Advertisement
PRODUCTION AND MANAGEMENT: Original Research| Volume 37, ISSUE 2, P176-185, April 2021

Download started.

Ok

Comparison of milk replacer composition and effects on growth and health of preruminant lambs, and health-associated costs of artificial rearing

      ABSTRACT

      Objective

      This research evaluated the effects of 2 milk replacer (MR) formulations on lamb performance, morbidity, mortality, and antibiotic usage and health-associated costs of artificial lamb rearing.

      Materials and Methods

      East-Friesian male lambs (n = 206; BW = 4.9 ± 0.24 kg; 2–5 d of age) were stratified by BW and age and randomly allocated to 1 of 8 pens per treatment (10–15 lambs/pen). Lambs were artificially reared on 1 of 2 commercially available MR formulations [MR1 (100% milk protein): 25.3% protein, 26.5% milk fat, 34.9% lactose; MR2 (milk protein + hydrolyzed wheat protein): 23% protein, 24.3% vegetable oil, 30.4% lactose]. The MR was offered ad libitum via automatic feeders, mixed on-demand at 230 g/L of MR at 37°C. Lambs had free access to grass hay throughout the study. Lamb BW was recorded on entry and weekly thereafter to determine ADG and the time taken to reach a minimum of 13.5 kg of BW. Individual animal health assessments were undertaken daily for the first 4 d and weekly thereafter, and any animal health issues were recorded. All animal health interventions including antibiotic use, mortality, and labor requirements for animal health and hygiene management were recorded.

      Results and Discussion

      Lamb mortality was similar between MR1 and MR2 lambs (8 vs. 10%, P = 0.79). Overall, ADG was greater for MR1 than MR2 (mean ± SE: 296 ± 17.6 vs. 242 ± 17.7 g/d, P = 0.02). For lambs not treated with antibiotics, ADG was greater in MR1 versus MR2 lambs (331 ± 12.3 vs. 305 ± 13.5 g/d, P = 0.03) resulting in fewer days to reach a minimum of 13.5 kg of BW (target for weaning: 30 ± 1.3 vs. 33 ± 1.4 d, P = 0.03). Thus, the percentage of lambs that reached 13.5 kg without antibiotic treatment was greater in MR1 than in MR2 lambs (73 ± 4.4 vs. 48 ± 4.9%, P < 0.001). Overall, 4 times more lambs failed to reach 13.5 kg by the end of the study in MR2 than in MR1 (16 vs. 4%, P = 0.009) reflecting their 53 g/d lower ADG. A much lower incidence (range from 1.5 to 13 times) of animal health issues and associated antibiotic use was observed with MR1 compared with MR2 lambs. As a result, the costs associated with animal health interventions were greater for MR2 than for MR1 ($NZ17.2 vs. $NZ7.32 per head).

      Implications and Applications

      Milk replacer formulation did not affect mortality rates; however, ADG was greater and morbidity, antibiotic use, and costs of animal health interventions were lower in lambs reared on a MR formulated from 100% milk proteins and fats compared with MR containing a combination of milk protein, hydrolyzed wheat protein, and vegetable oil.

      Key words

      INTRODUCTION

      At the farm level, management of diet composition is one of the easiest strategies to implement to enhance animal health, productivity, and profitability, contributing to meeting consumer expectations for animal products that are produced sustainably and ethically (
      • Martin G.B.
      • Kadokawa H.
      “Clean, green and ethical” animal production. Case study: reproductive efficiency in small ruminants..
      ). Artificial lamb rearing is used either in commercial dairy systems to increase the amount of milk available for processing (
      • Demiroren E.
      • Shrestha J.N.B.
      • Boylan W.J.
      Breed and environmental effects on components of ewe productivity in terms of multiple births, artificial rearing and 8-month breeding cycles..
      ;
      • Napolitano F.
      • De Rosa G.
      • Sevi A.
      Welfare implications of artificial rearing and early weaning in sheep..
      ) or for rearing of orphans in commercial sheep production systems. Improving the survival, health, and growth of lambs is paramount to reduce rearing costs and meet animal welfare expectations.
      The high cost of milk proteins has driven the development of cheaper formulations containing more whey protein or vegetable proteins (e.g., hydrolyzed wheat and soybean protein) as a cheaper alternative to casein protein (

      Davis, C. L., and J. K. Drackley. 1998. The Development, Nutrition and Management of the Young Calf. Iowa State Univ. Press, Ames, IA.

      ). Use of spray-dried milk proteins in lamb milk replacers is usually recommended (

      Frederiksen, K. R., R. M. Jordan, and C. E. Terrill. 1980. Rearing Lambs on Milk Replacers. Farmers Bull. 2270. Sci. Educ. Admin., UDSA, Washington, DC.

      ;

      Gorrill, A. D. L., G. J. Brisson, D. B. Emmons, and G. J. St.-Laurent (revised by J. W. G. Nicholson). 1982. Artificial Rearing of Young Lambs. Publ. 1507/8. Communication Branch, Agric. Canada, Ottawa, Canada.

      ), especially when high growth rates are required (
      • Treacher T.T.
      Artificial rearing of lambs: A review..
      ). Large-scale lamb rearing systems use automatic feeders to reduce labor costs and to enhance lamb growth by increasing milk allowance. Therefore, identifying lamb milk replacers (MR) that improve lamb growth and health for ad libitum milk-fed rearing systems is important. Furthermore, much of the published research evaluating lamb MR protein sources on lamb performance is >30 yr old and has focused on soy protein (

      Soule, R. P., Jr. 1972. Alternate sources of nonmilk protein for calf, lamb, pig and foal milk replacers. Pages 10–12 in Proc. 32nd Semi-Annual Meeting, American Feed Manufacturers Association Nutrition Council, New Orleans, LA.

      ;
      • Heaney D.P.
      • Shrestha J.N.B.
      Effects of soyflour in milk replacer on the performance of artificially reared lambs..
      ). Inclusion of hydrolyzed wheat protein as a cheaper alternative to soy protein is also now common in commercially available lamb MR. In calves, substituting milk protein with vegetable-based protein sources (e.g., soybean, wheat, peanuts, rice) has variable effects on calf growth depending on the protein source (
      • Lalles J.P.
      • Toullec R.
      • Pardal P.B.
      Hydrolyzed soy protein isolate sustains high nutritional performance in veal calves..
      ;
      • Hill T.M.
      • Bateman H.G.
      • Aldrich J.M.
      • Schlotterbeck R.L.
      Effects of using wheat gluten and rice protein concentrate in dairy calf milk replacers..
      ;
      • Li H.
      • Diao Q.Y.
      • Zhang N.F.
      • Fan Z.Y.
      Growth, nutrient utilization and amino acid digestibility of dairy calves fed milk replacers containing different amounts of protein in the preruminant period..
      ;
      • Huang K.
      • Tu Y.
      • Si B.
      • Xu G.
      • Guo J.
      • Guo F.
      • Yang C.
      • Diao Q.
      Effects of protein sources for milk replacers on growth performance and serum biochemical indexes of suckling calves..
      ). The effects of changes in MR formulation including inclusion of vegetable ingredients on lamb growth and health have not been reported to our knowledge.
      The objective was to evaluate the effects of 2 commercially available lamb MR that differed in protein and fat ingredient sources on lamb growth, health, antibiotic use, survival, and health costs associated with artificial lamb rearing at a commercial scale. We hypothesized that MR formulated with 100% milk protein and fat, compared with milk protein and hydrolyzed wheat protein and vegetable oil, would promote greater growth rates and improved health, thereby reducing antibiotic use.

