Ketosis Research Articles

Phenotypic and Genetic Analyses of Mastitis, Endometritis, and Ketosis on Milk Production and Reproduction Traits in Chinese Holstein Cattle.

Mastitis (MAS), endometritis (MET), and ketosis (KET) are prevalent diseases in dairy cows that result in substantial economic losses for the dairy farming industry. This study gathered 26,014 records of the health and sickness of dairy cows and 99,102 data of reproduction from 13 Holstein dairy farms in Central China; the milk protein and milk fat content from 56,640 milk samples, as well as the pedigree data of 37,836 dairy cows were obtained. The logistic regression method was used to analyze the variations in the prevalence rates of MAS, MET, and KET among various parities; the mixed linear model was used to examine the effects of the three diseases on milk production, milk quality, and reproductive traits. DMU software (version 5.2) utilized the DMUAI module in conjunction with the single-trait and two-trait animal model, as well as best linear unbiased prediction (BLUP), to estimate the genetic parameters for the three diseases, milk production, milk quality, and reproductive traits in dairy cows. The primary findings of the investigation comprised the following: (1) The prevalence rates of MAS, MET, and KET in dairy farms were 20.04%, 10.68%, and 7.33%, respectively. (2) MAS and MET had a substantial impact (p < 0.01) on milk production, resulting in significant decreases of 112 kg and 372 kg in 305-d Milk Yield (305-d MY), 4 kg and 12 kg in 305-d Protein Yield (305-d PY), and 6 kg and 16 kg in 305-d Fat Yield (305-d FY). As a result of their excessive 305-d MY, some cows were diagnosed with KET due to glucose metabolism disorder. The 305-d MY of cows with KET was significantly higher than that of healthy cows (205 kg, p < 0.01). (3) All three diseases resulted in an increase in the Interval from Calving to First Service (CTFS, 0.60-1.50 d), Interval from First Service to Conception (FSTC, 0.20-16.20 d), Calving Interval (CI, 4.00-7.00 d), and Number of Services (NUMS, 0.07-0.35). (4) The heritabilities of cows with MAS, MET, and KET were found to be low, with values of 0.09, 0.01, and 0.02, respectively. The genetic correlation between these traits ranged from 0.14 to 0.44. This study offers valuable insights on the prevention and control of the three diseases, as well as feeding management and genetic breeding.

The use of ultrasonography in the transition period to estimate adipose tissue depots and their association with risk of early postpartum hyperketonemia in Holstein dairy cattle

An elevated prepartum BCS is a risk factor for postpartum hyperketonemia (HYK) and elevated fatty acid (NEFA) concentrations in dairy cattle. The association between different adipose tissue depots, such as subcutaneous (SCAT) as well as visceral adipose tissue (VAT) depots and HYK and elevated NEFA concentrations remains unknown. The objective of this 2-part study was to describe SCAT and VAT depots using ultrasonography during the transition period and to associate them with metabolic markers of negative energy balance in early postpartum dairy cows. Multiparous Holstein cows were enrolled in a prospective observational cohort study with 2 cohorts in subsequent study years (Cohort 1: n = 31; Cohort 2: n = 28). At −6, −4, −2, and 2 wk relative to calving (Cohort 1) or −2 and 2 wk relative to calving (Cohort 2) BCS was determined and cows were examined via transcutaneous ultrasound at 6 locations for prediction of adipose tissue mass in 5 depots: 1) abdominal adipose tissue (AAT), 2) retroperitoneal adipose tissue (RPAT), 3) omental adipose tissue (OMAT), 4) mesenteric adipose tissue (MAT), and 5) subcutaneous adipose tissue (SCAT). Postpartum serum NEFA and BHB concentrations were determined twice weekly from 1 to 14 DIM. Cows were categorized as having HYK or high NEFA concentrations (NEFAH) if ≥1 sample resulted in a BHB ≥1.2 mmol/L or NEFA ≥720 µEq/L, respectively. Critical thresholds associated with HYK or NEFAH for each depot at −2 wk relative to calving and the time of maximum estimated depot size were evaluated using logistic regression and a receiver operator characteristic analysis. Abdominal AT increased from −6 to −2 wk relative to calving in cohort 1 but did not differ from −2 to 2 wk relative to calving. Subcutaneous AT did not change from −6 to −2 wk but decreased from −2 to 2 wk relative to calving in cohort 1 and 2. Omental AT accurately (AUC = 0.77) predicted HYK in cohort 1 but was non-informative for the prediction of HYK in cohort 2 (AUC = 0.49). Predicted AT depots were not informative for the prediction of NEFAH (AUC ≤0.59) in either cohort. Results from this study suggest that AT can be monitored during the transition period using the described technique; however, estimated prepartum AT depots at −2 wk relative to expected calving were inaccurate in distinguishing between postpartum NEFAH and non-NEFAH or HYK and non-HYK.

