Data were obtained from studies in Australia, Canada, and the United States using individual cow data from 28,230 Holstein cows to evaluate associations between parity and disease. Our goal was to develop understanding of disease risks for cows of differing parity. We hypothesized that there would be increased risks of disease and changes in metabolite concentrations with increased parity. Parity ≥5 represented 2,533 cows or 9.0%, parity 4 was 9.8% (2,778), parity 3 as 19.0% (5,355), parity 2 as 28.1% (7,925), and parity 1 was 34.1% (9,639) of the sample. Of these cows, 15.5% were in Australia, 14.7% in Canada, and 69.8% in the United States. Lactational incidence (LI) risk of clinical hypocalcemia increased with parity from 0.1% for parity 1 to 13% for parity ≥5 cows. The marked increase suggests profound differences in metabolism with increased parity. The LI of clinical mastitis was 17.4%. The odds of mastitis increased with parity to 2.5 times greater in parity ≥5 than in parity 1. The LI of lameness increased with parity; specifically, the odds of lameness was 5.6 times greater for parity ≥5 than parity 1. Dystocia incidence was 8.7% and greatest for parity 1 cows. The LI of retained placenta was 7.4% and increased with parity, with the odds for parity ≥5 2.3 times greater than for parity 1. The LI of metritis was 10% and of endometritis 14%, with the greatest odds in parity 1. The LI of clinical ketosis was 3.3% with a marked increase in odds with parity. The prevalence of subclinical ketosis was 26.8% with only cows in parity 1 having lower odds than other parities. Parity ≥5 cows had greater odds (odds ratio = 1.7) of respiratory disease than parity 1 cows, which were lesser than other parities. Metabolite concentrations were evaluated in 5,154 Holstein cows in the precalving, calving, and immediate postcalving data sets. Metabolic measures near peak lactation provided 1,906 observations. Concentrations of β-hydroxybutyrate (BHB) and nonesterified fatty acids increased with parity on d 1 to 3 of lactation and at peak lactation. On d 1 to 3 after calving differences in glucose, nonesterified fatty acids, and BHB indicated a greater reliance on mobilized lipid to export energy to peripheral tissues as BHB for greater parity cows. Differences in concentrations among parity groups were marked at times, for example >0.20 mM in Ca for parity 1 and 2 to parity ≥5 and >0.33 mM for all older parities compared with parity 1 for P on the day of calving. The marked increase suggests profound differences in metabolism with increased parity are probably influenced, in part, by increased production. We found marked differences in concentrations of metabolites with parity that are consistent with reduced reproduction, health, and body condition for higher parity cows. These unfavorable differences in metabolism in Ca, P, glucose, and cholesterol concentrations for higher parity cows also complement the often-substantial differences in disease risk with parity and suggest a need to carefully consider the parity structure in study design. Managers and advisors will need to consider methods to reduce risk of health disorders tailored to cows of different ages.

Dairy farm use of antimicrobial drugs (AMD) is a risk for the selection of antimicrobial resistance (AMR); however, these resistance dynamics are not fully understood. A cohort study on two dairy farms enrolled 96 cows with their fecal samples collected three times weekly, for the first 60 days in milk. Enterobacteriaceae were enumerated by spiral plating samples onto MacConkey agar impregnated with 0, 1, 8, 16 and 30 µg/mL ceftiofur. Negative binomial regression analyzed AMR over time. The continuum of ceftiofur concentrations permitted estimation of the minimum inhibitory concentration (MIC) and analysis using interval regression. The most common systemic AMD was ceftiofur, administered in 94% of treatments (15/16 cows). Enterobacteriaceae did not grow in 88% of samples collected from non-AMD treated cows at 8 µg/mL ceftiofur. Samples from AMD treated cows had peak counts of resistant Enterobacteriaceae during AMD treatment and returned to baseline counts by 3–4 days post-treatment at 8 µg/mL. Sensitive Enterobacteriaceae (0–1 µg/mL ceftiofur) were reduced below pre-treated levels for 29–35 days post-AMD treatment. Population MIC peaked during AMD treatment and returned to baseline levels by 7–8 days. We conclude that the effect of systemic ceftiofur on the resistance of Enterobacteriaceae in early lactation dairy cows was limited in duration.

Summary: The cornual nerve block was developed to desensitize the horn in adult cows and subsequently adapted for disbudding calves. Failure to fully desensitize the horn bud region is often reported, resulting in numerous iterations of recommended blocking techniques without consensus on the most reliable and repeatable approach. Potential causes for nerve block failure include biologically important variation in the zygomaticotemporal nerve and its cornual branches, secondary innervation to the horn bud, and technical errors resulting in poor nerve perfusion with the chosen anesthetic agent. Revisiting regional perfusion may potentially circumvent the previously listed causes for failure. Without a consistent and reliable approach, the welfare of calves undergoing disbudding will be compromised. Graphical abstract created with BioRender.com.

