The effect of feeding a whey-based colostrum replacer product to calves during the first two weeks of life on calf heath and performance

Abstract

Feeding transition milk to dairy calves to improve calf health is an approach that is gaining adoption on farm. However, management of transition milk can be laborious and may limit implementation. The objective of this study was to determine the effect of prolonged feeding with a whey-based colostrum replacer product (CR, Premolac, Zinpro Corporation, Eden Prairie, MN) added into the milk replacer for the first 14 d after arrival to a calf ranch on health and growth of dairy calves. A total of 1,037 newborn calves sourced daily into a calf raising facility were enrolled in the study. Calves were randomly assigned to one of three treatment groups upon arrival and fed through day 14: 1) 3.78 L/d of milk replacer not supplemented with CR (CON), 2) 3.78 L/d of milk replacer supplemented with 23 g of the CR providing 10 g^.calf^−1.d⁻¹ of IgG (CR10), or 3) 3.78 L/d of milk replacer supplemented with 46 g of the CR providing 20 g^.calf^−1.d⁻¹ of IgG (CR20). Treatments did not have an effect on overall grain intake (P = 0.295). However, calves fed CR20 gained more weight than calves fed CR10, and calves fed CR10 gained more than CON calves during the first 14 d of the study (P < 0.01). Average daily gain through 14 d was 0.15, 0.20, and 0.24 kg^.d⁻¹ for calves fed CON, CR10, and CR20. Supplementing milk replacer with CR20 tended to reduce (P = 0.06) the incidence of calves treated with antibiotics for diarrhea. There was no treatment effect (P = 0.11) on incidence of calves with an overall respiratory score ≥ 5 or for any of the respiratory score components (eye, nasal, ear, cough, and breathing scores). Overall, CR supplementation significantly reduced (P = 0.03) the incidence of calves treated with antibiotics for any reason. The incidence of calves treated with antibiotics was 92.4%, 88.7%, and 86.2% for CON, CR10, and CR20. Finally, mortality was significantly reduced (P < 0.01) by more than two-thirds for CR20. Mortality was 6.6, 5.4, and 2.0% for CON, CR10, and CR20. In conclusion, supplementing milk replacer with 46 g of CR (20 g IgG) for 14 d after arrival at a calf ranch was a successful strategy to significantly reduce disease incidence, antimicrobial use, and calf mortality. The addition of 46 g of CR (20 g IgG; CR20) had a greater magnitude of effect on reducing disease, antibiotic use, and mortality than 23 g of CR (10 g IgG; CR10).

Although feeding colostrum to dairy calves beyond day one is not common practice, results from this study show that extending the duration of feeding a commercially available colostrum replacer product in the liquid diet of young calves can improve health and reduce death loss on farm. This strategy provides another non-antibiotic option to the industry.

Introduction

With increasing attention on antibiotic use, there is a need for alternative methods to reduce disease incidence and consequently lessen the number of animals treated with antibiotics. Newborn dairy calves are a vulnerable population susceptible to disease and death and may benefit from such strategies. In a study conducted as part of the calf component of the NAHMS Dairy 2014 study, Urie et al. (2018) reported that 33.8% of pre-weaned heifers had ≥1 morbidity event and 5.0% died; among calves with clinical signs, 90.2% were treated and 73.8% received an antibiotic, corresponding to 26.8% of all enrolled calves receiving ≥1 antibiotic (treatment or prevention).

The importance of colostrum for the dairy calf is well recognized (Geiger, 2020). To provide calves adequate (passive) immunity, high quality colostrum should be fed as early as possible within the first 24 h after birth (Weaver et al., 2000). Shortly after initial colostrum feeding, gut closure occurs, and the absorption of immunoglobulin G (IgG) declines rapidly. However, antibodies from colostrum that remain in the gut lumen after gut closure can provide localized immunity against enteric viral infections, bacterial, or enterotoxin caused diarrhea, and may enhance intestinal villus development (Snodgrass et al., 1980, 1982; Saif and Bohl, 1983; Bühler et al., 1998; Geiger, 2020). Results from previously published studies indicate that continuous colostrum feeding, even after gut closure (>24 h of age), can benefit overall pre-weaning calf health (Snodgrass et al., 1982; Berge et al., 2009; Chamorro et al., 2017). However, some studies directly assess the impact of supplementing IgG to the calf, whereas others evaluate feeding colostrum or a colostrum replacer (CR) product. Because colostrum and CR products contain bioactive factors in addition to IgG, comparisons across studies are not always straightforward.

Berge et al. (2009) conducted trials on three California dairies to assess the effect of prolonged oral IgG supplementation. Calves were fed either an unsupplemented control; 10 g^·calf^−1.d⁻¹ of IgG in the form of a spray-dried whole bovine colostrum powder for 14 d, or nutritionally equivalent supplement (similar nutrient profile to the colostrum powder supplement, minus IgG) for 14 d. Calves fed the 10 g^·d⁻¹ of IgG had reduced diarrheal disease, antibiotic use, and increased ADG through the first 4 wk. However, only 38% of calves included in this study had successful passive transfer of immunity (serum IgG at 24 h > 10 mg^·mL⁻¹).

Chamorro et al. (2017) evaluated supplementation with a spray-dried bovine colostrum powder providing 64 g IgG daily for the first 14 d of life. All calves enrolled in the study met the selection criteria of adequate passive transfer of immunity based on serum IgG. While calf growth was unaffected, prolonged colostrum feeding reduced therapeutic antibiotic use and lowered the likelihood of abnormal fecal, respiratory, depression, umbilical, and joint scores) during the pre-weaning period. Both prior interventions used whole colostrum powder; by contrast, the present trial evaluated a whey-based CR.

