Factors Affecting the Immunoglobulin Concentration of Colostrum
The immunoglobulin concentration of colostrum is known as colostrum quality. At the herd level colostrum quality is affected by breed, parity, and climate. For individual cows the biggest determinants are colostral volume and time from calving until milking.66,67 Colostrum concentrations of Holstein Friesian cows varied from 20 g/L of immunoglobulin to more than 110 g/L of IgG1 in cows from a single herd.66 First milking colostrum samples collected within 4 hours of milking from cows at 11 dairies in Pennsylvania varied from 9 to 166 g/L IgG1.68 The mean concentration of IgG1 in first milking colostrum in three large studies of dairy cows varied between 37.5 ± 30.2 and 48.2 ± 28.9 g/L.66,68,69 Colostrum IgG concentration declines with time after calving, even if the cow is not milked.66,67,70,71 One study showed that colostral IgG concentration decreased by 3.7% in each subsequent hour after calving.67 However, several studies have demonstrated that this decline is minimal until the cow has been calved 8 to 9 hours.66,70 There is no increase in colostral volume if postpartum milking is delayed, so it appears that the declining IgG is not due to dilution.67,71,72 During the colostrum phase mammary cells have leaky tight junctions,73,74 so it is likely that once parturition occurs, the active transcytosis of IgG1 ceases and it is passively reabsorbed.
Studies of colostrum and calf immunoglobulin levels in specific beef breeds have failed to demonstrate consistent differences between specific breeds, and many studies showed evidence of variations within breed lines. In dairy breeds colostrum from Holstein cows was statistically lower in total IgG than colostrum from Jersey, Ayrshire, and Guernsey cows.75,76 In other studies, high-producing Holstein Friesians have a tendency to have lower IgG concentrations in their colostrum than lower producing Jersey cows.66,75,77 Prepartum dairy cows have a significantly greater decline in serum IgG compared with beef cows,7 but the colostrum of dairy cows has lower concentrations of IgG due to the much larger volume.
Some studies have shown very low volumes of colostrum (with lower quality colostrum, higher serum IgG levels will be achieved when two feeds of 2 L are given at 2 and 6 hours postpartum than when 4 L is given in one feed.110 The pathophysiology underlying these observations is not fully understood, but 22% of the variation in the effective absorption of colostrum is attributed to abomasal emptying rate, and it is likely that the excessive mechanical distention of the abomasum with 4 L of colostrum delays outflow.65,110,111Calves should be fed a minimum of 150 g of IgG within 4 to 6 hours of birth and earlier whenever practical. The exact volume at each feed should be determined after measuring, usually by indirect estimation of colostrum IgG levels, and is more important to optimize where lower quality colostrum is the only source (Table 19.2). Calf serum IgG levels will be
■ TABLE 19.2
| Liters of Colostrum Required to Achieve Adequate Passive Transfer (Blood IgG Level ≥13.4 mg/mL) for Different Birth Weights, Absorption Rates, and Colostrum Qualities | ||||||
| Calf Weight | Hours After Birth | Brix (%) | ||||
| 14-16 | 18-20 Antibod | 22-24 y Concentratio | 26-28 >n (g/L) | 30-32 | ||
| 20-30 | 40-50 | 60-70 | 80-90 | 100-110 | ||
| 30 | 0-3 | 5.6c | 2.8b | 1.9a | 1.5a | 1.5a |
| 3-6 | 6.4c | 3.2b | 2.1a | 1.6a | 1.5a | |
| 6-9 | 7.1c | 3.6b | 2.4a | 1.8a | 1.5a | |
| 9-12 | 8.3c | 4.1b | 2.8b | 2.1a | 1.7a | |
| 12-18 | 9.4c | 4.7b | 3.1b | 2.3a | 1.9a | |
| 18-24 | 10.5c | 5.3c | 3.5c | 2.6c | 2.1a | |
| 40 | 0-3 | 7.5c | 3.8b | 2.5a | 2.0a | 2.0a |
| 3-6 | 8.5c | 4.3b | 2.8a | 2.1a | 2.0a | |
| 6-9 | 9.5c | 4.8b | 3.2b | 2.4a | 2.0a | |
| 9-12 | 11.0c | 5.5b | 3.7b | 2.8a | 2.2a | |
| 12-18 | 12.5c | 6.3c | 4.2b | 3.1b | 2.5a | |
| 18-24 | 14.0c | 7.0c | 4.7c | 3.5c | 2.8a | |
| 50 | 0-3 | 9.4c | 4.7b | 3.1a | 2.5a | 2.5a |
| 3-6 | 10.6c | 5.3b | 3.5a | 2.7a | 2.5a | |
| 6-9 | 11.9c | 5.9b | 4.0b | 3.0a | 2.5a | |
| 9-12 | 13.8c | 6.9c | 4.6b | 3.4a | 2.8a | |
| 12-18 | 15.6c | 7.8c | 5.2c | 3.9b | 3.1a | |
| 18-24 | 17.5c | 8.8c | 5.8c | 4.4c | 3.5a | |
Calculations of total IgG required and apparent efficiency of absorption are based on Chigerwe et al.
