Milk Fever Control Principles: A Review
© The Author(s) 2002
Received: 27 September 2001
Accepted: 28 September 2001
Published: 31 March 2002
Three main preventive principles against milk fever were evaluated in this literature review, and the efficacy of each principle was estimated from the results of controlled investigations. Oral calcium drenching around calving apparently has a mean efficacy of 50%–60% in terms of milk fever prevention as well as prevention of milk fever relapse after intravenous treatment with calcium solutions. However, some drenches have been shown to cause lesions in the forestomacs. When using the DCAD (dietary cation-anion difference) principle, feeding rations with a negative DCAD (measured as (Na + K) – (Cl + S)) significantly reduce the milk fever incidence. Calculating the relative risk (RR) of developing milk fever from controlled experiments results in a mean RR between 0.19 and 0.35 when rations with a negative versus positive DCAD are compared. The main drawback from the DCAD principle is a palatability problem. The principle of feeding rations low in calcium is highly efficient in milk fever prevention provided the calcium intake in the dry period is kept below 20 g per day. Calculating the relative risk (RR) of developing milk fever from controlled experiments results in a very low mean RR (between 0 and 0.20) (daily calcium intake below versus above 20 g/d). The main problem in implementing the low-Ca principle is difficulties in formulating rations sufficiently low in calcium when using commonly available feeds. The use of large doses of vitamin D metabolites and analogues for milk fever prevention is controversial. Due to toxicity problems and an almost total lack of recent studies on the subject this principle is not described in detail. A few management related issues were discussed briefly, and the following conclusions were made: It is important to supply the periparturient cow with sufficient magnesium to fulfil its needs, and to prevent the dry cows from being too fat. Available information on the influence of carbohydrate intake, and on the effect of the length of the dry period and prepartum milking, is at present insufficient to include these factors in control programmes.
Keywordsdairy cows parturient hypocalcaemia milk fever prevention
Principper for kontrol af mælkefeber. En litteraturoversigt.
I dette review blev 3 hyppigt anvendte forebyggende principper mod mælkefeber gennemgået: Oral calcium tildeling i tiden omkring kælvning, tildeling af forsurende rationer (DCAD = dietary cation-anion difference) samt tildeling af rationer med lavt calciumindhold i goldperioden. Effektiviteten af hvert princip blev estimeret ud fra resultaterne af kontrollerede forsøg.
Oral calcium tildeling i tiden omkring kælvning har tilsyneladende en effektivitet omkring 50%-60%, hvad angår forebyggelse af mælkefeber såvel som forebyggelse af tilbagefald efter i.v. behandling med calciumpræparater. Forsøg har vist, at visse af præparaterne har bivirkninger i form af læsioner i formaverne. Betydningen af disse læsioner er endnu ikke undersøgt.
Ved anvendelse af forsurende rationer i goldperioden vil rationer med DCAD (beregnet som (Na + K) – (S + Cl)) under 0 sænke mælkefeberincidencen signifikant. Udfra de kontrollerede forsøg inkluderet i dette review er den relative risiko (RR) for af udvikle mælkefeber blandt køer fodret med rationer med DCAD < 0 i forhold til køer fodret med rationer med DCAD>0 estimeret til at ligge mellem 0.19 og 0.35. Dog varierer mælkefeberincidencen voldsomt (0%- 80%) blandt køer fodret med rationer med positiv DCAD. Det primære problem forbundet med anvendelsen af DCAD princippet er smagelighedsproblemerne.
Tildeling af goldrationer med lavt calciumindhold er meget effektivt til forebyggelse af mælkefeber, forudsat det daglige calciumindtag ikke overstiger 20g/d i goldperioden. Blandt de i reviewet inkluderede undersøgelser var den relative risiko for udvikling af mælkefeber blandt køer med dagligt Ca-indtag under 20g/d i forhold til køer med dagligt Ca-indtag over 20g/d estimeret til at ligge mellem 0 og 0.2. Dog var mælkefeberincidencen stærkt varierende blandt køer med dagligt Ca-indtag over 20g/d (0%-80%). Problemet forbundet med implementering af Lav-Ca princippet er, at de hyppigst anvendte fodermidler til kvæg har et højt indhold af calcium, hvilket gør det vanskeligt at formulere rationer med tilstrækkeligt lavt calciumindhold.
Anvendelse af vitamin D samt vitamin D metabolitter og analoger til forebyggelse af mælkefeber er på grund af toxicitetsproblemer samt mangel på nyere undersøgelser kun behandlet kort i dette review. Ud over de ovennævnte forebyggelsesprincipper blev enkelte managementrelaterede emner med relation til mælkefeberforebyggelse diskuteret, og følgende konklusioner blev draget: Det er vigtigt at tildele den drægtige goldko tilstrækkeligt med magnesium samt at undgå, at goldkøerne bliver for fede. Tilgængelige informationer vedrørende betydningen af kulhydratindtaget, længden af goldperioden og malkning inden kælvning for udviklingen af mælkefeber er for utilstrækkelige til, at disse faktorer på nuværende tidspunkt kan inkluderes i mælkefeberkontrolprogrammer.
Keywordsdairy cows parturient hypocalcaemia milk fever prevention
Milk fever (paresis puerperalis), the clinical manifestation of parturient hypocalcaemia, is a disease of considerable importance for dairy cow welfare and economy. Although treatment with intravenous infusion of calcium salt solutions cure most clinical cases of hypocalcaemia, such cows are later more susceptible to other metabolic and infectious diseases [25, 24]. In many countries prevention of parturient hypocalcaemia is therefore given a high priority.
It has been proposed that a specific control program is relevant when the incidence of milk fever increases to above 10% among high-risk cows, i.e. cows entering third or later lactations .
Oral drenching around calving with a supplement of easily absorbed calcium.
The feeding of acidifying rations by anionic salt supplementation during the last weeks of pregnancy.
Feeding low calcium rations during the last weeks of pregnancy.
Prepartum administration of vitamin D, vitamin D metabolites and analogues.
Dietary magnesium level control peripartum.
Body condition control.
Controlling dietary carbohydrate intake peripartum.
Shortening of the dry period.
Reduced milking in early lactation.
The purpose of this review is to give an overview of the various control principles.
Three (I-III) of the most widely used control principles will be discussed in detail. The use of vitamin D administration (IV) and the less specific control measures (V-X) will be addressed more briefly in the present review, which primarily focuses on controlled studies.
I. Oral calcium drenching around calving
Controlled investigations on the prophylactic effect of oral calcium drenching on milk fever. Preventive effect calculated as percentage reduction in milk fever incidence among treated cows as compared to controls.
Preventive effect on milk fever1) (MF incidence in experimentals vs. controls, %)
Calcium chloride gel × 4–10
Around 40 g Ca/dose
(7.7 vs. 53.2)
Average effect obtained in seven separate studies. Occational diarrhoea and loss of appetite
Calcium chloride gel × 3–4
54 g Ca/dose
(22.6 vs. 46.6)
More cases of diarrhoea (17% vs. 10%)
Calcium chloride gel × 4–10
36 g Ca/dose
(25.6 vs. 48.8)
More cases of milk fever > 48 hours after calving among treated cows (12.8% vs. 2.4%)
Calcium chloride + calcium sulphate capsule × 4
46 g Ca/dose
(14.6 vs. 54.8)
No side-effects Administration of capsules eliminates the risk of aspiration
Calcium propionate paste × 4
37 g Ca/dose
(29 vs. 50)
No effect on the incidence of milk fever in herds with low milk fever incidence
Calcium chlorid + tricalcium phosphate gel × 4
54 g Ca/dose
Significantly fewer cases of displaced abomasums (1.0% vs. 7.8%)
Calcium chloride paste × 4
50 g Ca/dose
(14.3 vs. 42.9)
Increased salivation following administration of the paste.