Although successful, previous work assessing prolonged CR or IgG feeding often used treatments that may not be economically viable in commercial settings or did not represent the levels of passive transfer experienced by the USA dairy calf population. Therefore, the objective of this study was to evaluate the effect of prolonged feeding of two doses of a whey-based CR powder (23 or 46 g for 14 d) on calf growth and health in a commercial calf-rearing operation. It was not an objective of this study to partition or differentiate the effects of IgG from additional nutrients present in the CR products; therefore, treatment effects are attributable to CR supplementation as a whole, not solely to IgG. Our hypothesis was that supplementing neonatal dairy calves with a CR product for the first 14 d would improve growth and reduce morbidity and mortality.

Materials and Methods

Animal handling and experimental design

A total of 1,043 newborn calves entering a California Central Valley calf raising facility sourced from 14 different dairy farms were enrolled in the study from May 8 to June 9, 2018; follow-up measures were completed by mid-August 2018. All procedures were approved by the DairyExperts Institutional Animal Care and Use Committee (IACUC #: DE18004). Newborn calves (<24 h of age; n = 1,037) were sourced daily from 14 local dairy farms (≤30 miles) into a calf-rearing facility (Hanford, CA, USA). Initial colostrum feeding was done at the source dairies. Upon arrival to the calf ranch, calves were vaccinated with Nasalgen^® 3 (Merck Animal Health, Rahway, NJ) and again at week 5 and 8 with Bovi-Shield GOLD^® 5 (Zoetis, Kalamazoo, MI). Calf hutches were filled with calves following arrival order and a systematic randomized allocation procedure was used to assign calves to the different treatment groups. Treatments were as follows: 1) milk replacer (Calva^® Liquid Xcel^®, Acampo, CA) supplemented with no additional IgG (CON; negative control group; n = 345) for 14 d, 2) milk replacer supplemented with 23 g^·calf^−1.day⁻¹ of CR (CR10; 10 total g of IgG; n = 346) for 14 d, or 3) milk replacer supplemented with 46 g^·calf^−1.day⁻¹ of CR (CR20; 20 total g of IgG; n = 346) for 14 d. The CR source was a commercially available, whey-based CR (Premolac, Zinpro Corporation, Eden Prairie, MN, USA). Brix (%) was measured from each batch of milk replacer prepared, on average CR10 was 0.4% above CON and CR20 was 0.4% above CR10. Treatments were fed via bottles from arrival through d 14, and the CR supplement was fed equally across two daily feedings. Calves were observed for a total of 10 wk.

Diet, feeding, and intake measurements

Calves in all treatment groups were fed a milk replacer solution (13.75% solids) via bottle with a final nutrient content of 24% crude protein and 20% fat. Calves fed CON, CR10, and CR20 received 1.89 L of milk replacer solution with 0 g CR (0 g of IgG), 11.5 g CR (5 g of IgG) or 23 g CR (10 g of IgG) in each of the two daily feedings (prepared at approximately 05:00 and 14:00 h) from day 1 to 14 after arrival (3.78 L total^·d⁻¹). After the initial 14 d feeding period all calves continued to receive 3.78 L milk replacer daily, without added CR, from day 15 to 21. From day 22 to 56, milk replacer was offered at a rate of 5.68 L^·d⁻¹. In preparation for weaning, calves were fed 2.84 L of milk replacer once per day from day 57 to 64. Thereafter, calves did not receive milk.

One mixer tank was used to prepare the milk replacer solution for the three treatment groups. A total of 1,192 L of milk replacer were mixed and a portion of the milk replacer was used to fill bottles for CON calves. The CR was added to the remaining milk replacer solution to prepare the CR10 treatment, bottles were filled. Finally, additional CR was added to the remaining milk replacer volume left in the tank and used to fill bottles to feed calves enrolled in the CR20 group. Researchers were present at each feeding to monitor the mixing process and provide the specific amount of the CR.

After feeding, IDs of calves less than 3 wk of age not drinking all milk were recorded and refusals recorded by research personnel blinded to study treatment assignments. After day 3, calves that refused milk at any feeding had a rectal temperature taken and recorded. The incidence of calves refusing milk represents calves not drinking all milk offered in at least one meal at one of the feedings. Milk refusal duration refers to the number of meals that calves refused milk following an initial refusal event (days being consecutive). Milk refusal amount per meal is the volume of milk refused at a feeding for calves that had a milk refusal event.

Grain intake was measured once a week by study technicians blinded to treatment assignments, for all calves, while calves were in hutches. Grain was weighed and added to buckets for each calf, in the morning and afternoon, any grain left the following morning was weighed before more grain was added and this amount was recorded. Grain intake was calculated for each calf as follows [(weight of grain added on the morning of day 1 + weight of grain added on the afternoon of day 1) − (weight of grain before adding grain on the morning of day 2)].

Body measurements and health

Body weight and rump height measurements were taken by study technicians blinded to treatment assignments when calves entered the hutch, on day 14 after arrival, pre-weaning (day before reducing milk feeding to once a day), and when moved out of the hutch (between 63 and 67 d of age). Weight and rump height were measured using a digital floor scale (Salter Brecknell PS-1000, Fairmont, MN) and Aluminum Measuring Stick (Weatherbeeta, Easton, PA). Total and daily gain of calves from enrollment until they were weaned and moved out of the hutches were calculated.

