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Are current cut-points for passive transfer of immunity appropriate for dairy calves fed colostrum replacers?

      ABSTRACT

      Objective

      Passive transfer of immunity (PTI) is a metric used on farm to assess colostrum management. With multiple colostrum replacers available differing in composition, classical total serum protein cut points may not apply to all products. The aim of this analysis was to determine whether calves fed a whey-based colostrum replacer that successfully achieved PTI (serum IgG ≥10 mg/mL) would have been classified as having PTI using typical benchmarks (total serum protein <5.0, 5.2, or 5.5 g/dL or Brix% <8.4).

      Materials and Methods

      In total, 1,220 calves were assigned to 1 of 2 treatments: (1) maternal colostrum (MC) or (2) whey-based colostrum replacer supplying 150 g of IgG (CR). Serum samples were collected at 0 and 24 h of life to determine serum IgG, total serum protein, Brix%, and apparent absorption efficiency.

      Results and Discussion

      When comparing serum IgG values with current on-farm cut points, the proportion of calves incorrectly classified as having PTI failure was greater (P < 0.01) for the CR treatment compared with the MC treatment. The proportion of calves incorrectly classified for CR versus MC using current total serum protein or Brix% cut points were as follows: 5.0 g/dL (31.2 vs. 8.8%, P < 0.001), 5.2 g/dL (52.5 vs. 15.5%; P < 0.001), and 5.5 g/dL (82.0 vs. 34.0%, P < 0.001) or serum Brix 8.4% (73.2 vs. 29.2%; P < 0.01).

      Implications and Applications

      These data suggest when analyzing serum on farm from calves fed a whey-based colostrum replacer, traditional cut points for PTI should be revised.

      Key words

      INTRODUCTION

      Consuming adequate amounts of high-quality maternal colostrum quickly after birth is of paramount importance to the newborn calf (
      • Geiger A.J.
      Invited review: Colostrum: Back to the basics with immunoglobulins..
      ). Colostrum contains a high content of antibodies, or Ig, designed to be absorbed by the newborn calf to provide passive transfer of immunity (PTI). This is of extreme importance in newborn mammals because in many mammalian species, placental transfer of Ig does not occur (

      Tizard, I. R. 2013. Veterinary Immunology. 9th ed. Elsevier Inc., St. Louis, MO.

      ). Therefore, the newborn calf relies on PTI for the first 2 to 3 wk of life (
      • Heinrichs A.J.
      • Elizondo-Salazar J.S.
      Reducing failure of passive immunoglobulin transfer in dairy calves..
      ). Sufficient PTI is defined as serum IgG, measured at 24 h after colostrum feeding, exceeding 10 mg of IgG/mL of serum (
      • Quigley J.D.
      Passive immunity in newborn calves..
      ). As recently as 2011, the USDA conducted a survey and determined that 100% of US dairy operations were feeding colostrum to calves. Among farms surveyed, 64.3% were feeding colostrum originating from the dairy, whereas 53.8% of farms used a colostrum replacer in some capacity (

      USDA-NAHMS. 2011. Dairy Heifer Raiser. USDA-Natl. Anim. Health Monit. Syst., Fort Collins, CO.

      ). Additionally, this survey found roughly 40% of farms were monitoring PTI rates on farm.
      Monitoring PTI on farm is a way to gauge colostrum program effectiveness. Total serum protein (TSP) and, in some cases, Brix% are methods used on farm for estimating serum IgG levels and PTI for calves. It is generally accepted that TSP >5.5 g/dL is equivalent to serum IgG >10 mg/mL (
      • McGuirk S.M.
      • Collins M.
      Managing the production, storage, and delivery of colostrum..
      ;
      • Tyler J.W.
      • Hancock D.D.
      • Parish S.M.
      • Rea D.E.
      • Besser T.E.
      • Sanders S.G.
      • Wilson L.K.
      Evaluation of 3 assays for failure of passive transfer in calves..
      ).
      A variety of colostrum replacers are available on the market. Previously (
      • Lago A.
      • Socha M.
      • Geiger A.
      • Cook D.
      • Silva-del-Río N.
      • Blanc C.
      • Quesnell R.
      • Leonardi C.
      Efficacy of colostrum replacer versus maternal colostrum on immunological status, health, and growth of preweaned dairy calves..
      ), calves were fed maternal colostrum or a whey-based colostrum replacer shortly after birth. Mean TSP (5.84 g/dL) was acceptable for gauging PTI in maternal colostrum–fed calves, but the mean TSP for calves fed colostrum replacer was lower than traditional benchmarks. The lower TSP readings when feeding a whey-based colostrum replacer may be due to (1) removal of casein during the manufacturing process of whey-based colostrum replacer, (2) concentrating of IgG during the manufacturing process resulting in a lower feeding rate, or (3) the lower feeding rate resulting in less total protein consumption by the calf. Therefore, the study objective was to determine whether there is a difference in the number of calves fed maternal colostrum or a whey-based colostrum replacer that have serum IgG values greater than 10 mg/mL at 24 h of life but would be classified as calves experiencing failure of passive transfer on farm based on traditional PTI cut points. These calves are referred to as “false failures.” We hypothesized that casein absence in the whey-based colostrum replacer, resulting in less total protein intake, would lead to a greater proportion of calves being classified as PTI false failures compared with maternal colostrum–fed calves.