Altered bile acid and correlations with gut microbiome in transition dairy cows with different glucose and lipid metabolism status

The transition from pregnancy to lactation is critical in dairy cows. Among others, dairy cows experience a metabolic stress due to a large change in glucose and lipid metabolism. Recent studies revealed that bile acids (BA), besides being involved in both the emulsification and solubilization of fats during intestinal absorption, can also affect the metabolism of glucose and lipids, both directly or indirectly by affecting the gut microbiota. Thus, we used untargeted and targeted metabolomics and 16S rRNA sequencing approaches to investigate the concentration of plasma metabolites and BA, the composition of the rectum microbial community, and assess their interaction in transition dairy cows. In Experiment 1, we investigated BA and other blood parameters and gut microbiota in dairy cows without clinical diseases during the transition period, which can be seen as well adapted to the challenge of changed glucose and lipid metabolism. As expected, we detected an increased plasma concentration of β-hydroxybutyrate (BHBA) and nonesterified fatty acids (NEFA) but decreased concentration of glucose, cholesterol, and triglycerides (TG). Untargeted metabolomic analysis of the plasma revealed primary BA biosynthesis was one of the affected pathways, and was consistent with the increased concentration of BA in the plasma. A correlation approach revealed a complex association between BA and microbiota with the host plasma concentration of glucose and lipid metabolites. Among BA, chenodeoxycholic acid derivates such as glycolithocholic acid, taurolithocholic acid, lithocholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites (such as glucose, TG, and NEFA). In Experiment 2, we investigated early postpartum dairy cows with or without hyperketonemia (HPK). As expected, HPK cows had increased concentration of NEFA and decreased concentrations of glucose and triglycerides. The untargeted metabolomic analysis of the plasma revealed that primary BA biosynthesis was also one of the affected pathways. Even though the BA concentration was similar among the 2 groups, the profiles of taurine conjugated BA changed significantly. A correlation analysis also revealed an association between BA and microbiota with the concentration in plasma of glucose and lipid metabolites (such as BHBA). Among BA, cholic acid and its derivates such as taurocholic acid, tauro α-muricholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites. Our results indicated an association between BA, intestinal microbe, and glucose and lipid metabolism in transition dairy cows. These findings provide new insight into the adaptation mechanisms of dairy cows during the transition period.

Identification of genetic markers associated with hyperketonemia patterns in early lactation Holstein cows.

Ketosis, evidenced by hyperketonemia with elevated blood β-hydroxybutyrate (BHB) levels, is a significant metabolic disorder of dairy cattle, typically diagnosed within the first 6 weeks post-calving when high energy levels are essential to milk production. Our study aimed to identify genetic markers linked to hyperketonemia (HYK) patterns in Holstein cows during early lactation and compare these to HYK-negative cows. We screened 964 cows for HYK using a threshold of BHB ≥1.2 mmol/L during the first 2 weeks postpartum (screening period, SP). Cows that tested negative initially were retested the following week. Cows were deemed HYK-negative (CON group) if BHB levels were below 1.2 mmol/L in both tests, while those with BHB levels exceeding this threshold at any test were treated and classified as HYK-positive (HYK+). Post-treatment, HYK+ cows were monitored for two-week follow-up period (FP) and classified based on their recovery: cured (CUR; consistently low BHB), recurrent (REC; fluctuating BHB levels), severe (SEV; high initial BHB that decreased), or chronic (CHR; persistently high BHB). Using 489 cows that were genotyped, a GWAS was conducted using GCTA software, revealing significant associations of several SNPs across different HYK patterns when compared to the CON group. These SNPs were primarily linked to genes affecting milk traits and were enriched in biological pathways relevant to protein glycosylation, inflammatory response, glucose homeostasis, and fatty acid synthesis. Our findings highlight genomic regions, potential candidate genes, and biological pathways related to ketosis, underscoring potential targets for improving health management in dairy cattle. These insights could lead to better strategies for managing ketosis through genetic selection, ultimately enhancing dairy cattle welfare and productivity. Further research with a larger number of cows is recommended to validate these findings and help confirm the implicated SNPs and genes.

Effects of treatment with propylene glycol and cyanocobalamin on disease, milk production and reproductive outcomes of dairy cows diagnosed with hyperketonemia and hypoglycemia

Almost all periparturient dairy cows experience a period of negative energy balance, and despite improvements to fresh cow management, some dairy cows still experience clinical dis­ease associated with the periparturient period (Duffield et al., 2009; Taylor et al., 2004). Hyperketonemia (HK) remains an im­portant production and animal welfare concern (McArt et al., 2012; Tatone, Duffield, Capel, et al., 2016; Tatone, Duffield, LeB­lanc, et al., 2016), and recently several handheld meters which measure beta-hydroxybutyric acid (BHBA) have been validated in dairy cows and can be used to detect pre-clinical HK (Bach et al., 2016; Tatone et al., 2015). Several studies have explored the screening of post-parturient cows to detect HK and adminis­ter treatment in order to ward off clinical disease and increase milk production (Capel et al., 2021; Gordon et al., 2017; McArt et al., 2012). However, these studies have been inconsistent in their findings, and treatment may not be economically beneficial for farms with a relatively low incidence of HK (McArt et al., 2014). A 2017 study indicated that cows may have variable production responses to HK treatment based on blood glucose concentra­tion (Gordon et al., 2017). Because blood glucose can also be mea­sured cow-side, measurement of blood glucose concurrent with measurement of blood BHBA may be a means to target treatment to cows that will respond to current treatments. Therefore, our objective was to explore the effects of treatment with propylene glycol and cyanocobalamin in early post-partum cows based on both HK and glycemic status. We hypothesized that improve­ments to health, milk production, and reproduction would be greatest among cows that were hypoglycemic.

