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Postpartum intrauterine dextrose in clinical healthy dairy cows may impair uterine health.
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Treated cows may have higher incidence of clinical metritis.
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Higher incidence of clinical metritis in treated cows may be associated with lower milk yield.
Abstract
The objective of this study was to assess the effect of intrauterine dextrose infusion at 4 ± 1 d in milk (DIM) on the incidence of clinical metritis (CM), metabolic stress [i.e., body condition score (BCS), β-hydroxybutyrate (BHB) concentration, and subclinical ketosis incidence], systemic inflammation (i.e., haptoglobin concentration), and daily milk yield in clinically healthy postpartum dairy cows. Cows (n = 245) from a dairy farm located in southwest Pennsylvania were screened at 4 ± 1 DIM using a Metricheck (Simcro Tech Ltd.) device to assess vaginal discharge. In addition, overall cow health (e.g., lameness, abnormal breathing) and rectal temperature were assessed at this time. Cows (n = 134) that presented a clear dense vaginal discharge, were in clinically good health status, and had a normal rectal temperature (i.e., <39.7°C) were blocked by parity (primiparous = 64; multiparous = 70) and randomly assigned to 1 of 3 groups: (1) SAL (n = 45): 1 intrauterine infusion of isotonic saline solution (1 L/cow); (2) DEX (n = 44): 1 intrauterine infusion of a 50% dextrose solution (1 L/cow), or (3) CON (n = 45): cows remained untreated. Cows were re-screened at 7 d after enrollment (11 ± 1 DIM) using the Metricheck device to assess CM incidence (research clinical metritis incidence; RCMI). On-farm computer records (i.e., Dairycomp 305) were also used to collect clinical metritis incidence (farm clinical metritis incidence; FCMI). In addition, BCS was assessed and blood samples were collected at enrollment and at study d 7, 14, and 21. Furthermore, daily milk yield and clinical disease events for the first 60 DIM were collected from on-farm computer records. The data were analyzed using the MIXED and GLIMMIX procedures of SAS (SAS Institute Inc.) as a randomized complete block design. Although not significant, the RCMI and FCMI in DEX and SAL cows were on average 14.5 and 18.1 percentage points higher, respectively, compared with CON cows. The SAL cows had higher BHB and haptoglobin concentrations and higher incidence of subclinical ketosis compared with CON cows on study d 7. With regard to daily milk yield, there was a day by treatment interaction, where CON cows produced more milk on certain days compared with DEX and SAL cows. Based on these findings, authors conclude that intrauterine dextrose infusion in clinically healthy postpartum cows with normal vaginal discharge may be prejudicial for cow health and performance.
Graphical Abstract
Graphical AbstractSummary: This study assessed the effects of intrauterine dextrose infusion in clinically healthy dairy cows as a preventative strategy for clinical metritis. One hundred thirty-four cows that presented a clear dense vaginal discharge, were in clinically good health status, and had a normal rectal temperature were blocked by parity (primiparous = 64; multiparous = 70) and randomly assigned to 1 of 3 groups: (1) SAL (n = 45): 1 intrauterine infusion of isotonic saline solution (1 L/cow); (2) DEX (n = 44): 1 intrauterine infusion of a 50% dextrose solution (1 L/cow), or (3) CON (n = 45): cows remained untreated. The results suggest that this treatment approach may increase the incidence of clinical metritis, and therefore, negatively affect metabolic status and milk production of treated cows. Therefore, we do not recommend this treatment strategy for preventing clinical metritis in dairy cattle.
The uterus of a dairy cow is sterile throughout the gestation; however, during and after parturition the reproductive tract can become contaminated with a wide variety of bacteria. Although many cows can naturally overcome this bacterial contamination, around 13.5%, and up to 40%, of cows will develop a bacterial infection, known as clinical metritis (CM;
). Clinical metritis is characterized by the presence of a watery, red-brownish, fetid-smelling vaginal discharge within 21 d of parturition, without systemic signs of illness (e.g., fever, anorexia;
Clinical metritis causes important economic losses to the dairy industry due to decreased milk yield, decreased reproductive performance, and increased culling rate (
). It has been estimated that each case of CM costs approximately $329–386 to dairy producers, accounting for antibiotic treatment, decreased reproductive performance, milk production, and culling of the animal (
reported that cows with CM had higher concentrations of substance P, a biomarker used to measure nociceptive pain in cattle. Due to the important economic and animal welfare impacts of this disease to the dairy industry, it is imperative to identify effective and applicable preventative strategies.