Calcium chloride paste 1 × 3 + 1/2 × 2
50 or 25 g Ca/dose
(10.0 vs. 33.3)
Calcium propionate boli × 6
20 g Ca/dose
Calcium chloride in oil × 4
54 g Ca/dose
(25.3 vs. 36.0)
(23.2 vs. 36.0)
Large number of cows (194 experimental cows and 713 control cows)
Controlled investigations on the prophylactic effect of oral calcium drenching supplementary to i.v. treatment on milk fever recurrence. Preventive effect was calculated as percentage reduction in milk fever recurrence among orally supplemented cows as compared to controls.
Preventive effect on milk fever recurrence1) (Recurrence incidence in experimentals vs. controls, %)
Calcium chloride solution (aq.) × 1
126 g Ca/dose2)
(7.6 vs. 25.0)
No apparent side-effects. Two different types of i.v. treatment were used.
a) Calcium chloride solution (aq.) × 1
54.5 – 109.0 g Ca/dose 2)
b) Calcium chloride solution (aq.) × 1
54.5 – 109.0 g Ca/dose 2)
(12.8 vs. 55.6)
(9.5 vs. 27.1)
Different types of i.v. treatments in the two experiments (a and b). The amount of calcium given p.o. depended on the size of the cow.
a) Calcium chloride gel × 1
72.2 g Ca/dose 2)
b) Calcium chloride gel × 1
111.9 g Ca/dose 2)
(25.0 vs. 45.6)
(29.9 vs. 45.6)
Within each experiment (a and b) 4 different types of i.v. treatments were used.
Calcium chloride oil × 2
50 g Ca/dose
(7.7 vs. 24.3)
Main mechanism and effect
The principle was originally developed for therapeutic use in cows with milk fever, as an alternative to intravenous calcium infusions . A handful of calcium chloride was dissolved in a bucket of water and given by stomach tube. However, as discussed below, such calcium chloride drenchings were later discovered to have a prophylactic effect also, when given according to a programme covering the peak of the risk period. Oral calcium drenching should preferably provide free (ionised) calcium, because this form is most quickly absorbed from the rumen and abomasum.
Normally cows absorb calcium by 2 mechanisms: active transport across intestinal epithelial cells and passive transport between intestinal epithelial cells . Passive transport is dependent on diffusion down a concentration gradient, and passive diffusion of Ca from the lumen of the gut to the extracellular fluids occurs when the luminal ionised Ca concentration exceeds 1 mM . Oral calcium treatment presumably increases luminal Ca concentration above 1 mM, favouring passive transport of Ca into the extra cellular fluids . The capacity of the passive transport of Ca is in principle unlimited and independent of stimulation by 1.25-dihydroxyvitamin D. Thus, the net absorption of free Ca increases linearly with increasing luminal Ca concentrations . Increasing the amount and the number of drenchings with calcium compounds providing free calcium ions therefore quickly increases the amount of calcium ions absorbed into the bloodstream. Supplying the cow with CaCl2 salts may furthermore, due to the osmotic effect, stimulate the oesophageal groove reflex, permitting rumen bypass. The calcium solution thereby avoids dilution within the rumen, and a high concentration gradient would be obtained in the abomasum favouring passive Ca transport . The calcium absorption was studied by  by giving a calcium chloride gel product within 1 h of parturition. A significant (p < 0.01) rise in serum total calcium was recorded within 5 min of administration. Serum calcium levels had returned to baseline values after 24 h. Thus a significant increase in serum Ca can be obtained very quickly. On the other hand, the biological effect is short-lived, which explains the risk of recurrence.  discussed the short effect and believed it to be the result of an inhibition of the activation of those homeostatic mechanisms that should otherwise protect against parturient hypocalcaemia.
Chalk (calcium carbonate) does not provide readily absorbable calcium ions . It most likely needs exposure to the acid in gastric juice to be dissociated and such calcium is therefore primarily available for absorption in the small intestine. The digestibility of such bound calcium is therefore dependent on the calcium absorption capacity of the small intestine. This capacity is controlled by the calcium homeostatic mechanisms, which, in case of the milk fever cow, are operating at an insufficient level. Simply increasing chalk supplementation to calving cows, or drenching them with such substances, is therefore unreliable in preventing milk fever. Accordingly recent studies  have shown that milk fever was not prevented in control cows drenched with calcium carbonate after calving.
Table 1 shows the preventive effect calculated from controlled investigations on oral calcium drenching against parturient hypocalcaemia.
The preventive effect is calculated as 1 minus the relative risk (RR), where RR is the incidence rate of milk fever among cows in the experimental group divided by the incidence rate of milk fever among cows in the control group. In the majority of these investigations the material used are either cows, which had milk fever at the previous calving, or cows of third or higher parity. A frequency of milk fever at 20%–50% may be expected among such cows .
In the trials of [60, 99] and  the programme of giving 3–10 doses of calcium chloride as a water-soluble gel has a preventive effect of approximately 50%–55%. The early study of  is given less weight because essential details for efficacy estimation were not well described. According to  drenching with 4 doses of CaCl2/CaSO4 in capsules seems to have slightly higher efficacy (73%).
Calcium chloride in a paste formulation was reported to have a preventive effect of about 70% in 2 investigations [3, 2], and calcium as a propionate paste was tested in 1 study with an efficacy of 42% . A propionate bolus product was similarly reported in a single study, with an efficacy of 30% . The preventive effect of 2 doses, a widely used practice, has apparently not been investigated.
The limitation of using the above mentioned compounds for oral Ca drenching is the toxicity, as discussed below.
Table 2 shows the preventive effect calculated from controlled investigations on oral calcium drenching supplementary to i.v. treatment of milk fever cases. These investigations are therefore concerned with the risk of clinical relapse in cows already treated by the veterinarian with intravenous calcium infusion. In an average cow population, the recurrence rate after 1st treatment is of the order of 30%–35% without supplementary oral treatment . In particular aged cows can be very hard to get on their feet, and the recurrence rate may be considerably higher, as in the study of  (see Table 2).
In summing up the figures presented in Table 2, the mean preventive effect of such a post treatment drenching regime involving 1 or 2 oral doses against milk fever, recurrence may be assessed at approximately 60%.
Some dairy managers apply oral calcium drenching for a third purpose, i.e. for the tactical or preventive treatment of newly calved cows that appear to be borderline cases of milk fever. The early study of  support the conviction of many herd managers that such use is effective, but controlled studies are lacking. Because of potentially decreased swallowing reflex and rumen motility in cows with borderline milk fever oral calcium drenching should be done with caution.
Positive side effects following efficient milk fever prevention are reductions in hypocalcaemia-associated diseases and improved reproduction and production, as reviewed by .
Unwanted side effects following calcium chloride drenching were observed by  and later by . These side effects appeared when preparations containing calcium chloride in a concentrated form was used, and they were caused by a strong irritating effect on the mucous lining of the gastro-intestinal tract. Post mortem lesions vary in severity from focal haemorrhage to deep necrosis. Particularly severe lesions were seen after drenching with a commercial product based on calcium formate . Preparations containing calcium chloride in oil emulsions appear to be less harmful than preparations containing calcium chloride in aqueous gel or plain aqueous solution [62, 116], and the relatively low efficacy of propionate preparations should be weighed against the absence of reports on unwanted side effects after drenching with calcium propionate. The significance of most of the lesions in terms of cow welfare and production is frequently debated, but has not yet been investigated. The chloride ion from CaCl2 is readily absorbed into the blood, and blood pH therefore decreases to maintain electroneutrality of the blood . Besides the caustic effect on the mucous lining overdosing with calcium chloride preparations may therefore result in uncompensated systemic acidosis.
