S.J. LeBlanc

Postpartum uterine disease and dairy herd reproductive performance: A review

This paper reviews the causes, impact, treatment, and prevention of retained placenta (RP), metritis, and endometritis in dairy cows. The occurrence of each of these diseases largely depends on immune function in the transition period. Retained placenta affects 5-10% of calvings and greatly increases the risk of metritis and endometritis. More field studies are needed to validate criteria for treatment of metritis, but cows with at least two of RP, fever, dullness, and fetid uterine discharge appear to merit treatment with systemic antibiotics. Clinical endometritis affects 15-20% of cows at 4-6 weeks postpartum; an additional 30-35% have subclinical endometritis between 4 and 9 weeks postpartum. Under specific conditions, treatment of cows with endometritis improved pregnancy rate. Systematic use of prostaglandin F(2alpha) at 5 and 7 weeks postpartum may improve pregnancy rate. The economic benefit of efforts to identify and treat endometritis is herd-specific.

Risk factors for postpartum uterine diseases in dairy cows.

The objective of this observational study was to investigate the risk factors for metritis, purulent vaginal discharge, and cytological endometritis. The hypothesis was that purulent vaginal discharge and cytological endometritis would have different risk factors because they represent distinct manifestations of uterine disease. Data generated from 1,363 Holstein cows (3 herds) enrolled in a randomized clinical trial were used. Calving history, periparturient disease incidence, and body condition score at calving and at 63 d in milk (DIM) were recorded. Serum nonesterified fatty acid concentration was measured once during the week before expected calving. Serum nonesterified fatty acid, β-hydroxybutyric acid, and haptoglobin (Hapto) concentrations were measured at 4 ± 3, 11 ± 3, and 18 ± 3 DIM. Serum progesterone concentration was measured at 21 ± 3, 35 ± 3, 49 ± 3, and 63 ± 3 DIM. Metritis was diagnosed by farm managers within the first 20 DIM using a standardized definition. Cows were examined at 35 ± 3 DIM by a veterinarian for purulent vaginal discharge (mucopurulent or worse vaginal discharge; Metricheck device) and cytological endometritis (≥ 6% polymorphonuclear cells on endometrial cytology; cytobrush device). Statistical analyses were performed using multivariable logistic regression models for each disease, accounting for the random effect of herd. Risk factors for metritis included increased nonesterified fatty acid prepartum (≥ 0.6 mmol/L), dystocia, retained placenta, and increased Hapto in the first week postpartum (≥ 0.8 g/L). Risk factors for purulent vaginal discharge included twinning, dystocia, metritis, and increased Hapto (≥ 0.8 g/L) in the first week postpartum. Risk factors for cytological endometritis included low body condition score at parturition (≤ 2.75), hyperketonemia (≥ 1,100 μmol/L), and increased Hapto (≥ 0.8 g/L) in the first week postpartum. These results support the hypothesis that some of the risk factors for purulent vaginal discharge and cytological endometritis are different, which supports that they are distinct manifestations of uterine disease.

The association of serum metabolites with clinical disease during the transition period

The objective of this observational field study was to validate the relationship of serum concentrations of nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and calcium with disease in early lactation across different management systems. Fifty-five Holstein freestall dairy herds located across the United States and Canada were selected and visited weekly for blood sample collection from 2,365 cows. Only diseases that were consistently recorded across herds and blood samples collected before the disease occurred were considered. Metabolite concentrations in serum in wk -1 relative to calving were considered as predictors of retained placenta (RP) and metritis, and metabolite concentrations in serum in wk -1 and wk +1 relative to calving were considered as predictors of displaced abomasum (DA). For each disease, each metabolite, and week of sampling in the case of DA, a critical threshold was calculated based on the highest combined sensitivity and specificity and used to categorize the serum concentrations into high and low risk categories. Multivariable logistic regression models were built for each disease of interest and week of sampling, considering cow as the experimental unit and herd as a random effect. Cows with precalving serum NEFA concentrations ≥ 0.3 mEq/L were more likely to develop RP [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.3 to 2.6] and metritis (OR = 1.8; 95% CI = 1.5 to 2.9) after calving than cows with lower NEFA concentrations. Precalving NEFA ≥ 0.5 mEq/L (OR = 2.4; 95% CI = 1.5 to 3.7), postcalving NEFA ≥ 1.0 mEq/L (OR = 2.7; 95% CI = 1.7 to 4.4), and postcalving calcium ≤ 2.2 mmol/L (OR = 3.1; 95% CI = 1.9 to 5.0) were associated with subsequent risk of DA. In conclusion, elevated serum NEFA concentrations within 1 wk before calving were associated with increased risk of RP, metritis, and DA after calving. Serum NEFA and calcium concentrations in the 2 wk around calving in combination were associated with the risk of DA.