The effects of intrauterine infusions (IUI), such as solutions containing lactic acid bacteria (LAB), after calving has been investigated for their ability to enhance immune response and lower incidence of uterine disease. In one study, where cows received 2 intravaginal administrations of LAB per week during the 3 wk before calving or an intrauterine dose of LAB 1 d after calving, cows that received prepartum vaginal treatment had a lower incidence of metritis compared with the control (
). Although prepartum intravaginal administration of LAB may have the potential to prevent uterine diseases, the variability on the expected calving dates, on which this strategy greatly relies on, may challenge its application in commercial dairy farms. Thus, more applicable strategies should be assessed.
Intrauterine infusion of a 50% dextrose solution has proven to be effective in treating uterine diseases. It has been reported that the use of hypertonic solutions such as sucrose or dextrose inhibited the growth or adhesion of common CM-causing bacteria such as Escherichia coli (
Effect of intrauterine dextrose on reproductive performance of lactating dairy cows diagnosed with purulent vaginal discharge under certified organic management.
treated cows diagnosed with clinical endometritis at 27 ± 3 DIM with an IUI of 50% dextrose solution and found that treated cows had higher clinical cure rates, improved reproductive performance, and faster return to a normal estrous cycle when compared with the untreated cows. Similarly,
reported similar cure rates in cows diagnosed with clinical endometritis that were treated with either intrauterine dextrose or systemic ceftiofur. On the contrary,
found that cows diagnosed with clinical endometritis and were treated with intrauterine dextrose had lower cure rates compared with control cows. In the latter, authors mentioned that differences in disease definition and cure rate parameters may have been the main reasons for the different results observed in these studies (
Assessment of the effects of intrauterine dextrose infusion on clinical cure rate, daily milk yield, daily rumination, metabolic stress, systemic inflammation, and reproductive performance in post-partum dairy cows diagnosed with clinical metritis.
) reported that cows diagnosed with CM at 7 ± 3 DIM treated with 3 consecutive daily treatments of 1 L of 50% dextrose IUI had similar clinical cure rates as cows treated with systemic antibiotics (i.e., ceftiofur). Nevertheless, the effects of IUI of dextrose on the first days after calving on uterine health prevention and cow performance have not yet been assessed.
The objective of this study was to assess the effect of an intrauterine dextrose infusion at 4 ± 1 DIM on incidence of CM, metabolic stress (i.e., BCS, BHB concentration, subclinical ketosis incidence), systemic inflammation [i.e., haptoglobin (HP) concentration], and daily milk yield in postpartum dairy cows. We hypothesized that cows treated with a preventative IUI of 50% dextrose solution would have lower incidence of CM, lower BHB and HP concentrations, and higher daily milk yield compared with cows treated with IUI of isotonic saline solution or untreated control cows.
Postpartum (4 ± 1 DIM) Holstein dairy cows (n = 245) from a dairy farm located in Central Pennsylvania were enrolled in the present study. The farm milked approximately 1,200 cows with a yearly rolling herd average milk yield of 12,535 kg. Pregnant heifers and cows were moved to a far-off pen at 60 d before their expected calving date and were housed on separate pens. At 28 ± 3 d before expected calving date, pregnant heifers and cows were moved to a close-up pen and commingled together until calving. At the onset of calving (i.e., imminent signs of parturition observed by farm personnel), heifers and cows were moved to individual straw bedded calving pens and remained there until calving was finalized and colostrum was collected. Then, primiparous cows (PRIM) and multiparous (MULT) cows were housed together into a postpartum pen until approximately 21 d in lactation. Dry and postpartum animals were housed in 6-row freestall barns with water mattresses bedded with sawdust, and a TMR diet was delivered twice daily in the morning and the afternoon. The TMR diet was formulated to meet or exceed dietary nutritional requirements for high-producing lactating dairy cows (
). Postpartum cows were milked 3 times daily. All of the procedures described below were approved by the Institutional Animal Care and Use Committee at The Pennsylvania State University (protocol number 202001502).