Fatal cases due to application errors involving pharynx penetration, or lung aspiration of liquid products, are well known in practice but seldom reported in the literature .
Oral drenching with calcium preparations can prevent a significant proportion of milk fever cases when given to parturient cows. Most documented preventive programmes involve administration of 3–4 doses distributed evenly during the period from 12–24 h before calving to 24 h after calving [60, 82, 42, 75, 3]. Oral calcium drenching can also prevent a significant proportion of relapses when given as a 1 or 2-dose supplement to intravenous calcium therapy of milk fever cases. General drawbacks of oral drenching are that single cow handling is necessary, and that there is a risk of aspiration pneumonia. As mentioned above, products based on calcium chloride (and calcium formate) may give rise to irritation of the gastrointestinal mucosa and uncompensated systemic acidosis.
II. Acidifying rations (Dietary cation-anion difference, DCAD)
Under practical conditions this principle is applied by supplementing the dry cow ration with an anionic salt, or more common a mixture of salts, capable of acidifying the cow. The required amount of anionic salts is dependent on the DCAD of the prepartum ration, and it may, depending on the salt, range from around 50 to 500 g . Although the time period of feeding the salts has ranged from 21 to 45 days in most studies, it may be possible to reduce the time period without loosing the effect. It is suggested, however, that a feeding period of at least 10 days prepartum is required .
Main mechanism and effect
This principle, and the theories behind it, has been well described by others [30, 27, 102, 41, 114, 36, 52]. The cow must be brought into a physiological stage of compensated systemic acidosis. This is most efficiently achieved by the ingestion of rations having a surplus of acidifying anions. A useful method for determining whether an animal is responding to added dietary anions is to monitor urine pH. A urinary pH within the range 5.5 to 6.2 is accepted as an indicator of successful administration of anions .
Several methods for calculating the DCAD of the diet have been utilized, including the following equations:
DCAD (meq) = (Na + K + Ca + Mg) - (Cl + SO4 + H2PO4 + HPO4)
DCAD (meq) = (Na + K + Ca + Mg) - (Cl + S + P)
DCAD (meq) = (Na + K + .38 Ca + .30 Mg) -(Cl + .60 S + .50 P)
DCAD (meq) = (Na + K) - (Cl + S)
DCAD (meq) = (Na + K) - (Cl)
The equation most often used by dairy nutritionists is, however, the one considering (Na + K) - (Cl + S) .
During the years studies have been performed using a wide variety of anion sources (i.e. MgSO4, MgCl2, NH4Cl, (NH4)2SO4, CaCl2, CaSO4, HCl, H2SO4, AlSO4). The mechanism by which the acidotic stage affects calcium metabolism and homeostasis is not fully understood, but it is suggested that the effect is mediated via an enhancement of the stimulatory effects of PTH . Increased plasma hydroxyproline concentration suggests that bone resorption may be involved , and some studies reported an increase in the apparent calcium absorption from the digestive tract [113, 69], while others found no changes , or even a decrease . The extensive urinary calcium excretion seen in cows fed anionic salts, may stimulate the vitamin D-related calcium homeostatic mechanisms, and in this way help prevent parturient paresis .
Calculating the relative risk (RR) of developing milk fever in each experiment including groups receiving feeds with DCAD below and above (or equal to) zero, results in a mean RR of approximately 0.35 in favour of the negative DCAD. In studies including more than 2 groups, the milk fever incidence rate among positive DCAD versus negative DCAD groups is used for calculating the RR. The study done by  is not included in the calculations, as they did not include a group receiving feed with a negative DCAD. In 2 of the studies  and  the milk fever incidence was zero among cows in the positive as well as negative DCAD group (RR = 1). Excluding these results from the calculations, the RR changes from 0.35 to 0.19. The true RR is probably to be found somewhere in between.
It should be noted, that Fig. 1 is based solely on the results obtained in 11 studies, and because of this it only represents a limited number of animals. Furthermore, the experimental conditions (diet, number of cows, parity, duration, previous cases of milk fever etc.) vary considerably between the different studies. For instance some studies included cows of second or first parity [73, 107, 70], whereas others [10, 79, 67, 41, 8, 36, 37, 39] only included "high risk" cows (≥ third parity). The interpretation of Fig. 1 should therefore be done with caution.
The optimum calcium level in combination with the feeding of acidifying rations
Regarding the optimal amount of dietary calcium in combination with a low DCAD, recommendations are conflicting. Most authors [30, 69, 10, 79, 7, 76] recommend a high level of daily Ca intake. On the other hand  and  argue that low calcium and a low DCAD supplement each other and they therefore believe such a combination to be superior to the combination high Ca – low DCAD.  and  question whether the dietary calcium level has any influence at all on the blood calcium concentration at parturition in cows on an acidifying ration. It is noted, however, that when limestone is used to achieve a high level of dietary calcium, the alkalinising effect of the added calcium carbonate may be a factor of consideration .
The use of anions to reduce the DCAD is limited by problems with palatability of the anionic salts most commonly used . It may be added that the rather unnatural acidosis induced by the DCAD principle could possibly also contribute to a reduced feed intake.
Several studies have shown a negative effect on the dry matter intake (DMI) when adding anionic salts to the ration [32, 78, 36, 107, 70], whereas others found no effect on DMI [10, 79].  have shown that decreased feed intake and a negative energy balance before calving increase plasma NEFA and concentration of liver triglyceride at calving. This in turn may increase the risk also of displaced abomasum , as well as mastitis, and retained placenta post partum .
In order for the cation-anion principle to work, a surplus of absorbable anions must be fed for at least 10 days prepartum to prevent the cow from being alkalinised. A DCAD of -100 meq/kg (calculated as (Na + K) - (Cl + S)) has been recommended . A general disadvantage of this principle is the low palatability of the anionic salts most commonly used. In general, reducing the DCAD by supplementation of anionic salts should only be attempted if the DCAD of the diet is below 250 meq/kg .
III. Low calcium intake and low Ca/P in late pregnancy
This principle is based on the theory of preventing the calcium homeostatic mechanisms from becoming quiescent during the dry period.
Main mechanism and effect
The calcium demand of the dry cow is very limited: 33 g/day per 500 kg body weight in the last 2 months of pregnancy . Most dry cow rations do, however, contain considerably larger amounts. When calcium intake extensively exceeds the requirements, the calcium demand can be met almost entirely by passive diffusion from the intestinal tract, rendering the calcium homeostatic mechanisms relatively inactive [89, 51].
At calving the production of 10 litres of colostrum will result in a loss of 23 g of calcium in a single milking . This sudden and extensive draw on blood calcium must be replaced via increased intestinal calcium absorption and increased resorption of calcium from the bones. The reactivation of the calcium homeostatic mechanisms is, however, time-consuming. A significant increase in calcium absorption from the gut demands 24 h of preceding 1,25(OH)2D stimulation, while a significant increase in bone resorption demands 48 h of PTH stimulation. In milk fever cows, these adaptation processes may take even longer .
By feeding low calcium (< 20 g/d) diets in the dry period, the calcium homeostatic mechanisms are activated before calving, and the cow is thus capable of absorbing calcium more efficiently from the intestinal tract as well as drawing calcium from the bone around the time of calving . , however, claimed that diets extremely high as well as low in calcium decreased the incidence of milk fever. The apparent ability of high Ca diets to prevent milk fever has not been explained or documented.
