Development and evaluation of predictive models for pregnancy risk in UK dairy cows.

One suggested approach to improve the reproductive performance of dairy herds is through the targeted management of subgroups of biologically similar animals, such as those with similar probabilities of becoming pregnant, termed pregnancy risk. We aimed to use readily available farm data to develop predictive models of pregnancy risk in dairy cows. Data from a convenience sample of 108 dairy herds in the UK were collated and each herd was randomly allocated, at a ratio of 80:20, to either training or testing data sets. Following data cleaning, there were a total of 78 herds in the training data set and 20 herds in the testing data set. Data were further split by parity into nulliparous, primiparous, and multiparous subsets. An XGBoost model was trained to predict the insemination outcome in each parity subset, with predictors from farm records of breeding, calving and milk recording. Training data comprised 74,511 inseminations in 45,909 nulliparous animals, 86,420 inseminations in 39,439 primiparous animals, and 158,294 inseminations in 32,520 multiparous animals. The final models were evaluated by predicting with the testing data, comprising 31,740 inseminations in 19,647 nulliparous animals, 38,588 inseminations in 16,215 primiparous animals, and 65,049 inseminations in 12,439 multiparous animals. Model discrimination was assessed by calculating the area under receiver operating characteristic curves (AUC); model calibration was assessed by plotting calibration curves and compared across test herds by calculating the expected calibration error (ECE) in each test herd. The models were unable to discriminate between insemination outcomes with high accuracy, with an AUC of 0.63, 0.59 and 0.62 in the nulliparous, primiparous and multiparous subsets, respectively. The models were generally well-calibrated, meaning the model-predicted pregnancy risks were similar to the observed pregnancy risks. The mean (SD) ECE in the test herds was 0.038 (0.023), 0.028 (0.012) and 0.020 (0.008) in the nulliparous, primiparous and multiparous subsets respectively. The predictive models reported here could theoretically be used to identify subgroups of animals with similar pregnancy risk to facilitate targeted reproductive management; or provide information about cows' relative pregnancy risk compared with the herd average, which may support on-farm decision-making. Further research is needed to evaluate the generalizability of these predictive models and understand the source of variation in ECE between herds; however, this study demonstrates that it is possible to accurately predict pregnancy risk in dairy cows using readily available farm data.

Using Object-Oriented Simulation to Assess the Impact of the Frequency and Accuracy of Mobility Scoring on the Estimation of Epidemiological Parameters for Lameness in Dairy Herds.

Mobility scoring data can be used to estimate the prevalence, incidence, and duration of lameness in dairy herds. Mobility scoring is often performed infrequently with variable sensitivity, but how this impacts the estimation of lameness parameters is largely unknown. We developed a simulation model to investigate the impact of the frequency and accuracy of mobility scoring on the estimation of lameness parameters for different herd scenarios. Herds with a varying prevalence (10, 30, or 50%) and duration (distributed around median days 18, 36, 54, 72, or 108) of lameness were simulated at daily time steps for five years. The lameness parameters investigated were prevalence, duration, new case rate, time to first lameness, and probability of remaining sound in the first year. True parameters were calculated from daily data and compared to those calculated when replicating different frequencies (weekly, two-weekly, monthly, quarterly), sensitivities (60-100%), and specificities (95-100%) of mobility scoring. Our results showed that over-estimation of incidence and under-estimation of duration can occur when the sensitivity and specificity of mobility scoring are <100%. This effect increases with more frequent scoring. Lameness prevalence was the only parameter that could be estimated with reasonable accuracy when simulating quarterly mobility scoring. These findings can help inform mobility scoring practices and the interpretation of mobility scoring data.

A prospective cohort study of factors associated with the digital cushion thickness in dairy cattle.