      MATERIALS AND METHODS

      The animal study was conducted in the spring lambing season (August–September) of 2019. All animal manipulations in this study were conducted in compliance with the institutional Code of Ethical Conduct for the Use of Animals in Research, Testing, and Teaching, as prescribed in the Animal Welfare Act of 1999 and its amendments (New Zealand). The AgResearch Grasslands Animal Ethics Committee approved the manipulations (Approval number 13911).

      Animals, Treatment Allocation, and Husbandry

      A randomized experimental design with 206 East-Friesian crossbred male lambs was used. Male lambs were sourced from a commercial indoor lambing unit over a 2-wk period. The lambs were removed from the dams 2 to 5 d after birth to allow sufficient time for colostrum intake and immediately transported (<30-min drive) to a commercial indoor lamb-rearing unit. Upon trial entry, all lambs were weighed and tagged for identification, and their navels were dipped in iodine solution to reduce the risk of navel infection. In addition, a detailed animal health check was undertaken to confirm the suitability of the lambs for enrolment into the trial. This included assessment of BW (3–7 kg range) and absence of scours, navel and eye infections, lameness, body temperature outside the normal physiological ranges, injuries, or signs of ill thrift (e.g., poor body condition). Birth rank (i.e., single, twin, triplet born, and so on) data were not available and, therefore, were not used as criteria for allocation of lambs to treatment groups. Colostrum consumption was not considered as an entry criterion as all lambs were sourced at 2 to 5 d of age after removal from their dams, were sourced from one operation, and, therefore, were considered random. The lambs were randomly allocated to 1 of 2 treatment groups [milk replacer (MR) 1 (MR1) and 2 (MR2); n = 103 per treatment] balanced for live weight and date of birth, with 8 pens per treatment (n = 10–15 lambs per pen). To avoid large variation in lamb ages between pens, which can result in competition at the lamb feeders, lambs were allocated to treatment or control pens based on entry date and age at entry. As a result, equal numbers of lambs in each pen was not possible. However, the pen stocking density was equally balanced between the treatment groups by allocation date.

      Feeds and Feeding Procedures.

      The formulations of the milk replacers are provided in Table 1. The ingredients listed for each of the milk replacers were as follows: MR1: milk solids; milk fats; vitamins A, C, D, E, K, and B group; cobalt; copper; manganese; selenium; iron; magnesium; calcium; zinc; folic acid; and vanilla flavoring; MR2: skim milk powder; whey powder; vegetable fats; wheat flour; wheat protein (hydrolyzed); vitamins A, D3, and E; iron; iodine; manganese; selenium; and antioxidants propyl gallate and butylated hydroxyanisole. The lambs were group housed in pens (3 × 3 m) with 2 teats from the automatic feeder per pen, with water freely available. Intake of hay was not able to be measured due to high wastage. All pens were bedded with wood chip/miscanthus straw. The rearing facility had natural ventilation and dedicated rearing staff. Treatments were initiated upon entry to the rearing unit.
      Table 1Gross milk composition, individual milk proteins, and AA composition of milk replacer 1 (MR1; 100% bovine milk proteins: 25.3% protein, 26.5% milk fat, 34.9% lactose) and 2 (MR2; bovine milk proteins + hydrolyzed wheat protein: 23% protein, 24.3% vegetable oil, 30.4% lactose)
      ItemMR1MR2
      Composition
       Ash (% DM)7.27.2
       Protein (% DM)25.923.7
       Fat (% DM)27.624.9
       Lactose (% DM)39.344.2
       ME (MJ/kg of DM)21.320.6
       Casein protein (%)8050
       Whey protein (%)2040
       Hydrolyzed wheat protein (%)010
       Bovine milk fat (%)1000
       Vegetable fat (%)0100
      AA (mg/mL)
       EAA
        Histidine6.85.6
        Isoleucine12.611.5
        Leucine24.121
        Lysine19.917.7
        Methionine5.53.9
        Phenylalanine12.19.7
        Threonine11.210.7
        Tryptophan3.43.3
        Valine1613.4
       Conditionally EAA
        Arginine8.77.1
        Cystine22.8
        Glycine4.84.4
        Proline24.020.1
       NEAA
        Alanine8.68
        Aspartic acid19.517.7
        Glutamic acid55.550.2
        Serine14.211.1
       Total conditionally EAA39.534.4
       Total NEAA97.786.9
       Total EAA111.696.9
       Total AA260.7226.8
      Using concentrates to accelerate rumen development to aid early weaning is a common strategy as this provides a nutrient-dense feed to develop the rumen, supports growth, and provides the lamb with a quality feed source following milk weaning. Solid feed intake (concentrate or fiber) is low in the first 3 wk of life even when MR intake is restricted, with a gradual increase thereafter (
      • McCoard S.A.
      • Cristobal-Carballo O.
      • Knol F.W.
      • Heiser A.
      • Khan M.A.
      • Hennes N.
      • Johnstone P.
      • Lewis S.
      • Stevens D.R.
      Impact of early weaning on small intestine, metabolic, immune and endocrine system development, growth and body composition in artificially reared lambs..
      ). In this study, to avoid the potential confounding effects of concentrate intake on animal performance, concentrate was excluded from the diet. Grass hay was freely provided as a source of fiber to comply with animal welfare guidelines, i.e., to meet the animals’ drive to consume solid from ~2 to 3 wk of age to support rumen development (
      • Carballo O.C.
      • Khan M.A.
      • Knol F.W.
      • Lewis S.J.
      • Stevens D.R.
      • Laven R.A.
      • McCoard S.A.
      Impact of weaning age on rumen development in artificially reared lambs..
      ;
      • McCoard S.A.
      • Cristobal-Carballo O.
      • Knol F.W.
      • Heiser A.
      • Khan M.A.
      • Hennes N.
      • Johnstone P.
      • Lewis S.
      • Stevens D.R.
      Impact of early weaning on small intestine, metabolic, immune and endocrine system development, growth and body composition in artificially reared lambs..
      ), but no other source of solid feed was provided.
      Both MR used in this study were commercially available. Both products did not contain a coccidiostat. All lambs were reared using ad libitum MR using automatic feeders (DeLaval LKF1200, DeLaval, Hamilton, NZ) with warm MR (~37°C) mixed at 230 g/L and dispensed on demand. Lambs within each pen received the same treatment. The total amount of MR per treatment group used during the study was determined by recording the number of bags of MR used in each treatment, but individual intake could not be recorded due to this feature not being available on the automatic feeders. Weekly samples of each MR were collected and pooled at the end of the study to generate duplicate samples of each MR type and composition analyzed (Table 1) for ash (Furnace 550°C AOAC 942.05), CP (AOAC 968.06 Dumas method, N-P = 6.38), fat (Mojonnier, dairy AOAC 989.05), minerals (Vacuum oven, AOAC 990.19, 990.21), lactose (enzymatic method), and carbohydrate (by difference) by the Massey University Nutrition Laboratory (Palmerston North, New Zealand). Metabolizable energy of the MR was calculated using

      NASEM. 2001. Nutrient Requirements of Dairy Cattle. 7th rev. ed. Natl. Acad. Press, Washington, DC.

      equations [GE (Mcal/kg) = 0.057 × CP% + 0.092 × Fat + 0.0395 × Lactose%]. Amino acid profiling was performed by the Analytical Laboratory, AgResearch Limited (Palmerston North, New Zealand) via ion exchange chromatography (Shimadzu 20Ai HPLC) with ninhydrin postcolumn derivatization (Pickering Pinnacle PCX). Sulfur AA analyses were prepared after performic oxidation and 22 h reflux (110°C) alongside acid-stable AA analyses in 6 M hydrochloric acid as per AOAC 994.12 with minor modifications. Tryptophan AA analyses were prepared with 20-h alkaline hydrolysis (110°C) as per AOAC 988.15 with minor modifications.