The necessary period of exposure in order to obtain good preventive effect from feeding a low-Ca diet transpires from experiments using prepartum feeding periods of 14 days or more [43, 44, 66], whereas  suggested that a low-Ca feeding period of 7 days before calving was too short for prevention of parturient paresis.
The true relative risk is probably to be found somewhere between 0 and 0.20.
Because of problems in keeping the calcium intake sufficiently low using commercial available feeds, the low-Ca principle has been more or less abandoned in many countries. However, recent studies attempt to revive the low calcium principle by introducing induced reduced ration calcium availability by the addition of a calcium binder to the ration [64, 109, 63, 110, 119].
The Ca/P ratio has been suggested as another important factor in the development of milk fever. Early studies [12, 103] stressed the importance of keeping the dietary Ca:P ratio low in preventing parturient paresis. It was suggested that a high dietary P suppressed vitamin D hydroxylation in the kidney, thereby indirectly reducing calcium absorption. The reduced intestinal Ca absorption elicited an increase in PTH level, which in turn aided in the prevention of milk fever .  on the other hand, stated that the beneficial effect of feeding low Ca diets appeared independent of P. In addition they found that low dietary phosphorus seemed helpful in preventing parturient paresis, when dietary calcium was high. It was suggested that the low dietary phosphorus resulted in an increased formation of 1,25(OH)2D, which in turn increased the efficiency of intestinal absorption of calcium and phosphorus. This viewpoint was supported by  who found that although low dietary phosphorus did not prevent milk fever, the postpartum calcium and phosphorus homeostasis was enhanced, and by  in their epidemiological study of factors predisposing to parturient paresis.
As shown above there are many different opinions about the influence of the Ca/P ratio on the incidence of milk fever. In conclusion, the absolute amount of calcium in the diet is probably more important than the Ca/P ratio .
The low calcium principle is highly effective, approaching 100%, in preventing milk fever provided the daily calcium intake is kept below 20 g/d, and provided the exposure period includes at least the last 2 weeks before calving. Using commonly available feeds a calcium level of < 20 g/d is difficult to obtain. A possible solution to this problem may be the addition of a calcium binder to the feed. Regarding the influence of the Ca/P ratio, it is concluded that the absolute amount of calcium in the diet is apparently more important.
IV. Prepartum administration of vitamin D, vitamin D metabolites and analogues
The use of large doses of vitamin D metabolites and analogues for milk fever prevention is controversial. Efficacies vary greatly between studies and the dose required is very close to the toxic dose causing clinical symptoms  including marked anorexia, loss of body weight, dyspnoea, tachycardia, recumbency, torticollis and severe cardiovascular calcifications [46, 98, 81, 87]. The timing of the treatments is very important. Injection given 2–8 days before parturition has been considered optimal. If the cow fails to calve after the 8th day, another injection may be given and repeated every 8 days until calving . For security reasons most producers of these products do, however, not recommend the use of more than 2 doses per cow. Another potential problem in utilizing the vitamin D family of compounds is the risk of hypocalcaemia and clinical signs of milk fever 10–14 days post partum [55, 40]. Among these hypocalcaemic animals the plasma 1.25(OH)2D3 is not increased. The animal is apparently dependent on exogenous 1.25(OH)2D3 to reverse its hypocalcaemia . Despite these drawbacks, vitamin D3 injection has been the most commonly used method of prevention, principally because of its simplicity .
Because of the unwanted side effects, and because of an almost total lack of more recent controlled studies dealing with such side effects, production implications and consumer safety, the principle is not described further in this review. Readers are referred to the description given by .
V. Peripartum dietary magnesium control
Some herds with chronic hypomagnesaemia problems have been known to have very high incidences of milk fever, sometimes approaching 80%–90% of all calvings . Subclinically hypomagnesaemic cows are less able to mobilise calcium in response to hypocalcaemia [21, 95, 16], and chronic hypomagnesaemia can have deleterious effects on calcium homeostasis . More specifically,  found that the resorptive activity of the bones of magnesium deficient cows was significantly depressed, and  found that a slight degree of hypocalcaemia coupled with a greater degree of hypomagnesaemia could lead to clinical signs similar to those of severe periparturient hypocalcaemia.
Although magnesium is not directly involved in the aetiology of milk fever, checking of magnesium status should be part of a milk fever control programme since all studies indicate the importance of supplying the periparturient cow with sufficient magnesium to fulfil its needs. The recommended magnesium content of the diet for pregnant dry cows is 0.16% of DM intake .  found no improving effect on the calcium metabolism from feeding a high Mg diet (0.37% of DM) compared to a normal Mg diet (0.2% of DM) when the cows were fed acidogenic diets. With regard to Mg administration it is further important not to feed roughage from pastures over-fertilised with potassium, as a high [K+] decreases the uptake of magnesium .
VI. Body condition control
Over-conditioned cows at calving have a higher incidence of milk fever  and other diseases postpartum [108, 104, 94].  found that over-conditioned cows (body condition score (BCS) ≥ 4) had a 3.3 times higher risk of contracting milk fever. Accordingly,  found a relatively higher body weight in cows contracting milk fever. The most likely explanation for the increased risk of milk fever in over-conditioned cows is a low calcium intake caused by reduced appetite in the critical period around calving .
It is important to prevent the dry cows from being too fat. It is therefore recommended that the energy intake of cows in mid and late lactation is controlled to ensure a BCS of ≤ 3.75. Optimum BCS has been proposed to be 3.25 to 3.75 . However, if over-conditioned, cows in the late dry period should maintain body condition to prevent fatty liver .
VII. Controlling dietary carbohydrate intake peripartum
The influence of concentrate or grain feeding in the dry period was reviewed by . Results of studies concerned with the influence of carbohydrate feeding on the incidence of milk fever are conflicting.  found that grain fed at 1% of body weight reduced the incidence of milk fever, and  found an increased risk of milk fever in cows fed rations high in green fodder and calcium but low in cereals. On the other hand  found that a 100% overfeeding with energy (and 80% overfeeding with protein) during the last 8 weeks of pregnancy resulted in an increased incidence of parturient paresis. Accordingly [13, 14] found that overfeeding cows prepartum increased the incidence of milk fever.  found no effect of energy intake prepartum.
The informations are conflicting. Most authors do, however, believe that feeding large amounts of concentrate in the dry period leads to higher incidences of milk fever. The reason might be that "overfed" cows more easily loose appetite around calving and thereby absorb less calcium than required [4, 14]. Limiting energy intake prepartum will according to  prevent not only parturient paresis but also displaced abomasum.
VIII. Shortening of the dry period
The influence of the length of the dry period on milk fever was reviewed by . Cows with long non-lactating periods are predisposed to becoming excessively fat, since cows do not regulate intake according to their physiological requirements . Besides obesity, a long dry period may result in a more quiescent calcium homeostasis.  found a less profound post parturient drop in blood calcium of cows with a mean dry period of 4 days only as compared to a period of 8 weeks. There are, however, some side effects from reducing the length of the dry period.  reported a significant reduction in milk production in the subsequent lactation when shortening the dry period from 7 to 4 weeks.
IX. Prepartum milking
Prepartum milking has been found to have no effect on the incidence of milk fever [100, 29, 1], whereas others found a decrease in milk fever incidence following prepartum milking [101, 45]. Most studies on prepartum milking showed no effect on lactation milk yield [101, 121, 45], whereas the effect on retained placenta and udder oedema varies among studies. However, most of these studies are fairly old. In the large study by  it was concluded that prepartum milking can be practiced with no detrimental effects, but as there is no positive effect on lactation milk yield, prepartum milking is unlikely to be justified economically.