Key factors such as stage of lactation, parity, and body fat reserves have been associated with the digital cushion thickness (DCT), however, there are discrepancies between the results of previously published studies. The objective of this study was to examine the association of stage of lactation, body fat reserves, parity, and lesion incidence with DCT in a large cohort of intensively monitored cows. Across 4 UK farms, 2,352 cows were prospectively enrolled and assessed at 4 time points: before calving (T1-Precalving), immediately after calving (T2-Calving), in early lactation (T3-Early), and in late lactation (T4-Late). At each time point, BCS was recorded, the presence of sole lesions (sole ulcers and sole hemorrhage) and white line lesions was assessed by veterinarians, and an ultrasound image was taken to retrospectively measure the backfat thickness (BFT) in the pelvic region and the digital cushion on the hind left lateral claw. Mixed effects multivariable linear regression models, with the cow as a random effect, were fit to examine the association between the explanatory variables and DCT. The explanatory variables tested were farm, parity, stage of lactation, BCS, BFT, height, the presence of a lesion at the time of measurement, the chronicity of a lesion during early lactation, the predicted maximum daily milk yield, and the rate of milk production rise in early lactation. Stage of lactation and farm were both associated with DCT; however, an interaction was present, and this DCT pattern of change was farm-dependent. Two distinct patterns emerged; one indicated the nadir to occur shortly after calving, the other indicated the nadir to occur during early lactation. Neither BFT nor BCS were significantly associated with DCT. Heifers displayed thinner digital cushions compared with multiparous cows; however, this effect was dependent on the stage of lactation, with heifers having a thinner digital cushion up until late lactation, by which time DCT was commensurate with multiparous animals. Sole lesions and white line lesions at the time of measurement were associated with DCT (sole lesion: estimate = -0.07 mm, 95% CI = -0.14-0.00; white line lesion: estimate = 0.28 mm, 95% CI = 0.15-0.42).

A prospective cohort study examining the association of claw anatomy and sole temperature with the development of claw horn disruption lesions in dairy cattle.

Foot characteristics have been linked to the development of sole lesions (sole hemorrhage and sole ulcers) and white line lesions, also known as claw horn disruption lesions (CHDL). The objective of this study was to examine the association of claw anatomy and sole temperature with the development of CHDL. A cohort of 2,352 cows was prospectively enrolled from 4 UK farms and assessed at 3 time points: before calving (T1-precalving), immediately after calving (T2-calving), and in early lactation. At each time point body condition score was recorded, a thermography image of each foot was taken for sole temperature measurement, the presence of CHDL was assessed by veterinary surgeons, and an ultrasound image was taken to retrospectively measure the digital cushion and sole horn thickness. Additionally, at the postcalving time point, foot angle and heel depth were recorded. Four multivariable logistic regression models were fit to separately examine the relationship of precalving and postcalving explanatory variables with the development of either white line lesions or sole lesions. Explanatory variables tested included digital cushion thickness, sole horn thickness, sole temperature, foot angle, and heel depth. Farm, parity, body condition score, and presence of lesion at the time of measurement were also included in the models. A thicker digital cushion shortly after calving was associated with decreased odds of cows developing sole lesions during early lactation (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.65-0.84). No association was found between digital cushion thickness and development of white line lesions. Sole temperature after calving was associated with increased odds of the development of sole lesions (OR: 1.03, 95% CI: 1.02-1.05), and sole temperature before and after calving was associated with the development of white line lesions (T1-precalving OR: 1.04, 95% CI: 1.01-1.07; T2-calving OR: 0.96, 95% CI: 0.93-0.99). Neither foot angle nor heel depth was associated with the development of either lesion type. However, an increased sole horn thickness after calving reduced the odds of cows developing sole lesions during early lactation (OR: 0.88, 95% CI: 0.83-0.93), highlighting the importance of maintaining adequate sole horn when foot trimming. Before calving, animals with a lesion at the time of measurement and a thicker sole were more likely to develop a sole lesion (OR: 1.23, 95% CI: 1.09-1.40), compared with those without a sole lesion. The results presented here suggest that white line and sole lesions may have differing etiopathogenesis. Results also confirm the association between the thickness of the digital cushion and the development of sole lesions, highlight the association between sole horn thickness and sole lesions, and challenge the potential importance of foot angle and heel depth in the development of CHDL.

Single-step genome-wide association analyses of claw horn lesions in Holstein cattle using linear and threshold models.

