[Etiology, therapy and prophylaxis of bovine parturient paresis (hypocalcaemia)]. / Wesen, Ursachen, Therapie und Prophylaxe der hypokalzämischen Gebärparese beim Rind.

Due to the sudden increase of calcium demand at the onset of lactation many high yielding dairy cows experience a certain level of hypocalcaemia following parturition. The incidence of hypocalcaemia (parturient paresis) increases with age but also depends on many other factors such as the acid-base status and the availability of calcium as well as other minerals and trace elements. Hypocalcaemia can easily be treated by supplementation of calcium parenterally or orally, nonetheless, prophylaxis of the condition should be the main focus in modern dairy farming, in order to avoid its negative effects. Oral administration of calcium around parturition is the simplest way of prophylaxis, but results in a high work load and requires exact knowledge of the date of parturition. The latter also applies for the parenteral administration of vitamin D3, which should be injected 1 week before parturition. Additionally, repeated treatment with vitamin D increases the risk for calcinosis. Reducing the calcium concentration of the ration fed during the late dry period also decreases the risk for hypocalcaemia by activating the mechanisms for calcium homeostasis within the body. The induction of a mild (compensated) metabolic acidosis to increase the sensitivity of parathormone receptors and enhance intestinal calcium uptake may also be employed to prevent milk fever. For this purpose, a DCAD (dietary cation anion difference) diet is fed during the late dry period, in which the concentrations of strong cations (potassium and sodium) as well as strong anions (sulfate and chloride) are altered. This may either be achieved by reducing the potassium concentration (partial-DCAD) or by adding anionic salts (full-DCAD). This method, especially the full-DCAD variant, requires a substantial level of surveillance and monitoring. Suitable prophylactic measures for the prevention of hypocalcaemia must be chosen individually for each farm, depending on the incidence of hypocalcaemia as well as personnel and structural resources.

Risk factors associated with milk fever occurrence in grazing dairy cattle.

The aim of this study was to determine risk factors associated with milk fever (MF) occurrence in Costa Rican grazing dairy cattle. A total of 69,870 cows from 126 dairy herds were included in the study. Data were collected in the Veterinary Automated Management and Production Control Program software by the Population Medicine Research Program of the Veterinary Medicine School, National University of Costa Rica, from 1985 to 2014. To determine the risk factors for MF, 2 logistic regression mixed models were evaluated. The first model used breed, month of calving, ecological life zone, herd nested within ecological life zone, and parity as fixed effects. The second model excluded first-lactation animals and cows without production information, had the same fixed effects of the first model, and added previous MF case, previous lactation length, previous dry period length, previous corrected 305-d milk yield, and calving interval length as fixed effects. Both models used animal and year as random effects. Of the 235,971 recorded lactations, 4,312 (1.83%) reported MF event. The significantly associated risk factors for MF occurrence, ranked by their highest odds ratio (OR), were parity (OR = 52.59), previous dry period length (OR = 4.21), ecological life zone (OR = 3.20), breed (OR = 3.04), previous corrected 305-d milk yield (OR = 2.39), previous MF case (OR = 2.35), and month of calving (OR = 1.36). The findings of this study are the first data reported using an epidemiological approach to study risk factors for MF in Costa Rican dairy cattle. Some of these results might be used to improve preventive management practices at the farms to reduce the incidence of this metabolic disease in grazing dairy herds.

The association of subclinical hypocalcemia, negative energy balance and disease with bodyweight change during the first 30 days post-partum in dairy cows milked with automatic milking systems.

