Metabolic disorders of ewes usually occur when the nutritional demands of the ewe and the developing fetus(es) are not met. The three main disorders of the periparturient period are ovine pregnancy toxaemia, hypocalcaemia and hypomagnesaemia.
Ovine pregnancy toxaemia
Aetiology
In contrast with what is observed in dairy cattle, problems with negative energy balance and hypoglycaemia leading to hyperketonaemia are observed in the sheep's late gestation period. A large driving factor behind this is the fact that greater than 70% of foetal growth occurs in the last 6 weeks of gestation. The principal source of energy to the fetus is maternal glucose, and in early pregnancy this can meet the demands of fetal development. In late pregnancy the in-utero demand for glucose is 30–40 g per fetus per day (Iqbal et al, 2022). As the fetus(es) grow, there is less space for the rumen to expand, limiting feed intake and reducing metabolisable energy available per day, while daily glucose requirement increases. It is most commonly observed in ewes carrying multiple lambs in utero, however nutritional errors can lead to clinical cases in ewes carrying one lamb in utero.
This mismatch leads to a state of hypoglycaemia, and the hydrolysis of triacylglycerols (from the adipose tissue) to free-fatty acids (FFAs) and glycerol to act as an energy source for fetal growth. FFAs are converted into acetyl-CoA. Excess acetyl-CoA that cannot be used in the citric acid cycle (TCA) because of insufficient quantities of oxaloacetate, is converted into ketones. Increased production of ketones suppresses natural glycogen production, leading to ovine pregnancy toxaemia. As with excess fat mobilization in cattle, insulin resistance is a potential aetiological factor (Mezzetti et al, 2019)
These ewes also enter a state of metabolic acidosis because acetoacetate and β-hydroxybutyric acid (β-HB) are strong acids. The osmotic diuretic effect of the ketones leads to increased losses of potassium and sodium ions, and advanced cases will become uraemic (Sargison, 2007).
Impact
While many farmers, and vets, may think that the losses arising from ovine pregnancy toxaemia are limited to deaths (both ewes and lambs), the actual impact can be much greater. It is now known that farms seeing clinical cases can expect sub-clinical hyperketonaemia in as much as 40% of the flock (Sargison, 2007).
Sub-clinical cases can present with increased lamb mortality or increased abortion (as the ewe seeks to remove lambs as the source of the glucose drain). There is a reduction in the live birthrate of lambs, a reduction in lamb birthweight and a reduction in lamb viability as a direct effect of the metabolic issues in ewes with ovine pregnancy toxaemia. Ewes with ovine pregnancy toxaemia will also have poor quality colostrum and a decreased milking ability which will lead to potential increase in risk of neonatal disease and reduced daily liveweight gain (Barbagianni et al, 2015b).
Barbagianni et al (2015b) found that one in two ewes with clinical ovine pregnancy toxaemia suffered from dystocia. They also found that one in four were affected by metritis, and the risk of mastitis was also increased (Barbagianni et al, 2015a). Reduced milk production, increased risk of retained fetal membranes and an altered gestation length are also reported (Crilly et al, 2021).
When clinical cases are untreated, mortality rates can be high and 70–90% losses would not be uncommon (Rook, 2000; Macrae, 2020). The survival rate of lambs from affected ewes is equally bleak, with only 12% of ewes born alive (Sargison, 2007).
Diagnosis
Clinical signs are split into two stages, with the disease progressing over two or more days (Table 1). It is common to reach a diagnosis based on clinical signs alone, although consideration must be taken to carefully exclude hypocalcaemia. A thorough history can assist with the diagnosis, with special attention paid to scan results, recent (6-week) nutritional history, and any other notable management changes. Affected ewes often have a body condition score (BCS) <2.5 out of 5. There is also a risk in ewes with a high body condition score of 4+.
| Stage 1 | Stage 2 |
|---|---|
| Normothermic | All signs of stage 1 disease alongside: |
| Reluctance to move and ‘hanging back’ | Weakness |
| Inappetence | Recumbency |
| +/- poor body condition score | Depression |
| Hypoglycaemic encephalopathy leading to the development of: |
Ruminal atony +/- rumen stasis |
| Abdominal wall weakness | |
| Bruxism | |
| +/- abortion |
Pen-side tests of blood β-HB concentration are readily available, and most farm vets will have a ketone meter in their car. Advanced clinical signs are consistent with β-HB ≥3.0 mmol/l, with sub-clinical disease occurring when β-HB readings are between 1.1 and 2.9 mmol/l. As with cattle, some people will be able to smell ‘pear drops’ on the breath of affected ewes.
Measurement of fructosamine and non-esterified fatty acids (synonymous with FFAs) were found to be the most effective diagnostic indicators by Iqbal et al (2022), however the use in current veterinary practice is limited due to the cost and time involved in external laboratory testing.
