ABSTRACT

The health of dairy cows given bovine somatotropin (bST) for one lactation was evaluated in 28 commercial herds located in four regions of the United States. At least six herds were in a region and at least one herd/ region contained fewer than 60 cows. Cows (n = 1213) were assigned randomly to control or bST groups and were treated beginning in wk 9 to 10 of lactation and every 14 d until dry-off or d 400 of lactation. Management was according to site practices. Cows were observed for health-related signs by farm personnel daily and by the herd veterinarian biweekly. Average 305-d test-day milk yields were 932 kg greater for bST-treated cows. Pregnancy rates, days open, twinning, cystic ovaries, or abortions were unaffected by treatments. Supplementation of cows with bST had no effect on total mastitis cases, total days of mastitis, duration of mastitis, or the odds ratio of a cow to develop mastitis. Cows supplemented with bST used more medications for health events other than mastitis. This usage was associated primarily with treatments for disorders of the foot and hock. Supplemented cows had a slight increase in foot disorders. There was no effect of supplementation with bST on culling from the herd or removal from study. Overall, the results confirm that label directions for bST are adequate for safe use under field conditions. All clinical signs observed in this study occur normally in dairy herds and were managed in cows supplemented with bST.

(Key words: somatotropin, animal health, mastitis, reproduction)

Abbreviation key: PAMP = postapproval monitoring program, RHA = rolling herd average.

INTRODUCTION

Sometribove (United States Adopted Name) is a sterile formulation of methionyl bST for use in lactating dairy cows to increase milk production (Posilac., Monsanto Co., St. Louis, MO). It was commercialized in the US dairy industry beginning February 4, 1994. Because bST was the first production drug approved for use in lactating dairy cattle and the first recombinant peptide approved for production use in domestic animals, there was concern about its safety under field conditions. Therefore, a postapproval monitoring program (PAMP) composed of three parts was established to determine whether mastitis incidence and antibiotic use were manageable under label-use conditions and whether label directions were adequate.

One component of the PAMP was a controlled study in commercial dairy herds located in the four major geographic regions of the United States and concentrated in primary dairy states. The objective of this study was to evaluate the impact of bST on cow health in commercial dairy herds when used according to label instructions for one lactation.

Effects of bST on human and animal safety have been thoroughly investigated (Bauman, 1992; Cole et al., 1991, 1992; Marcek et al., 1989; Stanisiewski et al., 1992; Vicini et al., 1990). The effects of bST on milk yield in short-term studies under field conditions have been published previously (Thomas et al., 1991). Additionally, the impact of chronic use of bST under field conditions on clinical lameness was evaluated and reported (Wells et al., 1995). The effects of acute and chronic treatment of cows with bST on animal health under clinical conditions have been reported (Adriaens et al., 1992, 1995; Eppard et al., 1991; Vicini et al., 1990). However, no study has evaluated the impact of bST on animal health under commercial conditions for a full lactation. Thus, this study was designed to examine the general health of dairy cattle given bST for a single lactation under commercial conditions. A total of 1128 cows from 28 herds were included in the analyses, making it the largest single study of bST and herd health ever conducted.

MATERIALS AND METHODS

Herd Selection

A total of 28 commercial dairy herds located in four geographic regions of the United States (Northeast, Southeast, Upper Midwest, and West) were selected. Herds were primarily from the top 21 dairy-producing states. In addition, the dairies were selected to provide a minimum of six herds per region, and at least one small dairy farm (fewer than 60 lactating cows) was located in each region. Two of the herds used Jersey cows and the remaining 26 herds used Holstein cows.

Criteria for herd selection included reliable health records; a regular herd health program; and a rolling herd average (RHA) greater than 6350 kg for 2? milking, 7700 kg for 3? milking, and 8600 kg for 4? milked herds. Herds were required to have sufficient cows available to enroll all cows within 6 mo of study start. This interval was extended to 12 mo for small herds due to limitations of available animals.

Herds also had to have culling rates below 40% and have an average bulk tank SCC average of less than 300,000 cells/ml. A total of 96 herds were evaluated to obtain the 28 herds used in this study. Information on herd location, size, and average milk production of the 28 herds chosen is shown in Table 1.

Animal Selection and Management

The study was conducted as a randomized block design. Cows (n = 1213) were blocked by parity and herd and were assigned randomly within blocks to one of two treatments. Treatments were bST (500 mg of sterile sometribove zinc oil formulation/14 d) or control (oil excipient).

Eligible animals from each herd were assigned to a pool from calving to approximately 6 wk of lactation. Before treatment initiation for each cow, at least two milk and SCC records (DHIA or equivalent) no less than 20 d apart were required. At 2-wk intervals, animals in the pool that remained eligible on the start date (9 to 10 wk of lactation) were assigned randomly to treatment (A or B) based on starting order and parity. Cows were eligible for first injection at d 57 of lactation and remained eligible to start first injection up to and including d 70 of lactation.