Definitions and diagnosis of postpartum endometritis in dairy cows

The objectives of this observational study were to determine and compare diagnostic criteria for postpartum endometritis in dairy cows. Data generated from 1,044 Holstein cows (6 herds) enrolled in a randomized clinical trial were used. Cows were examined for endometritis at 35±3 d (exam 1) and 56±3 d (exam 2) after parturition, using endometrial cytology (cytobrush technique), vaginal discharge scoring (Metricheck device; Simcrotech, Hamilton, New Zealand), and cervical diameter measurement (transrectal palpation). Reproductive data were recorded until 200 d after parturition. Diagnostic criteria for cytological and clinical endometritis were determined based on detrimental effect on subsequent reproductive performance, using logistic regression and Cox proportional hazard models accounting for the effect of herd clustering. Comparison of diagnostic criteria was performed using endometrial cytology as reference test or by quantifying the agreement between diagnostic approaches. At exam 1, diagnostic criteria were ≥6% polymorphonuclear cells and mucopurulent or worse (purulent or foul) vaginal discharge for cytological and clinical endometritis, respectively. At exam 2, diagnostic criteria were ≥4% polymorphonuclear cells and mucopurulent or worse vaginal discharge for cytological and clinical endometritis, respectively. Cows were classified as having cytological endometritis only, clinical endometritis only, or both cytological and clinical endometritis. Prevalence at exam 1 was 13.5, 9.4, and 5.8% for cytological endometritis only, clinical endometritis only, and both cytological and clinical endometritis, respectively. The detrimental effects of cytological and clinical endometritis on reproductive performance were additive. Among cows with clinical endometritis, only 38 and 36% had cytological endometritis at exam 1 and exam 2, respectively. Combination of diagnostic criteria improved neither the accuracy for predicting cytological endometritis nor the agreement between cytological and clinical endometritis. Overall, these results suggested that cytological and clinical endometritis may represent different manifestations of reproductive tract disease. They also suggested that use of the terminology clinical endometritis may not be accurate and that purulent vaginal discharge may be more descriptive.

Lying behavior as an indicator of lameness in dairy cows

Lameness is widely recognized as one of the most serious welfare and production concerns in the dairy industry. Our objectives were to evaluate the associations between lying behavior and lameness, and to determine whether lying behavior can be used as a diagnostic tool for lameness. Electronic data loggers recorded lying behavior of 1,319 cows from 28 farms at 1-min intervals for 5 d. These cows were gait scored according to a 5-point Numerical Rating System (NRS), and categorized as NRS <or=2, NRS=3, or NRS=4; no cow was scored as NRS=5. Lameness was dichotomized twice: LAME (NRS >or=3) and SEVLAME (NRS=4). Data were divided into 2 groups: 11 farms using deep-bedded stalls (DB) and 17 farms using mattress stalls (MAT). Differences in the daily lying time (h/d), frequency of lying bouts (n/d), duration of lying bouts (min/bout), and the standard deviation of bout duration (min/bout) between LAME or SEVLAME cows and those that were not were tested using mixed models. Receiver operating characteristic curves were constructed to identify behavioral thresholds to distinguish SEVLAME cows from the rest. Odds ratios for SEVLAME were estimated using logistic regression. Overall, 28.5% of cows were LAME including 7.3% that were SEVLAME. The prevalence of SEVLAME was higher on MAT farms than on DB farms (9.3+/-1.3 vs. 4.4+/-1.2%, respectively). SEVLAME cows on DB farms spent 12.8 [confidence interval (CI): 12.0 to 13.7] h/d lying down compared with 11.2 (CI: 10.7 to 11.8) h/d for cows that were not SEVLAME. These cows had longer duration of lying bouts [95.3 (CI: 84.6 to 107.3) vs. 80.3 (CI: 74.9 to 86.1) min/bout] and greater SD of bout duration [44.4 (CI: 41.1 to 48.0) vs. 50.7 (CI: 44.1 to 58.3) min/bout]. There were no behavioral differences among lameness categories on MAT farms. Within DB farms, cows with lying times >14.5 h/d had 16.2 (5.8 to 45.2) times higher odds of being SEVLAME. Cows with average lying bouts >90 min/bout were at 3.0 (1.2 to 7.4) times higher odds of being SEVLAME, and cows with average SD of bout duration >55 min/bout were at 4.1 (1.7 to 9.9) times higher odds of being SEVLAME. These results show that high lying times, long lying bouts, and variability in the duration of lying bouts were associated with lameness, and that stall surface influenced the behavioral responses of lame cows.