      MATERIALS AND METHODS

      DairyExperts Inc. provided suitable orientation, appropriate materials, adequate resources, and training to enable research personnel to carry out their respective duties consistent with the Guide for the Care and Use of Agricultural Animals in Research and Teaching (

      FASS. 2020. Guide for the Care and Use of Agricultural Animals in Research and Teaching. 4th ed. FASS Inc., Champaign, IL.

      ).
      A total of 1,220 calves (1 d of age) were used in the experiment and fed 1 of 2 treatments: (1) maternal colostrum (MC; 178 g of IgG intake) or (2) a whey-based colostrum replacer (CR; 150 g of IgG intake, 96% DM, 47% CP, 15% fat). A subset of calves was randomly selected from the population and bled for determination of serum IgG (n = 300 and 292 calves for CR and MC, respectively) and TSP (299 and 294 calves for CR and MC, respectively) at 24 h after feeding and used for the present analysis.
      A more detailed explanation of methods can be found in a previous publication (
      • Lago A.
      • Socha M.
      • Geiger A.
      • Cook D.
      • Silva-del-Río N.
      • Blanc C.
      • Quesnell R.
      • Leonardi C.
      Efficacy of colostrum replacer versus maternal colostrum on immunological status, health, and growth of preweaned dairy calves..
      ) that used the same calves. Briefly, the trial was conducted on a commercial, freestall dairy farm in California, using both Jersey and Jersey × Holstein cross calves. The colostrum replacer fed was a commercially available product (First Day Formula, Accelerated Genetics, Baraboo, WI). Calves were randomly assigned to their respective colostrum treatment at birth and were either fed 2.8 L of MC or CR mixed into 1.9 L of water. All treatments were administered within 1 h ± 5 min of birth via an esophageal tube to ensure the entire colostrum treatment was consumed.
      Maternal colostrum used was harvested twice daily before onset of trial, pooled, and stored until feeding. Colostrum was sampled after collection for quality (n = 53 samples) and averaged 63.6 g of IgG/L (1.96 minimum to 96.9 g/L maximum,
      • Lago A.
      • Socha M.
      • Geiger A.
      • Cook D.
      • Silva-del-Río N.
      • Blanc C.
      • Quesnell R.
      • Leonardi C.
      Efficacy of colostrum replacer versus maternal colostrum on immunological status, health, and growth of preweaned dairy calves..
      ). Before feeding, colostrum was warmed and fed at 41°C. The bucket used to mix the colostrum replacer was filled with 1.9 L of warm water and a package of colostrum replacer (500 g of colostrum-replacer powder providing 150 g of IgG) was added. Mixing occurred for 40 to 60 s until complete dispersal of the colostrum replacer into the water, and the solution was fed at 41°C.
      Logistic regression models using the SAS LOGISTIC PROC version 9.2 (SAS Institute, Cary, NC) were constructed for each of the TSP (5.0, 5.2, and 5.5 g/dL) and Brix (8.4%) cut points. The effect of treatment and a dichotomous variable representing the serum IgG results (serum IgG ≥10 or <10 mg/mL) as a function of the TSP or Brix cut point used were modeled to determine how accurately a given cut point would correctly classify PTI compared with serum IgG for a given treatment. Other explanatory variables such birth weight, calving ease, and single versus twin were included in the model in a forward stepwise selection method where a variable was included when significant at P < 0.05.

