A large, multisite investigation into the lipidomics of survival in dairy cows

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.