Short communication: Haptoglobin as an early indicator of metritis

The purpose of this study was to determine whether haptoglobin (Hp) could be used as a predictive measure for metritis. Cattle were grouped into 3 health categories based on the condition of vaginal discharge and body temperature after calving: severe metritis (n = 12), mild metritis (n = 32), and healthy (n = 23). Blood was collected and analyzed for Hp concentration on d -20 +/- 5, -6 +/- 2, -2 +/- 1, and d 0 relative to calving, and then every 3 d after calving until d +21. Cows with mild and severe metritis had greater Hp concentrations than healthy cows between d 0 and d +12. Mean (+/-SE) Hp concentrations peaked on d +3 in the cows with mild metritis (1.06 +/- 0.15 g/L) and on d +6 in cows with severe metritis (1.62 +/- 0.47 g/L). Mean concentrations for the healthy group were 0.58 +/- 0.12 g/L and 0.31 +/- 0.08 g/L on d +3 and d +6, respectively. Clinical signs of pathological discharge for the mildly and severely metritic cows did not occur until, on average, 8.6 +/- 3.9 d and 5.3 +/- 1.9 d after calving, respectively. Cows with Hp concentrations >or=1 g/L on d +3 were 6.7 times more likely to develop severe or mild metritis; this predictive threshold has a sensitivity of 50% and specificity of 87%. These results indicate that an acute phase inflammatory response precedes clinical metritis and that Hp screening may assist in the early detection of metritis, providing increased opportunities for early treatment and prevention.

Invited review: Recommendations for reporting intervention studies on reproductive performance in dairy cattle: Improving design, analysis, and interpretation of research on reproduction

Abundant evidence from the medical, veterinary, and animal science literature demonstrates that there is substantial room for improvement of the clarity, completeness, and accuracy of reporting of intervention studies. More rigorous reporting guidelines are needed to improve the quality of data available for use in comparisons of outcomes (or meta-analyses) of multiple studies. Because of the diversity of factors that affect reproduction and the complexity of interactions between these, a systematic approach is required to design, conduct, and analyze basic and applied studies of dairy cattle reproduction. Greater consistency, clarity, completeness, and correctness of design and reporting will improve the value of each report and allow for greater depth of evaluation in meta-analyses. Each of these benefits will improve understanding and application of current knowledge and better identify questions that require additional modeling or primary research. The proposed guidelines and checklist will aid in the design, conduct, analysis, and reporting of intervention studies. We propose an adaptation of the REFLECT (Reporting Guidelines for Randomized Controlled Trials for Livestock and Food Safety) statement to provide guidelines and a checklist specific to reporting intervention studies in dairy cattle reproduction. Furthermore, we provide recommendations that will assist investigators to produce studies with greater internal and external validity that can more often be included in systematic reviews and global meta-analyses. Such studies will also assist the development of models to describe the physiology of reproduction.

Factors associated with morbidity, mortality, and growth of dairy heifer calves up to 3 months of age

Calfhood disease is an important problem on many dairy operations that can have substantial effects on heifer survival and productivity, and has economic and welfare impacts. Neonatal calf diarrhea (NCD) and bovine respiratory disease (BRD) are the most common causes of morbidity and mortality in young dairy cattle. The objective of this observational study was to investigate factors associated with the risks of morbidity and mortality, and with growth, in commercial dairy heifers calves. A total of 2874 heifer calves from 19 commercial dairy farms in Minnesota and Ontario were enrolled at 1-7 days of age and followed for approximately 3 months. Using cut-points of serum total protein of 5.2 and 5.7 g/dl, the incidences of failure of transfer of passive immunity (FTPI) were 11 and 32%, respectively. A cut-point of 5.7 g/dl was the most predictive of BRD before 5 weeks of age (sensitivity=40%, specificity=69%). The positive predictive value was poor (PPV=18%), but the negative predictive value was good (NPV=87%). A cut-point of 5.2g/dl was most predictive of death before 5 weeks of age (sensitivity=27%, specificity=89%, PPV=5%, NPV=98%). Serum total protein during the first week of life was a poor predictor of NCD. Over 23% of calves were treated for diarrhea. Risk factors were weight at enrollment, other diseases before 2 weeks of age, and an interaction between season of birth and herd-level incidence of NCD. Almost 22% of calves were treated at least once for BRD. Factors associated with an increased risk of BRD included herd-level incidence of BRD, season of birth, navel dipping, other diseases before 2 weeks of age, failure of transfer of passive immunity, and manual control of temperature in pre-weaning housing. Administration of supplemental antibody products at birth was associated with a reduced incidence of BRD. Overall mortality was 3.5%. Risk of mortality was increased by treatment for BRD and other diseases. The mean average weight gain was 0.95 kg/day (range: 0.11-1.62 kg/day; SD=0.2). Twinning status, FTP, treatment for NCD or other diseases, and month of birth influenced body weight. This study illustrated relationships among various diseases, mortality, and growth. Furthermore, it demonstrated the importance of colostrum for protection against BRD and improved growth performance, while bringing into question the optimal method of determining failure of transfer of passive immunity.