Two hundred forty-five dairy cows were screened at 4 ± 1 d after parturition using a Metricheck (Simcro Tech Ltd.) device. Only cows that presented a clear dense vaginal discharge, were in clinically good health status (did not present any visual signs of disease), and had a normal rectal temperature (i.e., <39.7°C) were included in the study (n = 134; PRIM = 64; MULT = 70). Study cows were blocked by parity and randomly assigned (RAND function, Microsoft Excel, 2017, Microsoft Corp.) to 1 of 3 treatment groups (study d 0) by the study team: control (CON; n = 45): no treatment was administered; dextrose (DEX; n = 44): 1 IUI of a 50% dextrose solution (1 L/cow; VetOne), and saline (SAL; n = 46): 1 IUI of a isotonic saline solution (1 L/cow; VetOne). Although the study team members were not blinded during treatment administration, all the outcome variables (e.g., BHB, BCS) collected after study d 0 (study d 7, 14, and 21) were collected blindly.
Blood samples were collected at study d 0 and 7 to assess serum circulating concentration of BHB. For serum concentration of HP, blood samples of a randomly selected subset of animals (DEX = 10; SAL = 11; CON = 11) were collected at study d 0, 7, 14, and 21. Samples were collected from coccygeal blood vessels into 8.5-mL evacuated sterile serum tubes. Tubes were placed on ice immediately after collection and centrifuged [15 min at 1,400 × g, at room temperature (25°C)] within 2 h of collection to harvest serum, which was stored at −20°C until further analysis. An electronic handheld device (PortaCheck) was used to assess serum concentrations of BHB. Haptoglobin concentration was determined using a commercially available bovine haptoglobin ELISA kit (Life Diagnostics) following the manufacturer's instructions. All samples and standards were analyzed in duplicate. The intraassay (within plate) coefficient of variation ranged from 2.87% to 5.29%, and the interassay (between plates) coefficient of variation ranged from 1.73% to 4.02%. The analytical sensitivity of the assay was 3.91 ng/mL (lower limit of quantification) and 250 ng/mL (upper limit of quantification). Body condition score was assessed at study d 0, 7, 14, and 21 using a 5-point scale (
Enrolled cows were screened for CM at study d 7 using the Metricheck device. Briefly, vaginal discharge was scored using a 5-point scale by the research team (
). Enrolled cows that presented a watery, red-brownish, foul-smelling vaginal discharge with or without fever were categorized as having CM (research clinical metritis incidence; RCMI;
). On-farm computer records (DairyComp305, ValleyAg Software) were also assessed for collecting CM incidence (farm clinical metritis incidence; FCMI). Briefly, farm employees examined cows daily after the morning milking for approximately the first 10 DIM. Employees assessed visually the presence of abnormal discharge through the vulva or utilized milk yield records to further inspect cows with low milk yield (i.e., rectal palpation and massage of the uterus). Serum BHB values were used to assessed subclinical ketosis incidence at study d 7. Subclinical ketosis was defined as a cow that presented a BHB serum concentration of >1.2 mmol/L (
). Due to on-farm record availability (GEA Farm Technologies), daily milk yields were collected for a subset of cows (DEX = 17; SAL = 25; CON = 27) for the first 60 DIM.
A power calculation was run to determine the required sample size for this field trial. To be able to detect a difference in 17.78 percentage points on CM incidence (13.33% vs. 31.11%;
) between DEX and CON cows, with adequate statistical power (1 − β = 0.8) and significance (α = 0.05), a sample size of 28 dairy cows per group (total of 84 animals) was required. There are several peer-reviewed articles that assessed the same outcome variables reported in this study and used similar sample sizes (
Comparison of ceftiofur hydrochloride and estradiol cypionate for metritis prevention and reproductive performance in dairy cows affected with retained fetal membranes.