Association between rumination behavior, hyperketonemia and milk production in early lactation

Increased blood beta-hydroxybutyrate (BHB), also known as hyperketonemia (HYK), is a common metabolic disorder in dairy cows, that occurs during first and second week postpar­tum, defined by elevated blood concentration of BHB ( ≥ 1.2 mmol/L). HYK is associated with impaired health, decreased performance, and decreased milk production. Nonetheless, ele­vated BHB concentrations in early lactation are not detrimental to all cows. Past studies from our group found that cows with HYK that had high milk production had similar performance (pregnancy rates and herd removal risk) to non-hyperketone­mic cows that also had high milk production. Moreover, there are reports showing that rumination time in the first week post­partum and milk production are positively correlated, with ani­mals that have a high rumination time producing more milk. For these reasons, our objective was to evaluate whether rumi­nation behavior modified the association between blood BHB concentration during the first week postpartum and milk yield during the first 3 herd tests.

Genetic analysis of health traits and their associations with longevity, fertility, production, and conformation traits in Holstein cattle

Health traits have high economic values in dairy cattle breeding, which can cause considerable financial loss through involuntary culling. In this study, fourteen health traits were analysed, including five composite health traits: reproductive disorders, udder health (UH), digestive disorders, metabolic disorders, locomotory diseases (LD), and nine independent health traits: gestation disorders and peripartum disorders, irregular estrus cycle and sterility, metritis (ME), mastitis (MA), abomasal displacement (AD), enteritis (EN), and ketosis, claw diseases (CD), laminitis complex. This study analysed variance components for health traits through both single and bivariate repeatability animal models. All health traits showed low heritability, ranging from 0.001 to 0.025. Most of the health traits in five categories showed negative genetic correlations, ranging from −0.012 (CD and EN) to −0.634 (ME and EN). Strong positive genetic correlations appeared within the same category, ranging from 0.469 (EN and AD) to 0.994 (UH and MA, LD and CD). Furthermore, approximate genetic correlations were evaluated between health traits and routinely collected traits (longevity, fertility, production, and conformation). In general, the low to moderate approximate genetic correlations were estimated between health traits and routinely collected traits. The estimated correlations between health traits and longevity, fertility, production, and conformation traits could provide an indirect reference for disease−resistance breeding in Holstein cattle.

Prepartum behaviors as early indicators for postpartum energy associated biomarkers status in Holstein dairy cows.

Our main aim was to investigate the predictive value of prepartum behaviors such as total daily rumination (TDR), total daily activity (TDA) and dry matter intake (DMI) as early indicators to detect cows at risk for hyperketonemia (HYK), hypoglycemia (HYG) or high non-esterified fatty acid (NEFA) status in the first (wk1) and second week (wk2) postpartum. In a case control study, 64 Holstein cows were enrolled 3 weeks before the expected time of calving and monitored until 15 days in milk (DIM). Postpartum blood samples were taken at D3 and D6 for wk1 and at D12 and D15 for wk2 to measure beta-hydroxybutyrate, NEFA and glucose concentration. Ear-mounted accelerometers were used to measure TDR and TDA. DMI and milk yield were obtained from farm records. Relationships between the average daily rate of change in prepartum TDR (ΔTDR), TDA (ΔTDA), and DMI (ΔDMI) with postpartum HYK, HYG and NEFA status in wk1 and wk2 post-partum were evaluated using linear regression models. Models were adjusted for potential confounding variables, and covariates retained in the final models were determined by backward selection. No evidence was found to support the premise that prepartum ΔTDR, ΔTDA or ΔDMI predicted postpartum HYK, HYG or NEFA status in wk1 or in wk2. Overall, prepartum ΔTDR, ΔTDA and ΔDMI were not effective predictors of HYK, HYG or NEFA status in the first 2 weeks postpartum.

Milk β-hydroxybutyrate metrics and its consequences for surveillance of hyperketonaemia on commercial dairy farms.

Dairy cows that are unable to adapt to a change in their metabolic status are at risk for hyperketonaemia (HK). Reported HK herd level prevalences range a lot and we hypothesized that this is partly due to differences in used tests and monitoring protocols. Insights in milk β-hydroxybutyrate (BHB) metrics can potentially explain why the reported incidences or prevalences vary between test strategies. Automated collection and repeated analyses of individual milk samples with the DeLaval Herd Navigator™ (HN) provides real-time data on milk BHB concentrations. We aimed to use that information to gain insight in BHB metrics measured in milk from 3 to 60 days in milk (DIM). Using different cut-offs (0.08, 0.10 and 0.15 mmol/L), 5 BHB metrics were determined. Furthermore, the impact of 4 arbitrary test protocols on the detected incidence of HK was assessed. We used HN data of 3,133 cows from 35 herds. The cumulative incidence of HK between 3 and 60 DIM varied between 30.5 and 76.7% for different cut-off values. We found a higher HK incidence for higher parity cows. The first elevated BHB concentrations were roughly found between one and two weeks after calving. For higher parity cows the maximum BHB concentrations were higher, the onset of HK was earlier after calving, and the number of episodes of HK was higher. It appeared that the sensitivity of a HK test protocol can be increased by increasing the testing frequency from once to twice a week. Also extending the number of days of the test window from 4-14 to 4-21 days enhances the chance to find cows experiencing HK. In conclusion, HN data provided useful insights in milk BHB metrics. The chosen cut-off value had a large effect on the reported metrics which explains why earlier reported incidences or prevalences vary such a lot. Differences in test period and sample selection also had a large impact on the observed HK incidence. We suggest to take this in consideration while evaluating whether HK is an issue on farm level and use a uniform protocol for benchmarking of HK between farms.