(2008)43,198 using blood volume calculations from Quigley et al. (1998).325 The correlation between the Brix refractometer reading and serum IgG levels was calculated using Quigley et al. (2013).72 This table was compiled with the assistance of Zoe Vogels from The Vet Group, Timboon, Australia.It is assumed that the minimum volume fed would be 5% of body weight even where good-quality colostrum is available. It should be noted that below a Brix reading of 22%, it is not possible to achieve adequate passive transfer with a single feed of colostrum.
aCalves should be fed 7.5% of body weight or, at a minimum, the volume shown. IgG levels would be enhanced by 5% of body weight 6 to 12 hours later. bCalves should be fed 7.5% of body weight and an equivalent volume 6 to 12 hours later.
cIt is unlikely that adequate passive transfer will be achieved.
IgG, Immunoglobulin G.
significantly boosted by a further feed of 5% of body weight of colostrum within 12 hours of birth110; if less than 150 g of colostrum was fed at the initial feeding due to limitations of quality or volume, a further 7.5% should be fed.49 Emphasis should be placed on feeding colostrum with the highest concentration of immunoglobulin at the initial feed, when the effectiveness of absorption is higher. Many farmers are currently feeding 10% to 12% of body weight as a single initial feed. Although this will provide good levels of IgG where colostrum quality is adequate, it may result in moderate depression and discomfort in the calf.112
TIME OF FIRST FEED. Early ingestion of colostrum is crucial; IgG is absorbed by the intestinal epithelial cells of the newborn ruminant, and the ability of enterocytes to transport immunoglobulin declines linearly from 2 to 20 hours after birth and completely ceases (intestinal closure) between 24 and 36 hours.113 Serum IgG concentrations peak around 32 hours and then decline until the production of antibodies by the neonate exceeds the decay of passively acquired antibodies.
Any delay in first feeding of colostrum results in decreased absorption of immunoglobulin and a lower serum IgG.43,114 Absorption of immunoglobulins occurs along the whole length of the small intestine in calves, with the amount transported increasing from the duodenum to the ileum,115 whereas in lambs and kids there is virtually no absorption from the duodenum and most absorption occurs in the jejunum.116,117 IgG and other macromolecules are mainly absorbed by micropinocytosis, although some receptor-mediated endocytosis has been demonstrated, but this does not involve the FcRn.115,116,118 Preferential absorption of homologous IgG has been observed in pigs; however, recent studies in kids and lambs have shown that similar IgG transfer can be achieved by feeding bovine colostrum, although in lambs the apparent efficiency of absorption is lower.119-121The age of the calf when it receives its first feeding and the amount of immunoglobulins received will influence the time of closure of the intestinal permeability to colostral immunoglobulins and the final serum immunoglobulin levels of the calf.122-126 Cessation of absorption occurs by 24 hours in calves that receive a full feed of colostrum within the first 4 hours after birth. When the colostrum volume is less than 2 L, the gut will remain permeable for a longer time and the rate of absorption will increase in response to a subsequent feed. If the calf is older than 12 hours when it receives its first feed, there is a significant increase in the possibility of the calf being agammaglobulinemic. It is likely that the time of closure is related to the immunoglobulin concentration of the colostrum as well as the volume fed. Delay in colostrum feeding will also result in lower plasma insulin and IGF-1 for up to 48 hours after first colostrum intake and reduce plasma concentrations of betacarotene, retinol, and α-tocopherol for nearly a month after birth.127,128
METHOD OF FIRST FEED.
