The purpose of this study was to describe the epidemiology of subclinical ketosis (SCK) in dairy cows in early lactation and determine the association of (1) days in milk (DIM) at onset of SCK, and ...(2) blood β-hydroxybutyrate (BHBA) concentration at onset of SCK with development of displaced abomasum (DA) and removal from herd in the first 30 DIM, conception to first service, days to conception within 150 DIM, and early lactation milk yield. Cows from 4 freestall dairy herds (2 in New York and 2 in Wisconsin) were each tested 6 times for SCK from 3 to 16 DIM using the Precision Xtra meter (Abbott Laboratories, Abbott Park, IL). Subclinical ketosis was defined as a BHBA concentration of 1.2 to 2.9mmol/L. Mixed-effects multivariable Poisson regression was used to assess DA, removal from herd, and conception to first service. Semiparametric proportional hazards models were used to evaluate days to conception, and repeated-measures ANOVA was used to evaluate milk yield in the first 30 DIM. A total of 741 of 1,717 (43.2%) eligible cows had a least one BHBA test of 1.2 to 2.9mmol/L. Peak incidence of SCK occurred at 5 DIM, when 22.3% of cows had their first SCK-positive test. Peak prevalence of SCK occurred at 5 DIM, when 28.9% of cows had a SCK-positive test. Median time from first positive SCK test until BHBA test <1.2mmol/L was 5d. Cows first testing SCK positive from 3 to 5 DIM were 6.1 times more likely 95% confidence interval (CI) = 2.3 to 16.0 to develop a DA than cows first testing SCK positive at 6 DIM or later. Cows first testing SCK positive from 3 to 7 DIM were 4.5 times more likely (95% CI = 1.7 to 11.7) to be removed from the herd, were 0.7 times as likely (95% CI = 0.6 to 0.8) to conceive to first service, and produced 2.2kg less milk per day for the first 30 DIM than cows first testing positive at 8 DIM or later. Each 0.1mmol/L increase in BHBA at first SCK-positive test increased the risk of developing a DA by a factor of 1.1 (95% CI = 1.0 to 1.2), increased the risk of removal from herd by a factor of 1.4 (95% CI = 1.1 to 1.8), and was associated with a decrease in milk production by 0.5kg/d for the first 30DIM. These results show that time of onset and BHBA concentration of first SCK-positive test are important indicators of individual cow performance.
The objectives of this study were to 1) establish cow-level critical thresholds for serum concentrations of nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) to predict periparturient ...diseases displaced abomasa (DA), clinical ketosis (CK), metritis and retained placenta, or any of these three, and 2) investigate the magnitude of the metabolites’ association with these diseases within 30 d in milk. In a prospective cohort study of 100 freestall, total mixed ration-fed herds in the northeastern United States, blood samples were collected from approximately 15 prepartum and 15 different postpartum transition animals in each herd, for a total of 2,758 samples. Serum NEFA concentrations were measured in the prepartum group, and both NEFA and BHBA were measured in the postpartum group. The critical thresholds for NEFA or BHBA were evaluated with receiver operator characteristic analysis for all diseases in both cohorts. The risk ratios (RR) of a disease outcome given NEFA or BHBA concentrations and other covariates were modeled with multivariable regression techniques, accounting for clustering of cows within herds. The NEFA critical threshold that predicted any of the 3 diseases in the prepartum cohort was 0.29mEq/L and in the postpartum cohort was 0.57mEq/L. The critical threshold for serum BHBA in the postpartum cohort was 10mg/dL, which predicted any of the 3 diseases. All RR with NEFA as a predictor of disease were >1.8; however, RR were greatest in animals sampled postpartum (e.g., RR for DA=9.7; 95% CI=4.2 to 22.4. All RR with BHBA as the predictor of disease were >2.3 (e.g., RR for DA=6.9; 95% CI=3.7 to 12.9). Although prepartum NEFA and postpartum BHBA were both significantly associated with development of clinical disease, postpartum serum NEFA concentration was most associated with the risk of developing DA, CK, metritis, or retained placenta during the first 30 d in milk.