Evaluating variations in metabolic profiles during the dry period related to the time of hyperketonemia onset in dairy cows.

Hyperketonemia (HYK) in early lactation can have a different impact on health and productivity depending on the timing of HYK onset. While specific metabolites measured during the dry period may serve as biomarkers of HYK, the correlations between metabolites represent a challenge for the use of metabolic profiles dataset, and little has been explored on HYK. This exploratory cohort study aimed a) to characterize the correlations among metabolites measured during the late dry period in dairy cows, and b) to identify biomarkers in the late dry period associated with the onset of HYK at the first (wk1) and second (wk2) week of lactation. Individual blood samples from 440 Holstein dairy cows were collected at 21 ± 3 days before expected parturition. From each sample, 36 different metabolites were measured in serum and plasma. Hyperketonemia was diagnosed in wk1 and wk2 of lactation based on the blood concentration of beta-hydroxybutyrate (BHB > 1.2 mmol/L). Principal component analysis (PCA) was performed to reduce metabolites to a smaller number of uncorrelated components. Multivariable logistic regression models were applied to assess the associations between principal components (PC) and HYK at wk1 only (HYK+ wk1), wk2 only (HYK+ wk2), or both weeks (HYK+ wk1-2). The incidence of HYK was 16.2% in the first week, 13.0% in the second week, and 21.2% within the first two weeks of lactation. The results of PCA highlighted 10 PCs from which two were associated with HYK+ wk1 as compared with cows without HYK during the first two weeks of lactation (non-HYK); the PC a2 led by bilirubin and non-esterified fatty acids (OR = 1.29; 95%CI: 1.02-1.68), and the PC a5 led by alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) (OR = 2.77; 95%CI: 1.61-4.97). There was no evidence of an association between any PC and HYK+ wk2 (vs. non-HYK cows). Cows with elevated PC a5 (led by ALP and GGT) in the dry period were 3.18 times more likely to be HYK+ wk1 than HYK+ wk2 (OR: 3.18, 95%CI: 1.34-8.73; P = 0.013). Overall, the main hypothesis generated by our exploratory study suggests that cows with biomarkers of liver dysfunction (ALP, GGT, bilirubin) assessed by PCA at 3 weeks before calving are more likely to develop HYK during the first week of lactation compared to the second week. In addition, results suggest that cows with HYK in both of the first two weeks of lactation had an overall metabolic disbalance during the onset of the late dry period, which based on PCs, encompass biomarkers related to glucogenic and ketogenic metabolic pathways as well as liver dysfunction and fatty liver. Further research is needed to determine the underlying mechanisms associated with the different adaptations between cows that develop HYK during the first and second week of lactation.

A randomized controlled trial examining the effects of treatment with propylene glycol and injectable cyanocobalamin on naturally occurring disease, milk production, and reproductive outcomes of dairy cows diagnosed with concurrent hyperketonemia and hypoglycemia.

The objective of this study was to assess the effects of treatment with propylene glycol (PG) and cyanocobalamin (B12) on health, milk production, and reproductive outcomes of cows diagnosed with hyperketonemia (HK), hypoglycemia (HG), or concurrent HKHG. Glucose and β-hydroxybutyric acid (BHBA) concentrations were assessed in whole blood using a handheld device in lactating dairy cows (n = 2,418) between 3 and 9 d postpartum. Cows categorized as HK (n = 232, BHBA ≥1.2 mmol/L), HG (n = 161, glucose ≤2.2 mmol/L), and concurrent HKHG (n = 204, BHBA ≥1.2 mmol/L, and glucose ≤2.2 mmol/L) were randomized to receive treatment or to remain untreated (control). Treatment consisted of a single dose of B12 (10 mg, intramuscularly) and 300 mL of PG orally for 5 d, starting on the day of cow-side testing. Milk production, health, and reproductive outcomes were analyzed according to groups. Statistical analysis was carried out using SAS version 9.4 (SAS/STAT, SAS Institute Inc.). Treatment in HG cows decreased clinical ketosis, increased milk production in the fifth week of lactation for multiparous cows, and tended to increase 305-d mature-equivalent milk yield (305ME) for primiparous cows compared with untreated cows with the same metabolic profile. For cows with HKHG, treatment increased 305ME in multiparous cows and tended to increase 305ME in primiparous cows. No differences were found for treatment among any of the metabolic groups regarding reproductive outcomes, nor were any treatment effects found among HK cows. Glycemic status may help identify metabolically challenged early postpartum dairy cows, which may have differential response to PG and B12 treatment.

Incidence and Treatments of Bovine Mastitis and Other Diseases on 37 Dairy Farms in Wisconsin.

