Periparturient period in cattle and sheep

As milk production in dairy cows increases and as herds become larger, the incidence of metabolic disease increases. In dairy cows, the incidence of metabolic diseases is highest in the period commencing at calving and extending until the peak of lactation is reached and their susceptibility appears to be related to the extremely high turnover of fluids, salts and soluble organic materials during the early part of lactation. With this rapid rate of exchange of water, sodium, calcium, magnesium, chlorides and phosphates, a sudden variation in their excretion or secretion in the milk or by other routes, or a sudden variation in their intake because of changes in ingestion, digestion or absorption, may cause abrupt, damaging changes in the internal environment of the animal. It is the volume of the changes in intake and secretion and the rapidity with which they can occur that affects the metabolic stability of the cow. In addition, if the continued nutritional demands of pregnancy are exacerbated by an inadequate diet in the dry period, the incidence of metabolic disease will increase. The effect of pregnancy is particularly important in ewes, especially those carrying more than one lamb.

Transition period in dairy cows

The literature on managing the transition period of the cow from 3 weeks before parturition to 3 weeks after parturition to optimize health and productivity has been reviewed.¹ It is a crucial stage in the production cycle of the dairy cow; no other period can affect subsequent production, health, and reproductive performance so greatly.^1,2 The success of the transition period effectively determines the profitability of the cow during that lactation. Nutritional or management limitations during this time may impede the ability of the cow to reach maximal milk production. The primary challenge faced by cows is a sudden and marked increase of nutrient requirements for milk production, at a time when dry matter intake and thus nutrient supply, lags far behind. Dry matter intake typically declines during the final week before parturition. This decline and changes in endocrine profiles contribute to elevated blood nonesterified fatty acids which have been related to the occurrence of lipid-related metabolic diseases such as fatty liver and ketosis. The magnitude of the decline in intake as parturition approaches may be a better indicator of metabolic health of post partum cows than level of intake. Diet, body condition score and parity influence dry matter intake and energy balance. The occurrence of diseases during the transition period results in lost milk production during the time of illness and often for the entire lactation.

A key area of the biology of transition cows is lipid metabolism.³ Excessive lipid metabolism from adipose tissue is linked with greater incidences of periparturient diseases. Fatty livers have been described in ketotic cows in the 1950s. Hepatic fat accumulation was then noted in normal cows during early lactation. This was followed by a description of a ‘fat mobilization syndrome’ in early lactation, in which cows mobilized body lipids from adipose tissue and deposited lipids in the liver, muscle, and other tissues. This was followed by descriptions of elevated non esterified fatty acid concentrations during the last 7 days before calving being associated with a greater incidence of ketosis, displaced abomasum and retained fetal membranes but not of milk fever. Understanding the metabolism of NEFA by the liver is a critical component of understanding the biology of the transition cow. Extreme rates of lipid mobilization lead to increased uptake of NEFA by the liver and increases triglyceride accumulation. If this lipid infiltration becomes severe, the syndrome of hepatic lipidosis or fatty liver may result, which can result in a prolonged recovery from other diseases, increased incidence of other diseases, and increased susceptibility to induction of ketosis.

It is now known that lipid metabolism in the prepartum dairy cow is important in the occurrence of displaced abomasum.^4,5 Significant risk factors for displaced abomasum included a negative energy balance prepartum (as estimated from plasma NEFAs), a high body condition score, suboptimal feed bunk management prepartum, prepartum diets containing >1.65 Mcal of net energy for lactation/kg of dry matter, winter and summer seasons, high genetic merit and low parity.⁵

Metabolic tests can now be used to predict displaced abomasum in dairy cattle.⁴ In cows which develop a left-side displacement of the abomasum, mean NEFA concentrations begin to diverge from the mean in cows without LDA 14 days before calving, whereas mean serum β-hydroxybutyrate (BHBA) concentrations did not diverge until the day of calving.⁴ Prepartum, only NEFA concentration was associated with risk of subsequent LDA. Between 0 and 6 days before calving, cows with NEFA concentrations ≥0.5 mEq/L were 3.6 times more likely to develop a LDA after calving. For prospective application, among samples taken 4–10 days before expected calving, the optimum NEFA cutpoint remained 0.5 mEq/L. The sensitivity, specificity and likelihood ratio were 46%, 82%, and 2.6, respectively. Between 1 and 7 days post partum, retained placenta, metritis and increasing serum concentrations of BHBA and NEFA were associated with increased risk of subsequent LDA. The odds of LDA were eight times greater in cows with serum BHBA ≥1200 μmol/L. Cows with BHBA concentrations ≥1200 μmol/L were 3.4 times more likely to develop LDA. Serum calcium concentrations were not associated with LDA. In summary, strategic use of metabolic tests to monitor transition dairy cows should focus on NEFA in the last week prepartum and BHBA in the first week post partum.

The nutritional management strategies to optimize the metabolic health of transition cows has been reviewed.⁶ During the transition period, dairy cows undergo large metabolic adaptations in glucose, fatty acid, and mineral metabolism.⁶ The practical goal of nutritional management during this period is to support these metabolic adaptations. A 2-group nutritional strategy for dry cows to minimize overfeeding of nutrients during the early dry period but increase nutrient supply during the late dry period is now being recommended.⁶ Increasing the amount of energy supplied through dietary carbohydrate during the prepartum period results in generally positive effects on metabolism and performance of transition cows. But the form of that carbohydrate (whether starch or highly digestible neutral detergent fiber) may be of lesser importance. Attempts to increase energy supply by feeding dietary fat sources or decrease energy expenditure by supplying specific fatty acids such as trans-10, cis-12 conjugated linoleic acid to decrease milk fat output during early lactation do not decrease the release of nonesterified fatty acids (NEFA) from adipose tissue.

In addition to nutritional management strategies to optimize health of the transition cow, certain feed additives are in use to reduce subclinical ketosis and reduce the incidence of displaced abomasum.⁷ Monensin is a carboxylic polyether ionophore produced by a naturally occurring strain of Streptomyces cinnamonesis. Monensin exerts its many effects by shifting the microbial populations in the rumen. It changes the ratio of volatile fatty acids in the rumen, increasing propionic acid and reducing the molar percentages of butyric acid and acetic acid. Improved rumen propionic acid improves gluconeogenesis. When administered in controlled release capsule (CRC) 2–4 weeks before calving, monensin reduced the incidence of both clinical ketosis and displaced abomasum postcalving.⁸ In a large dataset, monensin showed a trend for a 25% reduction in the incidence of retained placenta. Monensin improves energy metabolism which reduces the incidence of all three ‘energy associated diseases’, retained placenta, displaced abomasum and clinical ketosis. In Canada, the monensin-controlled release capsule (CRC) is approved as an aid in the prevention of subclinical ketosis in lactating dairy cattle. The capsule delivers 335 mg of monensin daily for 95 days.⁹ Cows treated with the monensin CRC 3 weeks before calving had decreased NEFA and BHBA and increased concentrations of serum cholesterol and urea in the week immediately pre-calving. Monensin has no effect on calcium, phosphorus, or glucose in the pre-calving period. After calving, concentrations of phosphorus were lower and BHBA lower and cholesterol and urea higher in monensin-treated cows. The lower NEFA values indicate less fat mobilization and the higher cholesterol suggest greater lipoprotein export from the liver. The higher urea levels are thought to be due to a protein-sparing effect in the rumen, resulting in an increased supply of amino acids in the small intestine. There was no effect of treatment on NEFA, glucose, or calcium in the first week post-calving. Monensin treatment administered pre-calving significantly improved indicators of energy balance in both the immediate pre-calving and post-calving periods.

Abnormalities of the blood levels of the four macrominerals, calcium, phosphorus, magnesium, and potassium in the cow during the transition period are involved in subclinical hypocalcemia, clinical milk fever, hypomagnesemia, and acute hypokalemia.¹⁰

Knowledge of the complex behavioral needs of the dairy cow is essential in order to provide adequate housing during the transition period. In North American dairy herds, the flow of cows through the transition period often necessitates many changes of pens, which are disruptive to the social organization of cow groups. Stocking rates that exceed stall and feed bunk capacity place even greater challenges on the dairy cow at this time. Alternative strategies for cow grouping and improvements in pen and stall design which provide greater behavioral freedom for the dairy cow and improvements in health and productivity have been described.¹¹

Management of the dairy cow at calving time is a major topic which requires that the veterinarian educate the animal attendants and owners.¹² The objective is to ensure the delivery of a viable, live calf and smooth transition of the cow without complications, from the dry period to the lactation period. The two major problems encountered at calving time are dystocia and perinatal mortality.

The diagnosis and treatment of dairy cows with periparturient diseases requires a program suited to the particular herd.¹³ Particularly in large herds, there is a need for collaboration between the veterinarian, nutritionist, manager of the herd, and the animal attendants. Specific procedures should be developed for each herd based on past experience with the problems of recently-calved cows, the facilities, the skills of the workers, the priorities of management, and the flow patterns of cows in the herd. Every effort must be made to prevent periparturient diseases in the cows. In general, diseases in the early post partum period originate in the feeding and management of the dry cow. Important principles include a protocol of grouping parturient cows according to the feeding program and handling facilities on the farm. Groups of cows can be screened for mastitis, visual evidence of illness, daily milk yield, body temperature, urine pH, palpated for evidence of metritis. Individual cows which have been identified by a screening method must be examined individually to make a diagnosis and decide on a treatment protocol based on the particular diagnosis.

The use of reliable records to monitor the health and production of dairy cows during the transition period is essential to evaluate the efficacy of programs at the farm level.¹⁴ Monitors of transition cow management programs will assist in determining how well cows are prepared for milk production and good health in the coming lactation. Appropriate monitoring will focus on three areas: cows that die or are culled in early lactation, the productivity of the surviving cows in early lactation, and the rates of disease in the periparturient period.

Cows which leave the herd in the first 60 days of lactation are usually culled because of disease or injury.¹⁴ Removal rates and their causes can be a critical monitor of the efficacy of transition cow management programs. Measuring productivity and health of cows in early lactation involves monitoring peak milk, daily milk yields, first test mature equivalent 305-day projected milk, milk components at first Dairy Herd Improvement Association (DHIA) test day, milk fat percentage, ratios of test-day components, somatic cell count at first DHIA test day.¹⁴ DHIA records also allow comparison of the performance of each cow in early lactation to her performance in the prior lactation. Comparisons can be made of the changes in somatic cell count between the last test of the prior lactation and the first test of the current lactation and mature equivalent 305-day difference from the prior lactation to the first test of the current lactation

Health and production records in dairy herds have traditionally emphasized reproductive events and treatments given. The records should capture the information about the common diseases which occur in most dairy herds.¹⁴ The record system should be set up to:

An adequate record system will allow producers and veterinarians to determine the differences between actual performance and benchmark performance and then determine the causes of the shortfall. The most important determinants of profitability on dairy farms are milk income and feed cost and the difference between milk income and feed costs is the return over feed index (ROF).¹⁵ Many factors affect the ROF index. These include: three times daily milking, component percentages in the herd milk test, milk fat and protein percentages, use of an E. coli mastitis vaccine and use of monensin in the lactating cow diet.¹⁵ One of the most important factors associated with profitability is milk production. From 80% to 95% of the income on dairy farms is derived from milk sales. Thus, it is critical that the producer, the veterinarian and other advisors collaborate to plan the animal health and production program which will result in the optimum ROF.