The objectives were to evaluate the effects of elevated pre- and postpartum nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) concentrations during the transition period on reproductive ...performance and milk production in dairy cattle. In a prospective cohort study of 91 freestall, total mixed ration-fed herds in the northeastern United States, blood samples were collected from approximately 15 prepartum and 15 different postpartum transition animals in each herd. All samples were stratified based on pre- or postpartum status at the time of sample collection, and 2,259 and 2,290 animals were used to evaluate reproductive and milk production performance, respectively. Reproductive performance was assessed by time to conception within 70 d post-voluntary waiting period (VWP) and milk production was assessed using mature-equivalent 305-d (ME305) milk yield estimated at 120 d in milk. While controlling for body condition score (BCS), calving season, median ME305 milk production, and parity, NEFA and BHBA concentrations were evaluated with time to event analysis to investigate reproductive performance. These same predictor variables were used to determine the effects of elevated NEFA and BHBA concentrations on ME305 milk yield with herd as a random effect. Heifers and cows were grouped in the final analyses if the results between groups were similar. In all animals sampled prepartum, the risk of pregnancy within 70 d post-VWP was reduced by 19% when NEFA concentrations were ≥0.27mEq/L. In all animals sampled postpartum, those with NEFA concentrations ≥0.72mEq/L had a 16% decrease in risk of pregnancy and those with BHBA concentrations ≥10mg/dL had a 13% decrease in risk. In cows and heifers, ME305 milk yield was decreased by 683kg when prepartum NEFA concentrations were ≥0.33mEq/L. In heifers sampled postpartum, ME305 milk yield was increased by 488kg when NEFA concentrations were ≥0.57mEq/L and increased by 403kg when BHBA concentrations were ≥9mg/dL. In cows sampled postpartum, ME305 milk yield was decreased by 647kg when NEFA concentrations were ≥0.72mEq/L and decreased by 393kg when BHBA concentrations were ≥10mg/dL. With the exception of milk production in heifers, this study indicates that increased concentrations of serum NEFA and BHBA had a detrimental effect on reproductive performance and milk production.
In this study the herd alarm level was defined as the proportion of sampled transition cows per herd with increased prepartum nonesterified fatty acid (NEFA), postpartum β-hydroxybutyrate (BHBA), or ...NEFA concentrations that were associated with herd-level incidence of displaced abomasum (DA) or clinical ketosis (CK), pregnancy rate (PR), and milk production. The objectives were to 1) identify the herd alarm level for excessive negative energy balance and 2) describe the herd-level prevalence of this proportion. This was a prospective cohort study of 60 free-stall herds fed total mixed rations in the northeast United States. Two cohorts of approximately 15 animals were assessed for prepartum NEFA and postpartum BHBA and NEFA. The herd alarm level (i.e., the proportion of sampled animals above a certain metabolite threshold) was as follows: 15% had prepartum NEFA of 0.27 mEq/L; 15 and 20% had BHBA of 10 and 12 mg/dL, respectively; and 15% had postpartum NEFA of 0.60 and 0.70 mEq/L. The different herd alarm levels correspond to differences between the metabolites and respective herd-level effect. The herd-level effects for herds above the herd alarm level for prepartum NEFA were 3.6% increase in DA and CK incidence, 1.2% decrease in PR, and 282kg decrease in average mature equivalent 305-d (ME 305) milk. For BHBA, the herd-level effects were a 1.8% increase in DA and CK, 0.8% decrease in PR, and 534 and 358kg decrease in projected ME 305 milk yield for heifers and cows, respectively. For postpartum NEFA, the herd-level effects were 1.7% increase in DA and CK, 0.9% decrease in PR, and 288 and 593kg decrease in projected ME 305 milk yield for heifers and cows, respectively. The prevalence of herds in which more than 15% of animals sampled had prepartum NEFA concentration ≥0.30 mEq/L was 75%, BHBA ≥12 mg/dL was 40%, and postpartum NEFA ≥0.70 mEq/L was 65%. This study showed that there were detrimental herd-level effects if a large enough proportion of cows had increased metabolite concentrations, and further demonstrated that a high prevalence of herds have opportunity for improvement.
