Subclinical Hypocalcaemia

Background

Clinical hypocalcaemia, commonly referred to as milk fever, has been reported in bovine health literature for over 200 years. Cases are typically seen in the immediate postpartum period, with total blood calcium levels falling below 1.4mmol/l. This leads to an array of clinical signs such as recumbency, bloat, constipation, and tachycardia to name but a few. Significant advances in transition cow management through the critical days before and immediately after calving has dramatically reduced the incidence of milk fever in modern dairy herds, and the focus of recent research has been on the subclinical form of the condition.

Subclinical hypocalcaemia (SCH) refers to the state of low blood calcium levels in the absence of clinical signs. However, creating a clear definition of this is challenging, particularly with regards to a blood threshold and the exact timing at which this is actually detrimental to the cow. This also makes prevalence estimations of SCH difficult to interpret, with ranges from 20 – 78% reported across a range of studies, in different settings, using different thresholds and time points. Extensive work, predominantly from North America, has investigated the dynamics of postpartum blood calcium levels, and the impact this has on lactational performance. 

Diagnosis of SCH

As touched on above, the diagnosis of SCH is challenging because varying thresholds are reported in the literature and this introduces uncertainty as to when low blood calcium, in the absence of clinical signs, has a downstream impact. All cows at time of calving will see their blood calcium levels decline as they come into milk production so typically, unless there are clear signs of clinical hypocalcaemia, looking at total calcium levels at this stage does not yield much useful information. 

Serial blood sampling from 1 – 4 days in milk (DIM) has been performed in research settings to try and address the challenges of diagnosing SCH. Clearly, in practice this serial sampling is not practical. However, this work has demonstrated that SCH is only detrimental at 2 DIM for primiparous animals, and 4 DIM for multiparous animals. It should be noted here that work in primiparous animals is not as extensive. Naturally, these animals are at lower risk of calcium disturbances in early lactation so widespread data on this group is not currently available. For the remainder of this article, only work on multiparous animals will be discussed.

At 1 DIM, total blood calcium levels of between 1.8 and 2.0mmol/l have been used in the literature to define SCH. Though as discussed above detrimental impacts have only been associated with SCH from 4DIM, where a target threshold of 2.2mmol/l is consistently reported. Based on these findings, researchers have proposed the following dynamics for SCH, relevant to diagnosis at 1 and 4 DIM:

• Normocalcaemic: >1.8mmol/l on D1, >2.2mmol/l on D4

• Transient SCH: <1.8mmol/l on D1, >2.2mmol/l on D4

• Persistent SCH: <1.8mmol/l on D1, <2.2mmol/l on D4

• Delayed SCH: >1.8mmol/l on D1, <2.2mmol/l on D4

Interestingly, in some studies, cows that fall into the transient SCH group actually go on to produce more milk than those in other groups, including the normocalcaemic group, and do not suffer from reduced intakes or increased disease incidence. This may therefore be indicative of a beneficial homeorhetic adaptation to lactation. On the other hand, cows in the persistent and delayed group are those which have poorer health and production performance (discussed below) for the remainder of lactation. Therefore, simplification can be applied in classifying and diagnosing SCH, whereby cows with total blood calcium <2.2mmol/l on D4 can be classed as “dyscalcaemic”, and those with >2.2mmol/l on D4 as “eucalcaemic”. 

The final challenge with diagnosing SCH is knowing how many cows to sample and what the indications for investigating are. This is still somewhat of an unknown. The focus should be a herd level factor to investigate SCH, alongside other transition disorders. As with investigating other transition issues such as herd level ketosis, reasonable numbers of cows need to be sampled to achieve confidence in a diagnosis. This is clearly a challenge as many farms will not have sufficient cows at 4DIM at any one time to be able to sample, and costs may be prohibitive for some. Reasonable confidence should be achieved if 12 cows are sampled, and this can be done over time and may require training of staff to take the samples at 4DIM which can be refrigerated and collected at the next vet visit. Whether this makes up part of routine herd management, or in response to a wider transition cow issue, will vary and be dependent on the farm in question.

Impact and Prevention of SCH

Dyscalcaemia, as defined above, has been shown to have profound effects on health, yield and reproductive performance. Increased risk of a disease event (ketosis, metritis, left displaced abomasum) and herd removal within the first 60DIM has been shown in dyscalcaemic cows, as well as reduced dry matter intake in early lactation. Interestingly, when investigating yield impact, only the previously defined “delayed SCH” had a reduced average daily milk yield in early lactation, and this was not found to be the case in the “persistent SCH” cows. On fertility, all dyscalcaemic cows have been shown to have reduced odds of pregnancy to first service, reduced hazard of pregnancy by 150DIM, and an increased calving-conception interval. 

The exact mechanism for development of SCH is unknown, but it seems likely linked to dry matter intakes, periparturient inflammation and, more simply, an inappropriate transition cow diet. Prevention therefore lies with general transition cow management and the usual milk fever prevention strategies, details of which are beyond the scope of this article. There has been some work investigating treatment of SCH, particularly around the timing of calcium bolus administration. Though the theory behind delaying calcium bolus administration based on the dynamics of SCH discussed earlier seems appealing, there is very little evidence to show any benefit of this, beyond the usual impact of bolusing “higher-risk” milk fever cows, which is commonplace on many farms.  

Summary 

In summary, SCH can reasonably be defined as multiparous cows having total blood calcium concentrations <2.2mmol/l at 4DIM, with these cows having poorer health, production and reproductive outcomes. Though it should be noted that this definition has predominantly come from high input North American systems, and may not be directly translatable to other systems. Herd level diagnosis of SCH should lead to interventions in transition cow management and feeding, and continual monitoring may be beneficial to assess the impact of any interventions.

Further Reading:

McArt JAA, Oetzel GR. Considerations in the Diagnosis and Treatment of Early Lactation Calcium Disturbances. Vet Clin North Am Food Anim Pract. 2023 Jul;39(2):241-259. doi: 10.1016/j.cvfa.2023.02.009. Epub 2023 Apr 7. PMID: 37032301.

Seely CR, McArt JAA. The association of subclinical hypocalcemia at 4 days in milk with reproductive outcomes in multiparous Holstein cows. JDS Commun. 2022 Dec 14;4(2):111-115. doi: 10.3168/jdsc.2022-0279. PMID: 36974225; PMCID: PMC10039242.

Seely CR, Wilbur CN, Fang KM, McArt JAA. Effects of timing of oral calcium administration on milk production in high-producing early-lactation Holstein cows. J Dairy Sci. 2024 Mar;107(3):1620-1629. doi: 10.3168/jds.2023-23541. Epub 2023 Oct 6. PMID: 37806623.