Other recent developments indicate that environmental and management factors can be manipulated to ease the transition into lactation.¹⁶ The photoperiod, defined as the duration of light exposure an animal receives within a day, can be adjusted to produce dramatic effects on periparturient health and subsequent lactational efficiency. Increasing the frequency of milking in the immediate post partum period also produces persistent increases in milk yield and improvements in mammary health. In both techniques, evidence is emerging to support the concept that alteration of prolactin sensitivity is the mechanism underlying health and production responses.

The prospect of 0 days for dry periods are being explored as a possible alternative management scheme in dairy herds.¹⁷ In high-producing dairy cows, the dry period is influenced by parity and management practice. Multiparous cows that were continuously milked and treated with bovine somatotrophin (bST) demonstrated negligible production losses in the next lactation. First-calf heifers, however, demonstrated large reductions in milk yield.

Voluntary dry matter intake in periparturient dairy cattle

The factors affecting voluntary dry matter intake (VMDI) of lactating cattle are extremely important and have received much attention for many decades. The literature on the integration of metabolism and intake regulation in animals has been reviewed.¹⁸ A substantial dip in VMDI is initiated in late pregnancy and continues into early lactation.¹⁸ Pregnancy in dairy heifers has been shown to reduce VMDI from week 26 of pregnancy by 1.53% (approximately 0.17 kg) per week until 3 weeks before calving. In one study, in which the energy density of the diet remained constant during the last 168 days of pregnancy, a similar decline in energy intake during the last trimester of pregnancy both in heifers and lactating cows when diet energy was high (11.6 MJ of metabolizable energy/kg of DM), while the decline was much smaller or insignificant at lower energy densities (10.3 or 8.3 MJ of metabolizable energy/kg of DM).¹⁸ The lowest VMDI occurs at calving. Post partum VDMI increases, but the rate varies widely. In cows given diets of constant composition, the milk yield typically peaks at 5–7 weeks post partum, while the maximum intake is reached between 8 and 22 weeks after calving. The increase in intake from week 1 post partum to time of peak intake varies from between 2% and 111%. These differences in intake are affected by the diet fed during lactation but may also depend on prepartum feeding by way of, at least in part, the influence and the degree of fatness and or body condition score (BCS) of the animal. Voluntary dry matter intake is considerably higher in multiparous cows compared with primiparous cows. The intake capacity of primiparous cows calving at an age of 2 years is only about 80% of that of multiparous cows in the first part of lactation. The normal pattern of intake may be severely influenced by disease states. Both clinical and subclinical infections are known to substantially reduce appetite and performance.

The dip in VMDI has traditionally been attributed to physical constraints such as the enlarging uterus but this role may be overemphasized. The dip coincides with changes in reproductive status, fat mass and metabolic changes in support of lactation. A number of metabolic signals may have a role in intake regulation. These signals include nutrients, metabolites, reproductive hormones, stress hormones, leptin, insulin, gut peptides, cytokines and neuropeptides such as neuropeptide Y, galanin and corticotrophin-releasing factor.¹⁸

During late pregnancy and lactation, energy requirements increase considerably. Fetal energy requirements on day 250 of pregnancy have been calculated at 2.3 Mcal/d for Holstein cows. During lactation, energy requirement is increased to 26 Mcal net energy in cows producing 30 kg milk/day. Major changes in metabolism occur to cope with this increase in nutrient requirements. On a diet high in energy density, pregnant heifers will have a relatively high plasma concentration of glucose and a relatively low concentration of NEFA. Post partum, the concentration of NEFA is high while glucose is reduced. These changes reflect the large need for glucose and nutrients by the mammary gland and that dairy cows increase the use of lipid as a source of energy to support lactation. The NEFA begins to rise 2–3 weeks before calving and peaks at calving or during the first week of lactation. Glucose increases during the last week before calving and drops abruptly post partum to reach a minimum of 1–3 weeks into lactation. Post partum changes in the plasma concentration of BHBA are generally opposite those of glucose.

Immunosuppression during the transition period

In addition to the adaptations in classical metabolism which occurs during the transition period, cows during this period undergo a period of reduced immunological capacity during the periparturient period.¹⁹ The immune dysfunction is broad in scope, affects multiple functions of various cell types and lasts about 3 weeks prior to calving until about 3 weeks after calving. Cows during this period are more susceptible to mastitis. The etiology of periparturient immunosuppression is multifactorial and not well understood but seems to be related to physiologic changes associate with parturition and the initiation of lactation and to metabolic factors related to these events. Glucocorticoids are immunosuppressants, are elevated at parturition and have been postulated to have a role in periparturient immunosuppression.

The effects of parturition on cytoplasmic glucocorticoid expression (GR) in neutrophils and the correlation of the expression with serum cortisol concentration and total leukocyte count and neutrophil counts in periparturient cows has been examined.²⁰ Neutrophils from periparturient cows had a 49% reduction in GR expression at calving, compared with GR expression 2–4 weeks before calving and 39% reduction, compared with neutrophils from cows in mid-pregnancy. The reduction in neutrophil GR expression is detectable 1 week before calving and most severe at calving and 24 h after calving. Multiparous cows have prolonged GR down-regulation of their neutrophils compared with primiparous cows which may be associated with a higher incidence of mastitis in older cows. Serum cortisol concentrations and total leukocyte and neutrophil counts were significantly increased at calving and returned to baseline value by 24 h after calving. Thus, a cortisol-induced neutrophil GR down-regulation and neutrophil migration dysfunctions occur in periparturient dairy cows. There is impaired expression of adhesin molecules and decreased migration capacity of blood neutrophils. Rapid recruitment of neutrophils into newly infected mammary tissue is the key immunologic defense against mastitis-causing pathogens in ruminants.

Experimentally, nonesterified fatty acids in vitro significantly reduces immunosuppressiveness of mononuclear cells of ewes which may be associated with the impairment of cell-mediated and humoral immunity in sheep and cattle with ketosis.²¹

Because vitamin E is a fat-soluble membrane antioxidant which enhances the functional efficiency of neutrophils by protecting them from oxidative damage following intracellular killing of ingested bacteria, the parenteral administration of vitamin E has been explored for the prevention of peripartum diseases such as retained placenta, metritis, and clinical mastitis. Only cows with marginal vitamin E status (serum α-tocopherol <2.5×10⁻³) 1 week before calving will have a reduction in the risk of retained placenta following a subcutaneous injection of 3000 IU of vitamin E.²² In cows with an adequate level of serum vitamin E there was no reduction and primiparous animals were most likely to benefit from vitamin E 1 week before parturition. The associations between peripartum serum vitamin E, retinol and β-carotene in dairy cattle and disease risk indicated that an increase in α-tocopherol of 1 μg/ML in the last week prepartum reduced the risk of retained placenta by 20%, whereas serum NEFA concentrations ≥0.5 mEq/L tended to increase the risk of retained placenta by 80%. In the last week prepartum, a 100 ng/mL increase in serum retinol was associated with a 60% decrease in the risk of early lactation clinical mastitis.²³

Diseases of lactation

In the next phase of the production cycle, parturition is followed by the sudden onset of a profuse lactation which, if the nutrient reserves have already been seriously depleted, may further reduce them to below critical levels and clinical metabolic disease then occurs. The essential metabolite which is reduced below the critical level determines the clinical syndrome which will occur. Most attention has been paid to variations in balances of calcium and inorganic phosphates relative to parturient paresis; magnesium relative to lactation tetany; blood glucose and ketones and hepatic glycogen relative to ketosis; and, potassium relative to hyperkalemia on cereal grazing, but it is probable that other imbalances are important in the production of as yet unidentified syndromes.

The vast majority of production diseases of dairy cows occur very early in lactation. At this time, the cow is producing milk at a rate which is substantially less than her maximum. In terms of rate, high and low milk yielding cows are producing rather similar amounts at this time. However, in terms of acceleration, the change in milk yield per day, it is highest immediately after calving.

During the succeeding period of lactation, particularly in cows on test schedules and under the strain of producing large quantities of milk, there is often a variable food intake, especially when pasture is the sole source of food and instability of the internal environment inevitably follows. The period of early lactation is an unstable one in all species. Hormonal stimulation at this stage is so strong that nutritional deficiency often does not limit milk production and a serious drain on reserves of metabolites may occur.

Breed susceptibility

The fact that some dams are affected much more by these variations than others is probably explainable on the basis of variations in internal metabolism and degree of milk production between species and between individuals. Between groups of cows, variations in susceptibility appear to depend on either genetic or management factors. Certainly, Jersey cows are more susceptible to parturient paresis than cows of other breeds and Guernseys seem to be more susceptible to ketosis. Even within breeds, considerable variation is evident in susceptibility between families. Under these circumstances, it seems necessary to invoke genetic factors, at least as predisposing causes.

Management practices

The management practices of most importance are housing and nutrition. In those sections of North America where cattle are housed during the winter and in poor pasture areas, ketosis is prevalent. In the Channel Islands, local cattle are unaffected by lactation tetany, whereas the disease is prevalent in the UK. In New Zealand, metabolic diseases are complex and the incidence is high, both probably related to the practice of having the cows calve in late winter when feed is poor and to the practice of depending entirely on pasture for feed and to the high proportion of Jerseys in the cattle population.

A knowledge of these various factors is essential before any reasonable scheme of prevention can be undertaken. It should also indicate that although the more common disease entities are presented in this chapter, there is high probability that a disturbance of more than one of the metabolites mentioned may occur simultaneously in the one animal and give rise to complex syndromes which are not described here. The disease entities dealt with must be considered as arbitrary points in a long scale of metabolic disturbances.

Occurrence and incidence of metabolic diseases

A knowledge of the etiological and epidemiological factors involved will help in understanding the occurrence and incidence of the various metabolic diseases.²⁸ Largely because of variations in climate, the occurrence of metabolic disease varies from season to season and from year to year. In the same manner, variations in the types of disease occur. For example, in some seasons, most cases of parturient paresis will be tetanic; in others, most cases of ketosis will be complicated by hypocalcemia. Further, the incidence of metabolic disease and the incidence of the different syndromes will vary from region to region. Ketosis may be common in areas of low rainfall and on poor pasture. Lactation tetany may be common in colder areas and where natural shelter is poor. Recognition of these factors can make it possible to devise a means whereby the incidence of the diseases can be reduced.

