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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
Pregnancy toxemia is a disorder of energy and protein
metabolism that occurs in sheep, cattle, and goats. The
condition reflects an imbalance between fetal demand for
nutrients and the supply of nutrients by the dam from
either exogenous (dietary) or endogenous (body tissue)
reserves. Pregnancy toxemia has a greater gestational
incidence in polytocous animals, and this is reflected in
the synonyms for the disorder, which include twin dis-
ease, twin lamb disease, and pregnancy disease. The
condition is very similar to ketosis in cattle (see Diseases
of Dairy Animals: Non-Infectious Diseases: Ketosis) and
produces a profound hepatic lipidosis.
Pathogenesis
The pathogenesis reflects increased demand for nutrients
by the fetus and adnexa, including placenta and uterus,
during late gestation. The fetus requires glucose and amino
acids, in particular, for energy and protein deposition.
These requirements are difficult to meet from exogenous
sources when poor-quality forages are the basal diet or
when multiple fetuses are present. Unlike lactational keto-
sis, when ruminants reduce milk production, there is little
opportunity in pregnancy toxemia for the dam to reduce
the irreversible transfer of nutrients to the fetus.
In both sheep and cattle, the primary sources of macro-
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
The clinical signs of the disease include separation from
the herd or flock, followed by depression and recum-
bency. Neurological signs are common in sheep and
include tremors, myoclonic twitching of the facial mus-
cles, incoordination, circling, and apparent blindness. In
some cases, clonic seizures may occur. Physical examina-
tion of the animals indicates a decrease in pupillary light
reflexes and an absence of the eye preservation reflex.
The animals can assume a ‘star-gazing’ posture both while
walking and when recumbent. Even with treatment, the
prognosis for recumbent animals is poor, and death com-
monly results 3–7 days after recumbency.
-hydroxybutyrate by the fetus and adnexa is limited in
well-fed dams and the use of ketones and nonesterified free
fatty acids is limited in underfed dams. In the case of sheep
in late gestation, the contribution of glucose to the fetus and
adnexa on a daily basis exceeds that available in the blood
of the dam by 4 times. This implies a requirement for
substantial gluconeogenic activity in the dam to meet the
glucose requirements of the fetus and adnexa. The dam has
a decreased insulin sensitivity in late gestation, which
reduces glucose use by peripheral tissues and increases
dependence on lipid and ketone metabolism. There is
some evidence that high concentrations of ketones,
5–7 mmol l 1 in blood, decrease hepatic gluconeogenesis
and that 3-hydroxybutyrate clearance decreases in late
pregnancy as compared to dry nonpregnant lactating
ewes. Figure 1 shows the typical increase in plasma
Epidemiology
The condition is most prevalent in late gestation, espe-
cially during the 4 weeks before parturition in cattle and
sheep. Affected animals are almost invariably carrying
multiple fetuses. Younger animals, which are growing,
are at greater risk than older stock. A sudden onset of
cold weather for animals on poor-quality feed and with
inadequate shelter can precipitate a marked increase in
the incidence of the condition. Movement of stock will
exacerbate the condition. Older ewes with poor dentition
or flocks with a high prevalence of lameness may be at
greater risk of pregnancy toxemia.
246
Encyclopedia of Dairy Sciences, Second Edition, 2011, Vol. 2, 246-249
nonesterified free fatty acids and -hydroxybutyrate, and
the changes in glucose concentrations in well-fed cattle
around calving. The fatty acids mobilized from the body
stores are complexed with blood albumin for transport to
the liver and extrahepatic tissues. Uptake of fatty acids by
the liver is proportional to the concentration of fatty acids
in the blood. Fatty acids within the liver pool are stored as
triglycerides and may subsequently be converted to ketone
bodies, be oxidized, or be incorporated into lipoproteins in
the Golgi apparatus for release into general circulation.
Failure to provide sufficient amount of substrate to allow
oxidation of fatty acids results in the accumulation of
triglycerides in the hepatic cytosol. These can be exported
from the liver as lipoproteins; however, mechanisms that
 Author's personal copy
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
Stephenson KA, Lean IJ, Hyde ML, Curtis MA, Garvin JK, and
Lowe LB (1997) Effects of monensin on the metabolism of
periparturient dairy cows. Journal of Dairy Science 80: 830–837.
allow this are overwhelmed and hepatic lipidosis results in
pregnancy toxemia.
