Hypocalcemia in Dairy Cows: Meta-analysis and Dietary Cation Anion Difference Theory Revisited

Abstract

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.

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

“…The herds in the present study received Ca in the range from 4.9 to 10.2 g/kg DM, which, according to the model developed by Lean et al (2006), would result in considerable differences in predicted milk fever incidence. The conclusion of Lean et al (2006) is supported by the results obtained by Shappell et al (1987), where cows fed 11.6 g Ca/kg DM experienced subclinical hypocalcaemia to a much greater degree than cows fed 5.2 g Ca/kg DM. However, the results from the present study do not support the theory that a decrease in Ca intake within the range from 4.9 to 10.2 g Ca/kg DM prevents milk fever when the cows are fed Ca above the recommended level of 33 g/day.…”

“…Curtis et al (1984) found no effect of dietary Ca in commercial herds on the incidence of milk fever, although they concluded that all cows in their study were fed well above the recommendations. However, the models developed by Lean et al (2006) and Oetzel (1991) showed a large increase in predicted milk fever incidence when the Ca concentration in the diet increased up to 13 g/kg DM. The herds in the present study received Ca in the range from 4.9 to 10.2 g/kg DM, which, according to the model developed by Lean et al (2006), would result in considerable differences in predicted milk fever incidence.…”

“…However, the models developed by Lean et al (2006) and Oetzel (1991) showed a large increase in predicted milk fever incidence when the Ca concentration in the diet increased up to 13 g/kg DM. The herds in the present study received Ca in the range from 4.9 to 10.2 g/kg DM, which, according to the model developed by Lean et al (2006), would result in considerable differences in predicted milk fever incidence. The conclusion of Lean et al (2006) is supported by the results obtained by Shappell et al (1987), where cows fed 11.6 g Ca/kg DM experienced subclinical hypocalcaemia to a much greater degree than cows fed 5.2 g Ca/kg DM.…”

“…A model developed by Lean et al (2006) based on a meta-analysis showed a quadratic relationship between Ca concentration in the dry cow diet and the predicted incidence of milk fever, with both low and high Ca concentrations resulting in a lower predicted incidence. The highest predicted milk fever incidence was found with Ca concentrations of 13 g/kg dry matter (DM).…”

“…Lean et al (2006) showed a relationship between an increased dietary Mg concentration and a decreased risk of developing milk fever. The Mg status of the animal affects Ca homeostasis, with Mg deficiency reducing the production of the Ca-saving hormone parathyroid hormone as a response to hypocalcaemia (Suh et al, 1973), and also tissue responsiveness to parathyroid hormone (Reddy et al, 1973).…”