The objectives of this study were to obtain prevalence estimates for subclinical endometritis (SCE), determine cow- and herd-level risk factors, and evaluate the reproductive consequences of SCE. A ...cross-sectional study was used to determine prevalence and risk factors with cows followed in a prospective study to determine reproductive outcomes. Lactating Holstein cows were sampled between 40 and 60 d in milk using low-volume uterine lavage, and cytology was evaluated to determine SCE status. In total, 779 cows from 38 herds were used in the analysis. The cow-level prevalence of SCE was 25.9%. Within-herd level prevalence ranged from 4.8 to 52.6% (median 26.3%, interquartile range 15.6 to 33.3%). Cow-level risk factors identified were ketosis odds ratio (OR) 3.83; 95% confidence interval (CI) 1.82–8.07, acute metritis (OR 1.86; 95% CI 1.05–3.30, and the interaction between milk production and parity. Primiparous cows that produced more milk had increased odds of having SCE, whereas multiparous cows that produced more milk had decreased odds of having SCE. Herd-level risk factors identified were housing early postpartum cows on bedded packs (herd-level SCE=36.1%), which increased herd prevalence of SCE by 16.7% (SE 5.58) compared with early postpartum cows housed in freestalls (herd-level SCE=19.4%), and straw bedding in the calving pen, which decreased herd prevalence of SCE by 10.7% (SE 3.59) compared with herds that used other bedding material. In this study, primiparous cows with and without SCE had similar reproductive performance; however, multiparous cows with SCE had median days open 44 d longer (159 d; 95% CI 126–186 d) compared with unaffected multiparous cows (115 d; 95% CI 106–132 d).
The objective of this study was to determine the effects of subclinical hypocalcemia on reproductive performance in dairy cows. In a prospective cohort study, 97 cows on 2 dairy farms with automatic ...milking systems were monitored for subclinical hypocalcemia. Animals were enrolled 7 ± 3 days prior to estimated calving date and three parity groups were defined based on the lactation that the animals were going to start: lactation = 1, lactation = 2, and lactation ≥3. Serum calcium concentration (Ca) was measured in all animals in the first 3 DIM and subclinical hypocalcemia (SCH) was defined as Ca ≤ 8.6 mg/dL; animals that presented a low Ca level during all 3 days were classified as chronic SCH (cSCH). Return to cyclicity during the voluntary waiting period was analyzed based on weekly progesterone concentrations measured in serum. Information on reproductive outcomes (i.e., number of breedings, pregnancy status, days open, etc.), were collected from on-farm software after all study cows had completed their study period. Chronic SCH was present in all parity groups with higher incidence in multiparous animals (20% of parity = 1, 32% of parity = 2; and 46% of parity ≥ 3 animals). The cSCH animals took longer to show active ovaries when compared to eucalcemic and SCH animals. In a multivariable Cox's Proportional Hazard model animals with normal Ca were 1.8 times more likely to return to cyclicity by the end of the voluntary waiting period when compared to cSCH animals. Animals with cSCH also had 0.27 odds of being pregnant at first service compared to eucalcemic cows when analyzed by multivariable logistic regression. Subclinical hypocalcemia had a negative effect on return of ovarian function during the voluntary waiting period and decreased the odds of pregnancy at first service. Those cows with cSCH had an even more pronounced impaired reproductive function than those with one subclinical measurement.
•Chronic subclinical hypocalcemia (cSCH) was present in all parities groups.•Subclinical hypocalcemia had a negative effect on return of ovarian function.•Subclinical hypocalcemia decreased the odds of pregnancy at first service.•Cows with cSCH had impaired reproductive function.
Our aim in this Journal of Dairy Science centennial review is to describe the evolution of focus on metabolic indicators, from discovery and description to evaluation at the individual cow and ...subsequently herd levels, over the past 100 yr. Furthermore, we discuss current and future technologies that will be used in the dairy industry to utilize these indicators widely going forward. Knowledge of chemical changes in various fluids (e.g., blood, urine, and milk) accompanying numerous metabolic disease states in the dairy cow has existed since almost the beginning of the Journal of Dairy Science 100 yr ago. However, only during the last 25 yr have these metabolic indicators been developed into useful tools for cow- and herd-level monitoring for disease and management. From the 1920s through the 1940s, our understanding of the changes in blood chemistry accompanying milk fever and ketosis increased, as did our understanding of the underlying biology. In the 1950s and 1960s, workers studying ketosis and energy metabolism began to evaluate changes in lipid metabolism reflected by concentrations of circulating nonesterified fatty acids; furthermore, initial development occurred for on-farm tests of milk ketones. During the 1970s, blood metabolic profiling was applied to dairy farms but found to be of varied and limited usefulness. The turning point occurred when large epidemiologic studies of periparturient cow disease were pioneered in the United States, Canada, and Europe in the 1980s; these studies further solidified our understanding of risk factors and epidemiological interrelationships among disease, production, and reproduction. In the early 1990s, scientists first incorporated indicators of metabolic health into large observational studies and determined important epidemiological relationships between these indicators and outcomes of interest. This field of study blossomed during the 2000s as several research groups conducted multiple investigations into metabolic indicators related to energy metabolism and began to develop cow-level thresholds and herd-level alarms for use in monitoring and management. This work was accompanied by additional studies to validate point-of-care instruments that could be used to implement these strategies at the cow and herd levels. Work in the 2000s continued to identify and evaluate other physiological indicators of inflammation and oxidative stress; however, these have yet to be incorporated into large-scale cohort studies. Finally, use of technology (e.g., activity monitoring, cow-monitoring collars and tags, milk-based analysis using Fourier transform infrared spectroscopy) continues to receive significant attention going forward to eventually allow for real-time and automatic monitoring of metabolic indicators and improved health and herd management on dairy farms.