Individual calf health, including respiratory and fecal scores, was evaluated once a week by research personnel blinded to treatment assignments, while calves were in hutches. Respiratory disease was evaluated using the scoring system developed by Sheila McGuirk, described by Lago et al. (2006), and modified by Love et al. (2014). The following predictors and assigned values were used: coughing (spontaneous only, 2 points), nasal discharge (any, 4 points), ocular discharge (any, 2 points), ear and head carriage (ear droop or head tilt, 5 points), fever (≥ 39.2 °C, 2 points), and respiratory quality (abnormal respiration, 2 points). Calves with a total score ≥ 5 were considered to have respiratory disease. Rectal temperature was measured only when a calf’s total score based on all other clinical signs was equal to or greater than four. A rectal temperature of 39.2 °C (102.5 °F) or greater increased the calf’s score beyond the scoring system cut-point of 5.

Fecal consistency scores 0 or 1 were considered to be normal and dependent on the type and amount of milk or milk replacer being fed. A fecal score 2 was given to diarrhea that was loose but had enough consistency to form a pile on top of the bedding. A fecal score 3 was given to diarrhea that was so watery it sifted through the hutch floor. Rectal temperatures were measured on calves with fecal scores of 2 or 3.

Incidence of respiratory or fecal scores represents calves observed having the condition, respiratory disease or diarrhea, at least once during the trial. Duration is the number of days the condition persisted among calves that had at least one incidence.

Antibiotic treatment decisions and administration were done by farm personnel blinded to the study treatments assignments and recorded by the study technicians. Standardized treatment protocols were developed and monitored by the herd veterinarian. Calves diagnosed with diarrhea were given two to three doses of Excenel RTU^TM (Zoetis, Kalamazoo, MI) depending on return to normal fecal consistency after the 2nd dose, administered 24 h apart and Banamine^® (Merck Animal Health, Rahway, NJ) was given to calves with rectal temperatures ≥ 39 °C. Calves diagnosed with respiratory disease were treated first with Baytril^® (Elanco, Greenfield, IN; 2 doses 24 h apart) after day 4 if respiratory symptoms persisted calves were treated with Excenel RTU EZ^TM (2 doses 24 h apart). Banamine^® was given to calves with rectal temperatures ≥ 39°C. Treatment incidence and duration were reported for diarrhea, respiratory, and other diseases. Additionally, mortality incidence and hazard ratio were reported for the different treatment groups.

Blood samples

Blood samples were collected from each calf the day after arrival and from one-third of the calves selected at random on day 14. Blood samples were taken 2-h post feeding. An 8-mL venous blood sample was collected via the jugular vein into a 10-mL Vacutainer serum collection tube (cat. no. 366430; Becton Dickinson, Franklin Lakes, NJ). Blood samples were centrifuged (within 1 h of sampling at 3,000×g for 15 min) to separate the serum from the clot. Total protein (TP) was measured in all blood samples collected the day after arrival and day 14 using a digital refractometer (Misco, Model DD-2, Solon, OH). One third of the initial and all of the day 14 blood samples were used to measure IgG and whole blood glucose (the same calves were used for both the initial and day 14 samples). Serum IgG was analyzed using radial immunodiffusion (RID) with a commercially available kit (Triple J Farms kit, Bellingham, WA) at the DairyExperts laboratory. Blood glucose was measured using the Precision XTRA hand-held meter (Abbott Labs, Abbott Park, IL) by technicians at the time of sample collection.

Sample size estimation and statistical analysis

It was estimated that a total of 900 calves needed to be enrolled into the study (300 calves per treatment group). It provided more than 95% confidence and 80% power to detect a reduction of 10% in the incidence of diarrhea and respiratory disease in addition to possible losses to follow-up. Historical data from the calf ranch indicated that the incidence of diarrhea treatments was near 40% and respiratory disease incidence was 30%.

Data were analyzed using the SAS/STAT software, Version 9.4 of the SAS system for PC (Copyright 2002-2012 SAS Institute Inc., Cary, NC, USA). Overall summary statistics for baseline variables were produced using either the means or frequency procedures and were compared among treatments using either the MIXED procedure for continuous variables or chi-square test for categorical variables. Physical and clinical outcomes measured once or over time (post treatment administration), was analyzed using the MIXED procedure, with treatment as a fixed effect. Outcomes measured over time were analyzed as repeated measures. The model included the fixed effect of treatment, time, and their interaction. Where applicable the following variables were included in the model as covariates: sex, initial body weight, and serum total protein percent (≥ 5.2 g^·dL⁻¹) at arrival. Covariates were added in a forward stepwise method; the variable was included if its effect had a P < 0.05 or if it confounded the treatment effect. A confounding occurred when the ratio between the crude estimate (when a model included only the treatment effect) and the adjusted estimate was greater than 10%. Calf source was a blocking factor and included in the model as a random effect. One of the 14 farms used in this study only sourced 6 calves and was excluded from the analysis because it affected the stability of the model when source was included as a random effect. Calf within treatment was the repeated statement subject. A compound symmetry covariance structure was used as it had the best fit based on the Akaike Information Criterion. Residuals were independently, identically, and normally distributed with homogenous variance, unless otherwise specified.

The effect of treatment on survival time (time to death) was modeled using Cox proportional hazards regression with the PHREG procedure. Animals that survived were right censored. Occurrence of death, disease, and an abnormal disease score on at least one day during the study period or post treatment application were analyzed using the GLIMMIX procedure with a binary distribution and logit link. The number of disease days and an abnormal disease score, when present, were analyzed using the GLIMMIX procedure with a Poisson distribution and log link. Covariates were included in the model as previously described. Calf source was considered a blocking factor and included into the model as a random effect. Estimated odd ratios, probability of event, count of diseased days, when it occurred, and their 95% confidence interval were generated. Least square means and estimates were compared among treatments using Tukey’s adjustment for multiple comparisons. Significance was declared at P < 0.05 and a tendency was declared at 0.15 ≥ P ≥ 0.05.