Intravaginal lactic acid bacteria modulated local and systemic immune responses and lowered the incidence of uterine infections in periparturient dairy cows.
). Sample sizes for other biological outcomes (BCS, BHB, HP, milk yield) were not assessed. However, results for these variables were included to further illustrate the potential biological effects of this treatment (
This randomized complete block design study was analyzed using the SAS statistical software (version 9.4, SAS Institute Inc.). The UNIVARIATE procedure of SAS was used to assess the homogeneity and normality of variances (graphical method, such as histogram and Q-Q plot, and Barlett's tests; Shapiro-Wilk statistic) for the quantitative variables.
Continuous variables were analyzed with the MIXED procedure of SAS. For analysis of BCS, HP, BHB, and daily milk yield, the REPEATED statement was included in the MIXED procedure. The covariate structures were selected using the best fit according to Schwarz's Bayesian information criteria. The variables that remained in the model were selected using the Wald statistic backward selection criterion (P > 0.15). The variable cow was included in the RANDOM statement of the MIXED procedure. The variables originally offered to the models as fixed effects were parity, subclinical ketosis incidence, and BCS at study d 7, 14, and 21. The variable treatment, day, and day by treatment interaction (where the REPEATED statement was used) were forced in the models. In addition, because the first sample (i.e., study d 0) for these variables was collected immediately before treatment administration, the study d 0 values were forced into these models as covariates to be used as baseline data between treatment groups (
). The results are presented as least squares means and standard error of the mean, calculated and adjusted with Tukey-Kramer method using the LSMEAN statement. When the interaction between treatment and day or other variable was significant (P < 0.05), the “slice” option in the LSMEAN statement was used to determine differences among treatments on each level (single comparison) of the interacting variable. Due to lack of normality, the BHB variable (i.e., root square transformation) was transformed. Results are presented as geometric means and back-transformed 95% confidence interval.
The significance of the differences in the percentage of cows that had subclinical ketosis, RCM, and FCM was assessed using multivariable logistic regression models generated by the GLIMMIX procedure of SAS. The main variables of interest and their interactions were considered significant if P < 0.05, and 0.05 < P < 0.10 was considered a tendency.
A total of 245 cows were screened for this study. From this initial group of cows, 136 were excluded because they did not meet the study inclusion criteria. From the 134 cows that met the inclusion criteria, there were 8 cows that left the herd or died before 60 DIM (DEX sold = 5; SAL sold = 1; CON sold = 0; DEX died = 0; SAL died = 1; CON died = 1). Therefore, a total of 39 (PRIM = 21; MULT = 18), 43 (PRIM = 20; MULT = 23), and 44 cows (PRIM = 22; MULT = 22) remained in the DEX, SAL, and CON groups, respectively.
For BHB, the variables that remained in the model were day, treatment, day by treatment interaction, parity, BHB concertation at study d 0, and FCMI. For HP, the variables that remained in the model were day, treatment, day by treatment interaction, and HP concertation at study d 0. For analysis of BCS, day, treatment, day by treatment interaction, parity, and BCS at study d 0 remained in the model.
Overall, cows in the CON group had lower BHB concentrations compared with DEX and SAL cows (DEX = 1.11 mmol/L; 1.02–1.20 95% CI; SAL = 1.13 mmol/L; 1.05–1.23 95% CI; CON = 0.96 mmol/L; 0.88–1.05 95% CI; P = 0.006; Table 1). There was no difference in HP concentration between treatment groups (DEX = 119.72 ± 21.89 μg/mL; SAL = 140.62 ± 21.61 μg/mL; CON = 122.36 ± 18.27 μg/mL; P = 0.65); however, there was a tendency for a day by treatment interaction (P = 0.07; Table 1). Cows treated with SAL tended to have higher concentration of HP on study d 7 compared with CON cows (DEX = 137.35 ± 31.00 μg/mL; SAL = 181.23 ± 30.09 μg/mL; CON = 86.26 ± 27.78 μg/mL; P = 0.05; Table 1). There was no difference in BCS between treatment groups (DEX = 3.59 ± 0.03 points; SAL = 3.57 ± 0.03 points; CON = 3.57 ± 0.03 points; P = 0.53).