Shortening of the dry period as well as prepartum milking is unlikely to serve as an option in future herd control programmes, including programmes for milk fever prevention, unless the effect is documented by thorough cost-benefit calculations.
X. Reduced milking in early lactation
Although easy to apply, an effect of reduced milking in early lactation is questionable.  and  found no effect of the degree of milking after i.v. calcium treatment on the incidence of milk fever relapses. As no recent studies have been performed on this subject it is not evaluated further in this review.
The 3 most frequently used principles in Denmark for preventing milk fever are: Oral calcium drenching around calving, feeding acidifying rations (Dietary cation-anion difference, DCAD) and feeding rations low in calcium.
Oral calcium drenching around calving should preferably be done as recommended in the reference studies i.e. 3–4 times for milk fever prevention and 1–2 times for prevention of milk fever relapse. Giving fewer drenches may have some preventive effect, but it is unlikely to reach the effect of the full programme.
When using the cation-anion principle it is of crucial importance to feed a surplus of absorbable anions to convert the cow from being alkaline to moderately acidotic. The palatability of the anionic salts most commonly used limit the use of this principle. In general it should not be implemented on rations with a DCAD above 250 meq/kg DM.
When using the low-Ca principle, daily calcium intake should be below the requirements of the dry cow. Although difficult to obtain when using commonly available feeds, a daily intake of 20 g/d (or below) is recommended.
Unfortunately the above mentioned recommendations are rarely met in practice, resulting in low efficacy measures. Besides palatability problems and difficulty in formulating low-Ca rations, reasons for not following the recommendations may be found in economic considerations and time-consuming single cow handling.
These issues have to be thoroughly considered when choosing the method for milk fever prevention on each farm. The preventive principle suitable on one farm is not necessarily suitable on another.
Even when applied in the most optimal way the preventive effect of the described principles rarely reaches 100 per cent. Combining one or more of the principles is one potential way of improving efficacy. The low-Ca principle combined with oral calcium drenching around calving could be one option, whereas drenching cows on a negative DCAD ration with oral CaCl2 is discouraged by  due to the risk of inducing an uncompensated metabolic acidosis. Finally, recommendations are conflicting regarding the combined feeding of an acidified ration containing a minimum of calcium.
Although not uniquely designed for milk fever prevention certain management measures may be combined with the above-mentioned primary preventive principles.
There is only limited information about how the different principles are most efficiently implemented as detailed strategies. It is very much up to the individual farmer or adviser to choose which principle to use. Hopefully, the future will bring more detailed information on the optimal use of control strategies under different farming conditions.
- Ackerman RA, Henderson HO, VanLandingham AH, Weakley CE: Prepartum milking of dairy cows. Bulletin 378T. West Virginia Univ Agric Exp Stn. 1955, 3-18.Google Scholar
- Agger N: A field efficacy study of a calcium chloride paste formulation for oral dosing of dairy cows in the prevention of milk fever. XX World Buiatrics Congress. 1998, 530-Google Scholar
- Agger N, Katholm J, Lomborg K, Nygaard B, Rude-beck K, Zangenberg N: A pharmacokinetic study of plasma calcium concentration in dairy cows following four oral administrations at 12 hour intervals around calving of a calcium chloride paste formulation. The Bovine Proceedings. 1997, 30: 72-75.Google Scholar
- Allen WM, Davies DC: Milk fever, hypomagne-saemia and the 'downer cow' syndrome. Br Vet J. 1981, 137: 435-441.PubMedGoogle Scholar
- Barnouin J, Chassagne M: An aetiological hypothesis for the nutrition-induced association between retained placenta and milk fever in the dairy cow. Ann Rech Vet. 1991, 22: 331-343.PubMedGoogle Scholar
- Barton BA, Jorgensen NA, DeLuca HF: Impact of prepartum dietary phosphorus intake on calcium homeostasis at parturition. J Dairy Sci. 1987, 70: 1186-1191.PubMedGoogle Scholar
- Beede K: Preventing milk fever. Feed Management. 1992, 43: 28-31.Google Scholar
- Beede DK, Risco CA, Donovan GA, Wang C, Arch-bald LF, Sanchez WK: Nutritional management of the late pregnant dry cow with particular reference to dietary cation-anion difference and calcium supplementation. The Bovine Proceedings. 1992, 24: 51-55.Google Scholar
- Beitz DC, Burkhart DJ, Jacobson NL: Effects of calcium to phosphorus ratio in the diet of dairy cows on incidence of parturient paresis. J Dairy Sci. 1974, 57: 49-55.PubMedGoogle Scholar
- Block E: Manipulating dietary anions and cations for prepartum dairy cows to reduce incidence of milk fever. J Dairy Sci. 1984, 67: 2939-2948.PubMedGoogle Scholar
- Boda JM: Further studies on the influence of dietary calcium and phosphorus on the incidence of milk fever. J Dairy Sci. 1956, 39: 66-72.Google Scholar
- Boda JM, Cole HH: The influence of dietary calcium and phosphorus on the incidence of milk fever in dairy cattle. J Dairy Sci. 1954, 37: 360-371.Google Scholar
- van de Braak AE, van't Klooster ATh, Malestein A: Influence of prepartum calcium intake on calcium mobilisation rate around parturition in dairy cows fed a high prepartum feeding level. The veterinary quarterly. 1986, 8: 55-68.Google Scholar
- van de Braak AE, van't Klooster ATh, Malestein A, Faber JAJ: Effects of low and high calcium intake prepartum on calcium mobilization rate around parturition in dairy cows. The veterinary quarterly. 1986, 8: 41-52.Google Scholar
- van de Braak AE, van't Klooster ATh: Effects of calcium and magnesium intakes and feeding level during dry period on bone resorption in dairy cows at parturition. Res Vet Sci. 1987, 43: 7-12.PubMedGoogle Scholar
- van de Braak AE, van't Klooster ATh, Malestein A: Influence of a deficient supply of magnesium during the dry period on the rate of calcium mobilisation by dairy cows at parturition. Res Vet Sci. 1987, 42: 101-108.PubMedGoogle Scholar
- Breves G, Goff JP, Schröder B, Horst RL: Gastrointestinal calcium and phosphate metabolism in ruminants. Proceedings; Eight International Symposium on Ruminant Physiology. 1995, 135-151.Google Scholar