The purpose of this study was to determine the effect of oral propylene glycol (PG) administration on ketosis resolution and milk yield in cows diagnosed with subclinical ketosis (SCK). Cows from 4 ...freestall dairy herds (2 in New York and 2 in Wisconsin) were each tested 6 times for SCK from 3 to 16 d in milk on Mondays, Wednesdays, and Fridays. Subclinical ketosis was defined as a β-hydroxybutyrate (BHBA) concentration of 1.2 to 2.9mM/L, and clinical ketosis was defined as ≥3.0mM/L. Cows with SCK were randomized to the treatment group (oral PG) or control group (no PG); treatment cows were drenched with 300mL of PG once daily from the day they tested 1.2 to 2.9mM/L until the day they tested <1.2mM/L. Outcomes evaluated for all farms included time from SCK until BHBA test <1.2mM/L or until BHBA test ≥3.0mM/L. Individual milk weights for the first 30 d of lactation were evaluated for the 3 farms monitoring daily milk. Semiparametric proportional hazards models were used to evaluate time to event outcomes; repeated-measures ANOVA was used to assess milk weights. A total of 741 of 1,717 (43.2%) eligible enrolled cows had at least one BHBA test of 1.2 to 2.9mM/L. Of these, 372 were assigned to the treatment group and 369 to the control group. Based on hazard ratios, PG-treated cows were 1.50 times more likely (95% confidence interval=1.26 to 1.79) to resolve their SCK and 0.54 times less likely (95% confidence interval=0.34 to 0.86) to develop clinical ketosis than control cows. Across the 3 herds measuring individual milk weights, treated cows produced 0.23kg more milk per milking in the first 30 d of lactation than control cows, for a total difference of 0.69kg/cow per day. After identification of a treatment by herd interaction, stratification by herd showed that treated cows produced more milk per milking on farm A (0.44kg) and farm B (0.53kg) in the first 30 d of lactation than control cows, for a total difference of 1.34 and 1.59kg/d, respectively; milk production did not differ (0.02kg per milking) between the 2 groups on farm D. These results show the positive effects of oral PG administration in fresh cows with SCK by helping to resolve SCK and preventing clinical ketosis. In addition, oral PG improves milk yield during early lactation in cows diagnosed with SCK.