Table 1Concentration of serum BHB (overall, study d 0 and 7) and haptoglobin (HP; study d 0, 7, 14, and 21) in cows treated with an intrauterine 50% dextrose infusion (DEX), with an intrauterine isotonic saline infusion (SAL), or that remained untreated (CON) at 4 ± 1 d after calving
For RCMI, FCMI, and subclinical ketosis, the variables that remained in the model were treatment and parity. The percentage of cows with subclinical ketosis, RCMI, and FCMI can be found in Table 2. There were no differences in RCMI (DEX = 28.09 ± 8.87%; SAL = 34.5 ± 9.27%; CON = 12.64 ± 5.77%; P = 0.13) and FCMI (DEX = 18.90 ± 6.15%; SAL = 20.21 ± 6.21%; CON = 5.72 ± 3.36%; P = 0.11) incidences between treatment groups (Table 2). Regardless of treatment, PRIM cows had higher RCMI (PRIM = 37.11 ± 7.48; MULT = 14.00 ± 5.23; P = 0.01) and FCM (PRIM = 22.70 ± 5.57%; MULT = 7.39 ± 3.12%; P = 0.01) incidences compared with MULT cows (Table 2). Cows treated with SAL tended to have higher incidence of subclinical ketosis compared with CON cows (SAL = 49.84 ± 9.90%; CON = 21.64 ± 7.19%; P = 0.08; Table 2). Interestingly, regardless of treatment, MULT cows had a higher incidence of subclinical ketosis at study d 7 compared with PRIM cows (PRIM = 20.62 ± 6.12%; MULT = 54.2 ± 7.06%; P = 0.002; Table 2).
Table 2Percentage (LSM ± SEM) of clinical metritis recorded by research team and farm personnel in cows treated with an intrauterine 50% dextrose infusion (DEX), with an intrauterine isotonic saline infusion (SAL), or that remained untreated (CON) at 4 ± 1 d after calving
Percentage of cows with subclinical ketosis, which was defined as a cow that presented a BHB serum concentration of >1.2 mmol/L, assessed by the research team.
Percentage of cows with clinical metritis diagnosed with the Metricheck (Simcro Tech Ltd.) device by the research team on study d 7. Cows that presented a watery, red-brownish vaginal discharge were categorized as having clinical metritis.
Values with different superscripts within a row and group represent statistical significance at P < 0.05.
0.01
a,b Values with different superscripts within a row and group represent statistical significance at P < 0.05.
1 Percentage of cows with subclinical ketosis, which was defined as a cow that presented a BHB serum concentration of >1.2 mmol/L, assessed by the research team.
2 Percentage of cows with clinical metritis diagnosed with the Metricheck (Simcro Tech Ltd.) device by the research team on study d 7. Cows that presented a watery, red-brownish vaginal discharge were categorized as having clinical metritis.
3 Percentage of cows with clinical metritis recorded by farm personnel collected from on-farm computer records.
For daily milk yield, the variables that remained in the model were day, treatment, day by treatment interaction, and parity. There was no difference in daily milk yield between treatment groups (DEX = 39.71 ± 1.42 kg/d; SAL = 39.45 ± 1.26 kg/d; CON = 41.61 ± 1.14 kg/d; P = 0.36). However, there was a tendency for a day by treatment interaction (P = 0.10), where cows in the CON group had higher milk yields in several days compared with DEX and SAL cows (Figure 1).
Figure 1Daily milk yield (kg/d; LSM ± SEM) in cows treated with an intrauterine 50% dextrose infusion (DEX, n = 39), with an intrauterine isotonic saline infusion (SAL, n = 43), or that remained untreated (CON, n = 44) at 4 ± 1 d after calving, for the first 60 DIM. A day × treatment (P ≤ 0.10) interaction tendency was found. *P < 0.05; †0.05 < P ≤ 0.1.