In a prospective cohort study, the daily bodyweight (BW) and milk production of 92 cows were recorded using automatic milking systems. The objectives were to characterize calcium serum concentration variability on days 1-3 post-partum and to evaluate the association between subclinical hypocalcemia (SHPC) and change in BW over the first 30 days in milk (DIM) in Holstein dairy cows, while controlling for concurrent disease and negative energy balance (NEB). SHPC was defined as total serum calcium concentration between 6 and 8 mg/dL, NEB was defined as non-esterified fatty acids (NEFA) > 0.7 mEq/L or ß-hydroxybutyrate (BHB) ≥ 1.2 mmol/L. The peak incidence of SHPC was at 1 DIM for all groups (11%, 42% and 60% for parities 1, 2, and ≥3, respectively). All parity groups lost weight (21, 33, and 34 kg) during the first 30 DIM. Parity 1 animals with disease compared with those without disease lost the most weight (2.6 kg/day BW loss vs. <1.9 kg/day, respectively). Normocalcemic parity 2 animals with either NEB or disease lost the most weight (>5 kg/day) compared with those in the SHPC group (≤4.5 kg/day). In parity ≥ 3 animals, SHPC was an important factor for BW loss; SHPC animals lost the most weight (>3.7 kg/day) vs. normocalcemic cows (≤3.3 kg/day) regardless of NEB or disease status. Even though all animals lost weight during early lactation the effect of disease, NEB, and SHPC on BW loss was different in each parity group.

Diet-induced pseudohypoparathyroidism: A hypocalcemia and milk fever risk factor.

Subclinical hypocalcemia may affect half of all multiparous cows, and clinical hypocalcemia or milk fever affects approximately 5% of dairy cows each year. This disorder of calcium homeostasis can be induced by several dietary factors. Recent studies implicate high dietary potassium and high dietary cation-anion difference (DCAD) with increased risk of milk fever. The hypothesis tested in this study was that high-DCAD diets fed to prepartum cows reduce tissue sensitivity to parathyroid hormone (PTH), inducing a pseudohypoparathyroid state that diminishes calcium homeostatic responses. Multiparous Jersey cows were fed low- or high-DCAD diets in late gestation, creating a compensated metabolic alkalosis in the high-DCAD cows and a compensated metabolic acidosis in the low-DCAD cows. They then received synthetic PTH injections at 3-h intervals for 48 h. Parathyroid hormone is expected to cause an increase in plasma calcium by increasing renal production of 1,25-dihydroxyvitamin D and increasing bone calcium resorption. Plasma calcium concentration increased at a significantly lower rate in cows fed the high-DCAD diet. Cows fed the high-DCAD diet also produced significantly less 1,25-dihydroxyvitamin D in response to the PTH injections than cows fed the low-DCAD diet. Serum concentrations of the bone resorption marker carboxyterminal telopeptide of type I collagen were numerically lower in cows fed the high-DCAD diet but this difference was not statistically significant. These data provide direct evidence that high-DCAD diets reduce tissue sensitivity to PTH. The metabolic alkalosis associated with high-DCAD diets likely induces a state of pseudohypoparathyroidism in some dairy cows at the onset of lactation, resulting in hypocalcemia and milk fever.

Relationship between incidence of milk fever and feeding of minerals during the last 3 weeks of gestation.

This study evaluated whether differences in milk fever incidence among Swedish dairy herds could be explained partly by differences in mineral feeding during the last weeks of gestation. A case-control study was performed on dietary risk factors for a high incidence of milk fever at the herd level using information regarding feeding and management of the dry cows collected in a written questionnaire distributed by post in spring 2008. The study was conducted from September 2004 to August 2007. Data on the diets fed to dry cows, with an emphasis on the amounts of minerals (Ca, P, Mg and K) fed 3 weeks before calving and at calving, were obtained from 30 herds belonging to the 100 Swedish herds with the highest recorded incidence of veterinary treatment for milk fever (>8.8%) and from 22 herds with no recorded milk fever treatments. Multivariable logistic regression analysis showed that a linear increase in the total amount of K and less than 26 g of Mg/day fed to dry cows 3 weeks before calving was associated with an increased risk of high milk fever incidence. A large increase in the amount of dry matter (DM) fed (>3.1 kg DM extra per day at calving compared with 3 weeks before calving) was associated with a higher incidence of milk fever, but no differences were found for Ca or P intake. Breed composition, herd average milk yield and age composition of the herd did not explain any of the observed differences between the case and the control herds. The results indicate that differences in the frequency of milk fever among herds can be associated with differences in mineral feeding of the dry cows. A high amount of K in the diet may increase the risk of milk fever linearly, whereas Mg should probably be fed at a higher level than the current Nordic recommendation to prevent milk fever.