The metabolic diseases, because of high prevalence and high mortality rate, are of major importance in some countries, so much so that predictive systems are being set up. Rapid analysis of stored feed samples, pasture and soil is commonly used in Europe and North America but the interesting development has been the recognition of ‘production diseases’ and the consequent development of metabolic profile tests, particularly in the UK and in Europe.

Relationship between lactational performance and health of dairy cattle

The literature on the relationship between lactational performance and health in dairy cattle has been reviewed.²⁹ Based on a review of 11 epidemiological and 14 genetic studies there was little evidence that high yielding cows have increased risk of dystocia, retained placenta, metritis, and left-side displacement of the abomasum. The results for periparturient diseases were inconsistent. While no phenotypical relationship between milk yield and the risk of ketosis and lameness was found, selection for higher milk yield will probably increase the lactational incidence risk for these diseases. Mastitis was the only disease where there was a clear relationship between milk yield and risk of infection. Continued selection for high milk yield will worsen this situation.

However, some authors claim that ‘Reviewing existing literature, even with structured literature selection, is inadequate to the task of elucidating the relationship between the lactational performance and risk of production diseases’.²⁹ The most notable feature of the literature evaluation is the large variability that exists between studies. This strongly suggests that there are important factors that need to be considered before meaningful conclusions concerning the relationship between lactational performance and risk of disease can be drawn.

Usefulness of metabolic profile testing

Metabolic profiles in dairy cows were used initially in Britain in the 1960s. Success was limited primarily by the unjustified expectation that all biochemical concentrations in the blood of cows would reflect nutritional intake and status at all times.³⁴ However, the practical value was found in the approach as an aid to nutritional management. Later, in the 1970s the approach was reassessed and reinstituted, culminating in a program for farmers evaluating health and productivity using metabolic profile testing as an integral part of a health management program involving a multidisciplinary approach. The system now depends on a team approach involving farmer, veterinarian, and agricultural adviser. The blood testing part, if useful information is to be obtained, depends critically on following a set of firm criteria for selection of small groups of typical cows within each herd, the timing of testing in relation to concentrate feeds, feed changes, and stage of lactation and the collection of other data about the cows such as body weight and condition, productivity and feeding. The successful approach has been to look, following specific times of nutritional change, at metabolite levels in strictly defined small representative groups of cows within each herd in conjunction with information on body condition and weight, milk performance, and feeding. Comparison with optimum values, the degree of variation from them and comparisons between groups within herds have allowed information about nutritional constraints on productivity to be made available to farmers more quickly and more specifically than by other means.

Most metabolic profile testing has been used in temperate climates. The effectiveness of the technique for identifying constraints on productivity in small herds in tropical and sub-tropical countries has been examined.³⁴ The study involved 13 projects with 80 cows in each, done in six Latin American, six Asian, and one southern European countries. Data were also collected on feeding, body condition score and weight change, parasitism, and reproduction. In Chile, Mexico, Paraguay, Philippines, Uruguay, and Venezuela, globulin levels were high in >17% of cows samples on each occasion. In Paraguay, 49% of cows had high globulin levels at 2–3 months after calving. This suggests that inflammatory disease was present although this was not always investigated. In all countries except Mexico and Venezuela, high β-hydroxybutyrate levels before calving in many cows highlighted the presence of body condition loss in late pregnancy, an important potential constraint on productivity and fertility. Fewer cows had high BHB levels in lactation, whereas change in BCS and weight was more sensitive for measuring negative energy balance. Urea concentrations were low in only small numbers of cows suggesting that dietary protein shortages were not common. Albumin levels were low mainly in cows where globulin values were high and therefore did not provide additional information. In China, pregnant yaks over winter had high BHB and low albumin values, suggesting that they were seriously underfed. This resulted in a successful nutritional intervention in the following winter. Inorganic phosphorus values were within the reference range in most countries most of the time, suggesting, contrary to expectation, that this mineral was not commonly a constraint. In summary, the use of metabolic profile testing proved valuable in drawing attention to important potential constraints on productivity in dairy cows in tropical and subtropical environments and in confirming those which were not.³⁴

Metabolic profile testing has been used for the prevention of periparturient diseases in dairy cows in Japan.³⁵ In herds with a high incidence of periparturient disease, low blood values of hematocrit, albumin, glucose, cholesterol, calcium, and magnesium were observed in the dry period. The values correctly diagnose malnutrition as the cause of the periparturient diseases. Following feeding management changes, there was a low incidence of these diseases and the metabolic profiles were normal indicating that feeding management had improved. Because the traditional metabolic profile test is difficult to apply to peripartum cows because they are in state of physiological abnormality and the results are difficult to interpret, doing a test every 10 days during the dry and lactation periods has been evaluated.³⁶ The criteria were interpreted by the deviations from the reference mean values of metabolites rather than the actual values. The body condition score, albumin, blood urea nitrogen, glucose, total cholesterol, non-esterified fatty acids, γ-glutamyl transpeptidase, and aspartate aminotransferase, fluctuated during the dry and early lactation periods and there were large changes in the hematocrit, blood urea nitrogen, total cholesterol, and magnesium and high nonesterfied fatty acids in herds with a high incidence of peripartum diseases.

The values of the variables which deviated from the reference values for the metabolic profile components were able to assess milk production and feeding which is a practical tool for auxiliary feeding evaluation.³⁷

The Dairy Herd Health and Productivity Service (DHHPS) in the UK provides the opportunity for veterinarians to lead a multidisciplinary team which can monitor health, fertility, and production and can plan, when necessary, corrective action.³⁸ Metabolic profiling and body condition scoring found that at least a third of the cows sampled were mobilizing excessive fat during the transition from the dry period to early lactation. Improving both health and nutrition, before and after calving, would improve reproductive performance in many herds. A team approach, with farmers, veterinarians, nutritionists, and other advisors working together with well defined goals and objectives, is necessary if progress is to be made in improving reproductive performance. High milk yields cannot always be the excuse for suboptimal fertility.³⁸

Biological and statistical basis for herd testing

The interpretation of herd-based tests for metabolic diseases is different from interpreting laboratory tests for metabolites from individual cows.³⁹ Test results from individual cows are interpreted by comparing the value to a normal reference range established by the laboratory that did the testing. Normal ranges are often derived by calculating a 95% confidence interval (or a similar statistic) of test results from 100 or more clinically normal animals.

Herd test results for metabolic diseases can be interpreted as either the mean test result of the subgroup sampled or as the proportion of animals above or below a certain cut point within the subsample. If a metabolite is associated with disease when it is above or below a biologic threshold (cut point) then it should be evaluated as a proportional outcome. For example, subclinical ketosis in dairy herds can be monitored by testing for β-hydroxybutyrate (BHBA) or other ketone bodies in blood or milk. Subclinical ketosis is a threshold disease and cows are affected only when ketone concentrations are elevated. Blood BHBA concentrations above 1400 μmol/L is the most commonly used cut point for subclinical ketosis. Early lactation cows with BHB concentrations above this cut point are a threefold greater risk to develop either clinical ketosis or displaced abomasum. Non-esterified fatty acids (NEFA) concentrations in blood are an indicator of negative energy balance in prepartum cows. Elevated NEFAs before calving are associated with increased risk for displaced abomasum after calving. A threshold above 0.400 mEq/L for cows between 2 and 14 days of calving is suggested as an appropriate cut point.

It is also necessary to determine the alarm level for the proportion of animals above or below the described cut point. The alarm level is determined from research results or clinical experience. The suggested alarm level proportions for BHBA with a cut point of =1400 μmol/L is >10% and for NEFAs with a cut point of =0.400 mEq/L is >10%.

Herd-based testing is useful only when a sufficient number of cows within the herd are tested, which gives reasonable confidence that the results truly represent the entire population of eligible cows in the herd. The minimum sample size for herd-based tests with proportional outcomes is 12 cows. Cows to be sampled need to be selected from the appropriate eligible or at risk group.

The ‘proper’ use of metabolic profiles depends on care with the timing of blood tests, the selection of cows to be included and the collection and use of background information about the farm, feeding, and feeding system and physical state and performance of the cows.⁴⁰

As of 2005, for 5 years the Dairy Herd Health and Productivity Service (DHHPS) in the UK have been using the metabolic profile approach as an aid to the management of dairy cow nutrition. Effectively the approach has been to ‘ask the cows’ what they think of their nutrition – by following a set of ‘rules’ on timing, cow selection and the use of background information.³³ The involvement of a team approach at the farm, including private veterinarian and nutritional adviser, to put the findings in the correct context and to identify the appropriate responses has been vital. Data on health and fertility from many of these farms has also been collected.

Variables in dairy-herd metabolic profile testing

Selection of cows

Picking appropriate cows for blood sampling is very important. This is because some of the metabolites looked at, particularly those relating to energy balance, can quickly return to the optimum range as cows adapt themselves, including their productivity, to a nutritional constraint. It is possible for cows to experience a significant energy deficit in the first 2–3 weeks of lactation because of intake problems, lose excessive body condition, perhaps modify their milk yield, and have their subsequent fertility efficiency suppressed but yet still arrive at 4 weeks calved with all biochemical measurements within the optimum ranges. This is because the common appetite constraint of the new calved has worked its way out and there is plenty of food available for lower performance than anticipated. If blood is sampled at 4 weeks calved or longer, a farmer could see thin, under-producing cows with poor fertility but with nothing abnormal about their biochemistry. Thus, the farmer would be entitled to feel the metabolic profile test was of no value. However, if those cows had been blood sampled at 14 days calved instead of 27, the blood results would have been quite different and would have identified the nutritional constraint on productivity.⁵³

The ‘Rules’ for metabolic profiling of dairy cattle recommend sampling from the following groups:

• Early lactation (EL): between 10 and 20 days of lactation

• Mid lactation (ML): between 50 and 120 days of lactation

• Dry period (D): between 7 and 10 days of calving.

Individual variations in biochemical values are such that single cows should not be tested. Groups of no less than five should be sampled. They should not be picked at random but rather should be typical, average cows of their stage of lactation. Cows with extremes of performance – either very high or very low – should not be selected. Cows with problems should also not be included because the type of analysis carried out is not designed to clarify individual problems. It is important to make all this clear to farmers in advance because they cannot be expected to appreciate the limitations of the analyses made. Experience in the Dairy Herd Health and Productivity Service in the UK³³ suggests that selecting cows for metabolic profiles may be best done by the veterinarian in advance of the test after looking at the calving and production records. If there is a specific concern such as a poor conception rate, farmers may expect only cows which have failed to conceive to be sampled. This hardly ever delivers helpful information as any nutritional constraints have by then been compensated for and blood biochemical values are usually within optimum ranges. The best approach may be to include such cows as the mid-lactation group.