The objectives were as follows: (1) establish cow-level thresholds for prepartum nonesterified fatty acids (NEFA) and postpartum NEFA, β-hydroxybutyrate (BHB), and haptoglobin (Hp) concentrations ...associated with negative health events; (2) evaluate cow-level associations between biomarkers and 305-d mature equivalent milk at the fourth test day (ME305) and reproductive performance; and (3) identify herd-alarm levels (proportion of cows sampled above the critical threshold) for biomarkers that are associated with herd-level changes in disorder incidence (displaced abomasum and clinical ketosis), reproductive performance, and ME305. In a prospective cohort study, 1,473 cows from 72 farms were enrolled from the northeastern United States. Blood samples were collected from the same 11 to 24 cows per herd during the late-prepartum and early-postpartum periods. Whole blood was analyzed for postpartum BHB concentrations; plasma was analyzed for prepartum and postpartum NEFA and postpartum Hp concentrations. Critical thresholds for the biomarkers associated with health events for all cows were established using a receiver operating characteristic curve analysis. Poisson, linear mixed effects, and Cox proportional hazards models investigated the association of the biomarkers with health and performance. The prepartum NEFA and Hp threshold associated with culling was ≥0.17 mmol/L and 0.45 g/L, respectively. The postpartum NEFA and BHB thresholds associated with diagnosis of metritis, displaced abomasum, or clinical ketosis were ≥0.46 mmol/L and ≥0.9 mmol/L, respectively. Multiparous cows with prepartum NEFA concentration ≥0.17 mmol/L produced 479 kg less ME305. Multiparous and primiparous cows with postpartum NEFA concentration ≥0.46 mmol/L produced 280 kg less and 446 kg more ME305, respectively. Cows with BHB concentration ≥0.9 and ≥1.1 mmol/L produced 552 kg more ME305 and had a 20% decreased risk of pregnancy within 150 d in milk, respectively; however, multiparous cows with BHB concentration ≥1.5 mmol/L produced 376 kg less ME305. Cows with Hp concentration ≥0.45 g/L produced 492 kg less ME305 and had 28% decreased risk of pregnancy within 150 DIM. Cows with Hp concentration ≥0.45 g/L had 19% decreased pregnancy risk to first service (PRFS). Herds above the herd-alarm levels for prepartum NEFA had a 6.0-percentage unit increase in disorder incidence and a 6.0-percentage unit decrease in 21-d pregnancy rate (PR) for multiparous cows, a 3.9-percentage unit increase in PR and a 5.8-percentage unit increase in the probability of pregnancy for primiparous cows. Herds above the herd-alarm levels for postpartum NEFA had a 5.8- and 4.2-percentage unit increase in disorder incidence for multiparous and primiparous cows, respectively, a 789 kg decrease in ME305 for multiparous cows, and a 6.8- and 6.3-percentage unit decrease and increase in PR and PRFS for multiparous cows, respectively. Herds above the herd-alarm levels for BHB had an 8.5-percentage unit increase in disorder incidence, a 332 and 229 kg increase in ME305 for primiparous and multiparous cows, respectively, and a 3.2-, 5.2-, and 7.0-percentage unit decrease in PR, probability of pregnancy, and PRFS, respectively. Herds above the herd-alarm levels for postpartum Hp had a 5.3-percentage unit increase in disorder incidence. At the cow level and herd level, elevated biomarker concentrations were associated with an increased disorder risk and varied performance responses.
An algorithm using only computer-based records to guide selective dry-cow therapy was evaluated at a New York State dairy farm via a randomized field trial. DairyComp 305 (Valley Ag Software, Tulare, ...CA) and Dairy Herd Improvement Association test-day data were used to identify cows as low risk (cows that might not benefit from dry-cow antibiotics) or high risk (cows that will likely benefit). Low-risk cows were those that had all of the following: somatic cell count (SCC) ≤200,000 cells/mL at last test, an average SCC ≤200,000 cells/mL over the last 3 tests, no signs of clinical mastitis at dry-off, and no more than 1 clinical mastitis event in the current lactation. Low-risk cows were randomly assigned to receive intramammary antibiotics and external teat sealant (ABXTS) or external teat sealant only (TS) at dry-off. Using pre-dry-off and postcalving quarter-level culture results, low-risk quarters were assessed for microbiological cure risk and new infection risk. Groups were also assessed for differences in first-test milk yield and linear scores, individual milk weights for the first 30 d, and culling and mastitis events before 30 d in milk. A total of 304 cows and 1,040 quarters in the ABXTS group and 307 cows and 1,058 quarters in the TS group were enrolled. Among cows to be dried, the proportion of cows that met low-risk criteria was 64% (n = 611/953). Of cultures eligible for bacteriological cure analysis (n = 171), 93% of ABXTS cured, whereas 88% of TS cured. Of the non-cures, 95% were contributed by the minor pathogens coagulase-negative staphylococci (n = 19/20). These organisms also accounted for 57.5% of new infections (n = 77/134). We found no statistical differences between treatment groups for new infection risk (TS = 7.3% quarters experiencing new infections; ABXTS = 5.5%), milk production (ABXTS = 40.5 kg; TS = 41.2 kg), linear scores (ABXTS = 2.5; TS = 2.7), culling events (ABXTS, n = 18; TS, n = 15), or clinical mastitis events (ABXTS, n = 9; TS, n = 5). Results suggest that the algorithm used decreased dry-cow antibiotic use by approximately 60% without adversely affecting production or health outcomes.
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