Method of feeding also has a significant effect on colostrum intake. A high proportion of calves left to suckle their dams show evidence of FPT, compared to those artificially fed by teat or esophageal feeder.3,129,130 This is due to the reduced volume of colostrum, and therefore mass of IgG, consumed by the calf if left to suckle naturally during the first 24 hours; hence it is strongly recommended that dairy calves be administered colostrum containing 150 g IgG within 2 hours of birth.27 Teat-feeding stimulates a reflex closure of the esophageal groove allowing colostrum to pass directly to the abomasum, where it clots before moving to the small intestine for absorption. When an esophageal feeder is used, this reflex does not occur, and the colostrum passes to the reticulorumen.131,132 Promotion of the advantages of closure of the esophageal groove has resulted in the use of a nipple bottle as the more common method of administering colostrum. Calves fed a small volume of colostrum (1.5 L) via an esophageal feeder have a lower efficiency of absorption than calves fed colostrum via a teat feeder.133 However, several studies134 have demonstrated that there is no difference in immunoglobulin concentrations at 48 hours between calves that sucked larger volumes of colostrum from a nipple bottle and those that were administered a similar quantity via an esophageal feeder, although there may be a delay of approximately 3 hours before the serum IgG increases in the tube-fed calves.112,135,136 This delay is not due to the deposition of colostrum in the reticulorumen, as all except 400 mL will immediately pass into the abomasum due to the pressure gradient resulting from the placement of the reticulorumen dorsal to the abomasum in the neonatal calf.137 Instead the delay is likely to be due to delayed abomasal emptying resulting from distention and changes in 111138 physiologic and neuronal control mechanisms.111,138Calves fed by a nipple bottle will commonly not ingest sufficient colostrum to minimize the risk of FPT and should be encouraged to ingest the maximum volume they will voluntarily ingest within 1 to 4 hours of age.49 Calves should be fed as soon as they are standing; delaying up to 6 hours after birth or providing a heat lamp will not increase the amount of colostrum suckled.49,139 Calves that have a high degree of vigor during the first hour of life and during colostrum suckling will consume more colostrum from the bottle, as will larger calves.139 Bottle-fed calves that do not ingest their full allocation of colostrum at either the first or the second colostrum feed should be targeted for immediate esophageal feeding, and the total remaining should be fed.
To minimize trauma when an esophageal feeder is used, the calf should be standing with its rump against a solid wall or corner. The feeder used should have a total volume of at least 3 L so that intubation has to occur only once. The calf should be encouraged to swallow prior to insertion by sucking a finger to produce saliva or by being fed a few mouthfuls of colostrum. The tube should be introduced without physical exertion, and the head should be positioned slightly downward to allow swallowing as the tube is inserted into the esophagus. Before feeding, the knob at the end of the tube should be palpated on the left-hand side dorsal to the trachea to ensure that positioning is correct. At this point the calf head may be tilted slightly upward as the bottle is elevated to administer the colostrum. It is important that the tube remains fully inserted during colostrum delivery. It is common for calves to chew during administration, causing retrograde movement of the tube that may lead to the bulb of the tube migrating to the level of the pharynx, resulting in aspiration.