Results

Of the 1,037 calves included in the analysis, 345 calves were assigned to CON, 346 to CR10, and 346 to CR20. There were no differences (P > 0.45) among treatment groups at enrollment (baseline values) for calf gender enrolled per treatment, weight, height, serum total protein (mean or proportion of calves ≥ 5.2 g^·dL⁻¹), serum IgG (mean or proportion of calves ≥ 1,000 mg^·dL⁻¹), or blood glucose (Table 1).

Table 1.

Mean and standard deviation of performance and blood variables measured prior to calves being fed either a control diet or a diet supplemented with additional IgG from a whey-based colostrum replacer

Variables	n	Treatments1			Treatment effect
		CON	CR10	CR20
		Mean (SD2)			P-value
n	1,037	345	346	346	–
Weight, kg	1,037	39.9 (5.0)	39.9 (5.3)	39.9 (5.2)	0.998
Height, cm	1,037	79.5 (3.7)	79.7 (3.7)	79.5 (3.8)	0.724
Total protein, g.dL−1	1,031	5.4 (0.9)	5.4 (0.9)	5.4 (0.9)	0.453
IgG, mg.dL−1	347	1,717 (952)	1,798 (920)	1,792 (912)	0.760
Glucose, mg.dL−1	347	140.9 (34.4)	135.7 (33.4)	136.9 (31.5)	0.463
		% (n)
Male	1,037	58.6 (202)	56.9 (197)	55.5 (192)	0.719
Total protein, ≥ 5.2 g.dL−1	1,031	58.3 (200)	62.5 (215)	60.8 (209)	0.529
IgG, ≥ 1,000 mg.dL−1	347	75.9 (88)	80.2 (93)	76.5 (88)	0.699

¹CON, 3.78 L of milk replacer; CR10, CON supplemented daily with 23 g of whey-based colostrum replacer (CR; Zinpro Corporation, Eden Prairie, MN) providing 10 g of IgG; CR20, CON supplemented daily with 46 g of CR providing 20 g of IgG.

²SD, standard deviation.

Colostrum replacer supplementation had no effect (P > 0.48) on serum total protein, serum IgG, or blood glucose on day 14. Mean serum total protein was 4.8, 4.9, and 4.9 g^·dL⁻¹ for calves fed CON, CR10, and CR20 (SEM = 0.05; P = 0.48). Similarly, mean serum IgG was 1,306, 1,379, and 1,364 mg^.dL⁻¹for calves fed CON, CR10, and CR20 (SEM = 67 mg^·dL⁻¹; P = 0.67). Mean glucose concentration in blood was 91.5, 91.0, and 88.5 mg^·dL⁻¹ for calves fed CON, CR10, and CR20 (SEM = 2.0 mg^·dL⁻¹; P = 0.49).

There were significant effects (P < 0.05) of treatments on the incidence of calves refusing a milk replacer meal, the duration of time (feedings) milk replacer was refused, and the total amount of milk replacer refused (Table 2). The percentage of calves that did not consume all milk offered at a feeding during the first three weeks was 38.8 (95% CI [32.7, 45.2]), 23.3 (95% CI [18.5, 28.9]), and 20.0% (95% CI [15.5, 25.3]) for calves fed CON, CR10, and CR20. Calves fed CON refused 1.99 L over the course of 2.1 (95% CI [1.7, 2.5]) meals, CR10 refused 1.99 L over the course of 2.0 (95% CI [1.6, 2.5]) meals, and CR20 refused 1.51 L over the course of 1.5 (95% CI [1.1, 1.9]) meals. Rectal temperatures of calves refusing milk were not different (P > 0.05) among the three treatment groups and were 38.8, 38.8, and 38.9 °C (SEM = 0.1 °C) for CON, CR10, and CR20 calves.

Table 2.

Milk refusal estimates and rectal temperatures, for the first 21 d of the trial, for calves fed either a control diet or a diet supplemented with additional IgG from a whey-based colostrum replacer for 14 d following arrival to a commercial calf rearing facility (N = 1,037)

Variables	n	Treatment1,  4			Fixed effects
		CON	CR10	CR20	Treatment effect (P-value)	Covariates2
Incidence, %	1,031	38.8a (32.7, 45.2)	23.3b (18.5, 28.9)	20.0b (15.5, 25.3)	<0.0001	W, TP52
Duration, feedings	280	2.1a (1.7, 2.5)	2.0a,b (1.6, 2.5)	1.5b (1.1, 1.9)	0.031	TP52
Amount, L	280	1.99a (1.7, 2.4)	1.99a (1.6, 2.5)	1.51b (1.2, 1.9)	0.039	TP52
Rectal temperature, °C3	280	38.8 (0.1)	38.8 (0.1)	38.9 (0.1)	0.559	–
Rectal temperature ≥ 39.2  °C, %	277	39.8 (34.2, 45.7)	35.7 (28.8, 43.3)	37.7 (29.0, 47.4)	0.689	–

¹CON, 3.78 L of milk replacer; CR10, CON supplemented daily with 23 g of whey-based colostrum replacer (CR; Zinpro Corporation, Eden Prairie, MN) providing 10 g of IgG; CR20, CON supplemented daily with 46 g of CR providing 20 g of IgG.

²W, weight at enrollment (kg); TP52, serum total protein ≥ 5.2 g^·dL⁻¹.

³Temperature taken from animals with feed refusals at each feeding and modelled including treatment (P = 0.56), feeding time (P < 0.001) and treatment by feeding time interaction (P = 0.14).