      Animal Measurements.

      Lamb live weight was measured on entry to the rearing facility and weekly during the trial. The effect of MR on animal health was examined in all animals using a range of criteria including antibiotic use (both topical and systemic); prevalence of adverse behaviors (e.g., scrotal sucking); and incidence of scours, ORF (scabby nose), contagious conjunctivitis (pink eye or kerato-conjunctivitis), abomasal bloat, external infections (e.g., enlarged and infected navels), and lameness. Individual animal health monitoring was undertaken daily for the first 4 d and then weekly thereafter by a trained operator. Severity of scour events was based on the scoring system described by
      • Bentounsi B.
      • Meradi S.
      • Cabaret J.
      Towards finding effective indicators (diarrhoea and anaemia scores and weight gains) for the implementation of targeted selective treatment against the gastro-intestinal nematodes in lambs in a steppic environment..
      .
      All animal health issues that required treatment were recorded. Lameness was treated with antibiotics (enrofloxacin, Baytril, Bayer Animal Health, Auckland, NZ, or procaine penicillin, Pharmacillin, Phoenix Pharmcillin 300, Phoenix Pharm, Auckland, NZ) and a nonsteroidal anti-inflammatory drug (meloxicam, Metacam 20, Boehringer Ingelheim, Auckland, NZ). Pneumonia was treated with an oxytetracycline (Engemycin Injection 10%; MSD Animal Health, Wellington, NZ) and Metacam 20, and pink eye was treated with cloxacillin (Orbenin bactericidal eye ointment, Zoetis, Auckland, NZ). All animal health treatments were administered by trained staff according to the manufacturer’s instructions and under guidance from the farm veterinarian. All lamb deaths were recorded. The frequency of changing or replenishing the bedding material to maintain a clean housing environment was recorded along with the time taken to undertake animal health assessments/interventions and routine hygiene practices. Antibiotic use was also recorded. The lambs were not castrated or tail docked.
      New Zealand animal production systems are not high users of antimicrobials (
      • Hillerton J.E.
      • Irvine C.R.
      • Bryan M.A.
      • Scott D.
      • Merchant S.C.
      Use of antimicrobials for animals in New Zealand, and in comparison with other countries..
      ), but prudent use of antimicrobials in livestock is important to support a healthy rearing environment (
      • Kümmerer K.
      Significance of antibiotics in the environment..
      ;
      • Kumar S.
      • Ingle H.
      • Prasad D.V.R.
      • Kumar H.
      Recognition of bacterial infection by innate immune sensors..
      ;
      • Grenni P.
      • Ancona V.
      • Barra Caracciolo A.
      Ecological effects of antibiotics on natural ecosystems: A review..
      ) and address consumer concern around antibiotic use and antimicrobial resistance (
      • Lum E.P.
      • Page K.
      • Nissen L.
      • Doust J.
      • Graves N.
      Australian consumer perspectives, attitudes and behaviours on antibiotic use and antibiotic resistance: a qualitative study with implications for public health policy and practice..
      ). To evaluate the performance of lambs reared without the use of antibiotics, we employed a commonly applied minimum weaning weight target for artificially reared dairy sheep lambs of 13.5 kg coupled with no antibiotic use, as criteria for the exit of lambs from the study. Any lamb that did not reach the weaning weight target or was treated with antibiotics remained in the study until the end of the 52-d study period.

      Animal Health Costs.

      The health costs presented in this study are based on a comparison of input costs associated with animal health interventions. The labor requirements were calculated based on the time recorded for cleaning pens, bedding changes, animal health treatments, and daily health checks not including interventions and a common hourly rate of $NZ22. Bedding inputs were calculated based on the total amount of bedding used for each group and a common bedding unit cost of $NZ20/m3. Animal health treatment costs were based on total use of the following systemic drugs (Pharmacillin at $NZ0.61/head, Engemycin Injection 10% at $NZ0.63/head, and Metacam 20 at $0.83/head) for all animals during the study. While both topical and systemic antibiotics were used as a criterion for “antibiotic use,” there was low use of topical antibiotics and, therefore, these were not included in animal health costs.

      Statistical Analysis

      Lamb growth data and the number of days to slaughter were analyzed using linear mixed effects models. For both outcomes, pen entry weight (centered covariate), treatment group (factor), and their interaction were used as fixed effects. The pen entry weight covariate was centered by deducting each entry weight value by the overall mean entry weight. Random effects of pen entry date (factor) and pen (nested within time) were included in the model.
      A range of generalized linear mixed effects models using Poisson and negative binomial distributions, with and without zero inflation, were used to investigate the effects of treatment on the incidence rate of disease and health parameters. Treatment group (factor) was used as a fixed effect, and the pen number (factor) was used a random effect. The natural logarithm of the risk period (exit date minus the entry date) was included in the models as an offset to account for differences in risk periods between animals. The best fitting model for each health parameter was selected by evaluating model parsimony, minimizing Akaike information criterion, and assessing simulated quantile residuals generated using the “DHARMa” (

      Hartig, F. 2020. DHARMa: Residual diagnostics for hierarchical (Multi-level/mixed) regression models. R Package version 0.3.2.0. Accessed Feb. 2020. https://CRAN.R-project.org/package=DHARMa.

      ) R package.
      Contingency tables and chi-squared statistics were used to investigate the overall counts of antibiotic use, mortality incidence, proportion of animals slaughtered, and the proportion of animals failing to meet weaning weight by treatment group. The R package “epiR” (

      Stevenson, M., T. Nunes, C. Heuer, J. Marshall, J. Sanchez, R. Thornton, J. Reiczigel, J. Robison-Cox, P. Sebastiani, P. Solymos, K. Yoshida, G. Jones, S. Pirikahu, S. Firestone, R. Kyle, J. Popp, M. Jay, and C. Reynard. 2020. epiR: Tools for the analysis of epidemiological data. R package version 1.0–11. Accessed Feb. 2020. https://CRAN.R-project.org/package=epiR.

      ) was used for the calculating summary measures of association including the prevalence and the prevalence ratio.
      The R software program (

      R Core Team. 2016. R: A Language and Environment for Statistical Computing. R Found. Stat. Comp., Vienna, Austria.