Treatment assignments of individual cows in each herd were not identified so that the veterinarian and farm personnel were blind to treatment assignment. Syringes used for injections were labeled only as ‘A’ or ‘B’ and did not specify whether syringes were test or control article. Treatments were administered on the same day of the week every 14 d and generally at the same approximate time of day. Each site identified an injection day of the week to minimize injection errors because all cows were treated on the same weekday. Injections were administered subcutaneously in the tailhead or postscapular region according to instructions listed on the product label. If a cow received a partial injection, an additional syringe was administered to ensure that cows were not underdosed. Records were kept of all injections.

General management, health care, milking, and feeding management of cows were in accordance with established site practice, unless specified otherwise in the protocol. Cows remained on study until they were dried off or reached d 400 of lactation.

The normal reproductive management practices were followed at each site without regard to treatment assignment. Two cows were not bred intentionally, and data for these cows were excluded from all reproductive analyses. Data for cows that conceived before initiation of treatment were not included in analyses of percent pregnant or days to first insemination. Also, in one herd, cows were bred exclusively to a bull and individual cows in other herds were housed with a bull after a specified number of days. Data for these animals were not included in analyses of reproductive variables that required a conception date.

Normal culling practices were followed by all herds on the study. Before any animal was removed from the program, the veterinarian or Clinical Investigator was contacted and the reason(s) for removal was documented. If the removal was due to health problems, the animal was examined by the veterinarian, and clinical conditions for removal were documented. Animals that died while on study or required euthanasia because they were moribund were necropsied by the attending veterinarian. All available practical means were employed to determine the cause of any illness, death, or injury.

Observations, Examinations, and Tests

Starting at least 2 wk before treatment and continuing through 2 wk past the last injection, cows were observed daily by designated individuals at each site. All health-related observations were recorded using the existing record keeping system for the site. Before the start of the study, farm record keeping was reviewed and adjusted as required to assure that all farms were recording the required data. Daily observations were comprehensive and captured health conditions even if a condition persisted from the previous day. When taken, other health parameters were recorded such as temperature, pulse, respiration, ruminal motility, or assessments of appetite or animal activity. On the day of treatment administration, the veterinarian was pres

Table 1. Herd information for the postapproval monitoring program for bST.

Farm code	State	Milking cows in herd	Cows startedon study	Times milked perday	Rolling herd average(kg)
MA	MN	340	38	3	11,755
MB	MN	185	22	3	11,295
MC	WI	60	20	2	10,000
MD	WI	875	52	3	10,387
ME	WI	200	54	3	11,644
MF	WI	155	53	3	11,884
MG	WI	155	47	2	10,281
NA	NJ	199	53	2	11,541
NB	NJ	380	56	3	10,989
NC	PA	350	52	2	9560
ND	NY	125	48	2	8877
NE	NY	450	54	3	10,660
NF	NY	273	52	3	11,681
NG	PA	40	12	2	8533
NH	PA	42	14	2	10,956
SA	SC	53	18	2	76201
SB	FL	650	50	3	9299
SC	SC	316	49	2	63962
SD	SC	110	56	2	9072
SE	FL	396	48	4	10,037
SF	FL	363	41	2	8007
WA	ID	525	67	3	11,340
WB	CO	386	49	3	10,804
WC	CO	1400	48	3	9979
WD	CO	415	48	3	10,809
WE	ID	47	15	2	69812
WF	CA	1130	49	2	9027
WG	CA	1740	48	2	9356

¹Not on test before study, value is 305-d mature equivalent from herd software.
²Jersey breed. All others Holstein.

ent to observe all cows and record any health observations. Each site maintained a record of all medications and therapies administered throughout the study and reason(s) for administration of medications and therapies were recorded.

Cows were observed at every milking for signs ofclinical mastitis. Clinical mastitis was defined as thepresence of abnormal milk, such as visible flakes, clots,strings, clumps, or discoloration from blood or serum.Further evidence of infection, such as swelling, heat,pain in the affected quarter(s), depression, off-feed, ordrop in milk production may also have been presentand were also recorded. All mastitis records were maintainedby individual quarter, and quarters were treatedseparately in analyses. For calculation of cases and caseduration, a quarter needed to be free of clinical signsfor at least 21 d to be considered a new case.

Milk production and SCC data were obtained from DHIA (or equivalent program) records. Reproduction records were maintained according to site practices.