In the relative absence of propionate influx from the
rumen, there is a reliance on amino acid metabolism and
lactate to provide carbon chains for gluconeogenesis. Sheep
more susceptible to pregnancy toxemia have hepatocytes
that produce less glucose from glucogenic precursors,
including propionate, lactate, and alanine. The fetus has a
strong demand for amino acids. Remarkably, these amino
acids are used to supply energy to the fetus and adnexa
(Table 1) and are used with a very low efficiency for fetal
growth. Recent estimates suggest that up to 60 and 66% of
the amino acids transported to the fetus and adnexa are
catabolized in sheep and beef cattle, respectively. The
demand for amino acids for gluconeogenesis is met from
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-
tained gluconeogenesis than sheep previously fed on a low
plane of nutrition. Once the labile protein reserves are
depleted, there is little opportunity for the dam to produce
Encyclopedia of Dairy Sciences, Second Edition, 2011, Vol. 2, 246-249
exceed 2.5 mmol l 1. Plasma insulin and cortisol concen-
trations can be increased. Other changes in blood reflect
electrolyte imbalances associated with acidosis, renal fail-
ure, and muscle damage, and include increased creatinine
concentrations, increased serum aspartate aminotransfer-
ase, and dehydration. Plasma potassium concentrations
are particularly sensitive to energy deficits in target tis-
sues and increase with increasing deficit.
Necropsy
The most striking clinical finding is the characteristically
enlarged, pale, fat-infiltrated liver. The edges of the organ
are rounded and the liver is friable. Usually multiple
fetuses are present, although a large single fetus may be
found. There are signs of lipid mobilization from fat
stores, and the kidneys, heart, and adrenal glands show
signs of fat infiltration.
Diagnosis
Differential diagnoses usually include other conditions that
cause sudden death in large numbers of sheep or goats
 Author's personal copy
248 Diseases of Dairy Animals | Non-Infectious Diseases: Pregnancy Toxemia
within a flock. Usually, in sheep, an investigation of the
epidemiology of the condition clearly indicates a strong
probability of pregnancy toxemia. The diagnosis is con-
firmed following necropsy and the use of clinical
pathology. In sheep, it may be necessary to differentiate
the condition from hypocalcemia, which can also result
after prolonged walking or transport, or with sudden feed
change. In cattle, the condition is rarely as prevalent as in
sheep and goats and the differential diagnoses include
other causes of collapse and recumbency, including hypo-
calcemia and hypomagnesemia. The observation of body
tissue loss in late gestation in cattle may indicate indivi-
duals and herds at risk of pregnancy toxemia.
Prevention
Prevention of the condition is achieved by ensuring that
the nutrient requirements of heavily pregnant ruminants
are met. The needs of the fetus for protein must be
adequately recognized. This is particularly important
under extensive pasture or range conditions, where the
protein and energy content of forages may fall below
requirements. Problems of feed quality can be exacer-
bated by a shortage of dry matter. Some of these forages
may also be deficient in fat-soluble vitamins, which have a
protective role in controlling free-radical damage.
Steps to prevent pregnancy toxemia can be outlined as
follows:
1. Provide dry matter with sufficient energy, protein,
mineral, and vitamin content to meet or slightly
exceed the nutrient requirements of the stock. When
the diet is forage-based, allocation of better pastures to
8. Ensure that ionophores are present at recommended
rates (see Feed Ingredients: Feed Supplements:
Organic-Chelated Minerals). Ionophores increase
propionate flux and reduce ketone production.
9. Provide trace- and macroelements at recommended
rates (see Feed Ingredients: Feed Supplements:
Macrominerals; Feed Supplements: Microminerals).
Cobalt and phosphorus have important roles as
cofactors in energy metabolism, and transition metals
such as copper, selenium, and zinc have roles in
controlling free-radical damage.
10. Evaluate flocks for adequate dentition and control
lameness in breeding ewes and does.
Treatment
The prognosis is poor for stock that are recumbent,
whereas stock that are ambulatory with few clinical
signs have a good prognosis. Treatments selected should
reflect the severity of clinical signs. Costs of therapy are
significant, and careful cost–benefit analysis is indicated
before treatment can be recommended.
Hematology and blood chemistry can be useful in
determining the most appropriate therapies and prog-
noses. Animals that have a poor prognosis show
• dehydration,
volume
indicated by increased packed cell
• acidosis, indicated by low blood bicarbonate
• urea nitrogen
evidence of renal failure, indicated by elevated blood
and creatinine
• and free fatty acids inconcentrations
markedly increased
blood
stock in late pregnancy is a sensible strategy. When
pasture is limited, use of fertilizers to increase pasture
growth is advisable.