Milk fever in dairy cows: a review of pathophysiology and control principles.

The periparturient or transition period of 4 weeks before and 4 weeks after calving is characterised by a greatly increased risk of disease. Hypocalcaemia around calving is a risk factor for many of these diseases and is an indirect risk factor for increased culling. The incidence of clinical hypocalcaemia (milk fever) in the field generally ranges from 0-10%, but may exceed 25% of cows calving. In research trials conducted on milk fever the incidence has approached 80% of cows calving. Homeostasis of calcium (Ca) is regulated by calcitonin, parathyroid hormone and 1,25(OH)(2) vitamin D(3). Age increases the risk of milk fever by approximately 9% per lactation. Control of milk fever has revolved around stimulation of homeostatic mechanisms through feeding a pre-calving diet low in Ca. More recently, the role of the dietary cation anion difference (DCAD) in the prevention of Ca disorders has been examined, both by field research and meta-analysis. The most appropriate form of the DCAD equation has been contentious, but recent meta-analyses have shown that the equation (Na(+)+K(+))-(Cl(-)+S(2-)) is most effective for predicting milk fever risk. Decreased risk of milk fever is linear with DCAD, whereas the effect of DCAD on urinary pH is curvilinear. A pivotal role of providing dietary magnesium (Mg) before calving has been confirmed by meta-analysis, and a quadratic effect of Ca on milk fever risk was found with a peak occurring with dietary levels of 1.1-1.3% of dry matter. Risks of milk fever increase with increased dietary phosphorus (P) fed pre-calving and with increasing days of exposure to a pre-calving diet. Meta-analysis has revealed that the important roles of dietary Ca, Mg and P, as well as the duration of exposure to the pre-calving diet in milk fever control strategies are independent of DCAD. Studies on the effect of exposure to well designed pre-calving diets have shown that substantial improvements in production, reproduction and animal health can be made but further examination of the influence of the period of exposure to different diets is warranted.

Hypocalcemia in dairy cows: meta-analysis and dietary cation anion difference theory revisited.

Data from 137 published trials involving 2,545 calvings were analyzed using random effects normal logistic regression models to identify risk factors for clinical hypocalcemia in dairy cows. The aim of the study was to examine which form, if any, of the dietary cation anion difference (DCAD) equation provided the best estimate of milk fever risk and to clarify roles of calcium, magnesium, and phosphorus concentrations of prepartum diets in the pathogenesis of milk fever. Two statistically equivalent and biologically plausible models were developed that predict incidence of milk fever. These models were validated using data from 37 trials excluded from the original data used to generate the models; missing variables were replaced with mean values from the analyzed data. The preferred models differed slightly; Model 1 included prepartum DCAD, and Model 2 included prepartum dietary concentrations of potassium and sulfur alone, but not sodium and chloride. Other factors, included in both models were prepartum dietary concentrations of calcium, magnesium, phosphorus; days exposed to the prepartum diet; and breed. Jersey cows were at 2.25 times higher risk of milk fever than Holstein cows in Model 1. The results support the DCAD theory of greater risk of milk fever with higher prepartum dietary DCAD (odds ratio = 1.015). The only DCAD equation supported in statistical analyses was (Na(+) + K(+)) - (Cl(-) + S(2-)). This finding highlights the difference between developing equations to predict DCAD and those to predict milk fever. The results support a hypothesis of a quadratic role for Ca in the pathogenesis of milk fever (model 1, odds ratio = 0.131; Model 2, odds ratio = 0.115). Milk fever risk was highest with a prepartum dietary concentration of 1.35% calcium. Increasing prepartum dietary magnesium concentrations had the largest effect on decreasing incidence of milk fever in both Model 1 (odds ratio = 0.006) and Model 2 (odds ratio = 0.001). Increasing dietary phosphorus concentrations prepartum increased the risk of milk fever (Model 1, odds ratio = 6.376; Model 2, odds ratio = 9.872). The models presented provide the basis for the formulation of diets to reduce the risk of milk fever and strongly support the need to evaluate macro mineral nutrition apart from DCAD of the diet.