Treatment
When stage 2 clinical signs are observed, survival rates may fall as low as 30% (Sargison, 2007). Therefore, early intervention and prompt treatment when stage 1 signs are observed is essential. In advanced cases, euthanasia may be the appropriate intervention on welfare grounds to prevent further pain and suffering. By collaborating with farmers at ‘pre-lambing’ visits, or during flock health plans, to produce clear protocols for farmer intervention, survival rates can be maximised.
Protocols should consider supplementary feeding regimes (including feeding to scan results), housing space, feed-and-water trough space, and body condition scoring of ewes through gestation.
Ewes in late gestation require 2x maintenance energy requirements, approximately 16.8 MJ of metabolisable energy (ME) per day for lowland ewes ~70 kg liveweight (AHDB, 2024). In late pregnancy, feed intakes of 1.6 kg (2–2.5% of bodyweight) of dry matter can be achieved (AHDB, 2024). Therefore, supplementary concentrates are often required in addition to forage to meet the metabolisable energy requirements. The aim should always be to maximise the contribution from forage, while supplementing high protein and energy in the form of concentrates. A 75% forage:25% concentrate ration will achieve better digestion of the forage than a 75% concentrate:25% forage diet due to the effect of excess concentrate on the rumen flora and ruminal pH. If supplementary concentrates are fed it is important never to provide >500 g per feed to reduce the risk of ruminal acidosis.
Glucose precursors
It is important to elevate plasma and cerebrospinal fluid glucose concentrations before irreversible brain damage occurs. In the worst cases, where neurological signs are already present, intravenous glucose can be used. In other cases, glucose precursors, given orally, can be provided as they are used for gluconeogenesis in the liver. Toxicity arising from prolonged courses of glucose precursors can occur after 6 days (Brozos et al, 2011), and if the treatment course nears this duration euthanasia should be considered.
Propylene glycol has been used by farmers as treatment for ovine pregnancy toxaemia for a long time. It is widely available, and highly affordable. It is converted to pyruvate, before entering TCA to yield glucose.
It has been demonstrated that glycerol mixed with water can elevate serum glucose concentration within 1 hour, whereas propylene glycol requires at least 9 hours to achieve a similar effect (Alon et al, 2020). In cases where rapid correction of hypoglycaemia (which will reduce production of FFA, and so ketones) is time-critical, selecting a product with glycerol will be of benefit.
In their study on ewes in sub-clinical ovine pregnancy toxaemia, Cal-Pererya et al (2015) found that oral administration of a product containing 70 g of glycerol and 20 g of propylene glycol per dose was a more effective method of correcting hypoglycaemia and hyperketonaemia than intravenous glucose with insulin, or cracked corn per os.
It is not uncommon to come across farmers who use glucose powders in cases of ovine pregnancy toxaemia. As Crilly et al (2021) identify, this will not correct the hypoglycaemia, with the glucose only being fermented by the ruminal flora.
Rehydration
For over 50 years we have known that ewes in ovine pregnancy toxaemia benefit from rehydration. However, the conversation with farmers oft en tends to focus on the provision of glucose precursors, without considering rehydration of the ewe. This is particularly apparent if the ewe receives propylene glycol as the sole glucose precursor. Glycerol must be mixed with water to allow it to penetrate the rumen mat (Hippen et al, 2008); therefore, an element of rehydration will be achieved but oft en more could be done. These ewes are dehydrated for several reasons, including the fact that the ketones exert a diuretic effect at the kidney (Sargison, 2007), and these ewes have elevated cortisol which suppresses antidiuretic hormone (vasopressin) production leading to additional diuresis.
Electrolyte deficits
Correction of electrolyte deficits should be an important part of any treatment protocol, with the focus being on replacing potassium and sodium. The potassium deficit in clinical ovine pregnancy toxaemia can be as great as 1.5 mmol/l or ≥30% of serum potassium concentration. Subclinical cases are also deficient in potassium and sodium. Survivors of ovine pregnancy toxaemia have been demonstrated to have smaller deficits in serum potassium and sodium concentrations than non-survivors (Iqbal et al, 2022).
Around 25% of ewes with ovine pregnancy toxaemia are also affected by a concurrent hypocalcaemia (Macrae, 2020), and it has been demonstrated that hypocalcaemia will facilitate the development of the disease in hyperketonaemic ewes (Schlumbohm and Harmeyer, 2003). Iqbal et al (2022) showed that plasma calcium concentration was lower in ewes that did not survive ovine pregnancy toxaemia than those that did. Therefore, it may be prudent to select a product that provides oral calcium, or to provide an oral calcium product alongside the main treatment for ovine pregnancy toxaemia.