      RESULTS AND DISCUSSION

      Health, growth, and performance as they pertain to the current study are presented in a companion publication to this study (
      • Lago A.
      • Socha M.
      • Geiger A.
      • Cook D.
      • Silva-del-Río N.
      • Blanc C.
      • Quesnell R.
      • Leonardi C.
      Efficacy of colostrum replacer versus maternal colostrum on immunological status, health, and growth of preweaned dairy calves..
      ) and are only discussed when relevant to the current work. Colostrum treatment affected the likelihood that a calf was classified as a false failure when compared with a variety of TSP cut points (Table 1). A false negative in this example would be a calf that had a serum IgG value above 10 mg/mL at 24 h after feeding but a TSP value less than 5.0, 5.2, or 5.5 g/dL (classified as failure-of-passive-transfer calf on farm). For all TSP cut points evaluated, feeding CR versus MC resulted in more calves being classified as false failures (P < 0.001; 31.2 vs. 8.8%, 52.5 vs. 15.5%, and 82.0 vs. 41.0% for TSP <5.0, 5.2, and 5.5 g/dL, respectively). The magnitude of difference was 3.55-, 3.39-, and 2.05-fold for TSP values less than 5.0, 5.2, and 5.5 g/dL, respectively. One cut point for Brix% was evaluated as Brix cut points have been evaluated with less frequency (Table 2). When the Brix% cut point of 8.4 was evaluated, CR-fed calves were 2.05-fold more likely to be classified as a false failure (P < 0.001; 73.2 vs. 35.7% for CR vs. MC). Both TSP and serum Brix were correlated with serum IgG in this study regardless of colostrum treatment (P < 0.01; see Figure 1). In general, TSP was more correlated than serum Brix with serum IgG at 24 h. Additional MC generally resulted in better correlations for TSP or serum Brix with serum IgG than CR.
      Table 1Effects of feeding a whey-based colostrum replacer (CR) or maternal colostrum (MC) on the proportion of calves with serum IgG ≥10 mg/mL but falling below 3 established total serum protein (TSP) cut points
      TSP cut pointCR (n = 299)MC (n = 294)Treatment

      effect,

      P-value
      Model covariate
      Estimate95% CIEstimate95% CI
      <5.0 g/dL0.3117(0.2595, 0.3691)0.08758(0.05569, 0.1351)<0.0001BW at birth
      <5.2 g/dL0.5248(0.4649, 0.5840)0.1547(0.1103, 0.2127)<0.0001BW at birth
      <5.5 g/dL0.8201(0.7701, 0.8611)0.4093(0.3397, 0.4828)<0.0001BW at birth
      Table 2Effects of feeding a whey-based colostrum replacer (CR) or maternal colostrum (MC) on the proportion of calves with serum IgG ≥10 mg/mL but Brix reading less than 8.4%
      Brix cut pointCR (n = 299)MC (n = 294)Treatment