BACKGROUND: Lameness in dairy cattle is primarily caused by foot lesions including the claw horn lesions (CHL) of sole haemorrhage (SH), sole ulcers (SU), and white line disease (WL). This study investigated the genetic architecture of the three CHL based on detailed animal phenotypes of CHL susceptibility and severity. Estimation of genetic parameters and breeding values, single-step genome-wide association analyses, and functional enrichment analyses were performed. RESULTS: The studied traits were under genetic control with a low to moderate heritability. Heritability estimates of SH and SU susceptibility on the liability scale were 0.29 and 0.35, respectively. Heritability of SH and SU severity were 0.12 and 0.07, respectively. Heritability of WL was relatively lower, indicating stronger environmental influence on the presence and development of WL than the other two CHL. Genetic correlations between SH and SU were high (0.98 for lesion susceptibility and 0.59 for lesion severity), whereas genetic correlations of SH and SU with WL also tended to be positive. Candidate quantitative trait loci (QTL) were identified for all CHL, including some on Bos taurus chromosome (BTA) 3 and 18 with potential pleiotropic effects associated with multiple foot lesion traits. A genomic window of 0.65 Mb on BTA3 explained 0.41, 0.50, 0.38, and 0.49% of the genetic variance for SH susceptibility, SH severity, WL susceptibility, and WL severity, respectively. Another window on BTA18 explained 0.66, 0.41, and 0.70% of the genetic variance for SH susceptibility, SU susceptibility, and SU severity, respectively. The candidate genomic regions associated with CHL harbour annotated genes that are linked to immune system function and inflammation responses, lipid metabolism, calcium ion activities, and neuronal excitability. CONCLUSIONS: The studied CHL are complex traits with a polygenic mode of inheritance. Most traits exhibited genetic variation suggesting that animal resistance to CHL can be improved with breeding. The CHL traits were positively correlated, which will facilitate genetic improvement for resistance to CHL as a whole. Candidate genomic regions associated with lesion susceptibility and severity of SH, SU, and WL provide insights into a global profile of the genetic background underlying CHL and inform genetic improvement programmes aiming at enhancing foot health in dairy cattle.

Serum 1H nuclear magnetic resonance-based metabolomics of sole lesion development in Holstein cows.

Sole hemorrhage and sole ulcers, referred to as sole lesions, are important causes of lameness in dairy cattle. We aimed to compare the serum metabolome of dairy cows that developed sole lesions in early lactation with that of cows that remained unaffected. We prospectively enrolled a cohort of 1,169 Holstein dairy cows from a single dairy herd and assessed animals at 4 time points: before calving, immediately after calving, early lactation, and late lactation. Sole lesions were recorded by veterinary surgeons at each time point, and serum samples were collected at the first 3 time points. Cases were defined by the presence of sole lesions in early lactation and further subdivided by whether sole lesions had been previously recorded; unaffected controls were randomly selected to match cases. Serum samples from a case-control subset of 228 animals were analyzed with proton nuclear magnetic resonance spectroscopy. Spectral signals, corresponding to 34 provisionally annotated metabolites and 51 unlabeled metabolites, were analyzed in subsets relating to time point, parity cohort, and sole lesion outcome. We used 3 analytic methods (partial least squares discriminant analysis, least absolute shrinkage and selection operator regression, and random forest) to determine the predictive capacity of the serum metabolome and identify informative metabolites. We applied bootstrapped selection stability, triangulation, and permutation to support the inference of variable selection. The average balanced accuracy of class prediction ranged from 50 to 62% depending on the subset. Across all 17 subsets, 20 variables had a high probability of being informative; those with the strongest evidence of being associated with sole lesions corresponded to phenylalanine and 4 unlabeled metabolites. We conclude that the serum metabolome, as characterized by proton nuclear magnetic resonance spectroscopy, does not appear able to predict sole lesion presence or future development of lesions. A small number of metabolites may be associated with sole lesions although, given the poor prediction accuracies, these metabolites are likely to explain only a small proportion of the differences between affected and unaffected animals. Future metabolomic studies may reveal underlying metabolic mechanisms of sole lesion etiopathogenesis in dairy cows; however, the experimental design and analysis need to effectively control for interanimal and extraneous sources of spectral variation.

Genetic parameters of sole lesion recovery in Holstein cows.

Sole hemorrhage and sole ulcers, referred to as sole lesions, are important causes of lameness in dairy cattle. The objective of this study was to estimate the genetic parameters of a novel trait reflecting how well cows recovered from sole lesions and the genetic correlation of this trait with overall susceptibility to sole lesions. A cohort of Holstein dairy cows was prospectively enrolled on 4 farms and assessed at 4 timepoints: before calving, immediately after calving, in early lactation, and in late lactation. At each timepoint, sole lesions were recorded at the claw level by veterinary surgeons and used to define 2 binary traits: (1) susceptibility to sole lesions-whether animals were affected with sole lesions at least once during the study or were unaffected at every assessment, and (2) sole lesion recovery-whether sole lesions healed between early and late lactation. Animals were genotyped and pedigree details extracted from the national database. Analyses were conducted with BLUPF90 software in a single-step framework; genetic parameters were estimated from animal threshold models using Gibbs sampling. The genetic correlation between both traits was approximated as the correlation between genomic estimated breeding values, adjusting for their reliabilities. A total of 2,025 animals were used to estimate the genetic parameters of sole lesion susceptibility; 44% of animals recorded a sole lesion at least once during the study period. The heritability of sole lesion susceptibility, on the liability scale, was 0.25 (95% highest density interval = 0.16-0.34). A total of 498 animals were used to estimate the genetic parameters of sole lesion recovery; 71% of animals had recovered between the early and late lactation assessments. The heritability of sole lesion recovery, on the liability scale, was 0.27 (95% highest density interval = 0.02-0.52). The approximate genetic correlation between each trait was -0.11 (95% confidence interval = -0.20 to -0.02). Our results indicate that recovery from sole lesions is heritable. If this finding is corroborated in further studies, it may be possible to use selective breeding to reduce the frequency of chronically lame cows. As sole lesion recovery appears to be weakly genetically related to sole lesion susceptibility, successful genetic improvement of sole lesion recovery would benefit from selection on this trait directly.