Other options
In clinical cases, removing the lambs (as the source of the glucose drain) can aid prognosis for the ewe. Caesarean section can be performed, but success is limited more than 5 days prematurely. Induction with dexamethasone is possible, and can be achieved aft er day 135, and best success if it is performed aft er day 138. A dose of 16 mg BID until parturition is recommended by Zoller et al (2015). In practice, the author has achieved good results with 16 mg SID, and ewes tend to lamb 42–54 hours after the first dose.
Providing a high-energy, palatable feed (eg soaked fodder beet) can be a useful adjunctive treatment and encourage feed intake. However, there is no guarantee affected animals will eat and it will not provide sufficient energy quickly enough to be used as a sole treatment.
Non-steroidal anti-inflammatory drugs (NSAIDs) are indicated in the treatment of ovine pregnancy toxaemia. Around 73% of cases have an elevated pain score, and inflammation has a role to play in the aetiopathogenesis of hyperketonaemia. Practitioners should remember that there are currently no licensed NSAIDs for sheep in the UK, so statutory withdrawal periods of 7 days for milk and 28 days for meat should be applied. For meloxicam, the recommended dose for sheep is 1 mg/kg rather (Boehringer Ingelheim (NZ) 2016) than the 0.5 mg/kg dose licensed for cattle. NSAIDs are contraindicated in dehydrated, hypovolaemic, and hypotensive animals due to the risk of renal toxicity/damage (NOAH, 2024). Therefore, it is vitally important to ensure concurrent rehydration is provided.
Hypocalcaemia
Hypocalcaemia is usually seen in late gestation. As with ovine pregnancy toxaemia, it tends to occur in the last 6 weeks of pregnancy. Parturient paresis, caused by hypocalcaemia, is rare in sheep but there are cases recorded in the literature. Older ewes (third crop and above) are more likely to be affected, and estimates are that it affects 0.4–2% of the UK flock each year (Scott, 2013; Macrae, 2020).
While less prevalent than ovine pregnancy toxaemia an understanding of hypocalcaemia is equally important to vets and farmers as misdiagnosis is common. Cases are often confused for ovine pregnancy toxaemia or respiratory diseases (Scott, 2013), a ewe affected by hypocalcaemia can die within 24 hours, so accurate diagnosis and prompt treatment are essential to save lives. Farmer education is particularly important when it comes to hypocalcaemia of ewes, with Scott (2013) reporting that fewer than 5% of cases are presented to a vet.
Aetiology
Several causative factors of hypocalcaemia are reported. They can broadly be grouped into nutritional factors and stress events.
Fetal calcification of bone occurs approximately 3–4 weeks before parturition, and this can result in a transient hypocalcaemia due to ‘lag’ between the increased fetal requirement for calcium and the ewe's ability to mobilise calcium from the bone pool. On average it takes 24 hours to mobilise calcium from bone.
Nutritional factors
Hypocalcaemia can arise from nutritional imbalances. If the ration is not formulated correctly, the ewe will not receive sufficient calcium to supply the fetus on top of maintenance calcium requirements. Dietary cation-anion balance diets have not been shown to prevent hypocalcaemia in ewes (Macrae, 2020), and excess phosphorus will increase the risk of hypocalcaemia (Brozos et al, 2011; Cohrs et al, 2018) by reducing the synthesis of activated vitamin-D3 at the kidney.
Farmers should avoid feeding fodder beet tops and ryegrass in late pregnancy, as both feedstuffs are high in oxalate, which binds calcium.
Vitamin D deficiency may be associated with hypocalcaemia, as it is known that ewes deficient in vitamin D birth lambs with skeletal deficits. Insufficient dietary vitamin D limits intestinal calcium absorption to 10–15 % of dietary calcium in man, with similar effects reported in rodents and ruminants (Khazai et al, 2008; Hodnik et al, 2020). With vitamin D's essential role in intestinal transcellular and paracellular absorption of calcium, insufficient dietary vitamin D may well increase the risk of hypocalcaemia.
Stress events
Stress events can lead to hypocalcaemia, and in recent years sheep worrying by dogs has exponentially increased. One study from the National Sheep Association (2023) showed 70% of farmers had had an incident in the last 12 months. Likewise, a survey of police forces found 78% of forces reported an increase in reported cases, and no forces had had no cases in the past year (National Sheep Association, 2024).
Stress events redistribute calcium and magnesium in the body, which can lead to a reduction in serum calcium concentrations. Stress events (such as worrying by dogs) are often associated with hyperventilation which can lead to a respiratory alkalosis. Increased pH leads to an increase in the amount of calcium bound to protein, decreasing the amount of ionised calcium in the blood.
Other stress events which can trigger hypocalcaemia include severe weather events, housing of hill ewes and sudden dietary changes in late pregnancy.
Diagnosis
Diagnosis is regularly performed based on a thorough clinical examination and detailed history. Pen-side blood calcium concentration tests are not yet commercially available, and in the author's experience the time and cost of laboratory testing often preclude it from being performed.