The main findings of this study were as follows: (1) although not significant (RCMI P = 0.13; FCMI P = 0.11), the RCMI and FCMI in DEX and SAL cows was on average 14.52 and 18.16 percentage points higher, respectively, compared with CON cows; (2) SAL cows had higher BHB and HP concentration and higher incidence of subclinical ketosis compared with CON cows on study d 7; and (3) CON cows produced more milk on certain days compared with DEX and SAL cows during the first 60 DIM.
Study results suggest that there is an 87% and 89% chance (RCMI P = 0.13; FCMI P = 0.11) that cows treated with DEX and SAL had higher incidence of RCMI and FCMI, respectively, compared with CON cows. A possible explanation for the observed results could be that the administration of these solutions inside the uterus could have diluted proinflammatory local metabolites and affected normal inflammatory processes needed for proper uterine involution and bacterial removal. A previous study (
) reported that there were concentrations of important inflammatory metabolites, such as HP and neutrophil-derived haptoglobin-matrix metalloproteinase 9, in the vaginal discharge of nonmetritis cows. Although the uterus is aseptic during pregnancy, most dairy cows may experience uterine bacterial contamination during or after calving (
), and therefore important inflammatory processes are in place to fight off this bacterial contamination.
After calving, one of the main processes of uterine involution is the formation and expulsion of a large amount lochia discharge, which in normal conditions occurs in the first 12 d after calving (
). Perhaps, at 4 ± 1 d after calving, when study cows were enrolled, there was still large amount of lochia remaining inside the uterus, which could have affected treatment efficacy. The administered solutions may have been diluted with the lochia, and therefore, were not concentrated enough to kill contaminant bacteria (e.g., dextrose solution), or may have provided a fluid environment for bacteria to reproduce and thrive (e.g., isotonic saline solution).
Perhaps, the treatment effects observed in systemic inflammation, metabolic stress, and daily milk yield were related to the development of CM rather than caused by the actual treatment. The association between CM and systemic inflammation has been extensively reported. For instance,
found that cows that developed mild or severe CM in the first weeks of lactation had higher concentration of HP around calving compared with cows with a healthy uterus. Similarly, CM has been identified as an important risk factor for subclinical ketosis.
reported that cows with metritis were 4.9% more likely to develop subclinical ketosis compared with cows without metritis. Finally, there is extensive scientific literature describing the negative effects of CM on milk yield in the first weeks after calving (
The results from this study suggest that postpartum intrauterine preventative treatments in healthy cows may be prejudicial for uterine health and overall cow performance early in lactation. Based on these findings, authors conclude that intrauterine dextrose infusion in postpartum cows with normal vaginal discharge is not recommended.
Notes
The authors acknowledge and thank USDA National Institute of Food and Agriculture and Federal Appropriations (Project PEN04665; Accession Number 1017918) for providing partial funding for this experiment.
The authors thank the farm owners and personnel for the help provided and allowing the use of their animals and facilities to perform this project. In addition, authors thank the undergraduate students who helped with sample collection.
The authors have not stated any conflicts of interest.
References
Barragan A.A.
Lakritz J.
Carman M.K.
Bas S.
Hovingh E.
Schuenemann G.M.
Short communication: Assessment of biomarkers of inflammation in the vaginal discharge of postpartum dairy cows diagnosed with clinical metritis.
Intravaginal lactic acid bacteria modulated local and systemic immune responses and lowered the incidence of uterine infections in periparturient dairy cows.
Assessment of the effects of intrauterine dextrose infusion on clinical cure rate, daily milk yield, daily rumination, metabolic stress, systemic inflammation, and reproductive performance in post-partum dairy cows diagnosed with clinical metritis.
Effect of intrauterine dextrose on reproductive performance of lactating dairy cows diagnosed with purulent vaginal discharge under certified organic management.
Comparison of ceftiofur hydrochloride and estradiol cypionate for metritis prevention and reproductive performance in dairy cows affected with retained fetal membranes.
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