The aim of this research was to describe the incidence and treatments of mastitis and other common bovine diseases using one year of retrospective observational data (n = 50,329 cow-lactations) obtained from herd management software of 37 large dairy farms in Wisconsin. Incidence rate (IR) was defined as the number of first cases of each disease divided by the number of lactations per farm. Clinical mastitis (CM) remains the most diagnosed disease of dairy cows. Across all herds, the mean IR (cases per 100 cow-lactations) was 24.4 for clinical mastitis, 14.5 for foot disorders (FD), 11.2 for metritis (ME), 8.6 for ketosis (KE), 7.4 for retained fetal membranes (RFM), 4.5 for diarrhea (DI), 3.1 for displaced abomasum (DA), 2.9 for pneumonia (PN) and 1.9 for milk fever (MF). More than 30% of cows that had first cases of CM, DA, RFM, DI, and FD did not receive antibiotics. Of those treated, more than 50% of cows diagnosed with PN, ME and CM received ceftiofur as a treatment. The IR of mastitis and most other diseases was greater in older cows (parity ≥ 3) during the first 100 days of lactation and these cows were more likely to receive antibiotic treatments (as compared to younger cows diagnosed in later lactation). Cows of first and second parities in early lactation were more likely to remain in the herd after diagnosis of disease, as compared to older cows and cows in later stages of lactation. Most older cows diagnosed with CM in later lactation were culled before completion of the lactation. These results provide baseline data for disease incidence in dairy cows on modern U.S. dairy farms and reinforce the role of mastitis as an important cause of dairy cow morbidity.

A meta-analysis of the genetic contribution estimates to major indicators for ketosis in dairy cows

The present study aimed to perform a meta-analysis using the random-effects model to merge published genetic parameter estimates for major indicators of ketosis [milk concentrations of acetone (ACETm) and β-hydroxybutyrate (BHBAm), and blood concentration of β-hydroxybutyrate (BHBAb)] in dairy cows. Overall, 51 heritability estimates and 130 genetic correlations from 19 papers published between 2012 and 2022 were used in this study. The average heritability estimates for ACETm, BHBAm, and BHBAb were 0.164, 0.123, and 0.141, respectively. The genetic correlation estimates between BHBAm and milk yield (MY), milk protein percentage (PP), and body condition score (BCS) were negative and moderate (−0.252, −0.200, and − 0.314, respectively). Genetic correlation estimates between BHBAm and milk fat percentage (FP), milk fat to protein ratio (FPR), and ketosis (KET) were moderate to high (0.411, 0.512, and 0.614, respectively). The genetic correlation estimates between BHBAb and MY and FP were low and equal to 0.128 and 0.035, respectively. The genetic correlation estimates between ACETm-MY and ACETm-PP were negative and moderate (−0.374 and − 0.398, respectively). Estimates of genetic correlation between ACETm and FP, FPR, and KET were moderate to high (0.455, 0.626, and 0.876, respectively). The results of this meta-analysis indicated the existence of additive genetic variation for ketosis indicator metabolites which could be exploited in genetic selection programs to reduce ketosis in dairy cows. Moreover, the results propose that selection for lower concentrations of indicator traits could be an effective plan for indirect improvement of production and reproduction performance, and health in dairy cows.

Assessment of milk yield and composition, early reproductive performance, and herd removal in multiparous dairy cattle based on the week of diagnosis of hyperketonemia in early lactation

The purpose of this retrospective cohort study was to evaluate the effects of the timing of hyperketonemia (HYK) diagnosis during early lactation on milk yield and composition, reproductive performance, and herd removal. Plasma β-hydroxybutyrate (BHB) was measured twice a week during the first 2 wk of lactation in 362 multiparous Holstein cows for the diagnosis of HYK. In each week, cows were diagnosed as HYK positive (HYK+) if the plasma BHB concentrations were ≥1.2 mmol/L in at least one of the tests for the week evaluated. Milk-related outcomes (first 10 monthly milk tests) included milk yield, milk fat and protein content, milk urea nitrogen (MUN), and linear score of somatic cell count. Other performance outcomes of interest included risk of pregnancy within 150 d in milk (DIM) and herd removal (i.e., culling or death) within 300 DIM. Statistical models were built separately for cows diagnosed with HYK during the first week of lactation (wk1) and for cows diagnosed during the second week of lactation (wk2). All models for wk2 were adjusted by HYK diagnosed in wk1, along with other potential confounder variables. The association between HYK in each week and milk-related outcomes was assessed using generalized estimated equation models that accounted for repeated measures. Time to pregnancy and time to herd removal were analyzed using Cox's proportional hazard regression models. Seventy-eight cows (21.5%) tested positive for HYK during wk1, 60 cows (16.6%) in wk2, and 29 cows (8.0%) in both weeks. Hyperketonemia during wk1 was associated with a milk yield reduction of 3.7 kg [95% confidence interval (CI): -6.67 to -0.76] per cow per day throughout the lactation. Meanwhile, we did not observe evidence of an association between HYK diagnosed during wk2 and milk yield. During the first 2 monthly milk tests, cows diagnosed as HYK+ in wk1 had greater fat (0.42%; 95% CI: 0.16 to 0.67) and MUN (0.75 mg/dL; 95% CI: 0.26 to 1.24) content in milk than HYK-negative (HYK-) cows. We did not detect any evidence of an association between HYK diagnosed in wk2 and these outcomes. The HYK+ cows in wk1 had a 30% [hazard ratio (HR) = 0.70; 95% CI: 0.48 to 1.01] lower risk of pregnancy within 150 DIM and 2.48 times (95% CI: 1.63 to 2.89) higher risk of herd removal within 300 DIM than HYK- cows. Conversely, no evidence of association was observed between HYK+ cows in wk2 and risk of pregnancy by 150 DIM (HR = 0.98; 95% CI: 0.64 to 1.51) or removal from the herd within 300 DIM (HR = 0.91; 95% CI: 0.52 to 1.60). Our findings indicate that HYK diagnosed during wk1 of lactation is associated with negative performance in terms of milk yield, reproduction, and herd removal. No evidence of association was found for the same outcomes when HYK was diagnosed in wk2. Our results suggest the need to consider the timing when HYK is diagnosed when investigating its association with performance outcomes.