There is merit in taking a blood sample before providing any treatment, so that it can be sent away as a representative sample before treatment. The author regularly does this and keeps the sample in the fridge for 24–48 hours to assess the response to treatment before deciding with the client if laboratory tests are needed. This can reduce costs by removing the need for a second callout fee just to take a sample.
Clinical signs (Table 2) are similar to ovine pregnancy toxaemia, however, important differences are seen. These include a reduced pupillary light reflex, functional blindness, altered neck position, hypothermia, and faster progression to recumbency, depression and death.
| Parameter | Change |
|---|---|
| Rectal temperature | Reduced (<38.3°C) |
| Blood calcium concentration | Reduced |
| Respiratory rate | Elevated (>34 bpm) |
| Neck positioning | Outstretched or ‘swan necked’ |
| Rectal examination | Constipation +/- distension of rectum |
| Pupillary light reflex | Reduced or absent |
| Mentation | Reduced → depressed → coma → death (progression within 24 hours) |
| Rumen | Atony, followed by bloat and nasal discharge of ruminal content |
Treatment
The slow intravenous administration of 20–40 ml of a product containing 40% calcium borogluconate and 5% magnesium hypophosphite hexahydrate has a rapid effect on serum calcium concentrations. Historically, concurrent subcutaneous 20% calcium borogluconate would have been recommended, as the effects of intravenous calcium are short-lived and a rebound hypocalcaemia, and associated recumbency, is common (Blanc et al, 2014). In recent years, the licensed formulation for sheep was withdrawn from the market, and we have learnt that subcutaneous calcium is poorly absorbed and can be irritant to the tissues. For effective elevation of serum calcium concentration by the subcutaneous route, it must be given in small amounts at multiple sites. Oral calcium provides an easier, and more reliable way of providing long-lasting calcium to the ewe. Many ewes will be ambulatory, defecating and urinating within 5 minutes of treatment (Winters and Clarkson, 2012; Scott, 2013).
Prolonged hypocalcaemia in ewes is associated with a reduction in packed-cell-volume, indicative of dehydration (Fenwick and Daniel, 1992). Rehydration with a solution containing water, sodium and potassium will improve clinical outcomes.
Hypomagnesaemia
Typically, hypomagnesaemia (‘grass staggers’) is observed after turnout, and in the first 6 weeks of lactation when peak milk production presents a large requirement for magnesium. Milk from sheep contains calcium, magnesium and phosphorus in greater quantities than cows' milk (Chia et al, 2017). Sheep rely on ruminal absorption of magnesium to meet their needs, both for maintenance and milk production. When lush grass is ingested (especially if treated with fertilisers high in nitrogen or potassium) then insufficient magnesium may be available either due to the nitrogen or potassium inhibiting its absorption, or insufficient quantities being present in the fast-growing grass.
Diagnosis
Diagnosis is usually based on clinical signs (Table 3), response to treatment or post-mortem examination. Blood tests would confirm cases if magnesium concentration is below <0.6 mmol/l (Winters and Clarkson, 2012). These ewes often present as ‘sudden deaths’, therefore, a diagnosis at post-mortem using aqueous humour, and history can be achieved (<0.33 mmol/l within 24 hours of death (SRUC, 2024)).
| Clinical signs |
|---|
| Hyperaesthesia |
| Ataxia → collapse |
| Opisthotonus |
| Seizure |
| Muscle fasciculations |
| Sudden death |
Treatment
Ewes should receive 20 ml/70 kg warm calcium borogluconate with magnesium solution intravenously. At the same time, 50 ml/70 kg of 25% magnesium solution should be given subcutaneously.
Many of these ewes are found dead. Therefore, one confirmed clinical case should trigger preventative action in the group. Supplementing magnesium in the water, in the concentrates, or by intra-ruminal bolus can be performed. However, it should be noted that boluses only last for 3–4 weeks; while daily requirements for lactating ewes at pasture are 7 g magnesium/ewe/day (Macrae, 2020).
Conclusions
Prevention remains better than a cure and the use of ‘pre-lambing’ visits to assess nutrition (Macrae, 2017), body condition score and perform metabolic blood profiling (for which subsidies or packages are often available) (Dairy Herd Health and Productivity Service, 2014) will help farmers prevent large losses due to metabolic disorders in the periparturient period.
When clinical cases are observed, early intervention is essential to reduce losses. Often this will be done by the farmer, therefore, establishing evidence-based protocols with clients before the lambing period is beneficial. When presented with clinical cases for veterinary examination, blood sampling for β-HB, calcium and magnesium can afford a rapid diagnosis, and useful information about the risk status of the rest of the flock. As part of a post-lambing review, vets and farmers should review records. If a high incidence of metabolic disorders was recorded, then a clear action plan should be discussed and implemented ahead of the next lambing season.