2. Identify stock with multiple pregnancies when feasible.
Ultrasonic examination can achieve this, but good
husbandry practices, such as identifying stock with
greater abdominal fill and lower body condition, can
also be effective in identifying stock at risk.
3. Provide additional supplements for stock carrying
multiple fetuses and for stock on forages that do not
meet nutrient requirements. Supplements should be
grain-based and address protein needs in particular.
Crude protein content of diets for ewes in late gesta-
tion should be 12–14% of dry matter.
4. Ensure that there is effective parasite control of the
flock or herd.
5. Do not allow animals to become overly fat in
pregnancy.
6. Provide shelter for animals likely to be exposed to
marked adverse changes in weather conditions.
7. Do not allow animals to exercise excessively.
Encyclopedia of Dairy Sciences, Second Edition, 2011, Vol. 2, 246-249
of -hydroxybutyrate
Some animals may have evidence of sepsis associated with
the death of the fetus. Treatments are essentially directed
at correcting the changes in clinical chemistry or remov-
ing the irreversible loss of nutrients from the dam to the
fetoplacental complex. They include the following:
1. Increasing the supply of exogenous glucogenic precur-
sors by intravenous dextrose and glucose, and oral
glucose preparations that are often combined with
electrolytes to provide oral rehydration solutions, or
oral propylene glycol (30–60 ml, 2 or 3 times daily, for
ewes and does; 200–300 ml for cows).
2. Correcting electrolyte imbalances and dehydration by
the use of calcium borogluconate solutions, intrave-
nous fluids containing dextrose or glucose, and oral
rehydration solutions.
3. Removing the fetus (emergency cesarean section can
be indicated in valuable animals) and increasing endo-
genous glucogenic precursors by the use of
glucocorticoids, including dexamethasone-21-isonico-
tinate and dexamethasone sodium phosphate.
 Author's personal copy
Diseases of Dairy Animals | Non-Infectious Diseases: Pregnancy Toxemia
Corticosteroids may also increase the availability of
amino acids for gluconeogenesis, but corticosteroids
are generally not recommended in cases with sepsis.
4. Hormonal treatments. Various hormones have been
used to modify the metabolic changes that occur.
These include anabolic steroids (e.g., trenbolone
acetate; results are equivocal), insulin injections
(e.g., 20–40 IU of protamine zinc insulin adminis-
tered intramuscularly every 48 h for 4 days; results
are equivocal), and recombinant bovine somatotro-
pin (e.g., 0.15 mg per kg–1 of body weight daily;
results appear promising).
On a herd or flock basis, the provision of larger quantities
of better-quality feed is critical.
See also: Body Condition: Effects on Health, Milk
Production, and Reproduction. Diseases of Dairy
Animals: Non-Infectious Diseases: Fatty Liver; Non-
Infectious Diseases: Ketosis. Feed Ingredients: Feed
Supplements: Macrominerals; Feed Supplements:
Microminerals; Feed Supplements: Organic-Chelated
Encyclopedia of Dairy Sciences, Second Edition, 2011, Vol. 2, 246-249
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249
Minerals. Feeds, Ration Formulation: Systems
Describing Nutritional Requirements of Dairy Cows.
Further Reading
Bell AW (1995) Regulation of organic nutrient metabolism during
transition from late pregnancy to early lactation. Journal of Animal
Science 73: 2804–2819.
Harmeyer J and Schlumbohm C (2006) Pregnancy impairs ketone
body disposal in late gestating ewes: Implications for onset of
pregnancy toxaemia. Research in Veterinary Science
81(2): 254–264.
Marteniuk JV and Herdt TH (1988) Pregnancy toxaemia and ketosis of
ewes and does. In: Herdt TH (ed.) Veterinary Clinics of North
America: Food Animal Practice, Vol. 4: Metabolic Diseases of
Ruminant Livestock, pp. 307–315. Philadelphia, PA: W.B. Saunders
Company.
Rook JS (2000) Pregnancy toxemia of ewes, does and beef cows. In:
Veterinary Clinics of North America: Food Animal Practice, Vol. 16:
Metabolic Diseases of Ruminant Livestock, pp. 293–317.
Philadelphia, PA: W.B. Saunders Company.
Schlumbohm C and Harmeyer J (2004) Hyperketonemia impairs
glucose metabolism in pregnant and nonpregnant ewes. Journal
Dairy Science 87: 350–358.
Stephenson KA, Lean IJ, Hyde ML, Curtis MA, Garvin JK, and Lowe LB
(1997) Effects of monensin on the metabolism of periparturient dairy
cows. Journal of Dairy Science 80: 830–837.