Decreases in serum apolipoprotein B-100 and A-I concentrations in cows with milk fever and downer cows.

Milk fever occurring during the peripartum period has been suggested to be caused by fatty liver developed during the non-lactating stage because diseased cows have increased serum concentrations of non-esterified fatty acids (NEFA) and show hepatic lipidosis. In cows with fatty liver and related diseases such as ketosis, serum concentrations of apolipoprotein (apo) B-100 and apoA-I are decreased. The purpose of the present study was to examine whether apoB-100 and apoA-I concentrations are similarly decreased in cows with milk fever. Apolipoprotein concentrations were also measured in cows with downer syndrome, which has been suggested to be related, at least in part, to milk fever. Compared with healthy cows during early lactation, apoB-100 and apoA-I concentrations were decreased in cows with milk fever and also in downer cows. In cows with milk fever, the decreases in apoB-100 and apoA-I concentrations were associated with increased NEFA and decreased cholesterol and phospholipid concentrations. However, in downer cows, serum lipid concentration changes were not as distinct as in cows with milk fever. These results, coupled with previous findings on the decreases in apoB-100 and apoA-I concentrations of cows with fatty liver-related diseases, suggest that fatty liver is involved in the development of milk fever and partly in that of downer cow syndrome.

Milk fever and subclinical hypocalcaemia--an evaluation of parameters on incidence risk, diagnosis, risk factors and biological effects as input for a decision support system for disease control.

The present review analyses the documentation on incidence, diagnosis, risk factors and effects of milk fever and subclinical hypocalcaemia. It is hereby evaluated whether the existing documentation seems sufficient for further modelling in a decision support system for selection of a control strategy. Several studies have been carried out revealing an incidence of milk fever most often in the level of 5-10%. Few studies indicate that the incidence of subclinical hypocalcaemia is several times higher than milk fever. The diagnosis based on clinical or laboratory methods or based on presence of risk factors is outlined. The clinical symptoms of milk fever are highly specific and the disease level may thus be determined from recording of treatments. Diagnosis of subclinical hypocalcaemia needs to include laboratory examinations or it may be determined by multiplying the incidence of milk fever by a certain factor. From the documentation on risk factors, it is very complex to predict the incidence from the exposure level of the risk factors. Due to uncertainty, sensitivity analyses over a wide range of values for each parameter are needed. The documentation of cow characteristics, nutrition, environment and management as risk factors are described. Among cow characteristics, parity or age, body condition and production level were found to be important. Risk factors associated with nutrition included most importantly dietary cation-anion difference and calcium level whereas the importance of general feeding related factors like type of feed stuff and feeding level were less clear. Environment and management included season, climate, housing, pasturing, exercise, length of dry period and prepartum milking. Several of the parameters on environment and management were confounded among each other and therefore firm conclusions on the importance were difficult. The documentation of the effect of milk fever includes the downer cows, reproductive disorders, occurrence of other diseases and the effect on milk production, body weight and culling. The reproductive disorders included most importantly dystocia, uterine prolapse, retained placenta, metritis and repeat breeding, and occurrence of other diseases included ketosis, displaced abomasum and mastitis. The documentation was substantial and often quantifiable within certain limits. Overall it is concluded that the present documentation on milk fever concerning incidence, diagnosis, risk factors and effects seems sufficient for a systematic inclusion in a decision support system. A model on milk fever should take into consideration the variation in biological data and individual herd characteristics. The inclusion of subclinical hypocalcaemia would be more uncertain and probably should await further documentation on possibilities of determining the herd level incidence and also the effect of this condition on production.

Effects of the addition of potassium or sodium, but not calcium, to prepartum ratios on milk fever in dairy cows.