The association of serum metabolites in the transition period with milk production and early-lactation reproductive performance

The objective was to examine the associations of peripartum concentrations of nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and calcium with milk production in early lactation and pregnancy at the first artificial insemination (AI) across different management systems. Fifty-five Holstein freestall dairy herds located across the United States and Canada were visited weekly for blood sample collection from 2,365 cows. For each week of sampling (from wk -1 through wk 3 relative to calving) and for each metabolite, serum concentrations were dichotomized at various thresholds to identify the thresholds with the best negative associations with milk production and pregnancy at first AI. These thresholds were used to categorize the serum concentrations into higher and lower risk categories. Repeated-measures ANOVA and multivariable logistic regression were conducted for milk production and pregnancy at the first AI data, respectively, considering cow as the experimental unit and herd as a random effect. In the week before calving, serum NEFA ≥ 0.5 mEq/L, BHBA ≥ 600 μmol/L, and calcium ≤ 2.1 mmol/L were associated with 1.6 to 3.2 kg/d milk loss across the first 4 Dairy Herd Improvement Association (DHIA) milk tests. High levels of NEFA and BHBA in wk 1 and 2 after calving (≥ 0.7 and ≥ 1.0 mEq/L for NEFA, and ≥ 1,400 and ≥ 1,200 μmol/L for BHBA), and low levels of calcium (≤ 2.1 mmol/L) in wk 1, 2 and 3 after calving were associated with milk loss at the first DHIA milk test. Serum concentrations of NEFA and BHBA were not associated with pregnancy at first AI in any sampling week, whereas calcium <2.2 to 2.4 mmol/L from wk 1 through wk 3 postpartum were associated with reduced pregnancy at first AI. In conclusion, high serum concentrations of NEFA, BHBA, and low concentrations of calcium around parturition were associated with early lactation milk loss, and low calcium concentration around parturition was associated with impaired early lactation reproduction.

Randomized clinical trial of antibiotic and prostaglandin treatments for uterine health and reproductive performance in dairy cows

The objectives of this study were to assess the efficacy of antibiotic treatment for preventing postpartum uterine disease among cows at high risk of uterine disease, and to assess the efficacy of PGF(2α) for treating cytological endometritis (CYTO) and purulent vaginal discharge (PVD). A total of 2,178 Holstein cows in 6 herds were enrolled in a randomized clinical trial. Within 24h after parturition, cows were classified at being at high risk of uterine disease (HRUD; n=1,017) if they had twins, dystocia, or retained placenta. All remaining cows were classified as being at low risk of uterine disease (LRUD; n=1,161). Cows in the HRUD group were randomly allocated in a factorial design to receive ceftiofur crystalline free acid (CCFA) at 24h after parturition or be untreated, and to receive dinoprost (PGF(2α)) at 35 and 49 (±3) days in milk (DIM) or to be untreated. Cows in LRUD were randomly allocated to receive PGF(2α) at 35 and 49 (±3) DIM or to be untreated. Serum progesterone was measured at 21, 35, 49, and 63 (±3) DIM. Cows were examined at 35 (±3; exam 1) and 56 (±3; exam 2) DIM for CYTO (by cytobrush device; ≥6% polymorphonuclear cells in endometrial cytology) and for PVD (by Metricheck device; mucopurulent or purulent vaginal discharge). Statistical analyses were performed using multivariable logistic regression models accounting for herd clustering. Treatment with CCFA in HRUD cows was not associated with the probability of metritis overall, but interactions occurred such that CCFA decreased the incidence of metritis among HRUD cows that did not have retained placenta and among cows of parity ≥2. Treatment with CCFA in HRUD cows decreased the probability of PVD at exam 1. Treatment with PGF(2α) did not affect the probability of cure of CYTO or PVD irrespective of progesterone concentration at the time of treatment. Among cows affected by CYTO or PVD at exam 1, 66 and 63%, respectively, had spontaneously cured at exam 2. Cows persistently affected at exam 2 had an increased time to pregnancy and were more likely to have both CYTO and PVD at exam 1. Administration of PGF(2α) at both 5 and 7 wk postpartum did not mitigate the effects of CYTO or PVD on reproductive performance. Clinical approaches to treatment of chronic postpartum reproductive tract infection and inflammation should be reassessed.