      ) was used for statistical analysis. The “lme4” (
      • Bates D.
      • Maechler M.
      • Bolker B.
      • Walker S.
      Fitting linear mixed-effects models..
      ) and “glmmTMB” (
      • Brooks M.E.
      • Kristensen K.
      • van Benthem K.J.
      • Magnusson A.
      • Berg C.W.
      • Nielsen A.
      • Skaug H.J.
      • Maechler M.
      • Bolker B.M.
      glmmTMB balances speed and flexibility among packages for zero-inflated generalized linear mixed modelling..
      ) packages were used for modeling linear mixed effects and generalized linear mixed effects models, respectively. The “lmerTest” (
      • Kuznetsova A.
      • Brockhoff P.D.
      • Christensen R.H.B.
      lmerTest package: Tests in linear mixed effects models..
      ) package was used to derive ANOVA P-values, and the “emmeans” (

      Lenth, R. 2019. Emmeans: Estimated marginal means, aka least squares means. R package version 1.4.1. Accessed Feb. 2020. https://CRAN.R-project.org/package=emmeans.

      ) package was used to derive estimated marginal means, incidence rate ratios, confidence intervals, and P-values for contrasts.
      Statistical analysis of MR input data was not possible due to individual intakes or pen intakes not being available. However, total amount of MR used in each treatment group was recorded.

      RESULTS AND DISCUSSION

      The source of milk used for artificial rearing is one of the important factors that can influence lamb growth and health before weaning (
      • Hernández-Castellano L.E.
      • Suárez-Trujillo A.
      • Martell-Jaizme D.
      • Cugno G.
      • Argüello A.
      • Castro N.
      The effect of colostrum period management on BW and immune system in lambs: From birth to weaning..
      ;
      • Belanche A.
      • Cooke J.
      • Jones E.
      • Worgan H.J.
      • Newbold C.J.
      Short- and long-term effects of conventional and artificial rearing strategies on the health and performance of growing lambs..
      ;
      • Emsen E.
      • Yaprak M.
      • Bilgin O.C.
      • Emsen B.
      • Ockerman H.W.
      Growth performance of Awassi lambs fed calf milk replacer..
      ). The use of MR has become commonplace for artificial rearing of young ruminants. Feeding MR that have been specifically formulated for lambs is recommended (

      Frederiksen, K. R., R. M. Jordan, and C. E. Terrill. 1980. Rearing Lambs on Milk Replacers. Farmers Bull. 2270. Sci. Educ. Admin., UDSA, Washington, DC.

      ). One of the most important nutrients in MR is protein, and thus, feed quality and animal production costs are closely associated with the choice of protein source (
      • Erickson P.S.
      • Schauff D.J.
      • Murphy M.R.
      Diet digestibility and growth of Holstein calves fed acidified milk replacers containing soy protein concentrate..
      ). There are 2 primary protein and fat sources for MR: (1) milk protein and fat and (2) non-milk protein and fat commonly from vegetable sources. The lack of literature evaluating the effect of MR formulation on lamb growth and health has prompted this study.

      Growth Performance

      Growth rate is a key metric of animal performance. Faster growth translates into either a reduction in the time to weaning (and thus feed and labor costs) or an increase in weaning weights. Reducing or eliminating antibiotic use is also highly desirable to meet consumer demand for chemical-free food production, reduce input costs (antibiotics and labor for administration of animal health treatments), and reduce risks associated with antimicrobial resistance. Therefore, in this study, 2 approaches were taken to compare animal performance. First, we compared the growth performance of lambs that reach the exit weight criteria of a minimum of 13.5 kg combined with no antibiotic use (scenario 1). The second approach employed to compare animal performance and animal health costs was to evaluate the overall growth, survival, and health independent of achieving the minimum weight criteria or no antibiotic use (scenario 2).

      Scenario 1.

      A greater proportion of the lambs reared on MR1 compared with MR2 (73 vs. 48%) reached the exit weight criteria of 13.5 kg with no antibiotic use (Table 2). For lambs that reached the exit criteria, their trial exit weight was similar, but lambs on MR1 reached the exit weight on average 2 to 3 d sooner than lambs fed MR2, which reflected their 26 g/d greater ADG (Table 2). Although ADG was greater in the MR1 than MR2 lambs, their exit weights were numerically but not statistically different, likely reflecting the weekly weighing of the lambs. Entry weight was a significant predictor of ADG (P = 0.032), and there was a treatment by entry weight interaction (P = 0.044), indicating that lambs being heavier on entry to the rearing unit was associated with greater ADG in the MR1 but not MR2 lambs (Figure 1A). Entry weight also influenced the time to reach the exit weight (P < 0.001), but no entry weight by treatment interaction was observed (P = 0.53), which indicates that the time taken to reach the exit weight is reduced in lambs that are heavier at entry, which is expected. However, a similar proportion of lambs in each entry weight range, independent of treatment, achieved the exit weight criteria (Table 3). These results suggest that while entry weight can influence growth and, thus, time to slaughter, it is not a strong predictor of performance, thereby light lambs (e.g., <4 kg) have similar potential to meet minimum weight targets compared with heavy lambs. However, if the target outcome of the production unit is to achieve the target weight in the shortest possible time, then entry weight could be used as a criterion for selecting animals to enter such a system. For example, using the data from this study, if the target outcome of the production unit was to achieve a minimum weight of 13.5 kg in 30 d, lambs with an entry weight of >5 kg should be selected if rearing lambs on MR1, or >6 kg if rearing on MR2, with the difference in time frame reflecting the effect of MR type on ADG.
      Table 2Animal performance traits for lambs reared on milk replacer 1 (MR1) and milk replacer 2 (MR2)
      MR1 (100% bovine milk proteins): 25.3% protein, 26.5% milk fat, 34.9% lactose; MR2 (bovine milk proteins + hydrolyzed wheat protein): 23% protein, 24.3% vegetable oil, 30.4% lactose.
      ItemMR1MR2P-value
      MR inputs
      Includes all animals in the trial independent of achieving the minimum weight target of 13.5 kg or topical or systemic antibiotic use.
      (kg)
      1,2501,280
      Mortality
      Includes all animals in the trial independent of achieving the minimum weight target of 13.5 kg or topical or systemic antibiotic use.
      (%)
      8 ± 2.710 ± 3.00.788
      Achieved exit weight target
      Includes only lambs that reached the minimum weight target of 13.5 kg with no topical or systemic antibiotic use.
      (%)
      73 ± 4.448 ± 4.9<0.001
      Days to exit weight
      Includes only lambs that reached the minimum weight target of 13.5 kg with no topical or systemic antibiotic use.
      30.4 ± 1.2733.1 ± 1.390.029
      Exit weight
      Includes only lambs that reached the minimum weight target of 13.5 kg with no topical or systemic antibiotic use.
      (kg)
      14.82 ± 0.1414.95 ± 0.170.575
      ADG
      Includes only lambs that reached the minimum weight target of 13.5 kg with no topical or systemic antibiotic use.
      (g/d)
      331 ± 12.3305 ± 13.50.033
      ADG
      Includes all animals in the trial independent of achieving the minimum weight target of 13.5 kg or topical or systemic antibiotic use.
      (g/d)
      295 ± 17.6242 ± 17.70.024
      Failed to reach weight
      Includes all animals in the trial independent of achieving the minimum weight target of 13.5 kg or topical or systemic antibiotic use.
      (%)
      4 ± 1.916 ± 3.60.009
      Feed efficiency (kg of MR/kg of weight gain)
      Includes all animals in the trial independent of achieving the minimum weight target of 13.5 kg or topical or systemic antibiotic use.
      Calculated as the kilograms of MR inputs per kilogram of total weight gain for all animals in the trial independent of fate (i.e., alive or dead). Total MR input per pen was not available; therefore, statistical analysis was not undertaken.
      1.401.70
      1 MR1 (100% bovine milk proteins): 25.3% protein, 26.5% milk fat, 34.9% lactose; MR2 (bovine milk proteins + hydrolyzed wheat protein): 23% protein, 24.3% vegetable oil, 30.4% lactose.
      2 Includes all animals in the trial independent of achieving the minimum weight target of 13.5 kg or topical or systemic antibiotic use.
      3 Includes only lambs that reached the minimum weight target of 13.5 kg with no topical or systemic antibiotic use.
      4 Calculated as the kilograms of MR inputs per kilogram of total weight gain for all animals in the trial independent of fate (i.e., alive or dead). Total MR input per pen was not available; therefore, statistical analysis was not undertaken.
      Figure 1
      Figure 1The predicted relationship (solid line) and 95% CI (shaded areas) between entry weight and the number of days required to reach the minimum weight criteria with no antibiotic use (A), ADG for lambs reaching the minimum weight criteria with no antibiotic use (scenario 1; B), and ADG for all lambs in the trial (scenario 2; C) reared on milk replacer 1 (MR1) or 2 (MR2). MR1 (100% bovine milk proteins): 25.3% protein, 26.5% milk fat, 34.9% lactose; MR2 (bovine milk proteins + hydrolyzed wheat protein): 23% protein, 24.3% vegetable oil, 30.4% lactose.
      Table 3The distribution of lamb entry weights for all animals in the trial, and the number of animals that achieved the minimum weight criteria of 13.5 kg with no antibiotic use
      MR1 = milk replacer 1 (100% bovine milk proteins): 25.3% protein, 26.5% milk fat, 34.9% lactose; MR2 = milk replacer 2 (bovine milk proteins + hydrolyzed wheat protein): 23% protein, 24.3% vegetable oil, 30.4% lactose.
      ItemAll animals