The effects of prepartum dietary concentrations of K, Na, and Ca on the incidence of periparturient hypocalcemia or milk fever was determined for older (> or = 4th lactation) Jersey cows. Cows were fed one of six diets differing in K and Ca contents. In addition, the effect of dietary Na (tested only at the high concentration of dietary Ca, and low concentration of dietary K) was examined. Treatments were arranged in an incomplete 2 x 4 factorial design; dietary Ca (0.5 or 1.5%) and dietary strong cations (1.1, 2.1, and 3.1% K or 1.3% Na) were the main effects. Dietary Ca did not significantly affect the incidence of milk fever of the degree of hypocalcemia experienced by the cows. Milk fever occurred in 2 of 20 cows that were fed the prepartum diet containing 1.1% K and 0.12% Na. Increasing dietary K to 2.1 or 3.1% increased the incidence of milk fever to 10 of 20 cows and 11 of 23 cows, respectively. Increasing dietary Na to 1.3% in the diet containing 1.5% Ca induced milk fever in 5 of 8 cows. Addition of strong cations to the prepartum diet increased blood and urine pH and reduced plasma hydroxyproline concentrations, suggesting that bone resorption of Ca is inhibited in cows fed high K or high Na diets as a result of metabolic alkalosis. These data demonstrated that dietary Ca concentration is not a major risk factor for milk fever and that dietary strong cations, especially K, induce metabolic alkalosis in the prepartum dairy cow, which reduces the ability of the cow to maintain Ca homeostasis.

[The ecopathologic approach to the study of the relationship between nutrition and health in the dairy cow]. / Contribution de l'approche écopathologique à l'étude des relations nutrition--santé chez la vache laitière.

An ecopathological approach for examining nutrition-induced health disorders in dairy herds in France is described. Bovine dairy herds were surveyed for 4 yr to detect nutritional risk factors that discriminated between high and low disease incidence rates for retained placenta, milk fever, calf perimortality, metritis, liver disorders and infertility. In the cow, preventive feeding helps avoid nitrogen overnutrition, and reduces the requirements of Ca in the late gestation period, gives a satisfactory balance in polyunsaturated fatty acids before calving. The absence of feedstuffs including toxic components and a feeding system with few feedstuffs and few diet changes are also beneficial factors.

Meta-analysis of nutritional risk factors for milk fever in dairy cattle.

Data from 75 published trials were analyzed using meta-analysis techniques (pooling of data from many trials into one analysis) to determine nutritional risk factors for milk fever. Trials included in the analysis represented 1165 cows, 214 of which developed milk fever. Prepartum dietary concentrations of S and dietary anion-cation balance [(Na + K) - (C1 + S)] were the two nutritional factors most strongly correlated to the incidence of milk fever. Logistic regression analysis revealed that dietary S had the greatest influence on the incidence of milk fever. Increasing dietary S concentrations lowered the odds ratio of developing milk fever. Increasing dietary Na and CP increased odds ratios, but to a lesser extent. Relationship of dietary Ca to milk fever was nonlinear; relative risk of milk fever was greatest at 1.16% dietary Ca (DM basis) and was lowered as dietary Ca deviated either direction from 1.16%. Except when dietary Ca was extremely high or low, effects of changes in dietary Ca on the risk of milk fever were minor. Results of the analysis clarified the influence of Ca on the relative risk for milk fever and supported the theory that anion-cation balance exerts a strong, linear effect on the incidence of this disorder.

Enzymes and factors controlling vitamin D metabolism and action in normal and milk fever cows.

In milk fever (parturient paresis), calcium homeostatic mechanisms, regulated by parathyroid hormone and 1,25-dihydroxyvitamin D, fail to maintain normal blood calcium concentrations, resulting in severe hypocalcemia. The precise nature of the endocrine defect is unknown. Secretion of parathyroid hormone and production of 1,25-dihydroxyvitamin D is similar in most cows with milk fever or without. However, there are some cows that fail to produce adequate 1,25-dihydroxyvitamin D at the onset of lactation. These tend to be cows that will suffer prolonged hypocalcemia and relapse after treatment. Assuming that most cows produce adequate amounts of both hormones, the next logical cause of milk fever might be a failure of tissues to respond to calcium-regulating hormones. Older cows are more likely to develop milk fever than younger ones. We have found that tissue 1,25-dihydroxyvitamin D receptor concentrations decline with age, leaving the tissues less able to respond to 1,25-dihydroxyvitamin D. We also have found that tissue 1,25-dihydroxyvitamin D receptor concentrations increase during pregnancy and lactation in the cow. Intestinal 1,25-dihydroxyvitamin D receptor concentration does not appear to be different in cows with or without milk fever in cows of similar ages. However, intestinal 1,25-dihydroxyvitamin D receptor numbers decrease precipitously at parturition, which may in part be responsible for the development of hypocalcemia in dairy cattle.

