Pregnancy Toxemia

in Sheep

Overview

• Pregnancy toxemia in sheep and goats has also been called ketosis, lambing/kidding sickness, pregnancy disease and twin-lamb/kid disease. It most often affects ewes/does pregnant with twins or triplets and is characterized by low blood sugar (glucose).
• 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.

Pathogenesis

• 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.

Clinical signs

• 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.

Diagnosis and differentials

• 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.

Treatment and control

• 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.
• Serum concentrations of both NEFAs (>0.4 mEq/L) and BHB (subclinical/moderate ketosis >15 mg/dL; clinical ketosis > 25 mg/dL) are increased.
• Hypoproteinemia (hypoalbuminemia and hypoglobulinemia) can be observed in clinical cases of pregnancy toxemia and could potentially be attributed to hepatic and/or renal failure.
• In later stages of pregnancy toxemia, hyperglycemia (often associated with fetal death), hypokalemia, elevated creatinine, and elevated BUN may be evident.
• Elevated ketones on urinalysis; ketonuria is present and usually detected before
• Glucose levels should be evaluated before initiation of treatment. Severe hypoglycemia should be treated by administration of 250–500 mL of 10–20% glucose solution IV followed by slower infusion of a 5–10% glucose solution.
• Propylene glycol (60–200 mL PO q12h for 6 days), glycerol, calcium propionate, sodium propionate, or liquid molasses are routinely used as glucose precursors.
• Dexamethasone (10–20 mg IM) with parturition in ewes generally occurring 36–48 hours following administration. Recombinant bovine somatotropin (0.15 mg/kg q24h SC or single injection of 160 mg of slow-release formulation SC) may increase efficiency of glucose and ketone usage. (Not currently approved for use in
• Recombinant bovine somatotropin (0.15 mg/kg q24h SC or single injection of 160 mg of slow-release formulation SC) may increase efficiency of glucose and ketone usage. (Not currently approved for use in small ruminants in the US.)