Early lactation group (EL)

The definition used for this group is most critical for the reasons given in the previous paragraph. Since the original Compton metabolic profile where high yielding cow was used as the definition, the importance of this group has become increasingly apparent. The definition also has had to be changed to take into account changes in farm practice. The way cows are fed now – total mixed rations, increased out of-parlor concentrate feeding – has reduced the time after calving by when they can adapt themselves to an unsatisfactory diet. To be sure of detecting the presence of an energy constraint in particular, blood sampling should be carried out between 10 and 20 days calved– less than 10 days and the yield is still too far below peak for the test to be a realistic one for early lactation performance; more than 20 days and some cows will be thin, unproductive and subfertile but have compensated for their nutrition and they may have normal blood metabolite values.

Mid-lactation group (ML)

Some cows which are passed the period of peak yield and so passed the greatest period of potential nutritional stress should always be included. They should be between 50 and 120 days calved so that they are still relatively high yielding. This group provides a within-herd comparison with the early lactation cows. Without this it is very difficult to distinguish between problems caused by constraints on intake of food or protein and energy content; to identify changes in biochemical values caused by mistiming of tests in relation to feeding or by oddities in the diet such as silage with a high butyric acid content; and to make judgments on concentrate/forage usage within the herd.

Dry cow group (D)

As the dry period is so important to the success of the following lactation, blood sampling to make sure nutrition is adequate is essential. However, the nature of the measurements which can be made means that primarily cows in the last 7–10 days of pregnancy should be sampled. Cows tested with longer to go than that tend to have normal measurements of energy balance even though they can still get in to difficulty. This is because the period of greatest risk is when the volume of the pregnant uterus increases to the point that it can seriously inhibit food intake. It follows that, in a seasonal calving herd, the first dry cows which come in to these last 7–10 days ought to be blood sampled, so that the information can be used for the benefit of the others still to come in to the maximum risk period.

Blood sampling a group of dry cows with 1 month or longer to go to calving at the same time can sometimes provide a useful within herd comparison with respect to energy balance. It may also identify the presence of dietary protein inadequacy – specifically rumen degradable – in the early part of the dry period.

In the DHHPS program, a majority of farms do metabolic profiles 3–4 times a year at critical times as a check ‘ask-the-cows-what-they-think’ exercise. Thus metabolic profiles as part of a pro-active preventive health and productivity programme. Some of the larger farms may do more than 10 tests a year to cover feed changes and to check on the success of any corrective action.

In the DHHPS program, a standard DHHPS metabolic profile includes analysis on blood plasma for β-hydroxybutyrate (BHB), glucose, non-esterified fatty acid (NEFA), urea-nitrogen (urea N), albumin, globulin, magnesium, and inorganic phosphate.³³ Analyses for copper and glutathione peroxidase (GSHPx) are done on approximately one-third of samples received and thyroxine T4 on even fewer. Biochemical analysis is performed using two Bayer Opera auto-analysers, with standard internal controls. It also employs an independent, external quality control system. Derivation of optimum metabolite values are summarized in Table 29.2. They are BHB <1.0 mmol/L in cows in milk, <0.6 mmol/L in dry cows; glucose >3.0 mmol/L; NEFA <0.7 mmol/L in cows in milk and <0.5 mmol/L in dry cows; ureaN >1.7 mmol/L; albumin >30 g/L; globulin <50 g/L; magnesium >0.7 mmol/L; inorganic phosphate >1.3 mmol/L; copper >9.2 μmol/L; glutathione peroxidase (GSHPx) >50 U/g HB; thyroxine T4 >20 nmol/L.

Table 29.2 Metabolic profile parameters in cattle. Optimum values

Parameter		SI units
Butyrate Milkers		Below 1.00 mmol/L
	Dry cows	Below 0.60 mmol/L
Plasma glucose		Over 3.00 mmol/L
NEFA Milkers		Below 0.70 mmol/L
	Dry cows	Below 0.40 mmol/L
UreaN		1.70–5.00 mmol/L
Albumin		Over 30.00 g/L
Globulin		Under 50.0 g/L
Magnesium		0.80–1.30 mmol/L
Phosphate (inorganic)		1.40–2.50 mmol/L
Copper		9.40–19.00 μmol/L
Thyroxine T4 (iodine)		Over 20.00 nmol/L
GSHPx (selenium)		Over 50units/g Hb

Energy.

The data in Table 29.3 uses only the cows fitting precisely the definitions of EL, ML, and D. It shows that, overall, an average of 30% EL cows had metabolite results reflecting satisfactory energy status as did 61% of ML and 43% of D. In both EL and ML groups, glucose is the metabolite most commonly outside its optimum range, followed by BHB and NEFA. The percentage of NEFA values above optimum is low in ML cows. The most common finding is high BHB and low glucose in the same cow. In tests showing most cows in an EL group with results like that, there is usually one or two with high NEFAs as well. Some EL cows show only low glucose or only high NEFA. Where low glucose only predominates in EL cows, ML cows often show the same picture.

Table 29.3 Annual (April–March) percentages outside optimum ranges of metabolite results in blood plasma in adult dairy cows³³

Protein.

UreaN results in Table 29.3 show that the EL stage is more vulnerable to low values than later in lactation, even though the cows would have been on the same diets in virtually every case. In fact an even greater average percentage⁵¹ in 1361 cows blood sampled between 0 and 9 days after calving over the 5 years showed low ureaN.

The proportion of low ureaN results in D cows is high (Table 29.3). In addition to the category shown of 10 days or less before calving, 4335 cows were sampled at more than 10 days prepartum over the 5 years and 22% of them had low ureaN values too.

Results outside the optimum ranges for albumin (0.6%), magnesium (2.5%), inorganic phosphate (1.0%), copper (10%), GSHPx (3%) are relatively uncommon. Thyroxine T4 analysis was carried out in 836 samples on specific request and only 3% were below optimum.

Body condition score (BCS)

Managing body reserves is critical for successful cow management and requires an accurate assessment of the cow’s ‘condition’. Body condition scoring is an important aspect of metabolic diseases of farm animals. Body weight alone is not a valid indicator of body reserves, as cows of a specific weight may be tall and thin or short and fat. The energy stores may vary by as much as 40% in cows of similar body weight, which emphasizes the futility and inaccuracy of relying on body weight alone as an index of cow condition. In addition, because tissue mobilization in early lactation occurs as feed intake is increasing, decreases in body tissue weight can be masked by enhanced fill of the gastrointestinal tract, so that body weight changes do not reflect changes in adipose tissue and lean tissue weight.⁵⁴

There is a strong positive relationship (r² = 0.86) between body condition score (BCS) and the proportion of physically dissected fat in Friesian cows. Therefore, the visual or tactile (palpation) appraisal of the cow’s body condition score provides a good assessment of body fat reserves, ignoring, or minimizing the effect of, frame size and intestinal contents. Most animal and dairy scientists acknowledge successfully manipulating BCS as an important management factor, influencing or having a relationship to animal health, milk production, and reproduction in the modern dairy cow. For example, cows which lost 0.5–1.0 point in BCS between parturition and first service achieved pregnancy rate to first service of 53%, while those losing >1.0 point achieved a rate of 17%.⁵⁵ In a seasonal pasture-based system for Holstein–Friesian cows, it is necessary to maintain a BCS at ≥2.75 during the breeding season. Body condition score is important in achieving good reproductive performance. Loss of body condition between calving and first service should be restricted to 0.5 BCS to avoid a detrimental effect on reproductive performance.⁵⁵

BCS is a subjective method of assessing the amount of metabolizable energy stored in fat and muscle (body reserves) on a live animal. BCS in dairy cows is done using a variety of scales and systems. This method involves palpating the cow to assess the amount of tissue under the skin. Scoring body condition and assessing changes in the body condition of dairy cattle have become strategic tools in both farm management and research. BCS is being researched worldwide. But international sharing, comparing, and use of data generated are limited because different BCS systems are used. There is difficulty in interpreting the literature because of variability in the way authors apply scoring methods. In the USA, Canada, and Ireland a 5-point BCS system is used for dairy cows, whereas Australia and New Zealand use 8- and 10-point scales, respectively.⁵⁶ The following scoring method is recommended for the 0–5 scale. The BCS chart adapted from Edmonson et al. appears in Figure 29.1.⁵⁴

Fig. 29.1 Body condition scoring chart adapted from Edmonson et al. (1989).

Score: 0

• Condition: Very poor

• Tailhead area: Deep cavity under tail and around tailhead. Skin drawn tight over pelvis with no tissue detectable in between

• Loin area: No fatty tissue felt. Shapes of transverse processes clearly visible

• Animal appears emaciated.

Score: 1

• Condition: Poor

• Tailhead area: Cavity present around tailhead. No fatty tissue felt between skin and pelvis, but skin is supple

• Loin area: Ends of transverse processes sharp to touch and dorsal surfaces can be easily felt. Deep depression in loin.

Score: 2

• Condition: Moderate

• Tailhead area: Shallow cavity lined with fatty tissue apparent at tailhead. Some fatty tissue felt under the skin. Pelvis easily felt

• Loin area: Ends of transverse processes feel rounded but dorsal surfaces felt only with pressure. Depression visible in loin.

Score: 3

• Condition: Good

• Tailhead area: Fatty tissue easily felt over the whole area. Skin appears smooth but pelvis can be felt

• Loin area: Ends of transverse processes can be felt with pressure but thick layer of tissue dorsum. Slight depression visible in loin.

Score: 4

• Condition: Fat

• Tailhead area: Folds of soft fatty tissue present

• Patches of fat apparent under skin. Pelvis felt only with firm pressure

• Loin area: Transverse processes cannot be felt even with firm pressure. No depression visible in loin between backbone and hip bones.

Score: 5

• Condition: Grossly fat

• Tailhead area: Tailhead buried in fatty tissue. Skin distended. No part of pelvis felt even with firm pressure

• Loin area: Folds of fatty tissue over transverse processes. Bone structure cannot be felt.

Relationships among international body condition scoring

The New Zealand 10-point scale was compared with the scoring systems in the USA, Ireland, and Australia by trained assessors.³⁵ Cows were assessed visually in the USA and Australia and in Ireland, cows were assessed by palpating key areas of the cow’s body. Significant positive linear relationships were found between the New Zealand 10-point scale and the other scoring systems. The relationship between the 10-point BCS scale used in New Zealand and Ireland and the USA are summarized in Table 29.4.