Genetic parameters and genome-wide association study of digital cushion thickness in Holstein cows.

The digital cushion is linked to the development of claw horn lesions (CHL) in dairy cattle. The objectives of this study were to (1) estimate genetic parameters for digital cushion thickness (DCT), (2) estimate the genetic correlation between DCT and CHL, and (3) identify candidate genes associated with DCT. A cohort of 2,352 Holstein dairy cows were prospectively enrolled on 4 farms and assessed at 4 time points: before calving, immediately after calving, in early lactation, and in late lactation. At each time point, CHL was recorded by veterinary surgeons, and ultrasonographic images of the digital cushion were stored and retrospectively measured at 2 anatomical locations. Animals were genotyped and pedigree details extracted from the national database. Genetic parameters were estimated following a single-step approach implemented in AIREMLF90. Four traits were analyzed: the 2 DCT measurements, sole lesions (sole hemorrhage and sole ulcers), and white line lesions. All traits were analyzed with univariate linear mixed models; bivariate models were fit to estimate the genetic correlation between traits within and between time points. Single-marker and window-based genome-wide association analyses of DCT traits were conducted at each time point; candidate genes were mapped near (<0.2 Mb) or within the genomic markers or windows with the largest effects. Heritability estimates of DCT ranged from 0.14 to 0.44 depending on the location of DCT measurement and assessment time point. The genetic correlation between DCT and sole lesions was generally negative, notably between DCT immediately after calving and sole lesions in early or late lactation, and between DCT in early or late lactation and sole lesion severity in early or late lactation. Digital cushion thickness was not genetically correlated with white line lesions. A polygenic background to DCT was found; genes associated with inflammation, fat metabolism, and bone development were mapped near or within the top markers and windows. The moderate heritability of DCT provides an opportunity to use selective breeding to change DCT in a population. The negative genetic correlation between DCT and sole lesions at different stages of production lends support to current hypotheses of sole lesion pathogenesis. Highlighted candidate genes provide information regarding the complex genetic background of DCT in Holstein cows, but further studies are needed to explore and corroborate these findings.

Association between a genetic index for lameness resistance and the incidence of claw horn lesions in Holstein cows.

BACKGROUND: This study aimed to determine the association between the lameness advantage genetic index and four outcomes: sole haemorrhage (SH), sole ulcers (SU), white line lesions (WL), and lameness during mobility scoring. METHODS: We enrolled 2352 Holstein cows from four predominantly housed dairy herds in the UK. Cows were mobility scored and foot lesions recorded at four time points from before calving to late lactation. Cows were genotyped and genetic indexes were assigned to each cow following national genetic evaluations. Lameness records and genetic indexes were matched for 2107 cows. Four separate multivariable logistic regression models, which included farm and parity as covariables, were used to quantify the association between the lameness advantage index and whether animals were affected by SH, SU, WL, or lameness. RESULTS: The odds ratios (95% confidence intervals) for one-point increases in the lameness advantage index were 0.79 (0.72-0.86), 0.68 (0.59-0.78), 0.94 (0.84-1.04), and 0.82 (0.74-0.91) for SH, SU, WL, and lameness, respectively. The same trends were present when the sire's lameness advantage index was evaluated in place of the animal's own, although the strength of this association was generally weaker. CONCLUSION: The lameness advantage index is associated with SH, SU, and lameness, therefore selection on the lameness advantage index could be considered in herds aiming to reduce lameness. Where genomic testing of heifers is not conducted, sire lameness advantage index may still be effective to reduce SH and SU incidence.

Prospective cohort study of the association between early lactation mastitis and the presence of sole ulcers in dairy cows.

