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Lean IJ (2011) Diseases of Dairy Animals | Non-Infectious Diseases: Pregnancy

Toxemia. In: Fuquay JW, Fox PF and McSweeney PLH (eds.), Encyclopedia of Dairy
Sciences, Second Edition, vol. 2, pp. 246–249. San Diego: Academic Press.

ª 2011 Elsevier Ltd. All rights reserved.

 Author's personal copy

Non-Infectious Diseases: Pregnancy Toxemia

I J Lean, SBScibus and University of Sydney, Camden, NSW, Australia
ª 2011 Elsevier Ltd. All rights reserved.

Introduction Pathogenesis

Pregnancy toxemia is a disorder of energy and protein The pathogenesis reflects increased demand for nutrients
metabolism that occurs in sheep, cattle, and goats. The by the fetus and adnexa, including placenta and uterus,
condition reflects an imbalance between fetal demand for during late gestation. The fetus requires glucose and amino
nutrients and the supply of nutrients by the dam from acids, in particular, for energy and protein deposition.
either exogenous (dietary) or endogenous (body tissue) These requirements are difficult to meet from exogenous
reserves. Pregnancy toxemia has a greater gestational sources when poor-quality forages are the basal diet or
incidence in polytocous animals, and this is reflected in when multiple fetuses are present. Unlike lactational keto-
the synonyms for the disorder, which include twin dis- sis, when ruminants reduce milk production, there is little
ease, twin lamb disease, and pregnancy disease. The opportunity in pregnancy toxemia for the dam to reduce
condition is very similar to ketosis in cattle (see Diseases the irreversible transfer of nutrients to the fetus.
of Dairy Animals: Non-Infectious Diseases: Ketosis) and In both sheep and cattle, the primary sources of macro-
produces a profound hepatic lipidosis. nutrients for the fetus and placenta are glucose and amino
acids (Table 1). There appears to be limited capacity for
placental transport of ketone bodies or short- or long-
chain fatty acids. Consequently, use of acetate and
Clinical Signs -hydroxybutyrate by the fetus and adnexa is limited in
well-fed dams and the use of ketones and nonesterified free
The clinical signs of the disease include separation from fatty acids is limited in underfed dams. In the case of sheep
the herd or flock, followed by depression and recum- in late gestation, the contribution of glucose to the fetus and
bency. Neurological signs are common in sheep and adnexa on a daily basis exceeds that available in the blood
include tremors, myoclonic twitching of the facial mus- of the dam by 4 times. This implies a requirement for
cles, incoordination, circling, and apparent blindness. In substantial gluconeogenic activity in the dam to meet the
some cases, clonic seizures may occur. Physical examina- glucose requirements of the fetus and adnexa. The dam has
tion of the animals indicates a decrease in pupillary light a decreased insulin sensitivity in late gestation, which
reflexes and an absence of the eye preservation reflex. reduces glucose use by peripheral tissues and increases
The animals can assume a ‘star-gazing’ posture both while dependence on lipid and ketone metabolism. There is
walking and when recumbent. Even with treatment, the some evidence that high concentrations of ketones,
prognosis for recumbent animals is poor, and death com- 5–7 mmol l 1 in blood, decrease hepatic gluconeogenesis
monly results 3–7 days after recumbency. and that 3-hydroxybutyrate clearance decreases in late
pregnancy as compared to dry nonpregnant lactating
ewes. Figure 1 shows the typical increase in plasma
nonesterified free fatty acids and -hydroxybutyrate, and
Epidemiology the changes in glucose concentrations in well-fed cattle
around calving. The fatty acids mobilized from the body
The condition is most prevalent in late gestation, espe- stores are complexed with blood albumin for transport to
cially during the 4 weeks before parturition in cattle and the liver and extrahepatic tissues. Uptake of fatty acids by
sheep. Affected animals are almost invariably carrying the liver is proportional to the concentration of fatty acids
multiple fetuses. Younger animals, which are growing, in the blood. Fatty acids within the liver pool are stored as
are at greater risk than older stock. A sudden onset of triglycerides and may subsequently be converted to ketone
cold weather for animals on poor-quality feed and with bodies, be oxidized, or be incorporated into lipoproteins in
inadequate shelter can precipitate a marked increase in the Golgi apparatus for release into general circulation.
the incidence of the condition. Movement of stock will Failure to provide sufficient amount of substrate to allow
exacerbate the condition. Older ewes with poor dentition oxidation of fatty acids results in the accumulation of
or flocks with a high prevalence of lameness may be at triglycerides in the hepatic cytosol. These can be exported
greater risk of pregnancy toxemia. from the liver as lipoproteins; however, mechanisms that