Exploring the role of milk yield in the first week of lactation on the association between hyperketonemia and reproductive performance in dairy cattle

The objective of this retrospective cohort study was to investigate whether the association of hyperketonemia (HYK) with reproductive performance differs based on milk production during the first week of lactation (wk 1). Data between calving and 150 d in milk (DIM) from 2,091 Holstein dairy cows from 5 commercial dairy herds in Minnesota were collected. The concentration of β-hydroxybutyrate (BHB) was measured twice between 3 and 10 DIM in whole blood to diagnose HYK (defined as BHB ≥1.2 mmol/L). The average wk 1 milk yield was classified into 3 levels (low = lower 25th percentile; mid = 25th to 75th percentile; high = upper 75th percentile) according to parity and herd. Log-binomial regression, Cox-proportional hazard regression, and linear regression models were used to investigate the association of HYK with pregnancy to first insemination, pregnancy by 150 DIM, and calving-to-conception interval (CCI) between groups, respectively. To describe the differences in these estimates between each wk 1 milk yield level, an interaction term of HYK and stratified levels of wk 1 milk yield was added. The incidence of HYK between 3 to 10 DIM was 14.2% (4.6% in primiparous cows and 19.4% in multiparous cows). In the study population, the effect of HYK on reproduction was greater in cows with low milk yield. Among cows with low milk yield levels, HYK was associated with lower risk of pregnancy to first insemination [risk ratio = 0.62; 95% confidence interval (CI): 0.39–0.98], lower risk of pregnancy up to 150 DIM (hazard ratio = 0.70; 95% CI: 0.51–0.96), and extended days of CCI (mean difference = 13.0; 95% CI: 5.1–20.9). In contrast, among cows with mid and high wk 1 milk yield levels, hyperketonemic (HYK+) cows had a similar reproductive performance to non-HYK (HYK−) cows. Our results suggest that early-lactation milk yield plays a role in the association of hyperketonemia with reproductive performance. These results merit further investigation to determine the role that early milk yield has in the association of hyperketonemia with health and productivity outcomes.

Single-step genomic best linear unbiased predictor genetic parameter estimations and genome-wide associations for milk fatty acid profiles, interval from calving to first insemination, and ketosis in Holstein cattle

Milk fatty acids (FA) have been suggested as biomarkers for early-lactation metabolic diseases and for female fertility status. The aim of the present study was to infer associations between FA, the metabolic disorder ketosis (KET), and the interval from calving to first insemination (ICF) genetically and genomically. In this regard, we focused on a single-step genomic BLUP approach, allowing consideration of genotyped and ungenotyped cows simultaneously. The phenotypic data set considered 38,375 first-lactation Holstein cows, kept in 45 large-scale co-operator herds from 2 federal states in Germany. The calving years for these cows were from 2014 to 2017. Concentrations in milk from the first official milk recording test-day for saturated, unsaturated (UFA), monounsaturated (MUFA), polyunsaturated, palmitic, and stearic (C18:0) FA were determined via Fourier-transform infrared spectroscopy. Ketosis was defined as a binary trait according to a veterinarian diagnosis key, considering diagnoses within a 6-wk interval after calving. A subset of 9,786 cows was genotyped for 40,989 SNP markers. Variance components and heritabilities for all Gaussian distributed FA and for ICF, and for binary KET were estimated by applying single-step genomic BLUP single-trait linear and threshold models, respectively. Genetic correlations were estimated in series of bivariate runs. Genomic breeding values for the single-step genomic BLUP estimations were dependent traits in single-step GWAS. Heritabilities for FA were moderate in the range from 0.09 to 0.20 (standard error = 0.02-0.03), but quite small for ICF (0.08, standard error = 0.01) and for KET (0.05 on the underlying liability scale, posterior standard deviation = 0.02). Genetic correlations between KET and UFA, MUFA, and C18:0 were large (0.74 to 0.85, posterior standard deviation = 0.14-0.19), and low positive between KET and ICF (0.17, posterior standard deviation = 0.22). Genetic correlations between UFA, MUFA, and C18:0 with ICF ranged from 0.34 to 0.46 (standard error = 0.12). In single-step GWAS, we identified a large proportion of overlapping genomic regions for the different FA, especially for UFA and MUFA, and for saturated and palmitic FA. One identical significantly associated SNP was identified for C18:0 and KET on BTA 15. However, there was no genomic segment simultaneously significantly affecting all trait categories ICF, FA, and KET. Nevertheless, some of the annotated potential candidate genes DGKA, IGFBP4, and CXCL8 play a role in lipid metabolism and fertility mechanisms, and influence production diseases in early lactation. Genetic and genomic associations indicate that Fourier-transform infrared spectroscopy FA concentrations in milk from the first official test-day are valuable predictors for KET and for ICF.