- Bronner F: Intestinal calcium absorption: Mechanisms and applications. J Nutr. 1987, 117: 1347-1352.PubMedGoogle Scholar
- Cameron REB, Dyk PB, Herdt TH, Kaneene JB, Miller R, Bucholtz HF, Liesman JS, VandeHaar MJ, Emery S: Dry cow diet, management, and energy balance as risk factors for displaced abomasum in high producing dairy herds. J Dairy Sci. 1998, 81: 132-139.PubMedGoogle Scholar
- Chieze C, Baudet HM: Interet de l'administration orale d'une emulsion de chlorure de calcium dans la prevention des rechutes de fievre vitulaire. Recueil de Medicine Veterinaire. 1992, 168: 351-353.Google Scholar
- Contreras PA, Manston R, Sansom BF: Calcium mobilisation in hypomagnesaemic cattle. Res Vet Sci. 1982, 33: 10-16.PubMedGoogle Scholar
- Coppock CE, Noller CH, Wolfe SA, Callahan CJ, Baker JS: Effect of forage-concentrate ratio in complete feeds fed ad libitum on feed intake prepartum and the occurrence of abomasal displacement in dairy cows. J Dairy Sci. 1972, 55: 783-789.PubMedGoogle Scholar
- Curtis CR, Erb HN, Sniffen CJ: Path analysis of dry period nutrition, postpartum metabolic and reproductive disorders and mastitis in holstein cows. J Dairy Sci. 1985, 68: 2347-2360.PubMedGoogle Scholar
- Curtis CR, Erb HN, Sniffen CJ, Smith RD: Epidemiology of parturient paresis: Predisposing factors with emphasis on dry cow feeding and management. J Dairy Sci. 1984, 67: 817-825.PubMedGoogle Scholar
- Curtis CR, Erb HN, Sniffen CJ, Smith RD, Powers PA, Smith MC, White ME, Hillman RB, Pearson EJ: Association of parturient hypocalcaemia with eight periparturient disorders in Holstein cows. J Am Vet Med Assoc. 1983, 183: 559-561.PubMedGoogle Scholar
- Davicco MJ, Rémond B, Jabet WS, Bartel JP: Plasma osteocalcin concentrations in cows around parturition. The influence of a regular versus a very short dry period. Reprod Nutr Dev. 1992, 32: 313-319.PubMedGoogle Scholar
- Dishington IW: Prevention of milk fever (hypocalcemic paresis puerperalis) by dietary salt supplements. Acta Vet Scand. 1975, 16: 503-512.PubMedGoogle Scholar
- Dyk PD: The association of prepartum non-esterified fatty acids and body condition with peripartum health problems on 95 Michigan dairy farms. Master's Thesis. 1995, Michigan State University East LansingGoogle Scholar
- Eaton HD, Johnson RE, Heimboldt CF, Spielman AA, Matterson LD, Jungherr EL, Kramer JH, Slate RJ: Prepartum milking I. The effect of prepartum milking on some blood constituents of the cow. J Dairy Sci. 1949, 32: 870-876.Google Scholar
- Ender F, Dishington IW, Helgebostad A: Calcium balance studies in dairy cows under experimental induction and prevention of hypocalcaemic paresis puerperalis. Z. Tierphysiol., Tierernahrg. u. Futtermittelkde. 1971, 28: 233-256.Google Scholar
- Gardner RW, Park RL: Effects of prepartum intake and calcium to phosphorus ratios on lactation response and parturient paresis. J Dairy Sci. 1973, 56: 385-389.PubMedGoogle Scholar
- Gaynor PJ, Mueller FL, Miller JK, Ramsey N, Goff JP, Horst RL: Parturient hypocalcemia in jersey cows fed alfalfa haylage-based diets with different cation to anion ratios. J Dairy Sci. 1989, 72: 2525-2531.PubMedGoogle Scholar
- Gerloff B: Feeding the dry cow to avoid metabolic disease. Vet Clin North Am: Food anim Pract. 1988, 4: 379-390.Google Scholar
- Glawischnig EV: Zur Resorption peroral verabreichter Kalziumsalze. II. Internationale Tagung über Rinderk., Tierärztlichen Hochschule, Wien. 1962, 19-20.Google Scholar
- Goff JP, Horst RL: Calcium salts for treating hypocalcemia: Carrier effects, acid-base balance, and oral versus rectal administration. J Dairy Sci. 1994, 77: 1451-1456.PubMedGoogle Scholar
- Goff JP, Horst RL: Effects of the addition of potassium or sodium, but not calcium, to prepartum rations on milk fever in dairy cows. J Dairy Sci. 1997, 80: 176-186.PubMedGoogle Scholar
- Goff JP, Horst RL: Factors to concentrate on to prevent periparturient disease in the dairy cow with special emphasis on milk fever. The bovine proceedings. 1998, 31: 154-163.Google Scholar
- Goff JP, Horst RL: Oral administration of calcium salts for treatment of hypocalcemia in cattle. J Dairy Sci. 1993, 76: 101-108.PubMedGoogle Scholar
- Goff JP, Horst RL: Use of hydrochloric acid as a source of anions for prevention of milk fever. J Dairy Sci. 1998, 81: 2874-2880.PubMedGoogle Scholar
- Goff JP, Horst RL, Beitz DC, Littledike ET: Use of 24-F-1,25-dihydroxyvitamin D3 to prevent parturient paresis in dairy cows. J Dairy Sci. 1988, 71: 1211-1219.PubMedGoogle Scholar
- Goff JP, Horst RL, Mueller FJ, Miller JK, Kiess GA, Dowlen HH: Addition of chloride to a prepartal diet high in cations increases 1,25-dihydroxyvitamin D response to hypocalcemia preventing milk fever. J Dairy Sci. 1991, 74: 3863-3871.PubMedGoogle Scholar
- Goff JP, Horst RL, Jardon C, Borelli C, Wedam J: Field trials of an oral calcium propionate paste as an aid to prevent milk fever in periparturient dairy cows. J Dairy Sci. 1996, 79: 378-383.PubMedGoogle Scholar
- Goings RL, Jacobson NL, Beitz DC, Littledike ET, Wiggers KD: Prevention of parturient paresis by a prepartum, calcium-deficient diet. J Dairy Sci. 1974, 57: 1184-1188.PubMedGoogle Scholar
- Green HB, Horst RL, Beitz DC, Littledike ET: Vitamin D metabolites in plasma of cows fed a prepartum low-calcium diet for prevention of parturient hypocalcemia. J Dairy Sci. 1981, 64: 217-226.PubMedGoogle Scholar
- Greene WA, Galton DM, Erb HN: Effects of prepartum milking on milk production and health performance. J Dairy Sci. 1988, 71: 1406-1416.PubMedGoogle Scholar
- Greig WA: Hypervitaminosis D in cattle. Proceedings, XVIIth World Vet. Congress. 1963, 233-Google Scholar
- Hallgren W: Gepärparese. Begriff, name, behandlung, verhütung (Parturient paresis. Conception, name, treatment, prevention). Wien tierärztl. Mschr. 1965, 52: 359-369.Google Scholar
- Harris DJ: Factors predisposing to parturient paresis. Austr Vet J. 1981, 57: 357-361.Google Scholar
- Hemsley LA: Some observations on milk fever. Vet Rec. 1957, 69: 464-468.Google Scholar
- Heuer C, Schukken YH, Dobbelaar P: Postpartum body condition score and results from the first test day milk as predictors of disease, fertility, yield, and culling in commercial dairy herds. J Dairy Sci. 1999, 82: 295-304.PubMedGoogle Scholar
- Horst RL, Goff JP, Reinhardt TA: Symposium: Calcium metabolism and utilization. Calcium and vitamin D metabolism in the dairy cow. J Dairy Sci. 1994, 77: 1936-1951.PubMedGoogle Scholar
- Horst RL, Goff J, Reinhardt TA, Buxton DR: Strategies for preventing milk fever in dairy cattle. J Dairy Sci. 1997, 80: 1269-1280.PubMedGoogle Scholar