      [no. (%)]
      Animals that reached

      minimum weight

      with no antibiotics

      [no. (%)]
      MR1MR2MR1MR2
      <4 kg17 (17)16 (16)11 (15)4 (8)
      4–4.9 kg36 (35)37 (36)27 (36)16 (33)
      5–5.9 kg40 (39)40 (39)31 (41)24 (49)
      >6 kg9 (9)9 (9)6 (8)5 (10)
      Total1021027549
      1 MR1 = milk replacer 1 (100% bovine milk proteins): 25.3% protein, 26.5% milk fat, 34.9% lactose; MR2 = milk replacer 2 (bovine milk proteins + hydrolyzed wheat protein): 23% protein, 24.3% vegetable oil, 30.4% lactose.

      Scenario 2.

      This approach evaluated the overall growth, survival, and health of all lambs in the study independent of achieving the exit criteria in scenario 1. To achieve this, all lambs in scenario 1, combined with all other lambs treated with antibiotics or that failed to reach the exit weight criteria, were compared during the 7-wk study. Overall, 4 times more lambs failed to reach the minimum exit weight criteria of 13.5 kg in MR2 than in MR1 by the end of the study (16 vs. 4%), which reflects their 53 g/d lower ADG (Table 2).
      The ADG observed in this study was similar to prior studies where lambs were either naturally reared or artificially reared with ad libitum MR and creep feed (
      • Belanche A.
      • Cooke J.
      • Jones E.
      • Worgan H.J.
      • Newbold C.J.
      Short- and long-term effects of conventional and artificial rearing strategies on the health and performance of growing lambs..
      ). As observed in scenario 1, entry weight of the lamb influenced ADG (P = 0.014), with heavier lambs exhibiting greater ADG, but no entry weight by treatment interaction was observed (P = 0.61). In preruminant calves, as the milk protein substitution rate with vegetable protein sources increases, ADG decreases (
      • Hill T.M.
      • Bateman H.G.
      • Aldrich J.M.
      • Schlotterbeck R.L.
      Effects of using wheat gluten and rice protein concentrate in dairy calf milk replacers..
      ;
      • Li H.
      • Diao Q.Y.
      • Zhang N.F.
      • Fan Z.Y.
      Growth, nutrient utilization and amino acid digestibility of dairy calves fed milk replacers containing different amounts of protein in the preruminant period..
      ;
      • Huang K.
      • Tu Y.
      • Si B.
      • Xu G.
      • Guo J.
      • Guo F.
      • Yang C.
      • Diao Q.
      Effects of protein sources for milk replacers on growth performance and serum biochemical indexes of suckling calves..
      ). It is well established that in preruminants, the digestive system is poorly developed and is unable to digest a wide range of carbohydrates, fats, and proteins (

      Davis, C. L., and J. K. Drackley. 1998. The Development, Nutrition and Management of the Young Calf. Iowa State Univ. Press, Ames, IA.

      ). Replacing skim milk powder with a mixture of solubilized wheat protein concentrate and whey powder increases abomasal emptying of protein and fat and decreases the digestibility for most AA and total nitrogen but not fat (
      • Toullec R.
      • Formal M.
      Digestion of wheat protein in the preruminant calf: Ileal digestibility and blood concentrations of nutrients..
      ). In the present study, the source of milk protein and fats differed considerably; therefore, it is not possible to determine whether the observed differences in animal performance traits were due to substitution of casein with whey and vegetable protein, or replacement of milk fat with vegetable oil, or a combination of these effects. However, the CP (and thus AA content, Table 1) and fat content of MR2 was lower than that of MR1, which may have contributed to the observed differences. Furthermore, the profile of AA also differed between the 2 MR formulations. When compared as a proportion of total protein, MR1 had 11% more His, 29% more Met, 14% more Phe, 12% more Arg, 17% more Ser, and 35% less Cys with <10% difference in the other AA compared with MR2. The AA requirements of growing lambs are not known. However, it is well established that some specific AA have functional roles beyond being building blocks for proteins, including modulation of immune function and improving skeletal muscle growth (
      • Li P.
      • Yin Y.L.
      • Li D.
      • Woo Kim S.
      • Wu G.
      Amino acids and immune function..
      ;
      • McCoard S.
      • Sales F.
      • Sciascia Q.
      Amino acids in sheep production..
      ). Further trials where intake can be measured individually or in combination with changing the source and proportion of protein and fat in the MR are required to determine the cause of the differences in animal performance.

      Health Data

      Antimicrobials are widely used in livestock farming systems to improve animal health, welfare, and productivity, particularly in intensive farming systems (

      ESVAC (European Surveillance of Veterinary Antimicrobial Consumption). 2013 Third ESVAC report: Sales of veterinary antimicrobial agents in 25 EU/EEA countries in 2011. European Medicines Agency, London, UK. Accessed Jul. 17, 2013. www.ema.europa.eu/docs/en_GB/document_library/Report/2013/10/WC500152311.pdf.