Table 29.4 Relationship between the 10-point BCS scale used in New Zealand and the 5-point BCS scale used in Ireland and the USA, and the 8-point scale used in Australia

Occurrence

Morbidity and case fatality

Several epidemiological studies of milk fever have shown an incidence risk of 5–10%, calculated either as the lactational incidence or incidence per cow year.² Generally the disease is sporadic but on individual farms the incidence may rarely reach 25–30% of high-risk cows. In Victoria, Australia, 85% of dairy herds calve in the spring and the incidence of milk fever ranges from 2% to 5%.⁵ With early treatment relatively few deaths occur in uncomplicated cases but incidental losses due to aspiration pneumonia, mastitis, and limb injuries may occur. From 75% to 85% of uncomplicated cases respond to calcium therapy alone. A proportion of these animals require more than one treatment, either because complete recovery is delayed, or because relapse occurs. The remaining 15–25% are either complicated by other conditions or incorrectly diagnosed.

Risk factors

The literature on the risk factors associated with milk fever has been reviewed.²

Hypocalcemia

Plasma calcium concentration is normally maintained between 2.1 and 2.6 mmol/L (8.5 –10.4 mg/dL). Almost all dairy cows will experience subclinical hypocalcemia, <1.8 mmol/L (7.5 mg/dL) within 24 h after calving. In some cows, the hypocalcemia is more severe, <1.25 mmol/L (5 mg/dL) causing neuromuscular dysfunction resulting in clinical milk fever. Without treatment, levels may continue to decline to about 0.5 mmol/L (2 mg/dL) which is usually incompatible with life.¹³

Hypocalcemia is the cause of the signs of typical ‘milk fever’. Atony of skeletal muscle and plain muscle are well-known physiological effects of hypocalcemia. Hypophosphatemia and variations in levels of serum magnesium also occur and have secondary roles. In experimental hypocalcemia in cattle, there is:

Total plasma calcium concentration at calving is not significantly related to fat and protein-corrected milk yield at any lactation period.¹⁴

In rare cases, pathological changes in the myocardium of hypocalcemic parturient cows have been reported.⁹ The cows were hypocalcemic, recumbent, with tachycardia, arrhythmia, and dyspnea and failed to respond to calcium therapy, however, the cause of the lesions was not determined. The plasma natriuretic peptide concentrations were elevated indicating myocardial injury.¹⁵

Hypomagnesemia

When hypomagnesemia coexists with hypocalcemia the clinical signs continue but with normal or higher than normal levels, relaxation, muscle weakness, depression, and coma supervene. It is likely that the hypocalcemic tetany is overcome by the relative hypermagnesemia (the ratio of Ca:Mg may change from 6:1 to 2:1) approximating the ratio at which magnesium narcosis develops. There is normally a rise in serum magnesium levels at calving but in those cases of parturient paresis in which tetany is a feature serum magnesium levels are low. These low levels are in many cases expressions of a seasonal hypomagnesemia.

Hypophosphatemia

Low serum phosphorus levels occur in milk fever and contribute to the clinical signs. Some cases of milk fever may not respond to calcium injectins even though the serum calcium levels return to normal but may appear to recover when the udder is inflated and serum phosphorus levels rise. Field observations indicate sodium acid phosphate given orally or IV may result in recovery of cases not responding initially to calcium salts. However, it is difficult to reconcile the biochemical and clinical findings with low serum phosphorus levels because of the absence of recumbency in other animals with profound hypophosphatemia for long periods. A possible explanation is that the hypophosphatemia which occurs in milk fever is secondary to the hypocalcemia and recumbency rather than being a concurrent event. There is experimental evidence to support this and it also seems probable that the hypophosphatemia could prolong the duration of recumbency.

Cattle

Three stages of milk fever in cattle are commonly recognized and described.

Sheep and goats

The disease in pastured ewes is similar to that in cattle. The early signs include a stilty, proppy gait and tremor of the shoulder muscles. Recumbency follows, sometimes with tetany of the limbs but the proportion of ewes with hypocalcemia which are recumbent in the early stages is much less than in cattle. A similar generalization applies to female goats. The characteristic posture is sternal recumbency, with the legs under the body or stretched out behind. The head is rested on the ground, there may be an accumulation of mucus exudate in the nostrils. The venous blood pressure is low and the pulse impalpable. Mental depression is evidenced by a drowsy appearance and depression of the corneal reflex. There is loss of anal reflex, constipation, tachycardia, hyposensitivity, ruminal stasis and tympany, salivation and tachypnea.²² Response to parenteral treatment with calcium salts is rapid, the ewe is normal 30 min after a SC injection. Death often occurs within 6–12 h if treatment is not administered. The syndrome is usually more severe in pregnant than in lactating ewes, possibly because of the simultaneous occurrence of pregnancy toxemia or hypomagnesemia. Fat late pregnant ewes on high grain diets indoors or in feedlots show a similar syndrome accompanied by prolapses of the vagina and intestine.

Pigs

As in cattle, signs develop within a few hours of farrowing. There is restlessness, a normal temperature and anorexia followed by inability to rise and later lateral recumbency and coma. Milk flow is decreased.

Metabolic diseases

Hypomagnesemia may occur as the sole cause of recumbency or it may accompany a primary hypocalcemia so that the case presented is one of parturient paresis complicated by lactation tetany. Hyperesthesia, tetany, tachycardia, and convulsions are common instead of the typical findings of depression and paresis in milk fever.

Hypophosphatemia, which commonly accompanies milk fever, is suggested as a cause of continued recumbency in cows after partial response to calcium therapy; serum inorganic phosphorus levels are low and return to normal if the cow stands or following treatment with phosphate salts. A sudden onset of recumbency in dairy cows associated with a marginal deficiency of phosphorus has been reported.²⁴

Hypokalemia in dairy cows is characterized by extreme weakness or recumbency, especially after treatment for ketosis with isoflupredone. Hypokalemia is marked as ranging from 1.4 to 2.3 mEq/L. The case-fatality rate is high in spite of therapy with potassium. Hypokalemic myopathy is present at necropsy.

Ketosis may complicate milk fever, in which case the animal responds to calcium therapy by standing but continues to manifest the clinical signs of ketosis, including in some cases the nervous signs of licking, circling, and abnormal voice.

Diseases associated with toxemia and shock

During the immediate postparturient period, several diseases occur commonly and are characterized by toxemia.

Peracute coliform mastitis is characterized by:

Aspiration pneumonia secondary to regurgitation and aspiration of rumen contents may occur as a complication of thirdstage milk fever. Fever, dyspnea, expiratory grunt, severe depression and anxiety are common. Auscultation of the lungs reveals the presence of abnormal lung sounds. Aspiration pneumonia should be suspected if the animal has been lying on its side, especially if there is evidence of regurgitation of ruminal contents from the nostrils, no matter how small the amount, or if there is a history of the animal having been drenched. Abnormal auscultatory findings may not be detectable until the second day. Early diagnosis is imperative if the animal is to be saved and the mortality rate is always high.

Acute diffuse peritonitis resulting from traumatic perforation of the reticulum or uterus is characterized by:

Carbohydrate engorgement results in:

Many cases resemble second-stage milk fever.

Toxemic septic metritis occurs most commonly within a few days after parturition and is characterized by:

The fetal placenta may be retained. Some affected cows are weak and prefer recumbency, which resembles milk fever. Prolapse and rupture of uterus causes varying degrees of:

A history of difficult parturition or assisted dystocia with fetotomy may be associated with rupture of the uterus. The administration of calcium salts may cause ventricular fibrillation and sudden death.

Although some elevation of the temperature may be observed in these severe toxemic states, it is more usual to find a subnormal temperature. The response to calcium therapy is usually a marked increase in heart rate and death during the injection is common. Every case of recumbency must be carefully examined as these conditions may occur either independently or as complications of parturient paresis. In our experience, about 25% of cases of postparturient recumbency in cows are due primarily to toxemia or injury rather than to hypocalcemia.

Injuries to the pelvis and pelvic limbs

Injuries to the pelvis and pelvic limbs are common at parturition because of the marked relaxation of the ligaments of the pelvic girdle. Seven types of leg abnormality have been described in this group at an incidence level of 8.5% in 400 consecutive cases of parturient paresis. The abnormalities included radial paralysis, dislocation of the hips and rupture of gastrocnemius muscle. In most instances the affected animals are down and unable to stand but they eat, drink, urinate and defecate normally, have a normal temperature and heart rate and make strong efforts to stand, particularly with the forelimbs.

Maternal obstetrical paralysis is the most common injury. Although this occurs most frequently in heifers after a difficult parturition, it may also occur in adult animals following an easy birth and occasionally before parturition, especially in cows in poor body condition. The mildest form is evidenced by a frequent kicking movement of a hindleg, as though something was stuck between the claws. All degrees of severity from this, through knuckling and weakness of one or both hindlegs, to complete inability to rise may occur, but sensation in the affected limb is usually normal. There is traumatic injury to the pelvic nerves during passage of the calf. There are often gross hemorrhages, both deep and superficial and histopathological degeneration of the sciatic nerves. In individual animals, injury to the obturator nerves is common and results in defective adduction of the hindlimbs. The position of the hindlimbs may be normal but in severe cases, especially those with extensive hematoma along the sciatic nerve trunk, the leg may be held extended with the toe reaching the elbow as in dislocation of the hip; however in the latter case there is exaggerated lateral mobility of the limb. Additional injuries causing recumbency near parturition include those associated with degenerative myopathy, dislocation of the hip and ventral hernia.

Dislocation of the coxofemoral joint can cause recumbency and inability to stand in some cows, while others can stand and move around. Recumbent cows are usually in sternal recumbency and the affected limb is abducted excessively. In standing cows, the affected limb is usually extended, often difficult to flex and often rotated about its long axis. The diagnostic criteria are:

Manual replacement by closed reduction is successful in 80% of craniodorsal dislocation and 65% in caudodorsal dislocation. The ability to stand before reduction is the most useful prognostic aid.

Degenerative myopathy (ischemic muscle necrosis)

Degenerative myopathy affecting primarily the large muscles of the thighs, occurs commonly in cattle which have been recumbent for more than several hours. At necropsy, large masses of pale muscle are present surrounded by muscle of normal color. Clinically it is indistinguishable from sciatic nerve paralysis. Markedly increased serum levels of CPK occur in cows recumbent for several hours following the initial episode of milk fever due to ischemic necrosis. Persistent elevation of CPK indicates progressive ischemic muscle necrosis due to continued compression of large muscle masses of the pelvic limbs. Rupture of the gastrocnemius muscle or separation of its tendon from either the muscle or the tuber calcis may also cause myopathy.