      effect,

      P-value
      Model covariate
      Estimate95% CIEstimate95% CI
      8.4%0.7320(0.6769, 0.7808)35.70(0.2917, 0.4280)<0.0001BW at birth
      Figure 1
      Figure 1Correlation between serum total protein (A) or serum Brix (B) and Serum IgG in calves fed either high-quality maternal colostrum (MC; black circles) or a whey-based colostrum replacer (CR; gray triangles). Blood samples were collected from calves at 24 h of life. (A) Correlation for serum total protein and serum IgG for MC calves [serum total protein = 3.4565 (0.1222) + 0.0968 (0.0056) × IgG; r = 0.7778; P < 0.01] and CR calves [serum total protein = 3.3116 (0.1369) + 0.0938 (0.0069) × IgG; r = 0.6255; P < 0.01]. (B) Correlation for serum Brix and serum IgG for MC calves [Brix = 6.4083 (0.2394) + 0.0975 (0.0111) × IgG; r = 0.5344; P < 0.01] and CR calves [Brix = 5.9218 (0.2364) + 0.1069 (0.0120) × IgG; r = 0.4661; P < 0.01].
      Although serum IgG can be considered a direct measure to evaluate PTI and immune status after colostrum is fed, TSP and Brix% both are merely estimates of serum IgG and not exact measures of serum or blood IgG content (
      • McGuirk S.M.
      • Collins M.
      Managing the production, storage, and delivery of colostrum..
      ). The clear difference in the ability to use traditional TSP cut points to correctly classify PTI in calves fed MC versus CR should call into question whether traditional TSP cut points are valid for colostrum replacer, particularly, whey-based colostrum replacer. From a practical standpoint, consultants, veterinarians, and on-farm personal should not blindly trust traditional TSP cut points to appropriately estimate PTI in calves. This appears especially true for calves fed colostrum replacer, unless published data exist to confirm the validity of the cut points or provide valid new cut point estimates.
      In the case of CR versus MC (or possibly dried maternal colostrum), the potential explanation of these results may be a function of protein intake or nutrient profile. Although both colostrum treatments result in adequate levels of IgG at 24 h of life (
      • Lago A.
      • Socha M.
      • Geiger A.
      • Cook D.
      • Silva-del-Río N.
      • Blanc C.
      • Quesnell R.
      • Leonardi C.
      Efficacy of colostrum replacer versus maternal colostrum on immunological status, health, and growth of preweaned dairy calves..
      ), the amount of non-IgG protein present in MC should be greater than in CR. Therefore, it is likely that additional protein consumption may provide additional protein for absorption, thus diluting the IgG content of the serum with excessive non-IgG proteins. The non-IgG proteins may not provide additional immunity protection to the calf but could falsely elevate TSP readings. As a result, lower TSP readings would be expected to estimate the same level of IgG among calves fed whey-based colostrum replacer. This hypothesis seems to be at least partly confirmed by recent work (
      • Lopez A.J.
      • Jones C.M.
      • Geiger A.J.
      • Heinrichs A.J.
      Comparison of immunoglobulin G absorption in calves fed maternal colostrum, a commercial whey-based colostrum replacer, or supplemented maternal colostrum..
      ). In this study, a similar product to that used in the current work was used and a similar feeding rate of IgG employed (150 or 110 g). No calves in the referenced study experienced failure of passive transfer when fed 150 g of IgG from colostrum replacer, but average TSP was below traditional TSP cut points (4.45 g/dL). It was concluded that a TSP of 4.2 g/dL was a better indicator of PTI than traditional cut points such as 5.2 g/dL (
      • Tyler J.W.
      • Hancock D.D.
      • Parish S.M.
      • Rea D.E.
      • Besser T.E.
      • Sanders S.G.
      • Wilson L.K.
      Evaluation of 3 assays for failure of passive transfer in calves..
      ). It should be noted, however, that previous work conducted with whey-based colostrum replacer was done before and did not take into account recently published work suggesting updated benchmarks for assessing PTI on farm (
      • Lombard J.
      • Urie N.
      • Garry F.
      • Godden S.
      • Quigley J.
      • Earleywine T.
      • McGuirk S.
      • Moore D.
      • Branan M.
      • Chamorro M.
      • Smith G.
      • Shivley C.
      • Catherman D.
      • Haines D.
      • Heinrichs A.J.
      • James R.
      • Maas J.
      • Sterner K.
      Consensus recommendations on calf- and herd-level passive immunity in dairy calves in the United States..
      )
      Further, data indicate excess casein content found in some colostrum sources may inhibit effective IgG absorption. Some IgG may get captured by the casein curd formation, inhibiting absorption (
      • Davenport D.F.
      • Quigley III, J.D.
      • Martin J.E.
      • Holt J.A.
      • Arthington J.D.
      Addition of casein or whey protein to colostrum or a colostrum supplement product on absorption of IgG in neonatal calves..
      ). The inhibitory effects of casein may require greater feeding rates of other colostrum-replacer sources to supply the same level of IgG as a whey-based colostrum replacer. The number of animals in the present work combined with other recent reports (
      • Lopez A.J.
      • Jones C.M.
      • Geiger A.J.
      • Heinrichs A.J.
      Comparison of immunoglobulin G absorption in calves fed maternal colostrum, a commercial whey-based colostrum replacer, or supplemented maternal colostrum..
      ) seem to indicate differences in colostrum diet composition may have effects on absorption of IgG and the ability of PTI to be evaluated on farm using traditional metrics.

      APPLICATIONS

      From these results, it is clear that standard TSP cut points may not apply to calves fed colostrum replacer. This appears to be especially true for whey-based colostrum replacer, although both TSP and serum Brix positively correlated with serum IgG in CR-fed calves. Therefore, calf-side estimates of PTI for calves fed colostrum replacer should be viewed with skepticism and not used as the sole metric for evaluation until additional research is conducted. More work is needed in this area to further define appropriate TSP cut points for calves fed various forms of colostrum replacer.

      ACKNOWLEDGMENTS

      Financial support for this research was provided by Accelerated Genetics (Baraboo, WI), Milk Products Inc. (Chilton, WI), and Zinpro Corporation (Eden Prairie, MN).

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        • Martin J.E.
        • Holt J.A.
        • Arthington J.D.
        Addition of casein or whey protein to colostrum or a colostrum supplement product on absorption of IgG in neonatal calves..
        J. Dairy Sci. 2000; 83: 2813-2819
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        Invited review: Colostrum: Back to the basics with immunoglobulins..
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        Reducing failure of passive immunoglobulin transfer in dairy calves..
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        Efficacy of colostrum replacer versus maternal colostrum on immunological status, health, and growth of preweaned dairy calves..
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