses (generally over 2–4 days), blindness, ataxia, and finally sternal recumbency, coma, and death. Cerebral hypoglycemia coupled with ketosis, ketoacidosis, and reduced hepatic and renal function lead to the clinical signs and fetal death. Blood glucose levels may return to normal or even become high terminally, possibly indicating death of the fetus(es). Septicemia develops in the ewe after fetal death.
Postmortem changes demonstrate varying degrees of fatty liver, enlarged adrenal glands, and often include multiple fetuses in a state of decomposition indicating premortem death. Very thin ewes may appear starved (eg, serous atrophy of the kidney and heart fat). However, these signs alone are not pathognomonic for death due to pregnancy toxemia. Postmortem samples of aqueous humor or CSF can be analyzed for β-hydroxybutyrate (BHB). Levels >2.5 and 0.5 mmol/L, respectively, are consistent with a diagnosis of pregnancy toxemia.
Laboratory findings in individual ewes may include hypoglycemia (often <2 mmol/L), elevated urine ketone levels (evaluated by commercial qualitative test tablets), elevated BHB levels (normal <0.8 mmol/L, subclinical ketosis >0.8 mmol/L, and clinical disease >3.0 mmol/L), and occasionally hypocalcemia. Hypoglycemia is not a consistent finding, with up to 40% of cases having normal glucose levels and up to 20% having hyperglycemia. If the diagnosis needs further confirmation, CSF glucose levels may be more accurate than blood; they remain low even when serum glucose rebounds in advanced cases after fetal death. BHB is a more reliable indicator of disease severity than are blood glucose levels. Nonesterified fatty acids can also be elevated above 0.4 mmol/L, indicating likely hepatic lipidosis resulting in impaired hepatic function.
While hypocalcemia is often found in cases of pregnancy toxemia, it should also be considered when formulating hypotheses regarding recumbent late gestational sheep. This is similarly true with hypomagnesemia, which is a common finding in cases of pregnancy toxemia but should also be considered as a differential diagnosis for periparturient CNS disease. Other CNS diseases to be considered include polioencephalomalacia, pulpy kidney disease, rabies, lead poisoning, chronic copper toxicity, and listeriosis. These can be differentiated based on clinical and laboratory findings.
Treatment of advanced cases of pregnancy toxemia is frequently unrewarding. If a ewe is already comatose, treatment should focus on the rest of the flock. However, if the ewe or lambs are valuable, then aggressive therapy should be directed against the ketoacidosis and hypoglycemia. Before starting this therapy, it should be determined whether the fetuses are alive (eg, real-time or Doppler ultrasonography). If the fetuses are alive and within 3 days of a calculated due date (gestation length 147 days), then an emergency cesarean section may be considered but is often economically unfeasible. If the fetuses are dead or too premature to survive a cesarean section, it is less stressful to the ewe to induce early lambing with dexamethasone (15–20 mg, IV or IM). Prophylactic antibiotics (usually procaine penicillin G at 20,000 IU/kg, sid) are appropriate if the fetuses are thought to be dead.
Hypoglycemia can be treated by a single injection of 60–100 mL 50% dextrose IV, followed by balanced electrolyte solution with 5% dextrose. IV drips and lower dextrose levels in solution might cause less of a diuretic effect; however, this is often impractical in a field setting. Repeated boluses of IV glucose should be avoided because they may result in a refractory insulin response. Insulin can be administered (20–40 IU protamine zinc insulin, IM, every other day). Calcium (50–100 mL of a commercial calcium gluconate or borogluconate solution, SC) can be given safely without serum biochemistry data. If serum biochemistry demonstrates hypocalcemia, ~50 mL of a commercial calcium solution can be given by slow IV injection while monitoring the heart. Oral potassium chloride (KCl) can be given as well because serum potassium levels are often depressed. In trials using recombinant bovine somatotropin, treated ewes had fewer days to clinical recovery than untreated ewes (6.5 vs 7.8 days). While aggressive therapy and intensive nursing care may be successful, it is not unusual to see case fatality rates >40%. Given the cost, it is prudent to share the guarded prognosis with owners before undertaking treatment.
Ewes in the early stages can often be treated successfully with propylene glycol (60 mL, bid for 3 days). Adding oral calcium (12.5 g calcium lactate), oral potassium (7.5 g KCl), and insulin (0.4 IU/kg, SC, sid) has increased survival rates. Oral commercial calf electrolyte solutions containing glucose may also be given by stomach tube at a dose of 3–4 L, qid, or drenched as a concentrated solution. The contributing factors (eg, nutrition, housing, other stressors) should be corrected for the group, and feeding management assessed (eg, adequate feeder space, feeding frequency, protection from adverse weather).
A sample of late-gestation ewes can be tested for BHB levels to determine the extent of the risk in the rest of the flock. Generally, 10–20 ewes should be sampled (3–20% of the pregnant flock). The risk of the flock can be determined based on the mean value of these results: normal (low risk) 0–0.7; moderate underfeeding (moderate risk) 0.8–1.6; and severe underfeeding (high risk) 1.7–3.0 mmol/L. Other diseases should be treated (eg, contagious ovine footrot). Ewes off feed should be separated from the group and hand fed, keeping in mind that ewes should be able to see the group to feel comfortable.
Ewes should not enter the last 6 wk of gestation with a BCS <2.5; this can be prevented by good feeding management and ration formulation. During the last 6 wk of gestation, grain is required as a source of carbohydrates in the ration to maintain the health of multiple-bearing ewes. Amount varies depending on forage quality, adult body weight and condition score, and number of fetuses, but protein must also be balanced for rumen microbes to make optimal use of available carbohydrates.
Producers should ideally assess BCS at breeding and midgestation so that thin ewes can be fed as a separate group. If real-time ultrasound scanning allows for fetal number determination, then ewes should also be managed based on fetal numbers. Producers may find it convenient to feed pregnant ewe-lambs with twin-bearing ewes and thin single-bearing ewes (because of the added energy ewe-lambs need for growth). With prolific breeds, triplet-bearing ewes and thin twin-bearing ewes can be fed together. Overconditioned ewes are not as common but may be seen in small hobby flocks. Fat ewes are much less responsive to therapy, and owners should be advised on how to avoid the problem through proper feeding management. However, late pregnancy is not the time to reduce BCS in overconditioned ewes. BHB serum levels can be used as a flock screening test to detect flocks at risk of pregnancy toxemia. In flocks with values ranging from >0.80–3.0 mmol/L, feeding management should be corrected quickly to avoid clinical disease.
Recently, considerable research has supported the use of ionophores, particularly monensin, in transition dairy cows to prevent subclinical ketosis and other early postpartum diseases. Ionophores improve feed efficiency by changing microflora populations in the rumen, resulting in increased feed efficiency and production of propionic acid, followed by improved gluconeogenesis. There is some evidence that monensin may be beneficial for late-gestation ewes. It has improved feed efficiency by lowering feed intake. Treated ewes also showed lower serum BHB in late gestation, with no adverse effects on lamb birth weights. Lasalocid has been similarly studied. Again, feed intake was suppressed, but lamb survival was better in the treatment group. More work needs to be done with both drugs to assess their use in preventing pregnancy toxemia in prolific ewes.
Last full review/revision July 2011 by Paula I. Menzies