Downer cow syndrome

Downer cow syndrome is a common sequel to milk fever in which the cow was in sternal recumbency for several hours before being treated with calcium. Following treatment, most of the clinical findings associated with milk fever resolved except the animal was unable to stand. Clinically, the animal may be normal except for recumbency and will commonly recover and stand normally within several hours or a few days. Most downer cows eat and drink normally, their vital signs are within the normal range and their alimentary tract function is normal. However, some are anorexic, may not drink, exhibit bizarre movements of lying in lateral recumbency, and dorsally extend their head and neck frequently, moan and groan frequently, assume a frog-legged posture with their pelvic limbs and crawl or creep around the stall and may die or are euthanized for humane reasons in a few days. The diagnostic dilemma with these cows is that they resemble milk fever and whether or not to treat them with additional amounts of calcium salts is questionable.

Non-parturient hypocalcemia

Paresis with mental depression and associated with low total serum calcium levels can occur in cows at times other than at parturition. The cause is largely unexplained but the syndrome occurs rarely in animals other than ruminants. Hypocalcemia may occur after gorging on grain and may be a significant factor in particular cases. Sudden rumen stasis due to traumatic reticulitis may rarely cause hypocalcemic paresis. Diarrhea, particularly when cattle or sheep are placed on new lush pasture, may also precipitate an attack. Access to plants rich in oxalates may have a similar effect, particularly if the animals are unaccustomed to the plants. Affected animals respond well to calcium therapy but relapse is likely unless the primary cause is corrected. The differential diagnosis of diseases of non-parturient cows manifested principally by recumbency is also summarized in Table 29.5.

Hypocalcemic paresis in sheep and goats

Hypocalcemia in sheep must be differentiated from pregnancy toxemia in which the course is much longer, the signs indicate cerebral involvement and the disease is restricted to pregnant ewes. There is no response to calcium therapy and a positive test for ketonuria is almost diagnostic of the disease. At parturition, goats are susceptible to enterotoxemia and hypoglycemia (rarely), both of which present clinical signs similar to parturient paresis.

Hypocalcemia in sows

Hypocalcemia is rare in sows. The disease must be differentiated from the mastitis, metritis and agalactia complex, which is characterized by:

Treatment

Every effort should be made to treat affected cows as soon as possible after clinical signs are obvious. Treatment during the first stage of the disease, before the cow is recumbent, is the ideal situation. The longer the interval between the time the cow first becomes recumbent and treatment, the greater the incidence of the downer cow syndrome due to ischemic muscle necrosis from prolonged recumbency. Complications of milk fever occur when cows have been in sternal recumbency for more than 4 h. Farmers must be educated to appreciate the importance of early treatment. Cows found in lateral recumbency (third stage) should be placed in sternal recumbency until treatment is available. This will reduce the chances of aspiration if the cow regurgitates. Cows that have difficulty finding solid, non-slip footing beneath them, for example, a slippery barn floor or slippery mud, will often not try to stand and may develop ischemic myonecrosis. Avoidance of this complication necessitates the placement of rubber or other mats under the cow or transportation of the cow to a piece of pasture with a dense sward on it. A temperature of greater than 39°C (102°F) is an indication of a higher than average mortality rate due to pre-existing complications.

Standard treatment

Calcium borogluconate at 10–200 g is the treatment of choice. The solutions available vary from 18 to 40% calcium borogluconate. Most cows with milk fever can be treated successfully with 8–10 g of calcium (calcium borogluconate is 8.3% calcium). For cattle, 400–800 mL of a 25% solution is the usual dose. The dose rate of calcium is frequently under discussion. There is a general tendency for veterinarians to underdose with calcium salts, largely because of toxic effects which tend to occur when all of the calcium is given IV. As an initial dose a large cow (540–590 kg) requires 800–1000 mL of a 25% solution and a small cow (320–360 kg) 400–500 mL. Underdosing increases the chances of incomplete response, with inability of the cow to rise, or of relapse. In general, 12 g of calcium is superior to 8 g, which in turn is superior to 6 g.

The standard rate of administration is a rapid intravenous administration of the calculated dose of calcium borogluconate (often supplemented with phosphorus, magnesium, and glucose) over a period of 15 min. Hypercalcemia (up to 22 mg/dL) occurs following IV administration of calcium borogluconate over a period of 12–15 min. The plasma calcium concentration will gradually decline over a period of several hours by which time calcium homeostasis should begin to occur and levels return to normal by 12–24 h following treatment. However, in some cows calcium homeostasis is ineffective and subclinical or clinical hypocalcemia may recur.

Because up to 50% of cows may not respond to the initial rapid administration, it has been postulated that the increases in electrolytes are only transient and that slower IV infusion would be more effective.²⁵ The slow infusion of a calcium solution via an IV indwelling catheter over 6 h was compared with the conventional single IV administration of 600 mL of a 40% calcium borogluconate solution containing 18.78 g calcium gluconate and borogluconate with 6% magnesium hypophosphite (11.82 g magnesium hypophosphite) over 15 min in cows recumbent with milk fever.²⁵ Cows receiving the rapid infusion responded more quickly and stood sooner and their demeanor returned to normal more quickly. The slow infusion consisted of 200 mL IV over a 10 min period and the remaining 400 mL added to 10 L of a solution of 90 g sodium chloride and 500 g glucose and given via IV drip over a 6 h period at a rate of 1.7 L/h. In cows treated rapidly, the serum calcium and magnesium levels increased rapidly compared with the infused cows.²⁶ In both groups, the serum inorganic phosphorus increased slowly with the mean concentration reaching a maximum at 3 h and then decreasing slightly. Some cows are still hypophosphatemic several hours later.

In sheep and goats, the recommended amount is 15–20 g IV with an optional 5–10 g SC. Sows should receive 100–150 mL of a similar solution IV or SC.

Routes of administration

Typical response to calcium borogluconate

Cows with milk fever exhibit a typical pattern of response to calcium borogluconate IV if the response is favorable, including:

The feces are in the form of a firm fecal ball with a firm crust and covered with mucus, occasionally with a few flecks of blood. Urination usually does not follow until the cow stands. A slight transitory tetany of the limbs may also be observed. Many cows will eat and drink within minutes following successful treatment if offered feed and water.

The rate of response to treatment is affected by many factors as set out below and it is unwise to quote what might be expected as an acceptable rate of recovery after treatment. This is particularly true if cows are treated by the farmer and only difficult cases are presented to the veterinarian. In general, if all cases are considered and there are no exceptional circumstances, recovery can be expected immediately after treatment in about 60% of cases and in a further 15% after 2 h; 10% have recoveries complicated by one of the diseases discussed earlier and 15% can be expected either to die or to require disposal. Of those which recover after one treatment, 25–30% can be expected to relapse and require further treatment.

Unfavorable response to calcium borogluconate

An unfavorable response is characterized by a marked increase in heart rate in cows affected with toxemia and acute heart block in apparently normal animals especially with overdosage, with too rapid injection and in cases in which treatment has been unduly prolonged. In the latter, the maximum tolerated dose of calcium borogluconate by IV administration is about 250 mL of a 25% solution. Overdosage may occur when farmers treat cases unsuccessfully by multiple SC injections and these are followed by an IV dose. When the peripheral circulation is poor, it is probable that the calcium administered SC is not absorbed until the circulation improves following the IV injection and the large doses of calcium then absorbed cause acute toxicity. In all cases of IV injection, the circulation must be monitored closely. Some degree of arrhythmia occurs in most cases but if there is gross arrhythmia or a sudden increase in heart rate, the injection should be stopped temporarily or continued with great caution. In normal circumstances at least 10 min should be taken to administer the standard dose. The acute toxic effect of calcium salts seems to be exerted specifically on heart muscle with a great variety of defects occurring in cardiac action; the defect type depends on the specific calcium salt used and the speed of injection. ECG changes after induced hypercalcemia show increased ventricular activity and reduced atrial activity. Atropine is capable of abolishing the resulting arrhythmia.

Sudden death may also occur after calcium injections if the cow is excited or frightened, which may be due to an increased sensitivity to epinephrine. When affected cows are exposed to the sun or a hot, humid atmosphere, heatstroke may be a complicating factor. In such cases an attempt should be made to reduce the temperature to below 39.5°C (103°F) before the calcium is administered. The incidence of cardiac arrhythmia and other abnormalities as detected by ECG during treatment with calcium salts IV is so high that there are doubts expressed about the suitability of this form of treatment.

Chronic toxicity may also occur. In laboratory animals, severe uremia due to extensive calcium deposits in the kidney occur after the SC injection of calcium chloride and borogluconate and similar deposits are often seen at necropsy in cows dying after multiple injections of calcium salts administered at short intervals.

Failure to respond to treatment

A failure to respond favorably to treatment may be due to an incorrect or incomplete diagnosis, or inadequate treatment. A poor response to treatment includes: (1) no observable changes in the clinical findings immediately following the calcium administration or (2) the animal may respond to the calcium in all respects with the exception of being unable to stand for varying periods of time following treatment. An inadequate response also includes relapses after successful recovery, which usually occur within 48 h of the previous treatment. Relapses are more common in certain individual cows such as mature Jersey cows, which may experience as many as five or six episodes around one calving. Also, the incidence of relapse is much higher in cases which occur just before calving than in those which occur afterwards. The needs of individual animals for calcium replacement vary widely, depending on their body weight and the degree of hypocalcemia. Incomplete responses may be more common in older cows and may be associated with diminished skeletal reserves of calcium and inability of the normal mechanisms to maintain serum calcium levels during the period of excessive demands of lactation. The duration of the illness and the posture of the cow also affect the response. In an extensive field study, there were no downer cows or deaths in cows still standing when first treated, 13% of downers and 2% of deaths occurred in cows in sternal recumbency and 37% of downers and 12% of deaths occurred in cows in lateral recumbency when first treated.²⁸ Therefore, in general, the longer the period from onset of milk fever to treatment, the longer the period of post-treatment recumbency and the higher the case-fatality rate. In another study, 67% of cows recovered after a single treatment, 90% after two treatments, and 92–99% after three treatments. After routine treatment, 37% of cases rose unassisted within 10 min, 23% required some assistance, 26% recovered after longer periods of recumbency, and 14% died or were destroyed or sold for slaughter. The best procedure to follow if response does not occur is to revisit the animal at 12-hourly intervals and check the diagnosis. If no other cause of the recumbency can be determined, the initial treatment can be repeated on a maximum of three occasions. Beyond this point, further calcium therapy is seldom effective. A low body temperature, due probably to exposure to low environmental temperature and increased wind velocities, is positively correlated with a high proportion of deaths and poor responses.

At the second visit, solutions containing either phosphorus, magnesium, or dextrose may be administered, depending upon the clinical signs presented and the results of available biochemical tests. Glucose is usually administered as 500 mL of a 40% solution, sodium acid phosphate as 200 mL of a 15% solution, and magnesium sulfate as 200–400 mL of a 15% solution. Composite solutions containing calcium, magnesium, phosphorus and glucose are also in common use as initial treatments. There is controversy about these socalled ‘polypharmacy’ preparations. They have no advantage, but are likely to remain popular when milk fever cases are complicated by metabolic disorders other than hypocalcemia. They have no effect on the relapse rate when compared with calcium salts alone.