- Houe H, Østergaard S, Thilsing-Hansen T, Jørgensen RJ, Larsen T, Sørensen JT, Agge JF, Blom JY: 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. Acta Vet Scand. 2001, 42: 1-29.PubMedGoogle Scholar
- Hove K: Cyclic changes in plasma calcium and the calcium homeostatic endocrine systems of the postparturient dairy cow. J Dairy Sci. 1986, 69: 2072-2082.PubMedGoogle Scholar
- Hove K, Kristiansen T: Oral 1,25-dihydroxyvitamin D3 in prevention of milk fever. Acta Vet Scand. 1984, 25: 510-525.PubMedGoogle Scholar
- Jonsgaard K: A clinical study on parturient paresis in dairy cows. With special reference to factors related to recovery. Thesis. 1972, Dept. of obstetrics, Veterinary College of NorwayGoogle Scholar
- Jonsgaard K, Ødegaard SA, Øverby I: Peroralt tilskudd av kalsium-gel i tilslutning til intravenøs kalsiumterapi ved paresis puerperalis hos ku (Oral administration of calcium gel in support of intravenous calcium therapy in parturient paresis in the cow). Nord Vet -Med. 1971, 23: 606-619.Google Scholar
- Joyce PW, Sanchez WK, Goff JP: Effect of anionic salts in prepartum diets based on Alfalfa. J Dairy Sci. 1997, 80: 2866-2875.PubMedGoogle Scholar
- Jönsson G, Pehrson B: The effect of overfeeding in the dry period on the health of dairy cows. Proceedings. Fifth international conference on production disease in farm animals. Uppsala, Sweden, 300-303. Aug 10–12, 1983Google Scholar
- Jönsson G, Pehrson B: Trials with prophylactic treatment of parturient paresis. The Vet Rec. 1970, 87: 575-583.PubMedGoogle Scholar
- Jönsson G, Pehrson B, Lundström K, Edquist L-E, Blum JW: Studies on the effect of the amount of calcium in the prepartum diet on blood levels of calcium, magnesium, inorganic phosphorus, parathyroid hormone and hydroxyproline in milk fever prone cows. Zbl Vet Med A. 1980, 27: 173-185.Google Scholar
- Jørgensen RJ, Base A, Aslan V: Sequelae to oral calcium chloride gel dosing of cows. Proceedings, XVI World Buiatrics Congress. Salvador, Bahia, Brasil, 511-515. 13-17 August 1990Google Scholar
- Jørgensen RJ, Hansen T, Jensen ML, Thilsing-Hansen T: Effect of oral drenching with zinc oxide or synthetic zeolite A on total blood calcium in dairy cows. J Dairy Sci. 2001, 84: 609-613.PubMedGoogle Scholar
- Jørgensen RJ, Thilsing-Hansen T: A novel hypothesis for the prevention of parturient hypocalcaemia: 1. Theory and preliminary results. Proc. XXI World Buiatrics Congress, Punta del Este, Uruguay. 2000, 6441-6443.Google Scholar
- Kendall KA, Harshbarger KE, Hays RL, Ormiston EE: Preventing parturient paresis in the paretic suspect through grain feeding. J Dairy Sci. 1966, 49: 720-Google Scholar
- Kichura TS, Horst RL, Beitz DC, Littledike ET: Relationships between prepartal dietary calcium and phosphorus, vitamin D metabolism, and parturient paresis in dairy cows. J Nutr. 1982, 112: 480-487.PubMedGoogle Scholar
- Leclerc H, Block E: Effects of reducing dietary cation-anion balance for prepartum dairy cows with specific reference to hypocalcemic parturient paresis. Can J Anim Sci. 1989, 69: 411-423.Google Scholar
- Littledike ET, Horst RL: Vitamin D3 toxicity in dairy cows. J Dairy Sci. 1982, 65: 749-759.PubMedGoogle Scholar
- Lomba F, Chauvaux G, Teller E, Lengele L, Bienfet V: Calcium digestibility in cows as influenced by the excess of alkaline ions over stable acid ions in their diets. Br J Nutr. 1978, 39: 425-429.PubMedGoogle Scholar
- Moore SJ, VandeHaar MJ, Sharma BK, Pilbeam TE, Beede DK, Bucholtz HF, Liesman JS, Horst RL, Goff JP: Effects of altering dietary cation-anion difference on calcium and energy metabolism in periparturient cows. J Dairy Sci. 2000, 83: 2095-2104.PubMedGoogle Scholar
- Morrow DA, Hillman D, Dade AW, Kitchen H: Clinical investigation of a dairy herd with the fat cow syndrome. J Am Vet Med Ass. 1979, 174: 161-167.Google Scholar
- van Mosel M: Research on the mineral supply of dairy cows during the dry period in relation to prevention of milk fever. Thesis. 1991, Utrecht, Holland, Chapter VII:Google Scholar
- van Mosel M, Klooster A, Van't Th, van Mosel F, van der Kuilen J: Effects of reducing dietary ((Na+ + K+) - (Cl- + SO4--)) on the rate of calcium mobilisation by dairy cows at parturition. Res Vet Sci. 1993, 54: 1-9.PubMedGoogle Scholar
- NRC: Nutrient requirements of dairy cattle. Sixth revised edition. Update 1989. 1988, National Research Council. National Academic Press. Washington, DCGoogle Scholar
- Oetzel GR: Effect of calcium chloride gel treatment in dairy cows on incidence of periparturient diseases. JAVMA. 1996, 209: 958-961.PubMedGoogle Scholar
- Oetzel GR: Improving reproductive performance in dairy cattle via milk fever prevention. The Bovine Proceedings. 1996, 28: 52-59.Google Scholar
- Oetzel GR: Meta-analysis of nutritional risk factors for milk fever in dairy cattle. J Dairy Sci. 1991, 74: 3900-3912.PubMedGoogle Scholar
- Oetzel GR, Barmore JA: Intake of a concentrate mixture containing various anionic salts fed to pregnant, nonlactating dairy cows. J Dairy Sci. 1993, 76: 1617-1623.Google Scholar
- Oetzel GR, Olson JD, Curtis CR, Fettman MJ: Ammonium chloride and ammonium sulphate for prevention of parturient paresis in dairy cows. J Dairy Sci. 1988, 71: 3302-3309.PubMedGoogle Scholar
- Olsen MP, Jensen AE: Kælvningsfeberterapi. Et forsøg på forbedring, specielt med henblik på recidivtendensen. (Treatment of parturient paresis. An attempt at improvement, especially with regard to the tendency of recurrence). Nord Vet -Med. 1965, 7: 50-54.Google Scholar
- Payne JM, Manston R: The safety of massive doses of vitamin D3 in the prevention of milk fever. The Veterinary Record. 1967, 79: 214-216.Google Scholar
- Pehrson B, Jonsson M, Jönsson G: Försög att före-bygga kalvningsförlamning genom peroral till-försel av indkapslade Ca-salter. (An attempt to prevent milk fever by oral application of encapsulated calcium salts). Svensk Veterinärtidning. 1989, 41: 923-926.Google Scholar
- Pehrson B, Svensson C, Stengärde L: Förebyggande effekt av surgörande foder på kalvningsförlamning. (Prevention of milk fever by feeding acidifying diets). Svensk Vet Tidn. 1999, 51 (5): 241-247.Google Scholar
- Pehrson B, Svensson C, Jonsson M: A comparative study of the effectiveness of calcium propionate and calcium chloride for the prevention of parturient paresis in dairy cows. J Dairy Sci. 1998, 81: 2011-2016.PubMedGoogle Scholar
- Pickard D: The prevention of milk fever by dietary management. Br. Cattle Vet. Assoc. Proceedings for. 1987, 1-4. –88Google Scholar
- Queen WG, Miller GY, Masterson MA: Effects of oral administration of a calcium-containing gel on serum calcium concentration in postparturient dairy cows. JAVMA. 1993, 202: 607-609.PubMedGoogle Scholar