⁴Measures of estimate precision are 95% CI for milk refusal incidence, duration, amount and rectal temperature as percentage ≥ 39.2 °C and SEM for rectal temperature as °C).

^a,bNumbers with differing superscripts within a row indicate statistical differences between treatment.

Overall, there was no effect (P > 0.05) of CR supplementation observed for grain intake (Figure 1). The average grain intake was 836, 846, and 817 g (SEM = 20 g) for calves fed CON, CR10, and CR20.

Figure 1.

Least square mean grain intake (g) for calves receiving Control, whey-based colostrum replacer (CR; Zinpro Corporation, Eden Prairie, MN) providing 10 g of IgG (CR10), and CR providing 20 g of IgG (CR20), by week post birth. Effect of treatment (P = 0.295), week (P < 0.0001) and treatment by week interaction (P = 0.498).

Overall height and average daily height increase were not affected (P > 0.10) by CR supplementation. Average daily height increase was 0.17, 0.17, and 0.18 cm (SEM = 0.01 cm) for calves fed CON, CR10, and CR20. From enrollment to the end of the study, calf ADG was 0.51, 0.50, and 0.50 kg for calves fed CON, CR10, and CR20 (SEM = 0.01 kg; P = 0.99). However, in the first 14 d calves fed CR20 gained more weight (P < 0.05) than calves fed CR10, and calves fed CR10 gained more (P < 0.05) than CON calves. Calf ADG at day 14 was 0.15, 0.20, and 0.24 kg^·d⁻¹ (SEM = 0.02 kg^·d⁻¹) for calves fed CON, CR10, and CR20 (P < 0.01). At day 14, calves fed CR20 were the heaviest calves on trial and CON calves were the lightest (42.2, 42.9, and 43.5 kg; SEM = 0.3 kg; for calves fed CON, CR10, and CR20, respectively; Figure 2). Differences in calf weights did not remain at weaning or trial completion.

Figure 2.

Least square mean body weight (kg) for calves receiving Control, whey-based colostrum replacer (CR; Zinpro Corporation, Eden Prairie, MN) providing 10 g of IgG (CR10), and CR providing 20 g IgG (CR20), by week post birth. Effect of treatment (P = 0.359), week (P < 0.0001) and treatment by week interaction (P = 0.405).

Supplementing milk replacer with CR tended to reduce (P = 0.05) the incidence of calves treated with antibiotics for diarrhea (Table 3). The difference from CON was greatest for calves fed CR20, than for calves fed CR10. There was no effect (P = 0.89) of CR supplementation on the incidence of treatments for respiratory or any disease other than scours (data not shown). However, when reporting all antibiotic use, CR supplementation reduced (P = 0.03) the odds of calves being treated. This difference was significant for calves fed CR20, but not for calves fed.

Table 3.

Incidence probability and number of antibiotic treatments for calves fed either a control diet or a diet supplemented with additional IgG from a whey-based colostrum replacer for 14 d following arrival to a commercial calf rearing facility (N = 1,037)

Outcome	n	Treatment1			Fixed effects
		CON	CR10	CR20	Treatment effect		Covariates2
		Estimate (95% CI)			P-value
Diarrhea
Odd ratio	1,031	Ref.	0.81 (0.60, 1.11)	0.68 (0.50, 0.94)	0.058		SEX, TP52
Incidence, %	1,031	44.4a (37.8, 51.3)	39.3a,b (33.0, 46.1)	35.3b (29.2, 42.0)	0.058		SEX, TP52
Events, count	424	2.9 (2.6, 3.2)	2.8 (2.6, 3.1)	2.8 (2.6, 3.2)	0.967		–
Respiratory disease
Odd ratio	1,031	Ref.	1.10 (0.80, 1.52)	1.03 (0.75, 1.41)	0.818		TP52
Incidence, %	1,031	65.6 (60.4, 70.5)	67.8 (62.6, 72.6)	66.2 (61.0, 71.1)	0.818		TP52
Events, count	675	3.6 (3.4, 3.9)	3.4 (3.2, 3.7)	3.6 (3.3, 3.8)	0.496		TP52
All antibiotic treatments
Odd ratio	1,031	Ref.	0.65 (0.39, 1.07)	0.52 (0.32, 0.84)	0.028		W, TP52
Incidence, %	1,031	92.4a (89.3, 94.7)	88.7a,b (84.8, 91.7)	86.2b (82.0, 89.5)	0.028		SEX, TP52
Events, count	905	4.5 (4.2, 4.8)	4.4 (4.1, 4.7)	4.4 (4.1, 4.6)	0.743		TP52

¹CON, 3.78 L of milk replacer; CR10, CON supplemented daily with 23 g of whey-based colostrum replacer (CR; Zinpro Corporation, Eden Prairie, MN) providing 10 g of IgG; CR20, CON supplemented daily with 46 g of CR providing 20 g of IgG.

²W, weight at enrollment (kg); SEX, sex; TP52, serum total protein ≥ 5.2 g^·dL⁻¹.

^a,bNumbers with differing superscripts within a row indicate statistical differences between treatment (P < 0.01).

The incidence of calves with a fecal score ≥ 2 was similar among all three treatments (Table 4). Similarly, there was no treatment effect on the incidence of calves with an overall respiratory score ≥ 5 or for any of the respiratory score components (eye, nasal, ear, cough, and breathing scores), except high rectal temperature (Table 4). When calves on any of the treatments with a respiratory score ≥ 5 had a rectal temperature taken, the odds that a calf fed one of the CR treatments had a rectal temperature ≥ 39.2 °C was lower (P = 0.01) than that for CON calves.