Udder insufflation

Insufflation of the udder with air was an alternative treatment for cows which continued to relapse following repeated calcium injections. With the availability and effectiveness of orally administered calcium gels, udder insufflation cannot be recommended.

Dietary management during prepartum period

For purposes of optimal nutritional management of dairy cows which are fed prepared feeds (not pasture-based), the dry period is divided into at least two distinct categories – cows in the early and middle portion of the dry period (far-off or regular dry cow group) and cows in the final 3 weeks prior to their calving date (pre-fresh, transition, close-up, near, lead feeding, or steam-up group).³¹ Large herds may have additional subgroups of dry cows depending on management circumstances and facilities available. Special attention must be given to the mineral nutrition of the close-up group. Minerals should be provided to close-up cows in known quantities, either as part of a grain mixture or total mixed ration (TMR).

Acidifying rations in the prepartum diet: Cation–anion difference (DCAD)

A more reliable method of controlling milk fever in dairy cows when the calcium intake exceeds NRC requirements is to manipulate the dietary cation–anion difference (DCAD) during the prepartum period.^11,40 Diets high in cations, especially sodium and potassium, tend to induce milk fever compared with those high in anions, primarily chloride and sulfur, which can reduce the incidence. Because most legumes and grasses are high in potassium, many of the commonly used prepartum diets are alkaline resulting in metabolic alkalosis. The feeding of diets which are high in ratio of calcium to phosphorus and containing an excess of anions relative to cations will result in mild metabolic acidosis completely compensated by nonrespiratory mechanisms (decreased blood bicarbonate and base excess: Pco₂ and pH are unaffected).⁴¹ There is increased concentration of serum calcium due to an increase in the intestinal absorption of calcium. Two parathyroid hormone (PTH) dependent functions, bone resorption, and renal production of 1,25-dihydroxyvitamin D, are enhanced in cows fed diets with added anions which increase their resistance to milk fever and hypocalcemia.¹¹

The DCAD is expressed using the equation DCAD in mEq/kg DM = (Na + K) – (Cl + S). The equation does not include other dietary cations and anions such as Ca², Mg², and PO₄ which have a minor role. Most studies indicate that a DCAD of – 50 to 100 mEq/kg DM is optimal for the prevention of milk fever.¹ Supplementation of diets in the last 3 weeks prepartum with anionic salts at a rate sufficient to decrease DCAD to –15 mEq/100 g of dietary DM and urine pH to 6.0 prevented most cases of parturient hypocalcemia.⁴² Except for cows pregnant with twins, that rate of supplementation did not affect DM intake and energy balance. A moderate rate of supplementation to reduce the DCAD to 0 mEq/100 g dietary DM and urine pH to 7.3 also did not decrease feed intake or energy status but was less effective in preventing parturient hypocalcemia. Monitoring urine pH can be a useful aid to find the effective intermediate inclusion rate and it is suggested that a urine pH of about 6.5 is ideal.⁴² Commercial anionic products fed to non-lactating dairy cows in a total mixed ration, after 4 days reduced urine pH below the desired threshold of 6.5.⁴³

The equation assigns the same acidification potency to each mEq of Cl and SO₄, but Cl is absorbed to a greater extent than SO₄. Calculation of the DCAD of a diet requires use of the equivalent weights of the electrolytes. The equivalent weight is equal to the molecular weight divided by the valence. A milliequivalent (mEq) is used to express equivalent weights: 1 mEq equals 1/1000 of an equivalent. Table 29.6 provides reference values for calculating equivalent weights of important electrolytes and converting from percent diet dry matter (DM) to mEq/kg. Once mEq are calculated, the DCAD can then be determined by subtracting the anions from the cations.³¹

Table 29.6 Molecular weights, equivalent weights, and conversions from percent to milliequivalents (%–mEq) of anions and cations used in calculating dietary cation–anion difference

The DCAD is calculated from the percent element in the diet dry matter. The equation is as follows: mEq/100 g DM = [(% Na ÷ 0.023) + (% K ÷ 0.039)] – [(% Cl ÷ 0.0355) + (% S ÷ 0.016)]. Based on current evidence, the range which achieves the lowest incidence of milk fever is a DCAD of – 10 to – 15 mEq/100 g DM or – 100 to 150 mEq/kg DM.

Most typical diets fed to dry cows have DCADs of about 100–250 mEq/kg DM. Addition of a cationic salt such as sodium bicarbonate to the dry cow diets increases the DCAD and increases the incidence rate of milk fever. Adding an anion source or a mixture of anionic salts containing Cl and S relative to Na and K to the diet lowers the DCAD and reduces the incidence of milk fever. Commonly used sources of anion salts include the Cl and SO₄ salts of calcium, ammonium and magnesium. The phosphate salts have not been used because they are only weakly acidifying.

The addition of anions to the diet to reduce dietary DCAD is limited because of problems with palatability of the anionic salt sources commonly used. If the diet DCAD is >250 mEq/kg, it is difficult to add enough anionic salts to lower the DCAD to the recommended –100 mEq/kg of the diet without affecting palatability.

In one study, the incidence of milk fever was 47% when prepartum cows were fed a ration with a DCAD of +330.5 mEq/kg dietary DM and 0% when the prepartum ration had a balance of –128.5 mEq/kg dietary DM.⁴⁰ The incidence of milk fever was reduced by the addition of chloride and sulfur in excess relative to sodium and potassium in the diet.⁴⁰ Because anions are considered acidogenic and cations alkylogenic, an excess of acid-forming elements in periods of calcium stress will increase the concentration of calcium in the blood, either by intestinal absorption or bone mobilization.³¹ Cows fed prepartum diets containing alfalfa haylage with added chlorides of magnesium, ammonia, and calcium tended to have higher plasma calcium concentrations of calcium and a lower incidence of milk fever than did cows fed either of two cationic diets. Plasma hydroxyproline, an index of bone resorption, also increases prior to parturition in cows fed a high anion diet. The plasma levels of 1,25-(OH)₂D also increase prior to parturition in cows fed a high anion diet, which increases calcium absorption and bone resorption.³¹ Feeding rations with reduced mEq of dietary ([Na⁺ + K⁺] – [CI⁻ + SO₄=]) to – 4 mEq/kg dietary DM to dry cows significantly affected some of the parameters of bone formation but did not enhance the rate of bone resorption. Feeding acid diets to pregnant cows during the last 28 days of pregnancy increased the mobilization of calcium by 13% 14 days before parturition and 28% by the time of parturition, whereas it had declined by 14% at 14 days before parturition in alkali-fed cows. The increased concentrations of 1,25-(OH)₂D were responsible for the stimulation of both intestinal calcium absorption and bone resorption, which helped to prevent severe parturient hypocalcemia.

Anion salts for acidification of prepartum diets for dairy cows

Several anion salts are available for addition to the ration of prepartum dairy cows to prevent milk fever.⁴⁴ Generally, acidification of the cows occurs in approximately 36 h following addition of the anionic salts to the ration; it also takes less than 36 h for the cow to return to an alkaline state following removal of the salts from the diet. The relative acidifying activity of anionic salts commonly used to prevent milk fever has been evaluated.⁴⁴ Salts of chloride have about 1.6 times the acidifying activity of sulfate. Calcium and magnesium, which are usually not included in the DCAD equation, have a small but significant alkalinizing effect when accompanied by chloride or sulfate. The ranking of the anion sources tested at a dose of 2 Eq/day, from most to least potent urine acidifier was hydrochloric acid, ammonium chloride, calcium chloride, calcium sulfate, magnesium sulfate, and sulfur. Magnesium sulfate is the most palatable of the anionic salts commonly supplemented and calcium chloride is the least palatable. Sulfates are poor acidifiers and should be limited in use. It is best to add the anionic salts to a total mixed ration. Because of the low incidence of milk fever in heifers there is no need to feed anionic salts to heifers.⁴²

Anionic salts can reduce dry matter intake when more than 300 mEq of anions/kg diet DM are supplemented in the diet.³¹ The reductions in dry matter intake are commonly ascribed to decreased palatability but may represent a response to the metabolic acidosis induced by the salts.⁴¹ The duration of feeding anion salts ranges from 21 to 45 days before expected parturition. At least 5 days of consumption are necessary for maximal benefit.

Ammonium chloride.

Ammonium chloride is more effective than most other salts as an acidifier. The addition of ammonium chloride salts to prepartum diets offers considerable promise as a practical and reliable method of control of milk fever. Experimentally, the addition of ammonium chloride and ammonium sulfate, each at 100 g/head per day, to the prepartum diets 21 days prior to parturition, decreased the incidence of milk fever from 17% in the unsupplemented group to 4% in the supplemented group.

The advantages of ammonium salts are that they:

• Do not require the use of diets low in calcium

• Are relatively inexpensive

• Are convenient to use

• Are safe to feed.

Strategies for supplementing anion sources

A systematic protocol for the addition of anions to a prepartum diet and monitoring its effects is as follows:

1. Macromineral analysis of all available forages for prepartum cows.

2. Select feed ingredients with a low DCAD especially those low in potassium.

3. Calculate the DCAD of the diet without any supplemental anion sources. If the DCAD is more than 250 mEq/kg, then it is too high. Replace some of the forage with a lower DCAD forage.

4. Balance dietary magnesium at 0.40%, DM by adding additional magnesium chloride or magnesium sulfate. Magnesium chloride is preferred.

5. Evaluate the feeding management of the prepartum cows. Ensure adequate feeding space and quality of feed.

6. Add supplemental chloride to the prepartum cow diet to lower DCAD to about –150 mEq/kg DM.

7. Evaluate dietary non-protein nitrogen (NPN) and degradable intake protein (DIP) of the diet. If NPN is more than 0.50% of the diet DM or DIP is more than 70% of crude protein, then reduce the amount of ammonium salts or other NPN or DIP sources in the diet.

8. Elevate the dietary calcium to 1.5–1.8% DM or provide daily intake of about 150 g/head per day. Negative DCAD diets increase urinary calcium excretion and thus more dietary calcium is necessary to meet requirements.

9. Monitor dry matter intake of the prepartum cow group. Consider more palatable anion sources or a reduced dose of anion sources if dry matter intake is depressed. Low dry matter intakes in prepartum cows increases the risk for fatty liver and ketosis after calving.

10. After 1 week of feeding anionic salts, monitor the pH of close-up dry cows. Urinary pH is an accurate indication of optimal dietary acidification. Collect urine from at least six cows at one time and average the urinary results. Adjust the dose of supplemental anions to achieve an average urinary pH of between 6.0 and 7.0.