BACKGROUND: The objective of this study was to investigate the association between (sub)clinical mastitis (CM) in the first 30 days in milk (DIM) and the presence of sole ulcers (SU) later in lactation. METHODS: Holstein cows and heifers were examined for presence of sole haemorrhage and SU before calving, in the first 14 days postcalving and in early lactation (after 30 DIM). CM episodes and somatic cell counts (SCC) measurements were obtained from farm records. Multivariable logistic regression was used for data analysis. RESULTS: Odds of SU in early lactation were 2.44 times greater (95% confidence interval [CI] 0.97-5.54) in cows that had CM in the first 30 DIM compared to cows that did not have CM in the first 30 DIM. When cows that had SU precalving or at the calving check were excluded from the dataset, an association of CM in the first 30 DIM with later presence of SU was no longer statistically significant but the same numeric trend still existed (odds ratio [OR] 2.25, 95% CI 0.81-5.34). The odds of SU in early lactation were 1.70 times greater in cows that had high SCC compared to cows that did not have high SCC in the first 100 DIM (95% CI 1.13-2.55). CONCLUSION: An association was found between CM in the first 30 DIM and presence of SU in early lactation (after 30 DIM). Elucidating the mechanism behind this relationship could improve our understanding of the aetiopathogenesis of both diseases and lead to new preventive strategies.

Evaluation of the use of ketoprofen for the treatment of digital dermatitis in dairy cattle: A randomised, positive controlled, clinical trial.

BACKGROUND: The objective of this study was to evaluate the benefits of administering ketoprofen to cows suffering from active digital dermatitis (DD). METHODS: 158 cows presented with active DD (M1, M2 or M4.1 stage) were randomly allocated to either the control or the treatment group. All cows were treated with topical application of oxytetracycline spray. The treatment group also received an intramuscular injection of ketoprofen (3 mg/kg, Ketofen 10%, Ceva Animal Health). Cows were mobility scored just before they were treated and then again one week later. Information regarding their daily milk production was also collected. RESULTS: Animals in the control group were at 2.57 (95% confidence interval (CI): 0.82-8.01, p = 0.10) times higher odds to be lame at the second evaluation compared to those that received ketoprofen as well. This was a numeric but not statistically significant difference. When only cows that were lame prior to treatment were considered, cows that did not receive ketoprofen were at 20.20 (95% CI: 1.40-291.29, p = 0.03) higher odds of remaining lame week post-treatment comparing to cows that did receive ketoprofen. Freshly calved and lame at enrolment cows in the treatment group produced 58.38 ± 1.85 kg per day the week after treatment comparing to freshly calved and lame at enrolment controls that produced 47.89 ± 1.81 kg per day (p < 0.05). CONCLUSION: The addition of ketoprofen in the treatment of active DD lesions may be beneficial for animal welfare and for animal productivity.

Maternal influences on oral and faecal microbiota maturation in neonatal calves in beef and dairy production systems.

BACKGROUND: The dam is considered an important source of microbes for the calf; consequently, the development of calf microbiota may vary with farming system due to differences between the contact the calf has with the dam. The objective of this study was to characterise the early changes in the composition of oral and faecal microbiota in beef and dairy calves (N = 10) using high-throughput sequencing of the 16S rRNA gene. The microbiota of calves was compared to selected anatomical niches on their dams which were likely to contribute to the vertical transfer of microbes. RESULTS: A total of 14,125 amplicon sequence variants (ASVs) were identified and taxonomically assigned. The oral microbiota of calves and their dams were composed of more similar microbes after the first 4 weeks of life than immediately after calving. The faecal microbiota of four-week old calves was composed of microbes which were more similar to those found in the oral microbiota of calves and adult cows than the faecal microbiota of adult cows. Specific ASVs were identified in the oral microbiota of four-week old calves that were also present in cow niches at calving, whereas very few ASVs were present in the calf faecal microbiota at four-weeks of age were present in any adult cow niche at calving. These results were observed in both beef and dairy calves. CONCLUSIONS: We did not observe any marked differences in the maturation of the oral and faecal microbiota between beef or dairy calves, despite dairy calves having very limited contact with their dam. This suggests the development of gastrointestinal microbiota in calves may not be affected by continued vertical transmission of microbes from the dam. Although the calf faecal microbiota changed over the first four-weeks of life, it was composed of microbes which were phylogenetically closer to those in the oral microbiota of calves and adult cows than the faeces of adult cows. There was little evidence of persistent microbial seeding of the calf faeces from anatomical niches on the cow at calving in either beef or dairy animals.