On beef properties, routine administration of colostrum to the newborn calf is disruptive and delays the time until first sucking140 but will decrease the incidence of FPT.60,141 Feeding colostrum to high-risk calves is likely beneficial, most commonly after dystocia. Beef cows often produce smaller colostrum volumes; where volumes less than 1.5 L are fed, use of a nipple bottle is recommended, as serum IgG at 24 hours of age is higher compared to that of calves administered colostrum with an esophageal feeder.142 This most likely occurs because a greater percentage of the total colostrum is deposited into reticulorumen. Where dairy colostrum was fed, this was also shown to be a biosecurity risk.
OTHER FACTORS INFLUENCING IMMUNOGLOBULIN ABSORPTION. Calves that have experienced dystocia are more likely to have failure of passive transfer.27,84,85,143 Decreased vitality of the neonate, potential hypoxia in the small intestine secondary to respiratory acidosis, and in many cases edema of the head and tongue result in a slower time to stand and inadequate colostrum intake as a consequence. Calves born to primiparous cows have been shown to have a higher risk of FPT compared to those born to multiparous cows.27,75,144 This may be related to primiparous dams having lower IgG concentrations in their colostrum145 as a result of reduced exposure to antigens144 or an indirect effect of increased risk of dystocia in primiparous dams.146 Another study showed that there was no effect of dam parity or dystocia on calf serum IgG concentration.81,147 Respiratory acidosis did not result in decreased levels of IgG at 37 to 48 hours in studies where blood gases were measured promptly using arterial blood, although delayed absorption was observed in one study.148,149 The effects of twinning are equivocal, with two large studies, both in beef herds, demonstrating opposite effects of twinning on calf serum IgG. This is likely to be related to management, as the study that showed an increase in IgG with twinning moved all cows with twins to a barn for care and observation.82,143
It has been shown that the conformation of the dam's udder and ventral abdomen has a significant effect on the average teat-seeking time prior to first suckling. There was nearly a 30-minute delay in the time to suckle.150 Overall effect on the calf IgG was not measured, but a separate study demonstrated a significantly lower serum IgG in cows with pendulous udders.151
Protein restriction in the last third of gestation may affect uptake of IgG by the calf,152 although IgM concentration was unaffected. This finding was attributed to the selective absorption of IgM in newborn calves, which is highly efficient when colostrum intake is low. IgM is the primary immunoglobulin that provides protection to the neonatal calf during the first few days of life, and it has been suggested that the efficient absorption of IgM is a compensatory measure that provides immunity to calves even when they are hypogammaglobulinemic.153,154
There is a seasonal variation in the IgG levels of calves and efficiency of absorption after colostrum feeding, being lower in the winter in cold climates and lower in the summer in hot climates.61,144,155-157 Colostral immunoglobulin concentration is reduced in hot and cold weather,106-108 and this is exacerbated by calves also being less willing to suckle in extreme temperatures. Heat stress results in smaller calves that may be less vigorous,156,158 with one study demonstrating that calves subjected to a cold and wet environment had a slower rate of colostral absorption,159 although the serum immunoglobulin at 24 hours was not significantly different from that in the control calves. In that study the calves exposed to cold temperatures were fed colostrum via an esophageal feeder. The effect would be exacerbated in cold-stressed calves, as they are less likely to suckle voluntarily.
There is some evidence that IgG levels in calves at 24 and 36 hours have low to moderate heritability. The breed of the sire and dam has some effect, but there is variation within lines of the same breed.62,64,85,160 Haplotypes of both the FcGRT and β2M genes coding for the FcRn are associated with FPT in neonatal beef calves, as discussed previously.91,92 Since this receptor is not involved in the uptake of IgG by the calf, it is likely that the risk factor for FPT is the colostrum quality of the dam.
Calves that are allowed to remain with the dam for longer periods after birth have been shown to have a higher risk of FPT. Calves removed from the dam within 3 hours of birth are less likely to have FPT compared to those allowed to stay with the dam for more than 3 hours.45,47 The gender of the primary calf carer has also been shown to influence the odds of FPT,47 with female calf carers having a positive effect on serum protein levels compared to male calf carers.