      ), which has contributed to the growing concern around increased risk of resistance of animal and human pathogens (
      • Van De Sande-Bruinsma N.
      • Grundmann H.
      • Verloo D.
      • Tiemersma E.
      • Monen J.
      • Goossens H.
      Antimicrobial drug use and resistance in Europe..
      ). In the present study, antimicrobials were only used therapeutically. Rearing lambs on MR1 resulted in a lower percentage of animals treated with topical (10 vs. 15%) and systemic antibiotics (9 vs. 24%) compared with rearing lambs on MR2. Total antibiotic use in MR2 lambs was almost 2.5 times more likely than in MR1 lambs (Table 4). This applies to antibiotic type as well, with a tendency for MR2 lambs to be 3 times more likely to be treated with systemic antibiotics (Table 4). Neonates are especially vulnerable to infectious pathogens and other animal health issues due to the immaturity of their immune system (
      • Jones K.D.
      • Berkley J.A.
      • Warner J.O.
      Perinatal nutrition and immunity to infection..
      ). Therefore, increased use of therapeutic antibiotics during this time frame is not unexpected. The results of this study highlight the potential to reduce therapeutic antibiotic use in young animals through feeding high quality MR made from 100% milk protein and fat as a nutritional-based strategy to enhance lifetime animal health and welfare but also to lower the risk of drug residues and the possibility of contribution to developing drug-resistant pathogens.
      Table 4Incidence rate and ratio
      Incidence rate and incidence rate ratio per 100 animal weeks. In this study, incidence rate is a measure of new cases of disease per unit of time at risk (i.e., animal week at risk), e.g., incidence rate of 23.5 per animal week means we expect to see an average of 23.5 cases for every 100 animals observed during a 1-wk period within a treatment group. The incidence ratio is a measure of the incidence rates between 2 treatment groups, e.g., an incidence ratio of 7.59 means that the rate of disease is 7.59 time greater in lambs exposed to MR2 compared with lambs exposed to MR1.
      of other selected health issues in lambs reared on milk replacer 1 (MR1) and milk replacer 2 (MR2)
      MR1 (100% bovine milk proteins): 25.3% protein, 26.5% milk fat, 34.9% lactose; MR2 (bovine milk proteins + hydrolyzed wheat protein): 23% protein, 24.3% vegetable oil, 30.4% lactose.
      ItemMR1MR2Ratio (CI)P-value
      Total antibiotics3.899.132.34 (1.13, 4.85)0.022
      Topical antibiotics2.03.01.51 (0.61, 3.72)0.372
      Systemic antibiotics1.735.142.98 (0.88, 10)0.078
      Pneumonia0.812.493.09 (0.66, 14.6)0.153
      Scour2.621.18.09 (3.60, 18.10)<0.001
      Pink eye10.719.71.84 (1.10, 3.09)0.022
      Scabby mouth5.24.90.94 (0.29, 3.10)0.924
      External infection
      External infections included navel, pizzle, scrotal, and ear tag infections.
      3.111.13.59 (1.98, 6.55)<0.001
      Lameness0.21.57.46 (0.87, 64.10)0.067
      Adverse behaviors0.34.413.4 (2.45, 72.70)0.003
      1 Incidence rate and incidence rate ratio per 100 animal weeks. In this study, incidence rate is a measure of new cases of disease per unit of time at risk (i.e., animal week at risk), e.g., incidence rate of 23.5 per animal week means we expect to see an average of 23.5 cases for every 100 animals observed during a 1-wk period within a treatment group. The incidence ratio is a measure of the incidence rates between 2 treatment groups, e.g., an incidence ratio of 7.59 means that the rate of disease is 7.59 time greater in lambs exposed to MR2 compared with lambs exposed to MR1.
      2 MR1 (100% bovine milk proteins): 25.3% protein, 26.5% milk fat, 34.9% lactose; MR2 (bovine milk proteins + hydrolyzed wheat protein): 23% protein, 24.3% vegetable oil, 30.4% lactose.
      3 External infections included navel, pizzle, scrotal, and ear tag infections.
      Pneumonia is a common issue in indoor lamb rearing systems (
      • Alley M.R.
      • Ionas G.
      • Clarke J.K.
      Chronic non-progressive pneumonia of sheep in New Zealand—A review of the role of Mycoplasma ovipneumoniae..
      ). Fewer MR1 than MR2 lambs were affected by pneumonia (7 vs. 19% of all lambs), resulting in numerically but not statistically significant greater incidence rate and ratio (Table 4). Lambs reared on MR2 also exhibited almost 4 times more external infections (e.g., navel infections) and almost twice as many cases of pink eye compared with MR1-reared lambs (Table 4) as evidenced by the greater topical antibiotic use in the MR2 lambs. The incidence of scabby mouth was similar between the groups (Table 4). Almost 8 times more cases of lameness and 13 times more cases of adverse behaviors were also observed in MR2 compared with MR1 (Table 4); however, it is important to note that the incidence of these specific health issues was low in both groups and therefore the results should be treated with caution.
      The most striking difference in disease incidence between the groups was for scours, where lambs reared on MR2 experienced 8 times more cases of scours compared with lambs reared on MR1 (Table 4). Overall, 80% of MR2 lambs suffered from either mild (66%), moderate (31%), or severe (5%) scours compared with 14% of MR1 lambs suffering from mild (8%) or moderate (7%) scours. Although the scour events did not result in any deaths, scour incidence may contribute to lower ADG in the MR2 compared with MR1 lambs as previously observed in artificially compared with naturally reared lambs (
      • Belanche A.
      • Cooke J.
      • Jones E.
      • Worgan H.J.
      • Newbold C.J.
      Short- and long-term effects of conventional and artificial rearing strategies on the health and performance of growing lambs..
      ). In the study by
      • Belanche A.
      • Cooke J.
      • Jones E.
      • Worgan H.J.
      • Newbold C.J.
      Short- and long-term effects of conventional and artificial rearing strategies on the health and performance of growing lambs..
      , mild scours were observed in the artificially reared lambs, but incidence rates were not reported. Nevertheless, these authors suggested that ad libitum access to MR and the associated reduction in feed competition may explain the moderate scours in their study. These authors also speculated that automatic feeders may also help reduce scours by reducing feed competition. The present study used automatic feeders to deliver MR ad libitum to the lambs in both groups. Although nutritional scours were evident in both groups, the marked increase in incidence and severity of scours in the MR2 compared with MR1 groups indicates that MR composition is a more potent driver of scours in milk-fed lambs than feed competition.
      Nutritional scours are usually caused by either poor colostrum feeding management or stress, e.g., over or irregular feeding, sudden changes in MR concentration, incorrect temperatures for MR, or poor-quality milk replacers. In the present study, colostrum management was similar between groups, as were the feeding methods, MR concentration, and temperatures. The only difference between the groups was MR composition, indicating that MR ingredient type or quality was likely the primary cause of the high incidence of scours. Curd formation in the abomasum with casein-based products (i.e., skim milk) is slowly digested and released into the small intestine. In contrast, noncurding products (e.g., whey) pass quickly into the small intestine. Absence of curd formation in MR containing a high proportion of vegetable and whey proteins can cause rapid flow of undigested protein into the small intestine and cause scours (

      Roy, J. H. B. 1970. The Calf: Nutrition and Health. Pennsylvania State Univ. Press, University Park, PA.