DCAD and acid–base balance of dairy cows on pasture-based diets

The literature on the nutritional strategies for the prevention of hypocalcemia for dairy cows in pasture-based systems has been reviewed.⁶ The dairy industries of southern Australia and New Zealand are based largely on fresh pasture and pasture silage and grazed pasture is the key determinant of the DCAD. The concentration of potassium is often in excess of 4% and the DCAD >500 mEq/kg DM, in pasture-based diets yet the incidence risk of milk fever is not higher than those in other countries where dietary potassium is much lower. For a considerable part of spring and early summer, the DCAD of pasture in those countries may be in excess of +500–700 mEq/kg DM.^5,29 The variation in the DCAD of pasture and the difficulty in accurately assessing dry matter intake makes an accurate reduction in DCAD difficult to achieve practically.^5,45 Pasture cation–anion difference in those conditions is not greatly influenced by stocking rate or associated management practices. The urine pH of grazing dairy cows in south-eastern Australia remains relatively constant throughout the year despite changes in stage of lactation, management practices, season, weather, and large changes in DCAD. It appears that a very low DCAD (< + 150 mEq/kg DM is required to alter systemic pH substantially. The DCAD of pasture throughout the year in south-eastern Australia ranges from 0 to 800 mEq/kg DM and is often outside the levels previously recommended for optimal performance of lactating cows. A high DCAD at the time of parturition, for spring-calving herds on pasture, presents practical problems in administering the large amounts of anionic salts required to lower urine pH and to decrease the incidence of hypocalcemia.^5,29

The dietary cation–anion difference and the health and production of pasture-fed dairy cows in early lactation in southeastern Australia has been examined in an indoor feeding experiment.⁴⁶ The dairy industry there is largely perennial ryegrass-based and supplemented with cereal grains, pasture hay, and pasture silage. The DCAD can range from 0 to + 76 mEq/100 g. Blood pH and urine pH are reduced when a low DCAD ration is fed, but there is a threshold level, between + 52 and + 102 mEq/100 g, above which little change in systemic pH occurs.⁴⁶ As DCAD increased from + 21 to +127 mEq/100 g, DMI intake and milk yield decreased. In nonlactating periparturient cows fed freshly cut pasture supplemented with varying levels of salts to alter the DCAD which ranged from – 12 to + 69 mEq/100 g.⁴⁷ With decreasing DCAD, the pH of the blood and urine decreased resulting in a nonrespiratory systemic acidosis. When the DCAD was negative, the urinary output of calcium increased. No differences in milk production due to alteration of the DCAD. Due to the high DCAD in the base diet offered to pasture-fed dairy cows and the requirement for a negative DCAD to increase calcium absorption, it is unlikely that the DCAD concept is a practical means of preventing milk fever in pasture-fed cows.

In these pasture-based systems, sulfur (S) is considered a more important dietary constituent in determining the risk of hypocalcemia than either chloride or potassium.⁴⁵ The absorption efficiency of S is less than either Cl or K and would not be expected to incur the same change in systemic pH. Thus its importance in hypocalcemia prevention, does not fit with the current understanding of how manipulation of DCAD influences calcium homeostasis. Studies indicate that pre-calving dietary S is more important in the control of hypocalcemia than either K or Cl concentration. Although the effects of a systemic acidosis on Ca absorption is accepted, the effect of S on periparturient Ca homeostasis when absorption of S is low in comparison to Cl, Na, or K suggest that there are mechanisms involved that are not related to acid-base balance. Dietary S concentration was more important in the control of hypocalcemia than either dietary K or Cl concentration.

An increased incidence of milk fever may occur in pastured-based dairy when the diet is supplemented with Cl and S, even though calcium absorption, as indicated by urine calcium concentration increases. The increased incidence may be due to a greater demand for dietary calcium after calving following a reduction in the pH of body fluids pre-calving and the fact that pasture-based diets, as opposed to total mixed rations, are generally low in calcium. Supplementation of cows with calcium after calving increased plasma calcium concentration on the day of calving and during the subsequent 14 days.⁴⁸ Milk production was not affected by pre- or post-calving treatments.

Experimentally, the application of potassium fertilizer on pasture resulted in a DCAD ranging from 350 to 535 mEq/kg DM but calcium homeostasis in pasture-based dairy cows was not changed.⁴⁵ Plasma concentrations were increased and the risk of clinical periparturient hypocalcemia was reduced by MgCl₂ and MgSO₄ delivered by 150 g MgCl₂, 200 g MgSO₄, and 35 g MgO/head daily for 21 days prepartum.⁴⁵ After calving cows were supplemented with 150 g CaCO₃/head per day for 4 days. Improvements in calcium homeostasis were not due to an altered systemic pH.

The optimum DCAD for lactating cows grazing fresh pasture and the effect of deviating from the optimum on milk production has been examined under experimental manipulating the dietary DCAD using a drench in early-lactation dairy cows in New Zealand.⁴⁹ Dietary cation-anion differences ranged from + 23 to + 88 mEq/100 g of DM. As DCAD increased, there was a linear increase in blood pH and HCO₃ concentration and blood base excess. Plasma concentrations of Mg, K, Cl declined as DCAD increased and Na increased. Urinary excretion of Ca decreased as DCAD increased. Increasing DCAD did not significantly affect milk yield or milk protein but the concentration and yield of milk fat increased linearly. Milk production results suggest that DCAD for optimal production on pasture diets may be higher than the +20 mEq/100 g DM previously identified for total mixed rations.

Summary of macromineral nutritional strategies for the prevention of hypocalcemia in the soon-to-calve, or transition dairy cow in pasture-based systems. (Transition period is defined as 3–4 weeks prepartum and 3–4 weeks postpartum)

Circumstances and principles:

• When dairy cows are dried off, they are commonly moved onto nonirrigated pastures until calving. In the summer, dry cows would be put onto actively growing tropical pasture, whereas in autumn, winter and spring, the pasture is most likely to be tropical pasture carried over from the previous summer. This carryover pasture is likely to be supplemented with medium quality hay, silage and grain or molasses 2–3 weeks before calving. Anionic salts have been added to these diets

• The DCAD on a yearly basis ranges from 0 to 80 mEq/100 g DM⁵

• The incidence of milk fever in Australia ranges from 1.6 to 5.4% but in some years, the incidence in individual herds may reach 20%. The incidence of subclinical hypocalcemia can range widely; up to 40% of apparently normal cows had subclinical hypocalcemia (total plasma calcium <1.9 mmol/L during the first 12 days of lactation)

• The concentration of ionized calcium in blood plasma is under elaborate homeostatic control. This provides for the maintenance of a pool of readily available calcium which can be drawn on for the deposition of maternal and fetal bone and for colostrum and milk

• The traditional method of preventing hypocalcemia has been to restrict calcium intake during the dry period which stimulates renal synthesis of 1,25-dihydroxyvitamin D₃ prior to calving. The cow must be in negative calcium balance

• In temperate climates, reducing dietary calcium to recommended low levels can be difficult to achieve but in tropical pastures the levels are already low

• Excessive levels of potassium may be the most important dietary risk factor for milk fever in Australian feeding systems. Potassium contents of pastures may be as high as 4–5% of DM. The use of potassium fertilizers exacerbates the problem. Potassium and dietary DCAD peak in winter and are lowest in autumn. The majority of cows in Victoria, Australia, calve in winter to early spring when the potassium levels are high. Excess potassium results in alkalosis which reduces the sensitivity of bone and renal tissue to PTH

• Hypomagnesemia influences calcium homeostasis and diets high in potassium reduce the concentration of plasma magnesium. Magnesium supplementation of the transition diet should be done to ensure that magnesium requirements are met (0.2–0.4% of DMI)

• Excessive dietary phosphorus increases the concentration of phosphorus in plasma which can induce hypocalcemia and increase the incidence of milk fever at calving. Supplements likely to increase the dietary intake of phosphorus above 35 g/day should not be fed to cows in the weeks prior to calving

• Excessive intakes of sodium can contribute to the development of metabolic alkalosis and should be avoided.

Options for reducing the risk of hypocalcemia in pasture-fed dairy cows:

Low calcium intake prepartum.

A low calcium diet in the prepartum period will activate calcium homeostasis at calving. An alternative is to feed calcium binding agents for 1–3 weeks prepartum.

Magnesium supplementation.

Hypomagnesemia influences calcium homeostasis, potentially predisposing the cow to milk fever at calving. Diets high in potassium can reduce the concentration of plasma magnesium and may be a mechanism linking high dietary potassium to hypocalcemia. Recommended concentrations for dietary magnesium levels are within the range of 0.2–0.4% of total DM intake. Plasma levels are readily elevated when magnesium is added to the diet.

Calcium supplementation.

Oral administration of gels of calcium chloride or calcium propionate immediately after calving is effective in preventing milk fever. Feeding cows an excess of calcium in the form of calcium carbonate during the first few weeks of lactation is beneficial. Increasing dietary concentration of calcium from 0.68% to 1.02% DM within 8 h of calving has an immediate effect on plasma calcium.⁶

Manipulating dietary DCAD with anion feeds

The concept of manipulating the DCAD to reduce hypocalcemia under North American and European circumstances is well documented.⁶ Addition of anionic salts to the diet of transition dry cows to achieve a metabolic acidosis improves the ability of the cow to mobilize calcium at parturition. The pH of both blood and urine consistently fall in response to an appropriate decline in dietary cation excess. For the transition dry cow, the DCAD must fall to between – 10 and – 15 mEq/100 g DM to prevent milk fever.

In pasture-fed systems, such as in Australia and New Zealand, the pasture diets are high in DCAD (+ 50 mEq/100 g DM). The more positive the pasture DCAD, the more difficult it is to balance it with anionic salts. Because anionic preparations are relatively unpalatable, cows will not eat enough for total DCAD to fall below 0 mEq/100 g DM.

An alternative to anionic salts is to select feedstuffs with low to moderate DCAD. Lower quality hays and straws have a lower DCAD than high quality forages. However, the feedstuffs must be analyzed before making such a recommendation. Lower quality roughages are also low in calcium. Concentrates with high negative DCAD include molasses and brewer’s grain. Molasses is high in potassium but also high in sulfur.

Measurement of urine pH as a method of monitoring the efficacy of DCAD manipulations and its on-farm use should be encouraged. Urine pH is unlikely to fall to any degree until DCAD of the diet drops below approximately 10–20 mEq/100 g DM. For protection against milk fever, the urine pH needs to be maintained between 5.5 and 6.2 in the last weeks before calving.¹ This could be reduced to a cut-off in the range of pH 6.5–7.0.^13,31

General management practices

The following management practices are suggested: