Randomized controlled trial comparison of analgesic drugs for control of pain associated with induced lameness in lactating dairy cattle

Both the economic loss and welfare implications of lameness affect the dairy industry. Currently no analgesic drugs are approved to alleviate lameness-associated pain in lactating dairy cattle in the United States. In this randomized controlled trial, 48 lactating Holsteins were enrolled to evaluate the effect of oral meloxicam and i.v. flunixin meglumine on induced lameness. Cows were allocated to 1 of 4 treatment groups (n = 12 per group): lameness and flunixin meglumine (LAME + FLU); lameness and meloxicam (LAME + MEL); lameness and placebo (LAME + PLBO); or sham induction and placebo (SHAM + PLBO). Six hours before treatment, arthritis-synovitis was induced in the distal interphalangeal joint with 20 mg of amphotericin B, whereas SHAM cows were given an intra-articular injection of an equal volume (4 mL) of isotonic saline. Cows in LAME + FLU received 2.2 mg/kg flunixin meglumine i.v. and whey protein placebo orally; LAME + MEL were administered 1 mg/kg meloxicam orally and 2 mL/45 kg sterile saline placebo i.v.; LAME + PLBO were administered 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally; and SHAM + PLBO received 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally. The initial treatment of MEL, FLU, or PLBO was identified as time 0 h and followed by a second dose 24 h later with data collection for 120 h. The methods used to assess analgesic efficacy were electronic pressure mat, visual lameness assessment, visual analog score, plasma cortisol concentration, plasma substance P concentration, mechanical nociception threshold, and infrared thermography imaging. Linear mixed effect modeling was the primary method of statistical analysis. Visual lameness scoring indicated a lower proportion of the FLU + LAME group was lame at the T2 h and T8 h time points in comparison to the positive controls, whereas MEL therapy resulted in a lower proportion of lame cows at the T8 h time point. Cortisol area under the effect curve was lower following FLU therapy compared with LAME + PBLO for the 0–2 h (LSM difference = 35.1 ng·h/mL, 95% CI: 6.8, 63.3 ng·h/mL), 2–8 h (LSM difference = 120.6 ng·h/mL, 95% CI: 77.2, 164.0 ng·h/mL), and 0–24 h (LSM difference = 226.0 ng·h/mL, 95% CI: 103.3, 348.8 ng·h/mL) time intervals. Following MEL therapy, cortisol area under the effect curve was lower than LAME + PLBO for both the 2 to 8 h (LSM difference = 93.6 ng·h/mL, 95% CI: 50.2, 137.0 ng·h/mL) and 0 to 24 h time intervals (LSM difference = 187.6 ng·h/mL, 95% CI: 64.9, 310.4 ng·h/mL). Analysis of data from other assessment modalities failed to discern biologically relevant differences between treatment groups. We conclude that meaningful differences were evident for visual lameness assessment and cortisol from MEL and FLU treatment versus the positive control. Further clinical research is needed toward development of a model that will create reproducible events that are more pronounced in severity and duration of lameness which can be validated as a substitute for naturally occurring lameness cases.     

Effects of a single transdermal administration of flunixin meglumine in early postpartum Holstein Friesian dairy cows: Part 1. Inflammatory and metabolic markers,uterine health,and indicators of pain

The objectives of this study were to assess the effects of a single transdermal administration of flunixin meglumine (FM) in early postpartum Holstein Friesian dairy cows on serum concentrations of inflammatory and metabolic markers, uterine health, and indicators of pain. The hypothesis was that the anti-inflammatory, antipyretic, and analgetic effects of the pharmaceutic agent would reduce systemic inflammation, resulting in improved metabolic and inflammatory profile, diminished incidence of metritis, and reduced expression of pain. A total of 500 cows (153 primiparous, 347 multiparous) from 3 different commercial dairy farms in the northeast of Germany were included in a randomized controlled clinical trial. Farms were preselected based on high haptoglobin concentrations in their fresh lactating cows. Cows were excluded if they had experienced dystocia, stillbirth, or twin birth, or if they showed any signs of milk fever, retained fetal membranes, or fever (>40°C). The cows were treated once with either FM (3.33 mg/kg) or a placebo as control (CON) through transdermal administration between 24 to 36 h postpartum (d 2). General health examinations were performed (daily from d 2–8 and additionally on d 15 postpartum), vaginal discharge was assessed using the Metricheck device (d 8 and 15 postpartum) and serum samples were analyzed for inflammatory and metabolic markers (d 2, 4, and 6 postpartum). Effects of treatment, parity, sampling day, and their interactions were evaluated using mixed effects models. Primiparous cows treated with FM showed lower serum haptoglobin concentrations (0.90 ± 0.08 vs. 1.17 ± 0.07 g/L; ± standard error of the mean) and higher serum albumin concentrations (35.5 ± 0.31 vs. 34.8 ± 0.31 g/L) on d 6 postpartum. They also had a lower risk for purulent vaginal discharge with or without a fever compared with CON cows on d 15 postpartum (odds ratio for CON vs. FM: 1.63, 95% CI: 1.26–2.00), and body temperature was lower throughout the first 15 d in milk (39.1 ± 0.11 vs. 39.2 ± 0.11°C). Multiparous cows treated with FM had lower serum β-hydroxybutyrate concentrations on d 4 postpartum (0.71 ± 0.05 vs. 0.78 ± 0.05 mmol/L) and d 6 postpartum (0.74 ± 0.05 vs. 0.80 ± 0.05 mmol/L). Regardless of parity, FM-treated cows were significantly less likely to abduct their tail from their body (14.3 vs. 23.6%) and show an arched back (27.9 vs. 39.7%) on the day after treatment compared with CON cows. It can be concluded that FM treatment slightly reduced inflammation and diminished the risk for metritis in primiparous cows, improved metabolic profile in multiparous cows, and reduced expressions of pain in all cows.     

Short communication: Behavioral evaluation of the analgesic effect of flunixin meglumine in lame dairy cows

The objective of this study was to evaluate the effect of flunixin meglumine treatment on lameness pain in dairy cows. Twenty-four lactating Holstein cows were enrolled in the study based on visual observation of abnormal locomotion. The primary measurement endpoint was weight-shifting between the rear limbs. Weight-shifting was calculated as the standard deviation of the weight borne on the rear limbs over a 15 min period; this value correlates directly with lameness pain in dairy cows. After collecting baseline weight-bearing data, we randomly assigned cows to 1 of 2 treatment groups: 2.2 mg/kg body weight flunixin meglumine (2 mL/45 kg) or an equivalent volume of isotonic sterile saline solution. Weight-bearing data were collected from each cow at 2, 6, 12, and 24 h after a single intravenous drug treatment. Mean locomotion scores over the 2 d before treatment were 2.38/5 in the flunixin-treated group and 2.43/5 in the saline-treated control group; these values were not significantly different. Weight-shifting values were also not significantly different on either pretreatment day. Cows treated with flunixin meglumine showed significantly less weight-shifting between the rear limbs at 6, 12, and 24 h after treatment compared with saline-treated controls, providing evidence that flunixin meglumine alleviates lameness-associated pain.     

Randomized clinical field trial on the effects of butaphosphan-cyanocobalamin and propylene glycol on ketosis resolution and milk production

The purpose of this study was to determine the effects of a butaphosphan-cyanocobalamin combination product (B+C) and 2 durations of propylene glycol treatment (PG; 3 versus 5 d) on ketosis resolution and early lactation milk yield. Cows from 9 freestall herds (8 in Ontario and 1 in Michigan) were tested at weekly intervals between 3 and 16 d in milk. Ketosis was defined as blood β-hydroxybutyrate (BHB) ≥1.2 mmol/L. Ketotic cows were randomly assigned to treatment with 25 mL of B+C or 25 mL of saline placebo for 3 d and 3 or 5 d of 300 g of PG orally in a 2 × 2 factorial arrangement. Outcomes evaluated for all farms included ketosis cure (blood BHB <1.2 mmol/L at 1 wk after enrollment), maintenance of ketosis cure (blood BHB <1.2 mmol/L 1 and 2 wk after enrollment), and blood BHB concentrations at 1 and 2 wk after enrollment. Daily milk weights were collected in 3 herds. Poisson regression was used to evaluate cure and maintenance of cure, whereas repeated-measures ANOVA was used to evaluate blood BHB concentrations in the 2 wk after enrollment and average daily milk production in the 30 d after treatment. A total of 594 animals were enrolled in the study with 124 treated with B+C and 5 d of PG, 176 treated with B+C and 3 d of PG, 128 treated with saline and 5 d of PG, and 166 treated with saline and 3 d of PG. Animals with blood BHB >2.4 mmol/L at the time of enrollment were 1.7 times more likely [95% confidence interval (CI): 1.4 to 2.2] to cure and had a decrease of 0.25 ± 0.11 mmol/L blood BHB at 1 wk after enrollment if treated with 5 d of PG compared with 3 d, though this response was not seen in animals with BHB of 1.2 to 2.4 mmol/L at enrollment. Cows with blood glucose concentrations <2.2 mmol/L at enrollment produced 3.1 kg/d (95% CI: 1.3 to 5.0) more milk if treated with B+C and 3.4 kg/d (95% CI: 1.7 to 5.1) more milk if treated with 5 d of PG compared with their respective controls. This response was not seen in animals with blood glucose ≥2.2 mmol/L at enrollment and there was no interaction between treatments. These results indicate that extended PG treatment is beneficial in decreasing blood BHB concentrations in more severely affected animals. Additionally, both B+C treatment and extended PG treatment improved milk yield in animals with low blood glucose at the time of ketosis diagnosis.     

Effects of a combination butaphosphan and cyanocobalamin product and insulin on ketosis resolution and milk production

The objective of this study was to determine the effects of butaphosphan-cyanocobalamin (B+C), glargine insulin, and propylene glycol on resolution of ketosis and average daily milk yield after treatment. Cows from 16 herds in Ontario, Canada, and 1 herd in Michigan were tested at weekly intervals between 3 and 16 DIM. Ketosis was defined as blood β-hydroxybutyrate (BHB) ≥1.2 mmol/L. All ketotic cows were given a baseline treatment of 3 d of 300 g of propylene glycol orally. Animals were then randomly assigned to treatment with 3 doses of either 25 mL of B+C or 25 mL of saline placebo and 1 dose of either 2 mL (200 IU) of glargine insulin or 2 mL of saline placebo in a 2 × 2 factorial arrangement. Outcomes of interest on all farms were ketosis cure (blood BHB <1.2 mmol/L 1 wk postenrollment), maintenance of ketosis cure (blood BHB <1.2 mmol/L 1 and 2 wk postenrollment), and blood BHB concentrations at 1 and 2 wk postenrollment. Milk weights were collected daily in 1 large freestall herd. Repeated measures ANOVA was used to evaluate blood BHB concentrations 2 wk after treatment and milk production for 30 d after treatment. Poisson regression was used to examine the effect of treatment on cure and maintenance of cure. Due to a regulatory delay causing temporary unavailability of B+C in Canada, data were analyzed in 2 sets of models: one for insulin and the corresponding placebo (n = 620) and one for the full trial (n = 380). Animals with blood glucose concentrations ≤2.2 mmol/L at the time of ketosis diagnosis were 2.1 times more likely (95% CI = 1.2 to 3.7) to be cured if treated with B+C. Animals in lactation 3 or higher that had blood glucose concentrations <2.2 mmol/L at enrollment produced 4.2 kg/d (95% CI = 1.4 to 7.1) more milk if treated with insulin versus placebo and 2.8 kg/d (95% CI = 0.9 to 4.7) more milk if treated with B+C versus placebo. Animals in lactation 3 or higher with blood glucose ≥2.2 mmol/L that were treated with insulin produced 2.3 kg/d (95% CI = 0.3 to 4.4) less milk than untreated controls. No interaction was observed between treatments. This evidence suggests that B+C and insulin may be beneficial for ketosis treatment in animals with blood glucose <2.2 mmol/L at ketosis diagnosis. It also suggests that blood glucose concentration may be an important predictor of success of ketosis treatment.     

Effects of free-choice pasture access on lameness recovery and behavior of lame dairy cattle

Lameness is a common condition in dairy cows. Free-choice access to pasture may benefit lame cows by providing a softer and more comfortable lying and standing surface; however, the effects of this system on lameness have not yet been explored. We evaluated whether a 7-wk period of free-choice pasture access would improve lameness recovery and affect the lying behavior of lame dairy cows. Lactating Holstein cows, all clinically lame upon enrollment and housed inside a freestall barn, were pseudo-randomly allocated to 1 of 2 treatments (balancing for gait score, parity, and previous lameness history): free-choice access to pasture (n = 27; pasture) or indoor housing only (n = 27; indoor). Cows were gait scored weekly by an observer blind to treatment, using a 5-point numerical rating system (NRS 1 = sound, NRS 5 = severely lame), and hoof inspections were performed by professional trimmers at the start and end of the 7-wk period. Lying behavior was assessed using accelerometers. Cows were categorized as either having a sound period (NRS <2 over 2 consecutive weeks) or remaining lame. Cows spent, on average, 14.8 ± 10.0% (mean ± SD) of their total time on pasture, with much of this time spent outside at night. Over the 7-wk period, 42% of cows had at least one sound period (pasture: 55.6%, indoor: 26.9%), but this was more likely for cows with pasture access (odds ratio = 4.1; 95% confidence interval: 1.1–14.6%). Pasture cows also spent more total weeks sound compared with indoor cows (2.0 ± 0.34 vs. 0.81 ± 0.35 wk). Cows with pasture access lay down for less overall time than indoor cows (13.9 ± 0.29 vs. 12.7 ± 0.28 h/d) and spent more time standing on pasture (74%) than when indoors (47%). These results suggest that lame dairy cows will use pasture when provided with free-choice access, primarily at night, and that access to pasture aids in lameness recovery. We encourage future research to investigate longer-term effects on the recovery of hoof lesions and reoccurrence of lameness cases.     

Effects of pegbovigrastim administration on periparturient diseases,milk production,and reproductive performance of Holstein cows

The aim of this study was to evaluate the effects of treating Holstein cows with pegbovigrastim on periparturient diseases, milk production, and reproductive performance while exploring the mode of action of an immunomodulatory protein. Cows were randomly allocated to 1 of 2 treatments, untreated control (CTR, n = 423) and pegbovigrastim (PEG, n = 417). At 7 d from the anticipated calving date (d ?7), cows allocated to PEG received a subcutaneous injection of 15 mg of pegylated recombinant bovine granulocyte colony stimulating factor (pegbovigrastim injection, Imrestor, Elanco Animal Health, Greenfield, IN). A second injection was administered within 24 h after calving (d 0). Blood samples were obtained from a subset of cows (CTR, n = 103; PEG, n = 102) at ?7 and 0, 3, 7, and 14 d relative to parturition. Samples were used for hemogram and quantification of haptoglobin, nonesterified fatty acids, β-hydroxybutyrate, and trace and macro minerals. Vaginal cytobrush was performed on the same subset cows at d 0, 7, and 14 to assess the relative neutrophil count. Additionally, colostrum samples were collected to measure IgG, IgM, IgA, and lactoferrin concentrations. Postpartum disease occurrence was recorded from calving until 30 d in milk (DIM). Weekly milk yield was recorded for the first 12 wk after calving. Cows treated with PEG had a 3- to 4-fold increase in circulating polymorphonuclear leukocyte, lymphocyte, and monocyte numbers, with a peak at 3 d after treatment followed by a gradual decline, but the counts remained significantly greater compared with CTR at 14 DIM. The administration of PEG did not affect the incidence of clinical and subclinical mastitis, retained fetal membranes, metritis, puerperal metritis, and endometritis. Primiparous cows treated with PEG tended to have lower odds of developing hyperketonemia than CTR [odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.23 to 1.42]. Cows treated with PEG had higher odds of being diagnosed with lameness within 30 DIM compared with CTR (OR = 1.79, 95% CI = 1.16 to 2.76); however, we found no significant differences by 60 DIM. Treatment with PEG increased the odds of displaced abomasum (OR = 8.27, 95% CI = 1.02 to 66.6). Cows treated with PEG had higher odds of being diagnosed with 1 or more clinical diseases compared with CTR cows (OR = 1.39, 95% CI = 1.02 to 1.90). We observed no differences in linear scores or milk composition between treatments. Furthermore, primiparous cows treated with PEG produced more milk than CTR primiparous cows during the first 12 wk postpartum (PEG = 37.51 ± 0.66; CTR = 35.91 ± 0.65 kg), but no differences were observed on energy-corrected milk. Treatment did not alter reproductive performance; additionally, cows diagnosed with metritis or puerperal metritis and treated with PEG tended to have higher proportion of neutrophils in the vaginal mucosa when compared with CTR metritic cows. Although PEG treatment increased circulating polymorphonuclear leukocyte, monocyte, and lymphocyte numbers, as expected, it was detrimental to cow health because it increased morbidity.     

Application of udder surface temperature by infrared thermography for diagnosis of subclinical mastitis in Holstein cows located in tropical highlands

Several reports have indicated that udder surface temperature (UST) can be a useful indicator of subclinical mastitis (SCM). The objective was to evaluate UST by infrared thermography (IRT) as a diagnostic tool for SCM and intramammary infection (IMI), and to assess the influence of environmental conditions in the potential diagnosis of this disease in dairy cows located at high-altitude tropical regions. A total of 105 cows (397 quarters) from 3 dairy farms with mechanical and manual milking methods were enrolled in the study. Subclinical mastitis was diagnosed when quarter samples had a somatic cell count (SCC) ≥200 × 10³ cells/mL, microbial growth (MG) was defined when a major pathogen (≥1 cfu/plate) or Corynebacterium spp. (≥10 cfu/plate) was isolated, and IMI was defined as the presence of MG and SCC ≥100 × 10³ cells/mL. Infrared images were taken with a thermal camera placed 1 m away from the udder, and shots of the rear and left and right lateral view were made during the morning milking, before any manipulation of the udder and employing dark cardboard on the contralateral side to avoid artifacts in the background. A multilevel mixed effects linear regression model clustered within cows and herd was performed to evaluate the associations with UST. Clinical performance was evaluated using the Youden index to establish the optimum UST thresholds, which were set at 32.6°C for any case definition when milking was by hand, at 33.7°C for MG, and at 34°C for SCM and IMI in machine-milked quarters. Sensitivity (Se), specificity (Sp), area under curve (AUC), and positive likelihood ratio (+LR) were also assessed. Test agreement was assessed by kappa coefficient (κ). The UST of healthy quarters ranged between (95% CI) 32.4 and 32.6°C, lower than SCM quarters (n = 88) at 32.9°C (95% CI: 32.7–33.1 °C), MG quarters (n = 56) at 33.5°C (95% CI: 33.3–33.7°C), and IMI quarters (n = 50) at 33.5°C (95% CI: 33.2–33.7 °C). The UST was also related to the milking method: higher temperatures were observed for hand milking (n = 90) compared with machine milking (n = 185). No relation between environmental conditions such as wind speed, atmospheric temperature, relative humidity, and temperature-humidity index and UST were observed during this study. For hand milking, the optimal UST threshold was 32.6°C; for SCM, Se = 0.53, Sp = 0.89, AUC = 0.71, κ = 0.4; for MG, Se = 0.83, Sp = 0.93, AUC = 0.88, κ = 0.77; and for IMI, Se = 0.82, Sp = 0.92, AUC = 0.87, κ = 0.74. The machine milking threshold for SCM resulted in Se = 0.42, Sp = 0.97, AUC = 0.70, κ = 0.47; for MG, Se = 0.82, Sp = 0.89, AUC = 0.85, κ = 0.60; and for IMI, Se = 0.82, Sp = 0.98, AUC = 0.90, κ = 0.79. These findings suggest that UST determined by IRT is higher in machine-milked cows and in quarters with MG and IMI than in healthy quarters; therefore, UST by IRT is a reliable, clinically useful method for MG and IMI diagnosis.     

Effects of a single transdermal administration of flunixin meglumine in early postpartum Holstein Friesian dairy cows: Part 2. Milk yield,culling risk,and reproductive performance

This study was conducted to assess the effects of a single transdermal administration of flunixin meglumine (FM) in early postpartum Holstein Friesian dairy cows on milk yield, culling risk, and reproductive performance. We hypothesized that FM treatment would reduce systemic inflammation, leading to higher milk yield, reduced culling risk, and better reproductive performance in the subsequent lactation. Holstein Friesian dairy cows [n = 500, 153 primiparous (PRIM), 347 multiparous (MULT)] from 3 farms in northeast Germany were enrolled in a prospective, randomized controlled clinical trial. Farms at risk for cows with excessive postpartum inflammation were identified in a preliminary trial by measuring serum haptoglobin concentrations in their fresh lactating cows. Only cows that had a eutocic birth and delivered a singleton calf alive, with no signs of milk fever or retained fetal membranes and rectal temperature ≤40°C at first clinical examination, were included within 24 to 36 h postpartum. Treatment included a single transdermal administration of either FM (3.33 mg/kg) or a placebo as control (CON). Milk production, milk solids, urea, and somatic cell count were recorded monthly for 8 mo after calving. Culling risk, first-service conception risk, and days open were retrieved from the farms' herd management software. Separate models for PRIM and MULT cows were built for most parameters because of significant effects of parity and parity × treatment interaction. Energy-corrected milk yield from 8 monthly Dairy Herd Improvement-equivalent tests was slightly greater in PRIM cows treated with FM (29.51 and 30.73 ± 1.35 kg, CON vs. FM), whereas it was reduced in treated MULT cows (38.23 and 37.47 ± 1.17 kg, CON vs. FM) compared with CON. Milk fat and protein yields were greater in FM-treated PRIM cows and lower in treated MULT cows compared with CON. Milk urea and somatic cell count were not affected by treatment. No differences in culling risk, first-service conception risk, or days open were observed. We conclude that a single transdermal administration of FM in early postpartum dairy cows on farms at risk for excessive postpartum inflammation slightly increased milk, milk fat, and milk protein yields in PRIM cows and decreased these variables in MULT cows. Neither culling risk nor fertility was affected by treatment in this study.     

Associations of subclinical hypocalcemia with fertility in a herd of grazing dairy cows

The main objective was to assess the associations of subclinical hypocalcemia (SCH), diagnosed at parturition (SCH-0) and 7 d in milk (SCH-7), with fertility in a herd of grazing dairy cows. Additional objectives were to characterize Ca concentration on 0 and 7 d in milk (DIM), assessing the risk factors for SCH-0 and SCH-7 and also the relationship with health status (metritis, endometritis, subclinical ketosis, and culling). A prospective observational study was carried out in a dairy farm in Argentina. Holstein cows (n = 126) were body condition scored (BCS, 1–5) on ?21 ± 3, 0, 7 ± 3, and 28 ± 7 DIM and blood was collected on 0 and 7 ± 3 DIM to determine Ca and β-hydroxybutyrate concentrations. Calcium concentrations <2.0 and <2.14 mmol/L were used to define SCH-0 and SCH-7, respectively. The associations of SCH with (1) the odds for pregnancy to first service (P1AI) and pregnancy by 100 DIM (P100) were evaluated by logistic models, (2) the services per pregnancy was evaluated by a Poisson regression model, and (3) the hazards of insemination and pregnancy were evaluated with proportional hazards regression models whereas median days from calving to first insemination and to pregnancy were estimated by Kaplan-Meier method. Additionally, Ca concentration was assessed by linear regression models, and the associations of SCH-0 and SCH-7 with the odds for metritis, endometritis, subclinical ketosis, and culling were evaluated by logistic models. Calcium concentrations were similar at 0 and 7 DIM (2.40 vs. 2.41 mmol/L, respectively); they were higher in cows calving in fall than in summer (2.58 vs. 2.24 mmol/L), and they also were higher in primiparous than in multiparous cows (2.53 vs. 2.28 mmol/L, respectively). The proportion of cows having SCH-0 and SCH-7 was 27.3 and 39.3%, respectively. Fall-calving cows had lower odds for SCH-0 [odds ratio (OR) = 0.31, 95% confidence interval (CI) = 0.12–0.86] than summer-calving cows, multiparous cows had higher odds for SCH-0 (OR = 3.96, 95% CI = 1.09–14.39) than primiparous cows, and cows with prepartum BCS ≥3.00 had higher odds for SCH-0 (OR = 4.03, 95% CI = 1.17–13.89) than in cows with BCS <3.00. Conversely, parity and prepartum BCS were not important predictors for SCH-7. Surprisingly, SCH-0 was not a risk factor for SCH-7. Cows with SCH-0 had lower odds for P1AI (OR = 0.26, 95% CI = 0.07–0.99) than normocalcemic cows, given that P1AI was 14 versus 38%, respectively. The hazard of first service was not associated with SCH-0 (hazard ratio = 1.03, 95% CI = 0.63–1.70) but cows with SCH-0 had lower hazard of pregnancy (hazard ratio = 0.39, 95% CI = 0.16–0.98) and took 32 d longer to get pregnant (105 vs. 73) than normocalcemic cows. Conversely, SCH-7 was not associated with fertility. Finally, SCH-0 and SCH-7 were associated with the odds for subclinical ketosis and metritis, respectively. In conclusion, SCH-0 but not SCH-7 is associated with reduced fertility in a herd of grazing dairy cows, but both were associated with health status.     

Effect of reproductive management programs that prioritized artificial insemination at detected estrus or timed artificial insemination on the reproductive performance of primiparous Holstein cows of different genetic merit for fertility

Our objective was to compare reproductive outcomes of primiparous lactating Holstein cows of different genetic merit for fertility submitted for insemination with management programs that prioritized artificial insemination (AI) at detected estrus (AIE) or timed AI (TAI). Moreover, we aimed to determine whether subgroups of cows with different fertility potential would present a distinct response to the reproductive management strategies compared. Lactating primiparous Holstein cows (n = 6 commercial farms) were stratified into high (Hi-Fert), medium (Med-Fert), and low (Lo-Fert) genetic fertility groups (FG) based on a Reproduction Index value calculated from multiple genomic-enhanced predicted transmitting abilities. Within herd and FG, cows were randomly assigned either to a program that prioritized TAI and had an extended voluntary waiting period (P-TAI; n = 1,338) or another that prioritized AIE (P-AIE; n = 1,416) and used TAI for cows, not AIE. Cows in P-TAI received first service by TAI at 84 ± 3 d in milk (DIM) after a Double-Ovsynch protocol, were AIE if detected in estrus after a previous AI, and received TAI after an Ovsynch-56 protocol at 35 ± 3 d after a previous AI if a corpus luteum (CL) was visualized at nonpregnancy diagnosis (NPD) 32 ± 3 d after AI. Cows with no CL visualized at NPD received TAI at 42 ± 3 d after AI after an Ovsynch-56 protocol with progesterone supplementation (P4-Ovsynch). Cows in P-AIE were eligible for AIE after a PGF_2α treatment at 53 ± 3 DIM and after a previous AI. Cows not AIE by 74 ± 3 DIM or by NPD 32 ± 3 d after AI received P4-Ovsynch for TAI at 74 ± 3 DIM or 42 ± 3 d after AI. Binary data were analyzed with logistic regression, count data with Poisson regression, continuous data by ANOVA, and time to event data by Cox's proportional hazard regression. Pregnancy per AI (P/AI) to first service was greater for cows in the Hi-Fert (59.8%) than the Med-Fert (53.6%) and Lo-Fert (47.7%) groups, and for the P-TAI (58.7%) than the P-AIE (48.7%) treatment. Overall, P/AI for all second and subsequent AI combined did not differ by treatment (P-TAI = 45.2%; P-AIE = 44.5%) or FG (Hi-Fert = 46.1%; Med-Fert = 46.0%; Lo-Fert = 42.4%). The hazard of pregnancy after calving was greater for the P-AIE than the P-TAI treatment [hazard ratio (HR) = 1.27, 95% CI: 1.17 to 1.37)], and for the Hi-Fert than the Med-Fert (HR = 1.16, 95% CI: 1.05 to 1.28) and Lo-Fert (HR = 1.34, 95% CI: 1.20 to 1.49) groups. More cows in the Hi-Fert (91.2%) than the Med-Fert (88.4%) and Lo-Fert (85.8%) groups were pregnant at 200 DIM. Within FG, the hazard of pregnancy was greater for the P-AIE than the P-TAI treatment for the Hi-Fert (HR = 1.41, 95% CI: 1.22 to 1.64) and Med-Fert (HR = 1.28, 95% CI: 1.12 to 1.46) groups but not for the Lo-Fert group (HR = 1.13, 95% CI: 0.98 to 1.31). We conclude that primiparous Holstein cows of superior genetic merit for fertility had better reproductive performance than cows of inferior genetic merit for fertility, regardless of the type of reproductive management used. In addition, the effect of programs that prioritized AIE or TAI on reproductive performance for cows of superior or inferior genetic merit for fertility depended on the outcomes evaluated. Thus, programs that prioritize AIE or TAI could be used to affect certain outcomes of reproductive performance or management.     

Association between early postpartum rumination time and peak milk yield in dairy cows

Limited information is available on the relationship between rumination time (RT) in the early postpartum period and milk production later in lactation. Therefore, the objectives of this study were to (1) investigate the association of change in RT and average RT during the immediate postpartum period with peak milk yield (PMY) in dairy cows, and (2) determine the best model based on days in milk (DIM) to evaluate this association. Cows from 33 free-flow automatic milking system farms were included in this study, where retrospective milk production and RT data were collected for 12 mo. Cows were categorized by parity number into parity 1 (P1, n = 1,538), parity 2 (P2, n = 1,354), or parity ≥3 (P3+, n = 1,770). For each cow, PMY was identified as the highest daily milk yield up to 180 DIM for P1 and 120 DIM for P2 and P3+ cows. Five change in RT variables and 5 average RT variables were created corresponding to the first 2 to 6 DIM. Change in RT variables were the slope coefficients for change in RT/d related to DIM = 1 extracted from simple linear regressions, and average RT variables were the arithmetic mean RT. Five models analyzing PMY and corresponding variables calculated over the first 2 to 6 DIM had fixed effects of average RT, change in RT, parity, average RT × parity interaction, change in RT × parity interaction, and a random intercept for farm. Peak milk yield occurred at (median) 75, 44, and 46 DIM for P1, P2, and P3+, respectively. Overall PMY was (mean ± standard deviation) 54 ± 11 kg and it increased as parity increased. A positive association was found between change in RT and PMY, and average RT and PMY for P2 and P3+ cows in all 5 models corresponding to the first 2 to 6 DIM, indicating that greater average RT and quicker increase in RT after calving are associated with greater PMY for multiparous cows. Although the model including all 6 DIM had the greatest accuracy, results indicated that rumination data collected over the first 2 DIM may also provide adequate information for the association of average RT and change in RT with PMY in P2 and P3+ cows. For each 100 min/d increase in change in RT over the first 6 DIM, PMY increased by 4.3 (95% confidence interval: 2.2–6.3) and 4.8 (95% confidence interval: 3.2–6.5) kg for P2 and P3+ cows, respectively. Peak milk yield increased by 2.3 (95% CI: 1.7–2.8) and 2.2 (95% confidence interval: 1.7–2.6) kg for each 100 min increase in average RT over the first 6 DIM for P2 and P3+ cows, respectively. No association was observed between rumination behaviors and PMY for P1 cows. Results from this study indicate that the length of time for multiparous cows to achieve a stable RT in the early postpartum period combined with average RT during the same period may be useful in predicting their overall lactation milk production.     

Effect of lameness on ovarian activity in postpartum holstein cows

A longitudinal study was conducted to examine the relationship between lameness and delayed ovarian cyclicity during the first 60 d postpartum and days to first luteal activity during the first 300 d postpartum in Holstein cows. Two hundred thirty-eight cows from a 600-cow dairy that calved during a 12-mo period were used. Cows were classified into 1 of 6 categories of lameness during the first 35 d postpartum using a locomotion scoring system. Cows were blood-sampled weekly for detection of plasma progesterone concentrations during the first 300 d postpartum. Cows with delayed resumption of ovarian cyclicity were defined as those with progesterone concentrations consistently <1 ng/mL during the first 60 d postpartum. The null hypothesis that risk of delayed cyclicity is the same in cows classified as nonlame, moderately lame, or lame (after adjusting for potential modifying or confounding effects of loss of body condition and other variables related with delayed cyclicity) was tested using logistic regression. Analysis of results of the study reported here support the hypothesis that lameness is associated with delayed ovarian activity in Holstein cows during the early postpartum period. Cows classified as lame had 3.5 times greater odds of delayed cyclicity, compared with cows classified as nonlame. Attributable proportion analysis indicated that delayed ovarian cyclicity in lame cows would be reduced by 71%, if lameness had been prevented.     

Lameness during the dry period: Epidemiology and associated factors

Lameness has been extensively studied in lactating cows, whereas few studies have reported on lameness during the dry period. We conducted a prospective longitudinal study to describe the epidemiology of lameness during the dry period and to identify risk factors associated with onset, cure, and chronic cases of lameness. A total of 455 cows from 6 freestall commercial dairy farms were enrolled at 9 wk before calving and gait scored weekly until calving using a 5-point scale. A subset of cows was also followed fortnightly after calving to measure the association between lameness during the dry period and lameness during early lactation. Body condition score (BCS) was assessed in a 5-point scale using increments of 0.5. Hoof-trimming records, parity, and previous lactation milk production were retrieved from farm's database. Cows were considered sound when 2 consecutive scores were ≤2 and lame when 2 consecutive scores = 3, or any assessment with score >3; when in a sequence of scores only one score = 3 (or ≤2), the cow was considered sound (or alternatively lame). Following this lameness definition, we derived weekly lameness status for each cow and calculated the number of new cases of lameness, the number of cure cases and the number of chronic cases. The incidence rate of lameness cases during the dry period was 8.2 lameness cases/100 cow per wk, whereas cure rate was 7.1 cure cases/100 cow per wk; at the end of the dry period 50% of cows had developed lameness and 36% were cured. Multilevel logistic regression models using farm as random effect were fitted to assess (1) the association between being lame in wk 2 or 8 postcalving with being lame in the last week precalving, (2) risk factors for lameness onset, (3) risk factors for lameness cure, and (4) risk factors for chronic lameness. Cows that were lame in the week immediately before calving were more likely to be lame in wk 2 and 8 after calving. We found that the interaction between parity and hoof-trimming before dry-off was associated with lameness onset; primiparous cows that were trimmed before dry-off had lower odds of developing lameness, whereas the opposite was found for multiparous cows. The same interaction was also associated with the odds of chronic lameness. Cows that were diagnosed with noninfectious hoof lesions compared with cows that were not diagnosed with hoof lesions before dry-off, and cows that had BCS <3 compared with cows with BCS 3.0 to 3.5 at dry-off had higher odds of chronic lameness. Conversely, primiparous cows and cows with BCS 3.0 to 3.5 had higher odds of curing lameness during the dry period. Our results suggest that the dry period may be a period of high risk for lameness development and that hoof-trimming before dry-off may not be effective for all cows.     

Effect of analgesia during hoof trimming on gait, weight distribution, and activity of dairy cattle

Sixty-six lactating cows were either injected with flunixin meglumine (2.2 mg/kg of BW) immediately before hoof trimming (n = 28), injected with a saline solution immediately before hoof trimming (n = 28), or injected with a saline solution immediately before sham hoof trimming (control; n = 10). Gait scores, time spent lying down, frequency of steps, and how cows distributed their weight among their legs when standing before, during, and after injections were measured to assess whether automated measures of activity and weight distribution can detect lameness and the effects of pain mitigation during hoof trimming. The overall gait score was positively correlated with the variability of the weight applied the rear legs (r = 0.32) and negatively correlated with the rear leg weight ratio (LWR; r = −0.52) and the frequency of steps (r = −0.43). The rear LWR was the best predictor of cows being lame (NRS >3), accounting for 27% of the variation in the likelihood of a cow being lame and 11% of the variation in the likelihood of a cow having an infectious hoof lesion. For each 5% increase in the rear LWR, the likelihood of being lame decreased by 30% (odds ratio = 0.71; 95% confidence interval = 0.56, 0.90) and the likelihood of being afflicted with an infectious hoof disease decreased by 20% (odds ratio = 0.81; 95% confidence interval = 0.67, 0.98). Neither hoof trimming nor a combination of hoof trimming and analgesia significantly affected gait score or any measure of weight distribution. Daily lying time increased during the 2 d following hoof trimming independently of the flunixin meglumine injection. However, this increase was not sustained for longer than 2 d when cows were injected with flunixin meglumine. Measures of weight shifting between legs while cows are standing and measures of activity show great potential as automated methods of detecting lameness and may also provide a tool for future evaluation of lameness therapies, such as hoof trimming and pain mitigation.     