- Radostits OM, Gay CC, Blood DC, Hincliff KW: Veterinary Medicine. A textbook of the diseases of cattle, sheep, pigs, goats and horses. 2000, W. B. Saunders Co. Ltd, 9Google Scholar
- Rajala PJ, Gröhn YT: Disease occurrence and risk factors analysis in Finnish Ayrshire cows. J Dairy Sci. 1998, 81: 3172-3151.PubMedGoogle Scholar
- Ramberg JR, Johnson CFEK, Fargo RD: Calcium homeostasis in cows, with special reference to parturient hypocalcemia. Am J Phys. 1984, 15: 698-704.Google Scholar
- Reinhardt TA, Horst RL, Goff JP: Calcium, phosphorus, and magnesium homeostasis in ruminants. Vet Clin North Am: Food Anim Pract. 1988, 4: 331-350.Google Scholar
- Ringarp N: Om peroral kalciumterapi vid paresis puerperalis hos ko. (Treatment of milk fever by oral calcium supplementation). Svensk Veterinärtidning. 1965, 17: 234-237.Google Scholar
- Ringarp N, Rydberg C, Damberg O, Boström B: (The prophylaxis of milk fever in cattle by oral administration of calcium chloride gel). Zentralblatt für Veterinärmedizin. 1967, 14: 242-251.PubMedGoogle Scholar
- Rodriguez LA: Periparturient responses of cows fed varying dietary cation-anion differences and calcium contents prepartum. PhD Diss. 1998, Michigan State University, East LansingGoogle Scholar
- Rukkwamsuk T, Kruip TAM, Wensing T: Relationship between overfeeding and overconditioning in the dry period and the problems of high producing dairy cows during the postparturient period. Vet Quarterly. 1999, 21: 71-77.Google Scholar
- Sansom BF, Manston R, Vagg MJ, Mallinson CB, Contreras PA: Calcium mobilisation in hypomagnesaemic steers and cows. Proc. XIIth World congress on diseases of cattle. 1982, Amsterdam, Netherlands, 574-578.Google Scholar
- Schonewille JTh, van't Klooster ATh, Beynen AC: The addition of extra calcium to a chloride-rich ration does not affect the absolute amount of calcium absorbed by non-pregnant, dry cows. J Anim Physiol A, Anim Nutr. 1994, 72: 272-280.Google Scholar
- Scott DJ, van Wijk N: Compression in dairy cattle of mucosal toxicity of calcium formate and calcium chloride in oil. New Zealand Vet J. 1999, 48: 24-26.Google Scholar
- Seekles L, Wilson JHG: Is the use of massive doses of vitamin D (Duphafral 1.000) dangerous?. The Veterinary Record. 1964, 76: 486-487.Google Scholar
- Simesen MG, Hyldgaard-Jensen C: Kælvningsfeber-profylakse med CaC12-gel. (Prophylache treatment of partunent paresis with calcium chloride gel). Nord Vet-Med. 1971, 23: 35-43.PubMedGoogle Scholar
- Smith VR, Blosser TH: Parturient paresis. I. The incidence of parturient paresis and changes in total blood serum calcium at parturition in prepartum milked cows. J Dairy Sci. 1947, 30: 861-866.Google Scholar
- Smith EP, Keyes EA: The effect of prepartum milking upon the quality of milk produced during the subsequent lactation. J Dairy Sci. 1953, 36: 1178-Google Scholar
- Stewart PA: Modern quantitative acid-base chemistry. Can J Physiol Pharmacol. 1983, 61: 1444-1461.PubMedGoogle Scholar
- Stott GH: Parturient paresis related to dietary phosphorus. J Dairy Sci. 1965, 48: 1485-1489.PubMedGoogle Scholar
- Studer E: A veterinary perspective of on-farm evaluation of nutrition and reproduction. J Dairy Sci. 1998, 81: 872-876.PubMedGoogle Scholar
- Sørensen JT, Enevoldsen C: Effect of dry period length on milk production in subsequent lactation. J Dairy Sci. 1991, 74: 1277-1283.PubMedGoogle Scholar
- Takagi H, Block E: Effects of manipulating dietary cation-anion balance on macromineral balance in sheep. J Dairy Sci. 1991, 74: 4202-4214.PubMedGoogle Scholar
- Taurianen S, Sankari S, Pyorala S, Syrjala-Quist L: Effects of anionic salts in concentrate mixture and calcium intake on some blood and urine minerals, acid-base balance and feed intake of dry pregnant cows on grass silage based feeding. Agricultural and food science in Finland. 1998, 7: 535-543.Google Scholar
- Thatcher CD: Effects of nutrition and management of the dry and fresh cow on fertility. Bovine Pract. 1986, 21: 172-179.Google Scholar
- Thilsing-Hansen T, Jørgensen RJ: A novel hypothesis for the prevention of parturient hypocalcaemia: 2. Proof of concept. Proc. XXI World Buiatrics Congress, Punta del Este, Uruguay. 2000, 6481-6482.Google Scholar
- Thilsing-Hansen T, Jørgensen RJ: Prevention of parturient paresis and subclinical hypocalcemia in dairy cows by Zeolite A administration in the dry period. J Dairy Sci. 2001, 84: 691-693.PubMedGoogle Scholar
- Vagoni DB, Oetzel GR: Effects of dietary cation-anion difference on the acid-base status of dry cows. J Dairy Sci. 1998, 81: 1643-1652.Google Scholar
- VandeHaar MJ, Yousif G, Sharma BK, Herdt TH, Emery RS, Allen MS, Liesman JS: Effect of energy and protein density of prepartum diets on fat and protein metabolism of dairy cows in the peri-partum period. J Dairy Sci. 1999, 82: 1282-1295.PubMedGoogle Scholar
- Verdaris JN, Evans JL: Diet calcium and pH versus mineral balance in holstein cows 84 days pre- to 2 days postpartum. J Dairy Sci. 1976, 59: 1271-1277.PubMedGoogle Scholar
- Wang C, Beede DK: Effects of ammonium chloride and sulphate on acid-base status and calcium metabolism of dry cows. J Dairy Sci. 1992, 75: 820-828.PubMedGoogle Scholar
- Wang C, Beede DK: Effect of diet magnesium on acid-base status and calcium metabolism of dry cows fed acidogenic salts. J Dairy Sci. 1992, 75: 829-836.PubMedGoogle Scholar
- Wentink GH, van den Ingh TSGAM: Oral administration of calcium chloride containing products: Testing for deleterious side effects. Vet Quarterly. 1992, 14: 76-80.Google Scholar
- Westerhuis JH: Parturient hypocalcaemia prevention in parturient cows prone to milk fever by dietary measures. Tijdschr Diergeneeskd. 1975, 100 (4): 213-220.PubMedGoogle Scholar
- Wiggers KD, Nelson DK, Jacobson NL: Prevention of parturient paresis by low-calcium diet prepartum: A field study. J. Dairy Sci. 1975, 58: 430-431.PubMedGoogle Scholar
- Wilson GF: A novel nutritional strategy to prevent milk fever and stimulate milk production in dairy cows. New Zealand Vet J. 2001, 49: 78-80.Google Scholar
- Wittwer F, Ford EJH, Faull WB: An attempt to prevent milk fever. Proceed. 3rd. International Conference on production diseases, Wageningen, Netherlands. 1976, 115-116.Google Scholar
- Zeliger Y, Volcani R, Sklan D: Yield and protein composition in cows milked prepartum. J Dairy Sci. 1973, 56: 869-872.PubMedGoogle Scholar
- Østergaard S, Gröhn YT: Effects of diseases on test day milk yield and body weight of dairy cows from danish research herds. J Dairy Sci. 1999, 82: 1188-1201.PubMedGoogle Scholar