246
Encyclopedia of Dairy Sciences, Second Edition, 2011, Vol. 2, 246-249
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Diseases of Dairy Animals | Non-Infectious Diseases: Pregnancy Toxemia 247

Table 1 Fetal sources and requirements of energy and nitrogen in cows in late
pregnancy

Energy Energy Nitrogen

Nutrient sources and requirements (MJ day 1) (kcal day 1) (g day 1)

Sources
Glucose and lactate 184.5 775
Amino acids 311 1306 38
Acetate 60.7 255
Total 556.2 2336 38
Requirements
Tissue deposition 144 605 12
Heat 382 1605
Urea 29.8 125 23
Total 555.8 2335 35

Modified from Bell AW (1995) Regulation of organic nutrient metabolism during transition from
late pregnancy to early lactation. Journal of Animal Science 73: 2804–2819.

glucose if the diet fails to provide sufficient protein or

propionate. Because the ketones produced from the partial
oxidation of fatty acids are metabolic acids, metabolic
acidosis can occur in pregnancy toxemia.

Clinical Pathology

The clinical pathology associated with the condition

includes hypoglycemia, increased nonesterified free
fatty acids in plasma, hyperketonemia, and marked keto-
nuria. Blood glucose concentrations can fall below
Figure 1 Relative changes in free fatty acids (FFA), 2 mmol l 1, and -hydroxybutyrate concentrations can
-hydroxybutyrate (BHB), urea, and glucose. Adapted from
exceed 2.5 mmol l 1. Plasma insulin and cortisol concen-
Stephenson KA, Lean IJ, Hyde ML, Curtis MA, Garvin JK, and
Lowe LB (1997) Effects of monensin on the metabolism of trations can be increased. Other changes in blood reflect
periparturient dairy cows. Journal of Dairy Science 80: 830–837. electrolyte imbalances associated with acidosis, renal fail-
ure, and muscle damage, and include increased creatinine
allow this are overwhelmed and hepatic lipidosis results in concentrations, increased serum aspartate aminotransfer-
pregnancy toxemia. ase, and dehydration. Plasma potassium concentrations
In the relative absence of propionate influx from the are particularly sensitive to energy deficits in target tis-
rumen, there is a reliance on amino acid metabolism and sues and increase with increasing deficit.
lactate to provide carbon chains for gluconeogenesis. Sheep
more susceptible to pregnancy toxemia have hepatocytes
that produce less glucose from glucogenic precursors, Necropsy
including propionate, lactate, and alanine. The fetus has a
strong demand for amino acids. Remarkably, these amino The most striking clinical finding is the characteristically
acids are used to supply energy to the fetus and adnexa enlarged, pale, fat-infiltrated liver. The edges of the organ
(Table 1) and are used with a very low efficiency for fetal are rounded and the liver is friable. Usually multiple
growth. Recent estimates suggest that up to 60 and 66% of fetuses are present, although a large single fetus may be
the amino acids transported to the fetus and adnexa are found. There are signs of lipid mobilization from fat
catabolized in sheep and beef cattle, respectively. The stores, and the kidneys, heart, and adrenal glands show
demand for amino acids for gluconeogenesis is met from signs of fat infiltration.
dietary amino acids and by mobilization of the labile pro-
tein reserves. Sheep on a higher plane of nutrition before
being exposed to undernutrition are more capable of sus- Diagnosis
tained gluconeogenesis than sheep previously fed on a low
plane of nutrition. Once the labile protein reserves are Differential diagnoses usually include other conditions that
depleted, there is little opportunity for the dam to produce cause sudden death in large numbers of sheep or goats