Effect of nutritional immunomodulation and heat stress during the dry period on subsequent performance of cows

Heat stress in dairy cows during the dry period impairs milk yield in the next lactation. Feeding OmniGen-AF (OG; Phibro Animal Health Corp., Teaneck, NJ) to lactating cows during heat stress may increase dry matter intake (DMI) and lowers respiration rate (RR) and rectal temperature (RT), but the effects in dry cows are not known. We hypothesized that OG supplementation before, during, and after the dry period (approximately 160 d total) would overcome the effects of heat stress and improve cow performance in the next lactation. Cows were randomly assigned to OG or control (placebo) treatments for the last 60 d in milk (DIM), based on mature-equivalent milk yield in the previous lactation. Cows were dried off 45 d before expected calving and randomly assigned to heat stress (HT) or cooling (CL) treatments. Thus, cows received dietary supplementation during late lactation before they were exposed to either CL or HT. After dry-off, treatment groups included heat stress with placebo (HT, only shade, 56 g/d of placebo, n = 17), HT with OG supplementation (HTOG, 56 g/d of OG, n = 19), cooling with placebo (CL, shade, fans, and soakers, 56 g/d of placebo, n = 16), and CL with OG supplementation (CLOG, 56 g/d of OG, n = 11). After parturition, all cows were kept under the same CL system and management, and all cows continued to receive OG or control treatment until 60 DIM. Cooling cows during the dry period reduced afternoon RT (CL vs. HT; 38.9 ± 0.05 vs. 39.3 ± 0.05°C) and RR (CL vs. HT; 45 ± 1.6 vs. 77 ± 1.6 breaths/min). Respiration rate was also decreased by OG supplementation under HT conditions (HTOG vs. HT; 69.7 ± 1.6 vs. 77.2 ± 1.6 breaths/min). An interaction was observed between OG supplementation and HT; HTOG cows tended to have lower morning RT compared with HT cows. During the dry period, OG reduced DMI relative to control cows. Birth weight was greater in calves from CL cows (CL vs. HT; 40.6 ± 1.09 vs. 38.7 ± 1.09 kg). No differences were detected among treatments in hematocrit, total protein, and body condition score. Cows offered CLOG, CL, and HTOG treatments had greater body weight during the dry period (794.9 ± 17.9, 746.8 ± 16.7, and 762.9 ± 14.9 kg, respectively) than HT cows (720 ± 16.2 kg). Gestation length was approximately 4 d longer for CL cows compared with HT cows. Cows offered CLOG, CL, and HTOG treatments produced more milk (41.3 ± 1.6, 40.7 ± 1.6, and 40.5 ± 1.6 kg/d, respectively) than HT treatment (35.9 ± 1.6 kg/d). Body weight after parturition and DMI were evaluated up to 60 DIM and averaged 661.5 ± 15.8 and 19.4 ± 0.7 kg/d, respectively, with no differences observed among treatments. These results confirm that exposure of dry cows to heat stress negatively affects milk yield in the subsequent lactation. Active cooling of dry cows and OG supplementation can reduce the negative effects of heat stress in the dry period on subsequent performance.     

A field trial on the effect of propylene glycol on displaced abomasum, removal from herd, and reproduction in fresh cows diagnosed with subclinical ketosis

The purpose was to determine the effect of oral propylene glycol (PG) administration in fresh cows diagnosed with subclinical ketosis (SCK). Measured outcomes were development of displaced abomasum (DA) and removal from herd in the first 30 d in milk (DIM), conception to first service, and time to conception within 150 DIM. Cows from 4 freestall dairy herds (2 in New York and 2 in Wisconsin) were each tested 6 times for SCK from 3 to 16 DIM on Mondays, Wednesdays, and Fridays using the Precision Xtra meter (Abbott Laboratories, Abbott Park, IL). Subclinical ketosis was defined as a blood β-hydroxybutyrate concentration of 1.2 to 2.9 mmol/L. Cows with SCK were randomized to treatment group (oral PG) or untreated control group (no PG); treatment cows were orally drenched with 300 mL of PG once daily from the day they tested 1.2 to 2.9 mmol/L until the day they tested <1.2 mmol/L. Mixed effects multivariable Poisson regression was used to assess the effect of PG on DA, removal from herd, and conception to first service; a semiparametric proportional hazards model was used to evaluate the days-to-conception outcome. A total of 741 of 1,717 (43.2%) eligible enrolled cows had at least 1 β-hydroxybutyrate test of 1.2 to 2.9 mmol/L. Of these, 372 were assigned to the PG treatment group and 369 to the control group. Thirty-nine cows (5.3%) developed a DA after testing positive for SCK and 30 cows (4.0%) died or were sold within the first 30 DIM. Based on risk ratios, control cows were 1.6 times more likely [95% confidence interval (CI)=1.3 to 2.0] to develop a DA and 2.1 times more likely (95% CI=1.2 to 3.6) to die or be sold than cows treated with PG. In addition, PG-treated cows were 1.3 times more likely (risk ratio 95% CI=1.1 to 1.5) to conceive at first insemination than control cows in 3 of the herds. No difference was observed in days to conception within 150 DIM between treatment groups (hazard ratio for PG cows=1.1, 95% CI=0.8 to 1.4), with a median time to conception of 100 d (95% CI=93 to 111) and 104 d (95% CI=95 to 114) for PG-treated and control cows, respectively. These results show that intensive detection of SCK, followed by treatment of positive cows with oral PG decreased the risk of developing a DA or leaving the herd within the first 30 DIM and increased the risk of conception to first service.     