Potentiometric determination of ionized and total calcium in blood plasma of Holstein and Jersey cows.

The effects of stage of lactation and breed on total and ionized calcium in blood plasma were determined for eight Holstein and eight Jersey cows fed a diet containing .25% Ca during the dry period and fed a diet with .50% Ca after calving. Blood samples were obtained by jugular venipuncture at 2-wk intervals from 4 wk before calving through wk 10 of lactation. Total and ionized Ca contents of fresh plasma were determined potentiometrically with an ion-specific electrode. Total Ca in plasma also was determined by atomic absorption spectrophotometry. Average concentrations determined by atomic absorption were approximately .7 mg/dl higher than those for the ion-specific electrode. Plasma total and ionized Ca were lower in both breeds at calving than any other time during the sampling period. Jersey cows had lower total Ca (7.47 mg/dl) and ionized Ca (4.25 mg/dl) than Holsteins (8.10 and 4.66 mg/dl) on day of calving. Ionized Ca as a percentage of total calcium increased from 55 to 57% at parturition and then decreased slowly to 53% at peak lactation. Changes in percentage of ionized Ca may indicate the contribution of bone resorption relative to dietary Ca in meeting the Ca requirement for lactation.

An aetiological hypothesis for the nutrition-induced association between retained placenta and milk fever in the dairy cow.

In the dairy cow, a statistical association between milk fever (MF) and placental retention (PR) has been observed in epidemiological studies. In order to prevent both diseases, an understanding of their common aetiological mechanism is necessary. In this paper, a new causal hypothesis concerning the nutrition-induced association between PR and MF has been put forward. This hypothesis integrates the aetiological concepts arising from the studies carried out by the authors of this paper, and those reviewed from the literature. The aetiological pathway leading to associated MF and PR in the dairy cow appears to include 3 main interrelated mechanisms: 1), decreased synthesis of cyclooxygenase products (mainly PgF2 alpha) via precalving linolenic acid-rich diets; 2), lack of calcium availability at calving via calcium-rich diets before calving; 3), intensive lipomobilization around calving due to a lack of energy supply. The risk for both MF and PR appears to be maximum with old cows fed diets rich in green fodder (fresh or ensiled) and in calcium, and poor in cereals in the prepartum period.

Parturient hypocalcemia in jersey cows fed alfalfa haylage-based diets with different cation to anion ratios.

Jersey cows were fed three alfalfa haylage-based diets with different cation-anion balances beginning 6 wk preceding third or later calving and ending 24 to 36 h postpartum. Sodium and Cl as percentages of dietary DM were .08 and 1.66 in diet 1 (anionic, 5 cows), .44 and .91 in diet 2 (intermediate, 6 cows), and 1.60 and .34 in diet 3 (cationic, 6 cows). Cation-anion balances were 22, 60, and 126 meq/100 g DM; Ca:P ratios averaged 4:1. Cows fed diet 1 in comparison with cows fed diets 2 or 3 over 6 wk had similar concentrations of Ca, P, and Na but higher concentrations of Mg and K in plasma and higher urinary excretions of Ca and Mg. Concentrations of 1,25-dihydroxyvitamin D 3 d before parturition were higher in cows fed diet 1 than in cows fed diets 2 or 3. Within 36 h after calving, mean concentrations of Ca in plasma (mg/dl, range) of cows fed diets 1 to 3, respectively, were 7 (8.7 to 6.2), 6.5 (7.8 to 3.9), and 6.3 (7.8 to 3.8). Number of cases of clinical milk fever by diet were 0 of 5, 2 of 6, and 1 of 6 cows. Alteration of dietary cation-anion balance by addition of Cl may effectively reduce incidence and severity of parturient hypocalcemia.