Using a target trial approach to evaluate the role of hyperketonemia in sole ulcer and white line hoof lesion development

This observational cohort study enrolled cows from 7 freestall dairy herds in Minnesota and Wisconsin. The objective was to estimate the causal role of hyperketonemia on new sole ulcer and white line hoof lesions (SUWL). Multiparous cows were enrolled at the time of their precalving hoof trim, at the end of their previous lactation. Enrolled cows were hoof trimmed twice: precalving between 90 to 21 d before calving (n = 2,037), and postcalving between 21 to 150 d after calving (n = 1,408). We trained 7 commercial hoof trimmers, employed by the farms, in lesion identification to standardize lesion recording. Hoof trimmers conducted therapeutic trimming as well as diagnosing and treating lesions. After parturition, cows between 3 and 16 d in milk were tested once weekly for hyperketonemia using a hand-held ketone meter. Farm staff and research personnel conducted the β-hydroxybutyrate (BHB) testing. Cows were classified as hyperketonemic (HYK+) if they had a blood BHB ≥1.2 mmol/L or hyperketonemia-negative (HYK−) if blood BHB <1.2 mmol/L. At the precalving hoof trim, 15.6% of cows trimmed had a lesion and 1.9% of cows had a SUWL; thus, cows with a SUWL were excluded from further analysis (n = 38). At the postcalving hoof trim, 25.8% of cows trimmed had a hoof lesion, and 3.6% of cows had a SUWL. The most prevalent lesions at the pre- and postcalving hoof trims were digital dermatitis and corkscrew lesions. The incidence of hyperketonemia among cows was 21.1% (421/1,999) and the incidence on farms ranged from 5.7 to 29.1%. After excluding cows due to being hoof trimmed outside our designated window, the multilevel logistic regression model for the odds of SUWL at the postcalving hoof trim included 1,209 cows (HYK+ = 257/1,209; SUWL = 42/1,209). The odds of having SUWL in HYK+ was 0.66 (95% confidence interval: 0.29, 1.49) times the odds of that for HYK− cows. For cows diagnosed with a lesion (digital dermatitis, corkscrew, toe, foot rot, or other lesion) at their precalving hoof trim (n = 199), the odds of having SUWL for HYK+ cows were 0.43 (95% confidence interval: 0.05, 3.92) times the odds of that for HYK− cows. The wide range of compatible causal estimates suggest that hyperketonemia likely has a limited role in the development of SUWL in cows with or without a hoof lesion precalving. Future research should investigate other transition period factors such as inflammation or structural changes to the foot that may have a causative role in the development of SUWL.