Leptin genotype is associated with lactation performance and health of Holstein cows

The objectives were to evaluate the associations among single nucleotide polymorphisms (SNP) in the R4C locus in exon 2 of the leptin gene and the lactational performance and health of Holstein cows. Eight hundred and fourteen lactating dairy cows had their DNA sequenced in exon 2 of the leptin gene to determine the presence of SNP in the R4C locus. Cows were milked 3 times daily, and yields of milk and milk components were recorded monthly individually during the first 305 d of lactation. Cows were examined daily by herd personnel for diagnosis of health events such as retained fetal membranes, displacement of abomasum, lameness, and mastitis. Resulting genotypes were CC (34.6%), CT (48.2%), and TT (17.2%). Cows bearing the CT genotype had lower body condition (2.98 ± 0.02) during the first 62 d in milk (DIM) than cows homozygous for the C (3.02 ± 0.02) and T (3.04 ± 0.03) alleles. Leptin genotype was associated with yields of milk and milk components, and cows homozygous for the C allele were less productive than those carrying the CT and TT genotypes. The 305-d yields of 3.5% fat-corrected milk, milk fat, and milk true protein were less in CC compared with CT cows by 258, 12, and 10.7 kg, respectively. Cows carrying the TT genotype had increased incidence of displacement of abomasum (4.3%), but genotype did not affect the incidence of retained fetal membranes, clinical and subclinical mastitis, or lameness. Risk of developing at least one clinical health disorder was influenced by leptin genotype, and cows carrying the CT genotype had the lowest risk for developing any disease (19.6%). Mating decisions to increase the frequency of cows heterozygous in the R4C locus may improve productivity and health.     

Effect of mobility score on milk yield and activity in dairy cattle

Previous studies have indicated that lame cows have reduced milk yield both before and after they are treated for lameness. One explanation for the reduction in yield before treatment is delay to treatment; that is, cows have impaired mobility for some time before they are treated. The aim of this study was to test this hypothesis by investigating temporal associations between change in milk yield and change in mobility score. Mobility score (MS, on a scale from 0 to 3), milk yield, treatments for lameness, and cow activity were recorded on 312 cows in a dairy herd in Somerset, UK, for 1 yr. The MS was scored every 2 wk and compared with daily yield and activity (mean log steps/h) averaged over the previous 16 d. Approximately 52% of MS changed within 14 d, usually by 1 unit. Overall, milk yields of cows with MS 1 were greater than those of cows with other scores. Cows with MS 2 and 3 produced 0.7 (95% confidence interval: 0.35–0.97) and 1.6 (0.98–2.23) kg less milk/d, respectively, compared with cows with MS 1. In addition, cows with MS 1 were significantly more active than cows with MS 0, 2, or 3. Cows with MS 2 and 3 were 0.02 (0.01–0.03) and 0.03 (0.01–0.05) mean log steps less active than cows with MS 1. Six to 8 wk before nonlame cows became MS 2 or 3, their daily milk yield decreased by a mean (95% CI) of 0.5 kg (0.12–0.47) and 0.9 kg (0.16–1.65) respectively. Daily yield remained lower by 0.42 kg (0.09–0.75) for 4 wk after cows with MS 2 had recovered. The activity of cows was significantly less (0.01 mean log steps) with increasing MS; the associations between activity and parity (means 0.03–0.11) and month of lactation (means 0.03–0.36) were quantitatively larger. Results from a multistate model indicated that once cows were lame they remained lame or became lame again despite treatment. In conclusion, cows’ milk production started to decline before their mobility was visibly impaired.     

Controlled trial of the effect of negative dietary cation-anion difference prepartum diets on milk production,reproductive performance,and culling of dairy cows

Our objective was to assess the effects of feeding negative dietary cation-anion difference (DCAD) prepartum diets on milk production, reproductive performance, and culling. Cows from 4 commercial farms in Ontario, Canada were enrolled in a pen-level controlled trial from November 2017 to April 2019. Close-up pens (1 per farm) with cows 3 wk before calving were randomly assigned to a negative DCAD (TRT; ?108 mEq/kg of dry matter; target urine pH 6.0–6.5) or a control diet (CON; +105 mEq/kg of dry matter with a placebo supplement). Each pen was fed TRT or CON for 3 mo (1 period), and then switched to the other treatment for the next period (4 periods per farm). Data from 15 experimental units (8 pen treatments in TRT and 7 in CON), with a total of 1,086 observational units (cows), were included. The effect of treatment on milk yield at the first 3 milk recording tests of lactation was assessed with linear regression models accounting for repeated measures. The risk of pregnancy at first artificial insemination and culling by 30, 60, and 305 d in milk (DIM) were analyzed with logistic regression models, and effects on time to first AI, pregnancy, and culling were assessed with Cox proportional hazards models. All models included treatment, parity, and their interactions, accounting for pen-level randomization and clustering of animals within farm with random effects, giving 10 degrees of freedom for treatment effects. Multiparous cows fed TRT produced more milk at the first (42.0 vs. 38.8 ± 1.2 kg/d) and second (44.2 vs. 41.7 ± 1.3 kg/d) milk tests. However, multiparous cows fed TRT tended to have 0.2 percentage units less milk fat content at these tests. Although multiparous cows fed TRT tended to have greater energy-corrected milk at the first test (least squares means ± standard error: TRT = 46.1 ± 0.9 vs. CON = 43.8 ± 1 kg/d), there were no differences observed in energy-corrected milk at the second or third tests. In primiparous cows, there was no effect of treatment on milk production. Multiparous cows fed TRT had greater pregnancy to first insemination (TRT = 42 ± 3 vs. CON = 32 ± 4%) and tended to have shorter time to pregnancy [hazard ratio (HR) = 1.20; 95% CI: 0.96–1.49]. In primiparous cows fed TRT, time to pregnancy was increased (HR = 0.76; 95% CI: 0.59–0.99). Culling by 30 DIM tended to be less in TRT (3.3 ± 1.1%) than CON (5.5 ± 1.8%). No effect of treatment on culling by 305 DIM was detected in primiparous cows, but in multiparous cows, the TRT diets decreased the odds of culling (21.3 ± 1.9 vs. 31.7 ± 2.8%) and daily risk of culling to 305 DIM (HR = 0.64; 95% CI: 0.46 to 0.89). Under commercial herd conditions, prepartum negative DCAD diets improved milk production and reproductive performance, and reduced culling risk in multiparous cows. In primiparous cows, TRT diets had no effect on milk yield or culling, but increased the time to pregnancy. Our results suggest that negative DCAD diets should be targeted to multiparous cows.