Encyclopedia of Dairy Sciences, Second Edition, 2011, Vol. 2, 246-249

 Author's personal copy
248 Diseases of Dairy Animals | Non-Infectious Diseases: Pregnancy Toxemia

within a flock. Usually, in sheep, an investigation of the 8. Ensure that ionophores are present at recommended
epidemiology of the condition clearly indicates a strong rates (see Feed Ingredients: Feed Supplements:
probability of pregnancy toxemia. The diagnosis is con- Organic-Chelated Minerals). Ionophores increase
firmed following necropsy and the use of clinical propionate flux and reduce ketone production.
pathology. In sheep, it may be necessary to differentiate 9. Provide trace- and macroelements at recommended
the condition from hypocalcemia, which can also result rates (see Feed Ingredients: Feed Supplements:
after prolonged walking or transport, or with sudden feed Macrominerals; Feed Supplements: Microminerals).
change. In cattle, the condition is rarely as prevalent as in Cobalt and phosphorus have important roles as
sheep and goats and the differential diagnoses include cofactors in energy metabolism, and transition metals
other causes of collapse and recumbency, including hypo- such as copper, selenium, and zinc have roles in
calcemia and hypomagnesemia. The observation of body controlling free-radical damage.
tissue loss in late gestation in cattle may indicate indivi- 10. Evaluate flocks for adequate dentition and control
duals and herds at risk of pregnancy toxemia. lameness in breeding ewes and does.

Prevention Treatment

Prevention of the condition is achieved by ensuring that The prognosis is poor for stock that are recumbent,
the nutrient requirements of heavily pregnant ruminants whereas stock that are ambulatory with few clinical
are met. The needs of the fetus for protein must be signs have a good prognosis. Treatments selected should
adequately recognized. This is particularly important reflect the severity of clinical signs. Costs of therapy are
under extensive pasture or range conditions, where the significant, and careful cost–benefit analysis is indicated
protein and energy content of forages may fall below before treatment can be recommended.
requirements. Problems of feed quality can be exacer- Hematology and blood chemistry can be useful in
bated by a shortage of dry matter. Some of these forages determining the most appropriate therapies and prog-
may also be deficient in fat-soluble vitamins, which have a noses. Animals that have a poor prognosis show
protective role in controlling free-radical damage.
Steps to prevent pregnancy toxemia can be outlined as • dehydration,
volume
indicated by increased packed cell
follows:
• acidosis, indicated by low blood bicarbonate
1. Provide dry matter with sufficient energy, protein,
mineral, and vitamin content to meet or slightly
• urea nitrogen
evidence of renal failure, indicated by elevated blood
and creatinine
exceed the nutrient requirements of the stock. When
the diet is forage-based, allocation of better pastures to
• and free fatty acids inconcentrations
markedly increased
blood
of -hydroxybutyrate