Efforts to optimize the longevity of dairy cows are hindered by the increased risk of adverse health events, culling or dying on farm with increased parity. Lipidomics provides a platform to help identify important biomarkers and biological pathways associated with increased parity and associated aging. A large, multi-site (15 pasture-based, 15 TMR farms) cross-sectional study collected plasma samples from nonlactating, late pregnant, 'dry' cow (696 cows, ~27 d prepartum) and peak-milk cows (796 cows, ~58 DIM) in a disproportionate stratified (parity: 0, 1, 2, > 2 for dry cows; 1, 2, 3, > 3 for peak-milk cows) random sampling frame. A total of 185 lipid species, comprising the lipids classes of phospholipids, sphingomyelins (SM) and triacylglycerols, were quantified in a targeted, liquid chromatography-mass spectrometry (LC-MS) approach. Dry and peak-milk cohorts were analyzed separately throughout. Variation in lipid profiles was mostly attributed to farm of origin (36-41% of variation), with feeding system explaining 13-21% and parity 6-9%, according to ANOVA simultaneous component analysis (ASCA) modeling. Multiple linear regression (MLR) and orthogonal-partial least squares (O-PLS) investigated the association of the lipid profile with age (d), while discriminate analysis compared 1st parity with > 3 parity cows in O-PLS discriminate analysis (O-PLS-DA), random forest (RF) and support vector machine (SVM) models. Rankings of the most important lipid species for each model type were compared. Phospholipids with 40 carbon atoms and 6 double bond equivalents (40:6) were consistently decreased with increasing parity and age across both dry and peak-milk cohorts. These lipids most likely contained stearate (18:0) and docosahexaenoic acid (DHA, C22:6;n-3), an omega-3 fatty acid. Additionally, phospholipids with 40:5, 38:6, lysophosphatidylcholine (17:0), SM(35:1), and SM(35:2) were commonly identified lipids that decreased in concentration with parity and age. Docosahexaenoic acid has been associated with improved cattle health, reproduction, and milk production and quality. This study raises the hypothesis that reduced DHA levels in older cows may be a significant factor increasing susceptibility to adverse health events, reduced reproductive performance, and herd removal. Studies that supplement DHA or its precursors can test this hypothesis and may be important in optimizing longevity of cows.

Summary: Body condition scoring (BCS) and body weight (BW) measurements are associated with health and reproductive efficiencies of cows. We used raw data sets from 16 studies to evaluate associations of parity and feeding system (pasture-based or total mixed ration) with BCS at precalving and peak milk, and change in BCS, and BW at peak milk. With increasing parity, there is a general decrease in BCS and increase in BW regardless of feeding system, with most young cows having low BW and high BCS and older cows having high BW but low BCS.

Identifying physiological determinants of dairy cow survival and their potential modulation by parity may reveal opportunities to improve herd health and longevity. This multisite, prospective, observational study investigated culling and mortality hazards using targeted lipidomic and standard metabolite assays. Blood samples, stratified by parity, were collected from 2 cow cohorts (1) dry and (2) peak-milk, from across 29 commercial Australian farms (14 pasture-based, 15 confinement-based). There were 717 nonlactating, late-pregnant, dry cows (∼27 d prepartum) and 794 peak-milk cows (∼58 DIM) sampled. A total of 186 lipid species (including glycerophospholipids, sphingomyelin, and triacylglycerols) and 11 routinely measured metabolites were evaluated. Sample cows were followed for an average of 693 d and exit reasons recorded. Competing risk survival models were used to estimate the cumulative incidence of culling and mortality by parity and cohort. Blood analytes were autoscaled within cohort and farm, controlling for farm-level effect on metabolites. Survival analysis was performed using an adaptive least absolute shrinkage and selection operator (LASSO) Cox full likelihood model that explored associations among blood analytes and hazards of removal, with a shared frailty of farm (accounting for farm-level baseline hazards), and 2 removal outcomes considered: culling (censoring: death, cull from farm accident, end of follow-up) and mortality (censoring: cull, death from farm accident, end of follow-up). Separate models were used to estimate survival outcome by cohort and parity groupings (first, second and third, and greater than third) or with parity as a categorical covariate. Due to high correlations, analyte data were reduced to 25 clusters using Ward's hierarchical clustering criterion. Bootstrapping of the LASSO variable selection procedure identified clusters with high selection frequency for use in the final model. The hazards and cumulative incidence of culling and mortality increased with parity. Glycerophospholipids with very-long-chain n-3 fatty acids were associated with reduced hazards of culling in parity 1 peak-milk cows (0.39 hazard ratio [HR]), whereas glycerophospholipids with n-3 α-linolenic acid were associated with reduced hazards of culling in parity >3 peak-milk cows (0.18 HR). Sphingomyelin with >C18 fatty acyl chains was associated with increased hazards of culling in parity >3 peak-milk cows (2.02 HR). Clusters containing the routinely evaluated analytes albumin, globulin, urea, magnesium, glucose, triglycerides, β-hydroxybutyric acid, bilirubin, and nonesterified fatty acid were associated with culling and mortality, consistent with their roles in health and reproduction. Lipids collected from dry cows were poor predictors of survival. Many novel plasma lipid targets for future research into survival of cattle were identified, with proinflammatory lipid profiles associated with increased risk of culling and mortality.