Hyperketonemia Predictions Provide an On-Farm Management Tool with Epidemiological Insights.

Simple SummaryIn dairy cows, the transition to lactation period is metabolically challenging. Elevated blood ketone bodies, known as hyperketonemia or ketosis, is a postpartum metabolic disorder that is associated with negative energy balance, greater comorbidity risk, and decreased milk production. Research to understand the etiology of hyperketonemia has highlighted risk factors and unfavorable outcomes; however, analysis of real-world data is valuable for determining the outcomes across a region. Dairy herd improvement data from herds with diverse size and production were analyzed to determine potential risk factors for and production outcomes of hyperketonemia in the Midwest region (US). Cows predicted to have hyperketonemia had greater previous lactation dry period length, somatic cell count, and dystocia, which may represent risk factors for ketosis. Cows with predicted hyperketonemia had lower milk yield and milk protein but greater milk fat and somatic cell count in the current lactation. Culling rate within 60d of calving, days open, and artificial inseminations were all greater in cows predicted to have hyperketonemia. Prevalence of hyperketonemia decreased linearly in herds with greater rolling herd average milk yield. This work demonstrates the impact of hyperketonemia on production variables which underscores the importance on continued work to reduce hyperketonemia prevalence.Prediction of hyperketonemia (HYK), a postpartum metabolic disorder in dairy cows, through use of cow and milk data has allowed for high-throughput detection and monitoring during monthly milk sampling. The objective of this study was to determine associations between predicted HYK (pHYK) and production parameters in a dataset generated from routine milk analysis samples. Data from 240,714 lactations across 335 farms were analyzed with multiple linear regression models to determine HYK status. Data on HYK or disease treatment was not solicited. Consistent with past research, pHYK cows had greater previous lactation dry period length, somatic cell count, and dystocia. Cows identified as pHYK had lower milk yield and protein percent but greater milk fat, specifically greater mixed and preformed fatty acids (FA), and greater somatic cell count (SCC). Differential somatic cell count was greater in second and fourth parity pHYK cows. Culling (60d), days open, and number of artificial inseminations were greater in pHYK cows. Hyperketonemia prevalence decreased linearly in herds with greater rolling herd average milk yield. This research confirms previously identified risk factors and negative outcomes associated with pHYK and highlights novel associations with differential SCC, mixed FA, and preformed FA across farm sizes and production levels.

Association of Body Condition Score and Score Change during the Late Dry Period on Temporal Patterns of Beta-Hydroxybutyrate Concentration and Milk Yield and Composition in Early Lactation of Dairy Cows.

Simple SummaryIn order to develop strategies to monitor and mitigate high incidences of hyperketonemia in dairy herds, the factors associated with the fluctuations of beta-hydroxybutyrate (BHB) concentration during early lactation need to be assessed. Body condition score (BCS), as well as the change in BCS during the late dry period are elements that are highly related to the mobilization of body reserves, and the proper adaptation during the transition period of dairy cattle. Our objective was to describe the pattern of blood BHB concentration and the development of hyperketonemia during the first 14 days of lactation on the basis of both a single measurement of BCS (−21 d) and the change in BCS during the late dry period. Additionally, we aimed to characterize the association between changes in BCS and milk yield and milk composition in the first monthly test. Our results suggest that changes in BCS are associated with fluctuations in BHB concentration during early lactation. In addition, we observed that cows with a loss in BCS greater than 0.5 units during the late dry period have a higher risk of having elevated BHB concentrations and incidence of hyperketonemia than cows with no change in BCS in the late dry period. Moreover, these cows also experienced lower milk production at the first monthly milk test.Monitoring the body condition score (BCS) of dairy cows is a management strategy that can assist dairy producers in decision-making. The BCS and its variations reflect the level of body fat reserves and fat mobilization throughout the different stages of lactation. Cows that mobilize excessive amounts of fat reserves in response to the increased energy requirements of the transition period are more likely to have higher beta-hydroxybutyrate (BHB) concentration in blood, leading to a higher incidence of hyperketonemia postpartum. In this study, our main objective was to evaluate how both BCS (at 21 d prior to the expected calving date, −21 BCS) and change in BCS during the late dry period (−21 d to calving, ∆BCS) are associated with temporal patterns of blood BHB concentrations during the first two weeks of lactation. Our secondary objective was to characterize the relationship between the change in BCS in the late dry period, and milk yield and milk composition in the first milk test postpartum. In this retrospective cohort study, we assessed BCS at 21 (±3) days before the expected calving date and within three days after calving. Blood BHB concentration was measured at days 3 (±1), 7 (±1), and 14 (±1) postpartum. Hyperketonemia (HYK) was defined as blood BHB ≥ 1.2 mmol/L. To evaluate how −21 BCS and ∆BCS during the late dry period were associated with BHB in early lactation, linear mixed-effects regression models with an unstructured covariate matrix were performed. The association between ∆BCS and incidence of postpartum HYK were determined using a multivariable log-binomial model. A linear regression model was used to evaluate the association between ∆BCS and milk yield and milk composition in the first monthly test-day. Covariates used for model adjustment include parity, season, and baseline BCS. We observed that cows with BCS ≥ 4.0 at 21 d before their expected calving date had the highest BHB concentration postpartum, but no evidence that BCS ≥ 4.0 at 21 d was associated with fluctuations of BHB over time. Cows that experienced a large BCS loss (larger than 0.5 units) during the late dry period had a 61% (95% CI: 1.04, 2.50) higher risk of developing HYK in early lactation and had higher BHB concentrations during early lactation compared with cows with no ∆BCS prepartum. These associations were observed independently of the BCS at −21 d prepartum (baseline). In addition, cows that lost more than 0.5 BCS unit in the late dry period produced 3.3 kg less milk (95% CI: −7.06, 0.45) at the first milk test compared to cows that had no ∆BCS during the late dry period. No evidence of an association between −21 BCS and ∆BCS in the late dry period and milk composition was observed in our study. These results suggest that dynamic measures of BCS during the late dry period, such as ∆BCS, are better at evaluating blood BHB patterns in early lactation than BCS measured at a single time point. Cows with larger BCS loss during the late dry period and with greater parity are more likely to have higher concentrations of blood BHB postpartum, with the highest concentrations reported at 7 d post-calving.