stock in late pregnancy is a sensible strategy. When

Some animals may have evidence of sepsis associated with
pasture is limited, use of fertilizers to increase pasture
the death of the fetus. Treatments are essentially directed
growth is advisable.
at correcting the changes in clinical chemistry or remov-
2. Identify stock with multiple pregnancies when feasible.
ing the irreversible loss of nutrients from the dam to the
Ultrasonic examination can achieve this, but good
fetoplacental complex. They include the following:
husbandry practices, such as identifying stock with
greater abdominal fill and lower body condition, can 1. Increasing the supply of exogenous glucogenic precur-
also be effective in identifying stock at risk. sors by intravenous dextrose and glucose, and oral
3. Provide additional supplements for stock carrying glucose preparations that are often combined with
multiple fetuses and for stock on forages that do not electrolytes to provide oral rehydration solutions, or
meet nutrient requirements. Supplements should be oral propylene glycol (30–60 ml, 2 or 3 times daily, for
grain-based and address protein needs in particular. ewes and does; 200–300 ml for cows).
Crude protein content of diets for ewes in late gesta- 2. Correcting electrolyte imbalances and dehydration by
tion should be 12–14% of dry matter. the use of calcium borogluconate solutions, intrave-
4. Ensure that there is effective parasite control of the nous fluids containing dextrose or glucose, and oral
flock or herd. rehydration solutions.
5. Do not allow animals to become overly fat in 3. Removing the fetus (emergency cesarean section can
pregnancy. be indicated in valuable animals) and increasing endo-
6. Provide shelter for animals likely to be exposed to genous glucogenic precursors by the use of
marked adverse changes in weather conditions. glucocorticoids, including dexamethasone-21-isonico-
7. Do not allow animals to exercise excessively. tinate and dexamethasone sodium phosphate.

Encyclopedia of Dairy Sciences, Second Edition, 2011, Vol. 2, 246-249

 Author's personal copy
Diseases of Dairy Animals | Non-Infectious Diseases: Pregnancy Toxemia 249

Corticosteroids may also increase the availability of Minerals. Feeds, Ration Formulation: Systems
amino acids for gluconeogenesis, but corticosteroids Describing Nutritional Requirements of Dairy Cows.
are generally not recommended in cases with sepsis.
4. Hormonal treatments. Various hormones have been
used to modify the metabolic changes that occur. Further Reading
These include anabolic steroids (e.g., trenbolone
Bell AW (1995) Regulation of organic nutrient metabolism during
acetate; results are equivocal), insulin injections transition from late pregnancy to early lactation. Journal of Animal
(e.g., 20–40 IU of protamine zinc insulin adminis- Science 73: 2804–2819.
tered intramuscularly every 48 h for 4 days; results Harmeyer J and Schlumbohm C (2006) Pregnancy impairs ketone
body disposal in late gestating ewes: Implications for onset of
are equivocal), and recombinant bovine somatotro- pregnancy toxaemia. Research in Veterinary Science
pin (e.g., 0.15 mg per kg–1 of body weight daily; 81(2): 254–264.
results appear promising). Marteniuk JV and Herdt TH (1988) Pregnancy toxaemia and ketosis of
ewes and does. In: Herdt TH (ed.) Veterinary Clinics of North
On a herd or flock basis, the provision of larger quantities America: Food Animal Practice, Vol. 4: Metabolic Diseases of
Ruminant Livestock, pp. 307–315. Philadelphia, PA: W.B. Saunders
of better-quality feed is critical. Company.
Rook JS (2000) Pregnancy toxemia of ewes, does and beef cows. In:
Veterinary Clinics of North America: Food Animal Practice, Vol. 16:
See also: Body Condition: Effects on Health, Milk Metabolic Diseases of Ruminant Livestock, pp. 293–317.
Philadelphia, PA: W.B. Saunders Company.
Production, and Reproduction. Diseases of Dairy Schlumbohm C and Harmeyer J (2004) Hyperketonemia impairs
Animals: Non-Infectious Diseases: Fatty Liver; Non- glucose metabolism in pregnant and nonpregnant ewes. Journal
Infectious Diseases: Ketosis. Feed Ingredients: Feed Dairy Science 87: 350–358.
Stephenson KA, Lean IJ, Hyde ML, Curtis MA, Garvin JK, and Lowe LB
Supplements: Macrominerals; Feed Supplements: (1997) Effects of monensin on the metabolism of periparturient dairy
Microminerals; Feed Supplements: Organic-Chelated cows. Journal of Dairy Science 80: 830–837.

Encyclopedia of Dairy Sciences, Second Edition, 2011, Vol. 2, 246-249

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