Pregnancy toxemia affects ewes and does during late gestation and is characterized by partial anorexia and depression, often with neurologic signs, progressing to recumbency and death. It is seen more often in animals carrying multiple fetuses. Generally, clinically affected animals have other risk factors, at either the individual or flock/herd level.
The primary predisposing cause of pregnancy toxemia is inadequate nutrition during late gestation, usually because of 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, the energy requirement of a 70-kg ewe carrying a single lamb is 2.8 Mcal/day in early gestation compared with 3.45 Mcal/day in late gestation, or an increase of 23%. This change is more dramatic in ewes bearing twins, with an energy requirement of 3.22 Mcal/day in early and 4.37 Mcal/day in late gestation (36% increase), and in ewes bearing triplets, with an energy requirement of 3.49 Mcal/day in early and 4.95 Mcal/day in late gestation (42% increase). Dairy goats have similar changes in needs.
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 way to assure adequate energy for the 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.
Females with a poor body condition score (BCS ≤2) or that are overconditioned (BCS ≥4) and carrying more than one fetus are most at risk of developing pregnancy toxemia, although the condition can occur even in ideally conditioned ewes on an adequate ration. Susceptible, thin ewes or does develop ketosis because a chronically inadequate ration is offered or because other diseases limit intake (eg, lameness, dental disease) and, with increasingly insufficient energy to meet increasing fetal demands, the ewe or doe mobilizes more body fat, with resultant ketone body production and hepatic lipidosis. Overconditioned animals 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 animals less responsive to insulin production when nutritional intake is inadequate. 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). Dairy does often experience ketosis after kidding (serum β-hydroxybutyrate [BHB] >1.7 mmol/L), which may or may not be connected with pregnancy ketosis before kidding. Ketosis after kidding appears to be more common in herds using a complete pelleted ration.
Early clinical signs can be detected by an observant producer. Most cases develop 1–3 wk before parturition. 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. Animals will spend more time lying and have more frequent bouts of lying than their healthy herdmates. As the disease advances, ewes or does may also show signs of listlessness, aimless walking, muscle twitching or fine muscle tremors, opisthotonos, and grinding of the teeth. This progresses (generally over 2–4 days) to 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 or doe 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 animals 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 BHB. Levels >2.5 and 0.5 mmol/L, respectively, are consistent with a diagnosis of pregnancy toxemia.
Laboratory findings in individual animals may include hypoglycemia (often <2 mmol/L), increased urine ketone levels (evaluated by commercial qualitative test strips), increased serum BHB levels (normal <0.8 mmol/L, subclinical ketosis ≥0.8 mmol/L, and clinical disease >3 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 increased above 0.4 mmol/L, indicating likely hepatic lipidosis, resulting in impaired hepatic function.
Although hypocalcemia is often found in cases of pregnancy toxemia, it should also be considered when formulating hypotheses regarding recumbent late gestational sheep and goats (see Parturient Paresis in Sheep and Goats Parturient Paresis in Sheep and Goats Parturient paresis in pregnant and lactating ewes and does is a disturbance of metabolism characterized by acute-onset hypocalcemia and rapid development of hyperexcitability and ataxia, progressing... read more ). 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 (enterotoxemia), rabies, scrapie, maedi visna/ovine progressive pneumonia, lead poisoning, chronic copper toxicity, and listeriosis. These can be differentiated based on clinical and laboratory findings or during necropsy.
Ewes or does in the early stages (ie, are ambulatory, have a decreased appetite for grain, and are showing few nervous signs) can often be treated successfully with oral propylene glycol (60 mL, bid, for 3 days, or 100 mL/day). Adding oral calcium (12.5 g calcium lactate), oral potassium (7.5 g KCl), and insulin (0.4 IU/kg/day, SC) 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. It may also be prudent to induce parturition/abortion if the ewe or doe is also thin or fat and cannot manage fetal demands that late in pregnancy. This can be done by administering dexamethasone (20 mg, IV or IM). Parturition is expected within 24–72 hr, with most animals giving birth within 36 hr. Does may also benefit by the addition of prostaglandin F2α (dinoprost [10 mg, IM] or cloprostenol [75 mcg/45 kg body wt]). Contributing factors (eg, nutrition, housing, illness, other stressors) should be corrected for the group, and feeding management assessed (eg, adequate feeder space, feeding frequency, protection from adverse weather).
Treatment of advanced cases of pregnancy toxemia is frequently unrewarding. If a ewe or doe is already comatose, humane euthanasia is warranted, and treatment should focus on the rest of the flock. However, if the female is valuable and the owner wishes to pursue treatment despite the poor prognosis, 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 if economically viable. If the fetuses are dead or too premature to survive a cesarean section, it is less stressful to the ewe or doe to induce early parturition with dexamethasone (as above). Prophylactic antibiotics (usually procaine penicillin G at 20,000 IU/kg/day) are appropriate if the fetuses are thought to be dead.
Hypoglycemia can be treated by a single injection of 50% dextrose, 60–100 mL, 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. Use of flunixin meglumine at 2.5 mg/kg improved survival rate of ewes and their lambs, although the mechanism is unknown. Although 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.
A sample of late-gestation ewes or does can be tested for serum BHB levels to determine the extent of the risk in the rest of the flock. Generally, 10–20 animals in late gestation 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 mmol/L, moderate underfeeding (moderate risk) 0.8–1.6 mmol/L, and severe underfeeding (high risk) 1.7–3.0 mmol/L. Other diseases should be treated (eg, footrot). Females off feed should be separated from the group and hand fed, keeping in mind they should be able to see the group to feel comfortable.
Ewes or does should not enter the last 6 wk of gestation with a BCS <2.5; this can be prevented by good feeding management, eg, adequate feeder space for pregnant animals, sorting (based on BCS, fetal numbers, and animal size), forage analysis (for energy, digestible fiber, and protein levels), 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 females. 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, usually at the time of pregnancy scanning, so that thin animals can be fed as a separate group. It takes ~6 wk to raise BCS by 1 point, so early intervention is important to avoid late-gestation problems. If real-time ultrasound scanning allows for fetal number determination, then animals should also be managed based on fetal numbers. Producers may find it convenient to feed pregnant ewe-lambs or doelings with twin-bearing females and thin, single-bearing females because of the added energy young animals need for growth. With prolific breeds, triplet-bearing ewes and thin, twin-bearing ewes can be fed together. Overconditioned females (ie, BCS ≥4) are not as common but may be seen in small hobby flocks. Fat females 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 females. 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 >0.8–3 mmol/L, feeding management should be corrected quickly to avoid clinical disease.
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 (although not for dairy goats); it improved feed efficiency by lowering feed intake. Treated ewes also showed lower serum BHB levels in late gestation, with no adverse effects on lamb birth weights. It may help prevent ketosis in postpartum dairy goats. 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.