Table 4.

Incidence probability and number of high fecal or respiratory scores for calves fed either a control diet or a diet supplemented with additional IgG from a whey-based colostrum replacer for 14 d following arrival to a commercial calf rearing facility (N = 1,037)

Outcome	n	Treatment1				Fixed effects
		CON	CR10	CR20		Treatment effect	Covariates2
		Estimate (95% CI)				P-value
Fecal score ≥ 2
Odd ratio	1,020	Ref.	0.90 (0.63, 1.29)	0.73 (0.51, 1.04)		0.199	–
Incidence, %	1,020	77.7 (71.7, 82.6)	75.8 (69.7, 81.0)	71.7 (65.3, 77.4)		0.199	–
Events, count	771	1.7 (1.5, 1.8)	1.6 (1.5, 1.8)	1.6 (1.4, 1.8)		0.782	W
Rectal temperature ≥ 39.2  °C when fecal score ≥ 2
Odd ratio	654	Ref.	0.75 (0.52, 1.10)		0.76 (0.52, 1.11)	0.247	–
Incidence, %	654	52.6 (44.1, 61.0)	45.5 (37.1, 54.2)		45.7 (37.1, 54.5)	0.247	–
Respiratory score ≥ 5
Odd ratio	1,020	Ref.	0.91 (0.67, 1.23)		1.25 (0.92, 1.69)	0.109	–
Incidence, %	1,020	48.8 (41.9, 55.8)	46.3 (39.5, 53.3)		54.3 (47.3, 61.1)	0.109	–
Events, count	502	2.0 (1.8, 2.2)	1.9 (1.7, 2.1)		1.8 (1.6, 2.0)	0.484	–
Rectal temp. ≥ 39.2  °C when respiratory score ≥ 5
Odd ratio	502	Ref.	0.52 (0.34, 0.81)		0.63 (0.40, 1.00)	0.014	–
Incidence, %	502	69.9a (60.4, 78.0)	59.5b (49.3, 68.9)		54.8b (45.1, 64.2)	0.014	–
Events, count	290	1.5 (1.3, 1.7)	1.3 (1.1, 1.6)		1.4 (1.2, 1.6)	0.645	–

¹CON,  3.78 L of milk replacer; CR10, CON supplemented daily with 23 g of whey-based colostrum replacer (CR; Zinpro Corporation, Eden Prairie, MN) providing 10 g of IgG; CR20, CON supplemented daily with 46 g of CR providing 20 g of IgG.

²W, weight at enrollment (kg).

^a,bNumbers with differing superscripts within a row indicate statistical differences between treatment.

There was a significant effect of CR supplementation on calf mortality (Table 5 and Figure 3). Feeding CR20 significantly (P < 0.01) reduced calf mortality, but calf mortality was similar for calves fed CR10 or CON.

Table 5.

Death risk and hazard ratio (HR) with corresponding 95% confidence interval fed either a control diet or a diet supplemented with additional IgG from a whey-based colostrum replacer for 14 d following arrival to a commercial calf rearing facility (N = 1,037)

Outcome	n	Treatment1			Fixed effects
		CON	CR10	CR20	Treatment effect	Covariates2
		Estimate (95% CI)			P-value
Unadjusted
Death risk, %  3	1,037	8.4a (5.9, 11.8)	6.7a,b (4.5, 9.8)	2.9b (1.6, 5.3)	0.011	–
Death HR	1,037	Ref.	0.78 (0.45, 1.35)	0.33 (0.16, 0.69)	0.011	–
Adjusted
Death risk, %	1,031	6.6a (4.4, 9.8)	5.4a (3.4, 8.3)	2.0b (1.0, 4.0)	0.009	TP52
Death HR	1,031	Ref.	0.81 (0.46, 1.43)	0.29 (0.13, 0.65)	0.009	TP52

¹CON, 3.78 L of milk replacer; CR10, CON supplemented daily with 23 g of whey-based colostrum replacer (CR; Zinpro Corporation, Eden Prairie, MN) providing 10 g of IgG; CR20, CON supplemented daily with 46 g of CR providing 20 g of IgG.

²TP52, serum total protein ≥ 5.2 g^.dL⁻¹.

³The average death age (SD) was: 16 (19.1) d for control, 18.7 (20.7) d for CR10, and 16.7 (19.0) d for CR20.

^a,bNumbers with differing superscripts within a row indicate statistical differences between treatment (P < 0.01).

Figure 3.

Survival probability for calves fed Control, whey-based colostrum replacer (CR; Zinpro Corporation, Eden Prairie, MN) providing 10 g of IgG (CR10), and CR providing 20 g IgG (CR20), by week post birth. Effect of treatment (P = 0.009).

Discussion

The immune status of calves upon arrival was similar among treatments in this study, as intended. The percentage of calves (of the subset measured) with successful passive transfer of immunity defined as serum IgG values > 1,000 mg·dL⁻¹ was over 75% and similar to the ∼88% industry average reported in the calf component of the National Animal Health Monitoring System’s Dairy 2014 study (Shivley et al., 2018a). By contrast, previous work (Berge et al., 2009) with a similar study design used calves with an initial successful passive transfer rate < 40%. It is important to acknowledge these differences because calves with differing immune status may respond differently to interventions similar to the one evaluated here and in other trials.

Much recent work has focused on the beneficial effects of feeding calves more milk (Geiger et al., 2016). Multiple studies have reported performance and health benefits associated with feeding calves a higher plane of nutrition. In this study, calves were fed approximately 4 L of milk replacer per day for the first 3 wk of life and approximately 6 L of milk replacer per day until weaning. The authors acknowledge often that higher allowances are often recommended. However, the USDA National Animal Health Monitoring System’s Dairy 2014 study (USDA, NAHMS, 2014) reported that 74% of dairy operations fed 2 to < 3 L of milk to heifer calves at each feeding with 93.4% of operations feeding only twice daily. Accordingly, the current feeding rates reflect common practice, even if higher allowances are frequently recommended. Future work should evaluate whether similar results are achieved at different planes of nutrition.

Colostrum supplementation had no effect on blood glucose or serum IgG concentration at 14 d of age. This aligns with recent work showing that short- or longer-term CR supplementation does not impact serum IgG in calves through day 49 (McCarthy et al., 2024). It should be noted, that the CR product used provided additional nutrients (other bioactive factors and whey protein) beyond IgG, and this study did not aim to partition the effects of IgG from other nutrients. The added nutrients may not have been sufficient to increase blood glucose because the product is a concentrated whey-based powder that is > 80% CP, primarily in the form of IgG and whey proteins. The lack of increase in serum IgG on d 14 was anticipated; after gut closure, additional IgG is not absorbed (Snodgrass et al., 1982).

Benefits observed after gut closure likely arise from local gastrointestinal actions and other bioactives rather than sustained increases in circulating IgG. Repeated exposure to colostrum or transition milk has been associated with enhanced villus development, epithelial proliferation, and digestive enzyme activity (Blättler et al., 2001), and greater small‑intestinal development when calves receive colostrum, 1:1 colostrum: milk mixtures, or transition milk during the first 3–4 d (Hare et al., 2020; Pyo et al., 2020; Van Soest et al., 2022). In addition, the number of transition milk feeds after the initial colostrum meal has been linked to improved early health outcomes (Conneely et al., 2014).

To the authors’ knowledge, this is the first experiment to report the impact of prolonged CR feeding on the incidence of liquid diet refusals. Colostrum replacer supplementation at a rate of 46 g·calf⁻¹·d⁻¹ reduced the incidence of calves refusing milk in at least one meal, the average number of consecutive meals refused following an initial event, and the total amount of milk refused. Berge et al. fed calves one of three experimental diets for the first 14 d of life: 1) control diet with no supplementation, 2) 140 g of CR powder containing 20 g of IgG split evenly over 2 feedings, or 3) a nutritionally equivalent supplement fed at the same rate as the CR. The impact of colostrum supplementation on milk replacer refusals was not observed by Berge et al. (2009) when calves were supplemented with dry colostrum providing the same amount of IgG as the whey-based colostrum in the CR20 treatment; however, data were reported as total milk consumed per feeding (morning and evening), rather than explicit refusal counts. In Berge et al. (2009), the supplement was a spray‑dried whole bovine colostrum powder (not whey‑based), whereas the present product is whey‑based.

Overall ADG in this study was not different among the three treatment groups. However, calves fed CR20 gained more weight than calves fed CR10 in the first 14 d of the trial, and calves fed CR10 gained more than CON calves during the same time frame. The comparatively low growth rates observed are most likely due to the low milk replacer feeding rate used by the calf-rearing facility. Although many would consider this feeding rate low, it is representative of current industry practices (see above). Also, most days the temperature-humidity index during the study months was between 80 and 90, which is well above the ≥ 70 threshold previously associated with ADG of < 0.64 kg·d⁻¹ (Shivley et al., 2018b). Previous work assessing the impacts of CR supplementation (Berge et al., 2009; McCarthy et al., 2024) also reported improvements in ADG primarily within the first 4 wk of age, but not later. Similarly, Chamorro et al., (2017) did not find differences in ADG across the entire pre-weaning period. By contrast, calves had greater ADG and weaning weight when fed 700 g/d of maternal colostrum during the first 2 wk of age (Kargar et al., 2020). One plausible explanation for the higher ADG in the first 14 d among CR supplemented calves is that they were healthier and refused less milk early on. It must also be considered that CR supplements are not purified sources of IgG; observed differences cannot be attributed solely to the IgG content. A whey-based CR supplement is composed primarily of the isolated whey fraction of colostrum (not the curd fraction). The whey fraction of colostrum has been shown to concentrate IgG and at least some of the bioactive factors contained in colostrum (Al-Mashikhi and Nakai, 1987). Therefore, in addition to the IgG in whey-based colostrum these bioactive factors may also be contributing to the positive effects observed in this study. However, it must be noted that one limitation to the current study is the fact that CON calves did not receive a placebo powder; therefore, nutrient supply differed among treatments, which may account for some of the observed differences such as improved early weight gain and should be considered when interpreting results.

The observed reduction in the incidence of diarrhea treatments for calves fed CR20 vs. CON is biologically relevant (35.3 vs. 44.4%). Previous studies reported positive effects on diarrhea when supplementing colostrum powder in the milk replacer (Berge et al., 2009; Chamorro et al., 2017). The first study fed a daily dose of 140 g of dried colostrum powder containing 20 g of IgG, and the second fed 300 g of dried colostrum powder containing 64 g of IgG. The relative risk (Berge et al., 2009) and odds ratio (Chamorro et al., 2017) for abnormal feces in colostrum-supplemented vs. control calves were 0.61 and 0.15, respectively. Similarly, supplementing a low dose of a dried CR (45 g containing ∼12 g of IgG on days 2–14) lowered the hazard of diarrhea (McCarthy et al., 2024). Feeding 0.7 kg/d of maternal colostrum for 2 wk not only reduced the incidence of diarrhea but also resulted in fewer days with diarrhea (Kargar et al., 2020). By contrast, very short courses (days 2–4 only) of transition milk or supplementing a CR did not alter fecal scores in one commercial-farm study, underscoring that duration and dose likely matter (McCarthy et al. 2024). Although evaluation methods and analysis varied across studies, a dose-response pattern is suggested. Observed differences across studies may reflect improvements in intestinal development and barrier function with prolonged exposure to colostrum (Blättler et al., 2001; Van Soest et al., 2022).