      ), potentially due to overgrowth of pathogenic bacteria in the duodenum (
      • Roy J.H.B.
      Factors affecting susceptibility of calves to disease..
      ). These observations are consistent with the increased scours in the lambs fed MR2 compared with MR1.
      Anecdotally, claims have been made, in both small- and large-scale artificial lamb rearing systems, that MR made from only milk protein sources compared with those where some milk protein is substituted for vegetable protein cause bloat. In the present study, no cases of abomasal bloat were observed in either MR1 or MR2, indicating that factors other than MR composition may be the cause of abomasal bloat reported in rearing units. Such factors include preventing overfeeding (
      • Gorrill A.D.L.
      • Nicholson J.W.G.
      • Jones J.D.
      • Larmond E.
      • Cameron C.D.T.
      • Comeau J.E.
      Growth, mortality and meat quality of lambs fed milk replacers containing full-fat soybean flour..
      ) and maintaining good hygiene associated with feed preparation (
      • Edwards G.T.
      • Woodger G.A.
      • Barlow A.M.
      • Bell S.J.
      • Harwood D.G.
      • Otter A.
      • Wight A.R.
      Sarcina-like bacteria associated with bloat in young lambs and calves..
      ).

      Animal Health Costs

      The increased incidence of animal health issues that required treatment in MR2 versus MR1 also increased management costs associated with maintaining hygiene (i.e., changing bedding and cleaning pens) and animal health treatments (labor and drug costs). Using only these inputs, the management cost differential was calculated to be ~$NZ10/head ($NZ17.20 vs. $NZ7.32) based on labor $NZ8.64 versus $NZ4.68, bedding $NZ3.31 versus $NZ1.00, drug inputs $NZ0.62 versus $NZ0.23 per head for MR2 versus MR1. Collectively, increased labor and material inputs (bedding and drugs) required to manage hygiene in MR2 than MR1 lambs and reduction in lamb performance affect the costs associated with lamb rearing.

      Welfare

      Maintaining a high level of animal welfare is an important aspect of any animal production system.
      • Richmond S.E.
      • Wemelsfelder F.
      • de Heredia I.B.
      • Ruiz R.
      • Canali E.
      Evaluation of animal-based indicators to be used in a welfare assessment protocol in sheep..
      recently reported an animal welfare assessment protocol for sheep. While some of the metrics proposed in that study were not relevant to the present study, some key metrics of animal welfare were able to be assessed including aspects of good feeding, environment and health, and appropriate behaviors. Lambs in both MR1 and MR2 had similar lamb mortality, access to water and shelter, and stocking density and, therefore, met these feeding and environment welfare criteria. However, the greater incidence of animal health issues (e.g., scours, pink eye, infections, and antibiotic use) and adverse behaviors suggest that MR2 compared with MR1 had a lower level of animal welfare.

      APPLICATIONS

      Development of nutritional-based strategies that can enhance animal performance and prevent animal health issues, which are costly for both the animal and producer, will have a prominent role in food animal agriculture. The key findings were that feeding a MR containing vegetable versus 100% milk protein ingredients resulted in lower ADG and was associated with an increased incidence of animal health issues (notably, scouring, pneumonia, pink eye, and external infections) and increased therapeutic antibiotic use. These results indicate feeding neonatal lambs in the first 5 to 6 wk of life with MR containing vegetable proteins and fats should be avoided. The effects of different combinations of MR ingredients used in this study remain to be established. Improving early life nutrition through feeding of MR containing 100% milk-based ingredients supports growth, health, and welfare by providing protection against disease and reduces costs associated with health care. The reduction in therapeutic use of antibiotics also contributes to meeting consumer demands for chemical-free food production and reducing risk of antimicrobial resistance.

      ACKNOWLEDGMENTS

      The authors acknowledge John Rounce, Bryan Treloar, Li Day, Frederik Knol, and Michael Agnew for their technical support and David Pacheco for constructive review of this manuscript. This work was funded by NZAgbiz and the AgResearch Strategic Science Investment Fund, with access to animals and farm records from Spring Sheep Milk Co.

      LITERATURE CITED

        • Alley M.R.
        • Ionas G.
        • Clarke J.K.
        Chronic non-progressive pneumonia of sheep in New Zealand—A review of the role of Mycoplasma ovipneumoniae..
        N. Z. Vet. J. 1999; 47: 155-160
        • Bates D.
        • Maechler M.
        • Bolker B.
        • Walker S.
        Fitting linear mixed-effects models..
        J. Stat. Softw. 2015; 67: 1-48
        • Belanche A.
        • Cooke J.
        • Jones E.
        • Worgan H.J.
        • Newbold C.J.
        Short- and long-term effects of conventional and artificial rearing strategies on the health and performance of growing lambs..
        Animal. 2019;
        • Bentounsi B.
        • Meradi S.
        • Cabaret J.
        Towards finding effective indicators (diarrhoea and anaemia scores and weight gains) for the implementation of targeted selective treatment against the gastro-intestinal nematodes in lambs in a steppic environment..
        Vet. Parasitol. 2012; 187: 275-279
        • Brooks M.E.
        • Kristensen K.
        • van Benthem K.J.
        • Magnusson A.
        • Berg C.W.
        • Nielsen A.
        • Skaug H.J.
        • Maechler M.
        • Bolker B.M.
        glmmTMB balances speed and flexibility among packages for zero-inflated generalized linear mixed modelling..
        R J. 2017; 9: 378-400
        • Carballo O.C.
        • Khan M.A.
        • Knol F.W.
        • Lewis S.J.
        • Stevens D.R.
        • Laven R.A.
        • McCoard S.A.
        Impact of weaning age on rumen development in artificially reared lambs..
        J. Anim. Sci. 2019; 97: 3498-3510
      1. Davis, C. L., and J. K. Drackley. 1998. The Development, Nutrition and Management of the Young Calf. Iowa State Univ. Press, Ames, IA.

        • Demiroren E.
        • Shrestha J.N.B.
        • Boylan W.J.
        Breed and environmental effects on components of ewe productivity in terms of multiple births, artificial rearing and 8-month breeding cycles..
        Small Rumin. Res. 1995; 16: 239-249
        • Edwards G.T.
        • Woodger G.A.
        • Barlow A.M.
        • Bell S.J.
        • Harwood D.G.
        • Otter A.
        • Wight A.R.
        Sarcina-like bacteria associated with bloat in young lambs and calves..
        Vet. Rec. 2008; 163: 391-393
        • Emsen E.
        • Yaprak M.
        • Bilgin O.C.
        • Emsen B.
        • Ockerman H.W.
        Growth performance of Awassi lambs fed calf milk replacer..
        Small Rumin. Res. 2004; 53: 99-102
        • Erickson P.S.
        • Schauff D.J.
        • Murphy M.R.
        Diet digestibility and growth of Holstein calves fed acidified milk replacers containing soy protein concentrate..
        J. Dairy Sci. 1989; 72: 1528-1533
      2. ESVAC (European Surveillance of Veterinary Antimicrobial Consumption). 2013 Third ESVAC report: Sales of veterinary antimicrobial agents in 25 EU/EEA countries in 2011. European Medicines Agency, London, UK. Accessed Jul. 17, 2013. www.ema.europa.eu/docs/en_GB/document_library/Report/2013/10/WC500152311.pdf.

      3. Frederiksen, K. R., R. M. Jordan, and C. E. Terrill. 1980. Rearing Lambs on Milk Replacers. Farmers Bull. 2270. Sci. Educ. Admin., UDSA, Washington, DC.

      4. Gorrill, A. D. L., G. J. Brisson, D. B. Emmons, and G. J. St.-Laurent (revised by J. W. G. Nicholson). 1982. Artificial Rearing of Young Lambs. Publ. 1507/8. Communication Branch, Agric. Canada, Ottawa, Canada.