Nevşehir İli Süt Sığırcılığı İşletmelerinin Yapısı ve Hayvan Besleme Uygulamaları Yönünden Değerlendirilmesi*

Bu araştırmanın amacı Nevşehir ili süt sığırcılığının genel durumu ve hayvan besleme alışkanlıklarını belirlemek-tir. Araştırma kapsamında Nevşehir ilinde süt sığırı yetiştiriciliği yapılan 105 işletme ziyaret edilerek anket çalışması yapılmıştır. Anket formunda işletmeye ve işletme sahibine ait genel bilgiler, buzağı büyütme ve besleme, düvelerin beslenmesi ve tohumlanması, sağmal ineklerin bakım, besleme, sağım, yemleme ve görülen hastalıklara yönelik soru-lar sorulmuştur. 105 işletmede toplam 9228 hayvan mevcuttur. Yetiştiricilerin %97’sinin ilkokul mezunu oldukları ve bunların %75’inin sigortalı oldukları belirlenmiştir. İşletmelerin %78.1’inde günde iki öğün yem verildiği ve verilen yem-lerin %97.1’inin sağım sonrası verildiği belirlenmiştir. Tüm işletmelerde doğan buzağılara kolostrum verildiği ancak verilme zamanlarının farklı olduğu görülmüştür. Düvelere, sağmal ineklere, kuru dönemdeki ineklere çoğu işletmelerin özel besleme yapmadığı belirlenmiştir. İşletmelerin %56.2’sinde yemlerin karışık verildiği (kaba yem + konsantre yem), yem miktarlarını ise ölçülmeden tecrübeye dayanarak verildiği belirlenmiştir. İşletmelerin çoğunda kaba yem üretimi yapıldığı belirlenmiştir. İşletmelerin %23.8’inde asidozis ve ketozis, %64.8’inde abomasum deplasmanı, %9.5’inde süt humması, %2.9’unda laminitis görüldüğü tespit edilmiştir. Sonuç olarak araştırma yapılan işletme sahiplerinin hayvan bakım ve besleme konusunda yeteri kadar bilgi sahibi olmadıkları, buzağı beslemede kolostrum ve süt içirme konusun-da dikkatli oldukları ancak kaba ve kesif yem verme hususuna dikkat etmedikleri için buzağı gelişiminde sıkıntılar oldu-ğu gözlenmiştir. İşletmede düve, gebe düve ve sağmal ineklerin beslenmesine dikkat edilmediği görülmüştür. Kaba yem üretimi bakımından da çoğunlukla dışa bağımlı oldukları anlaşılmıştır.

Effect of hyperketonemia on the diurnal patterns of energy-related blood metabolites in early-lactation dairy cows

Most dairy cows experience a period of energy deficit in early lactation, resulting in increased plasma concentrations of nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHB). Our objectives were to determine (1) the diurnal variation in plasma BHB and NEFA, (2) the correlation between plasma NEFA and BHB when accounting for diurnal changes, and (3) the effect of hyperketonemia (HYK) on the diurnal pattern of blood metabolites. Jugular catheters were placed in 28 multiparous Holstein cows between 3 and 9 days in milk, and blood samples were collected every 2 h for 96 h. Cows were retrospectively classified as HYK positive (HYK; n = 13) if they had plasma BHB concentrations ≥1.2 mmol/L for ≥3 study days, or HYK negative (non-HYK; n = 15) if they had plasma BHB concentrations ≥1.2 mmol/L for ≤2 study days. Generalized linear mixed models were used to analyze concentrations of analytes over time and differences in metabolites between HYK groups. The correlation between total plasma NEFA and BHB was analyzed by calculating the area under the curve for plasma NEFA and BHB for all cows. Plasma NEFA reached a peak approximately 2 h before morning feed delivery, falling to a nadir in the late evening. Plasma BHB was at a nadir at the time of morning feed delivery, peaking 4 h later. We observed a strong positive correlation between daily plasma NEFA and BHB. Additionally, HYK cows had greater concentrations of plasma NEFA and BHB than non-HYK cows. The HYK cows also experienced a greater magnitude of change in BHB throughout the day than the non-HYK cows. Our results suggest that the time relative to feeding should be considered when analyzing plasma metabolites, as classification of energy status may change throughout a day.