The proportion of calves that had at least one fecal score ≥ 2 (loose or watery) at the weekly fecal consistency evaluation was not different between treatments. The combination of fewer diarrhea‑associated treatments with similar weekly fecal‑score incidence warrants comment. Weekly scoring captures point prevalence of loose feces but may miss short episodes or differences in severity and systemic involvement that trigger treatment decisions. This is especially relevant given evidence that colostrum‑derived interventions may shorten the clinical course at scours onset (Carter et al., 2022).

No differences in the incidence of treatment for respiratory disease or high respiratory scores were observed in this study. Across trials, respiratory outcomes show a generally favorable but mixed pattern with extended colostrum exposure. Berge et al. (2009) administered a daily dose of 20 g of IgG—approximately equivalent to the CR20 colostrum supplementation group—and did not find an effect on respiratory disease. Similarly, McCarthy et al. (2024) did not find an effect when supplementing a low-dose CR. However, when 64 g of IgG were supplemented, the odds of abnormal respiration were lower (OR = 0.46) despite no differences in respiratory scores (Chamorro et al., 2017). This is a substantial reduction, but the high IgG feeding rate in that study likely limits broad commercial adoption. Finally, Kargar et al. (2020) reported that when feeding maternal colostrum for 2 wk calves had fewer days with pneumonia than milk-only calves.

A finding of interest in the present study was that when calves had a respiratory score > 5, calves fed CR had a lower incidence of rectal temperatures ≥ 39.2 °C than CON calves (57 vs. 70%). A similar pattern was observed for calves with fecal scores ≥ 2 (45 vs. 55% for CR-fed and CON calves, respectively) regardless of CR dose. Overall, a lower proportion of calves fed CR20 were treated with antibiotics compared with CON calves. The overall impact of feeding the CR20 treatment on disease incidence is likely due to the high IgG content of the colostrum replacer and is consistent with previous reports. Taken together, these data indicate benefits to prolonged CR feeding in reducing antibiotic therapy, particularly for diarrhea. As a therapeutic approach after diarrhea onset, a 4-d CR course reduced disease severity and shortened duration, and calves grew 98 g/d more over 56 d versus control (Carter et al., 2022). In a targeted therapeutic context triggered by feeding behavior alarms, a 3-d CR course in calves with respiratory disease reduced recurrence of the disease and of lobar lung consolidation (Cantor et al., 2021).

The reduction in mortality from the CR feeding was not a subtle effect. Calves fed CR20 had three-fold lower probability of dying than CON calves, whereas mortality in CR10 did not differ statistically from CON. Across the literature, mortality effects are clearest in the most recent extended CR trials. Recent data (McCarthy et al., 2024) showed reduced mortality risk when calves received an extended colostrum feeding program through 14 d of age. Interestingly, similar results were observed despite product differences between studies (whey-based CR in the current study vs. whole spray-dried colostrum powder in McCarthy et al.). It should also be noted that the aforementioned study did not include any calves with serum IgG values < 10 g/L, indicating baseline health status comparable to the current cohort. Mortality differences were not seen with shorter duration CR supplementation regimens, suggesting that lower daily amounts over a longer period may be more effective than higher amounts for a shorter time, but more work is needed to confirm this. Chamorro et al. (2017) attributed low calf mortality (1.48%) to high serum IgG levels. However, Berge et al. (2009) enrolled calves with much lower initial serum IgG and a much higher percentage of passive transfer failure and did not find a mortality effect at IgG intakes equivalent to CR20. Although mortality incidence was not reported in that study, overall mortality can be calculated as 13.9% from the data provided indicating ample opportunity to detect differences. Therefore, mortality effects observed in the current study could be due to differences in colostrum product type, pathogen challenge, or other exposures and susceptibilities experienced by the calves. Although the reduction in mortality due CR feeding could plausibly be attributed to local actions of IgG in the gut, additional nutrients provided by CR—particularly under lower milk allowances and modest ADG—likely contributed as well.

Conclusion

Results herein indicate that supplementing pre-weaned dairy calves with a whey-based CR during the first 14 d after arrival at a commercial calf ranch is a practical approach to reduce antibiotic use. Supplementation with 46 g of whey-based CR for 14 d after arrival reduced the incidence of diarrhea, lowered antimicrobial use, and decreased mortality. Despite differences in product type and dose across studies, the overall direction of the effect of the whey‑based CR evaluated aligns with studies that used extended feeding programs with maternal colostrum or whole colostrum powder derived CR. More work is needed to further understand the benefits of supplementing a lower daily dose to calves and to determine the utility of this approach in other calf-rearing environments with differing management styles. Further work is needed to confirm the economic benefits of such alternatives.

Abbreviations:

CR

colostrum replacer

IgG

immunoglobulin G

RID

radial immunodiffusion

TP

total protein

Author contributions

Alfonso Lago (Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Writing—original draft, Writing—review & editing), Adam Geiger (Conceptualization, Methodology, Project administration, Supervision, Writing—original draft, Writing—review & editing), Chanda L. Engel (Validation, Visualization, Writing—review & editing), and Claudia Leonardi (Data curation, Validation, Writing—review & editing).

Conflict of interest statement. Two of the authors work for the company by whom the tested product is manufactured and sold. No other known potential conflicts of interest exist.