        • Gorrill A.D.L.
        • Nicholson J.W.G.
        • Jones J.D.
        • Larmond E.
        • Cameron C.D.T.
        • Comeau J.E.
        Growth, mortality and meat quality of lambs fed milk replacers containing full-fat soybean flour..
        Can. J. Anim. Sci. 1975; 55: 731-740
        • Grenni P.
        • Ancona V.
        • Barra Caracciolo A.
        Ecological effects of antibiotics on natural ecosystems: A review..
        Microchem. J. 2018; 136: 25-39
      5. Hartig, F. 2020. DHARMa: Residual diagnostics for hierarchical (Multi-level/mixed) regression models. R Package version 0.3.2.0. Accessed Feb. 2020. https://CRAN.R-project.org/package=DHARMa.

        • Heaney D.P.
        • Shrestha J.N.B.
        Effects of soyflour in milk replacer on the performance of artificially reared lambs..
        Can. J. Anim. Sci. 1987; 67: 757-763
        • Hernández-Castellano L.E.
        • Suárez-Trujillo A.
        • Martell-Jaizme D.
        • Cugno G.
        • Argüello A.
        • Castro N.
        The effect of colostrum period management on BW and immune system in lambs: From birth to weaning..
        Animal. 2015; 9: 1672-1679
        • Hill T.M.
        • Bateman H.G.
        • Aldrich J.M.
        • Schlotterbeck R.L.
        Effects of using wheat gluten and rice protein concentrate in dairy calf milk replacers..
        Prof. Anim. Sci. 2008; 24: 465-472
        • Hillerton J.E.
        • Irvine C.R.
        • Bryan M.A.
        • Scott D.
        • Merchant S.C.
        Use of antimicrobials for animals in New Zealand, and in comparison with other countries..
        N. Z. Vet. J. 2017; 65: 71-77
        • Huang K.
        • Tu Y.
        • Si B.
        • Xu G.
        • Guo J.
        • Guo F.
        • Yang C.
        • Diao Q.
        Effects of protein sources for milk replacers on growth performance and serum biochemical indexes of suckling calves..
        Anim. Nutr. 2015; 1: 349-355
        • Jones K.D.
        • Berkley J.A.
        • Warner J.O.
        Perinatal nutrition and immunity to infection..
        Pediatr. Allergy Immunol. 2010; 21: 564-576
        • Kumar S.
        • Ingle H.
        • Prasad D.V.R.
        • Kumar H.
        Recognition of bacterial infection by innate immune sensors..
        Crit. Rev. Microbiol. 2013; 39: 229-246
        • Kümmerer K.
        Significance of antibiotics in the environment..
        J. Antimicrob. Chemother. 2003; 52: 5-7
        • Kuznetsova A.
        • Brockhoff P.D.
        • Christensen R.H.B.
        lmerTest package: Tests in linear mixed effects models..
        J. Stat. Softw. 2017; 82: 1-26
        • Lalles J.P.
        • Toullec R.
        • Pardal P.B.
        Hydrolyzed soy protein isolate sustains high nutritional performance in veal calves..
        J. Dairy Sci. 1995; 78: 194-204
      6. Lenth, R. 2019. Emmeans: Estimated marginal means, aka least squares means. R package version 1.4.1. Accessed Feb. 2020. https://CRAN.R-project.org/package=emmeans.

        • Li H.
        • Diao Q.Y.
        • Zhang N.F.
        • Fan Z.Y.
        Growth, nutrient utilization and amino acid digestibility of dairy calves fed milk replacers containing different amounts of protein in the preruminant period..
        Asian-Austr. J. Anim. Sci. 2008; 21: 1151-1158
        • Li P.
        • Yin Y.L.
        • Li D.
        • Woo Kim S.
        • Wu G.
        Amino acids and immune function..
        Br. J. Nutr. 2007; 98: 237-252
        • Lum E.P.
        • Page K.
        • Nissen L.
        • Doust J.
        • Graves N.
        Australian consumer perspectives, attitudes and behaviours on antibiotic use and antibiotic resistance: a qualitative study with implications for public health policy and practice..
        BMC Public Health. 2017; 17: 799
        • Martin G.B.
        • Kadokawa H.
        “Clean, green and ethical” animal production. Case study: reproductive efficiency in small ruminants..
        J. Reprod. Dev. 2006; 52: 145-152
        • McCoard S.
        • Sales F.
        • Sciascia Q.
        Amino acids in sheep production..
        Front. Biosci. (Elite Ed.). 2016; 8: 264-288
        • McCoard S.A.
        • Cristobal-Carballo O.
        • Knol F.W.
        • Heiser A.
        • Khan M.A.
        • Hennes N.
        • Johnstone P.
        • Lewis S.
        • Stevens D.R.
        Impact of early weaning on small intestine, metabolic, immune and endocrine system development, growth and body composition in artificially reared lambs..
        J. Anim. Sci. 2020; 98 (skz356)
        • Napolitano F.
        • De Rosa G.
        • Sevi A.
        Welfare implications of artificial rearing and early weaning in sheep..
        Appl. Anim. Behav. Sci. 2008; 110: 58-72
      7. NASEM. 2001. Nutrient Requirements of Dairy Cattle. 7th rev. ed. Natl. Acad. Press, Washington, DC.

      8. R Core Team. 2016. R: A Language and Environment for Statistical Computing. R Found. Stat. Comp., Vienna, Austria.

        • Richmond S.E.
        • Wemelsfelder F.
        • de Heredia I.B.
        • Ruiz R.
        • Canali E.
        Evaluation of animal-based indicators to be used in a welfare assessment protocol in sheep..
        Front. Vet. Sci. 2017; 4: 210
      9. Roy, J. H. B. 1970. The Calf: Nutrition and Health. Pennsylvania State Univ. Press, University Park, PA.

        • Roy J.H.B.
        Factors affecting susceptibility of calves to disease..
        J. Dairy Sci. 1980; 63: 650-664
      10. Soule, R. P., Jr. 1972. Alternate sources of nonmilk protein for calf, lamb, pig and foal milk replacers. Pages 10–12 in Proc. 32nd Semi-Annual Meeting, American Feed Manufacturers Association Nutrition Council, New Orleans, LA.

      11. Stevenson, M., T. Nunes, C. Heuer, J. Marshall, J. Sanchez, R. Thornton, J. Reiczigel, J. Robison-Cox, P. Sebastiani, P. Solymos, K. Yoshida, G. Jones, S. Pirikahu, S. Firestone, R. Kyle, J. Popp, M. Jay, and C. Reynard. 2020. epiR: Tools for the analysis of epidemiological data. R package version 1.0–11. Accessed Feb. 2020. https://CRAN.R-project.org/package=epiR.

        • Toullec R.
        • Formal M.
        Digestion of wheat protein in the preruminant calf: Ileal digestibility and blood concentrations of nutrients..
        Anim. Feed Sci. Technol. 1998; 73: 115-130
        • Treacher T.T.
        Artificial rearing of lambs: A review..
        Vet. Rec. 1973; 49: 311-315
        • Van De Sande-Bruinsma N.
        • Grundmann H.
        • Verloo D.
        • Tiemersma E.
        • Monen J.
        • Goossens H.
        Antimicrobial drug use and resistance in Europe..
        Emerg. Infect. Dis. 2008; 14: 1722-1730