Data Analysis

Statistical analyses were conducted using SAS(1997). Separate analyses were conducted for each par-ity group (primiparous and multiparous). Treatmenteffects were examined using mixed model analyses employingREML algorithms. For normally distributed(continuous) variables, the MIXED procedure was used.Nonnormally distributed variables (counts, proportions)were examined using generalized mixed modelanalyses (% GLIMMIX macro; Littell et al., 1996).Treatment was the only fixed effect in the model. Randomeffects in the full model included location and theinteraction of treatment and location. Number of cowsaffected was fit as having a binomial error with a logitlink, while days affected rate was fit as having a Poissonerror with a log link and log of the period length as anoffset. In all cases, the extra-dispersion parameter wasallowed to vary, to accommodate possible over-dispersion.Results from these analyses are best linear unbiasedestimators and are referred to using the SAS designationas least squares means. When data were deemedsparse (fewer than five observations in any locationtreatmentcell) or when the macro failed to convergewithin 50 iterations, the exact analog of the Cochran-Armitage trend test was used, with location as a stratifyingvariable (Mehta and Patel, 1996). If fewer thanthree observations were in any location-treatment cell,no analysis was attempted. Survival analysis tech niques in the LIFETEST procedure were used to testfor associations between treatment and event-timevariables. For these latter analyses, raw means arereported. Treatment effects were considered significantat P < 0.05.

RESULTS

A total of 1213 cows were assigned and began the study and, of these, 85 cows were excluded due to protocol deviations such as initiation of treatment outside the 57 to 70 DIM range. Therefore, 1128 cows were included in the analyses. This included 419 primiparous and 709 multiparous animals. Cows within parity generally were distributed evenly between treated and control groups. Cows from the first to the eighth lactations were included in the study, with the majority (83.7%) in the first three lactations.

Milk Production

The mean RHA for the 27 of 28 herds with a RHA at study start was 10,100 kg (Table 1). Average test day-derived 305-d milk yield for control cows during the study was 10,247 kg, while average milk yield for cows treated with bST was 11,179 kg. Although this study was not designed to evaluate milk yield responses of cows treated with bST, the difference in milk yield for the two groups (932 kg) is similar to previous studies (Hartnell et al., 1991) in which milk yield responses to bST were measured directly.

Reproduction

The reproductive performance of primiparous and multiparous cows is presented in Table 2. Use of bST for either parity group did not affect (P > 0.05) days to first insemination, days open, percent pregnant, fetal loss, abortion, cystic ovaries, successful calving rate, multiple births, or gestation length.

Mastitis

Clinical mastitis results are presented in Table 3. The number of total cow-days during the treatment period for primiparous cows receiving bST was 55,704 d, which was greater than 53,961 d for controls. This increase in cow-days for the bST-treated cows is accounted for by the numerical increase in days open (Table 2) and concomitant slightly longer lactations in this group. Therefore, the number of days at risk for all health events including mastitis was increased in the group treated with bST. The health data are not corrected for this increase in days at risk or for the additional milk produced. Regardless, use of bST wasnot associated (P > 0.05) with increased mastitis incidencein numbers of cows affected, cases per 100 cowdays,days observed per 100 cow-days, or duration ofcases (Table 3).

Similar to data presented for primiparous cows, thenumber of total cow-days was greater for multiparouscows treated with bST. Average days were 87,075 and88,590 for control and bST-treated groups, respectively.The increased number of days at risk (1515) in thisgroup was also associated with a numerical increase indays open and subsequently longer lactations (Table2). Use of bST in multiparous cows did not affect (P >0.05) numbers of cows affected, cases per 100 cow-days,days observed per 100 cow-days, or duration of cases(Table 3). Thus, under commercial conditions in thefirst year of continuous use, there was no effect of bSTuse on mastitis incidence in primiparous or multiparouscows.

The odds ratios for mastitis and expected cases of mastitis in cows treated with bST are presented in Table 4. Odds ratios were not significantly different from 1.00 for either parity during the pretreatment or treatment periods. The odds ratios calculated for the treatment period for both primiparous (1.31) and multiparous cows (1.39) indicate no differences in the incidence of mastitis between control and bST-treated cows. The expected cases per cow for mastitis during the 252 d standardized treatment period were 0.23 and 0.28 for control and bST-treated primiparous cows and 0.38 and 0.50 for multiparous cows, respectively, and were unaffected by treatments.

Sampling of milk for components varied considerably between herds, but milk SCC were analyzed from samples taken from each cow at 154 ± 45 d following treatment initiation. The SCC were not affected by the administration of bST. Least squares means of linear scores ± SEM for control and bST-treated primiparous cows were 2.9 ± 0.23 and 3.1 ± 0.22, respectively. Values for multiparous cows were 3.9 ± 0.21 and 3.6 ± 0.21.

Medications

The results of the analyses of medication use in control and bST-treated cattle are shown in Table 5. As mentioned previously, there was an increase in total cow treatment days in both primiparous and multiparous cows treated with bST associated with slightly extended lactations (Table 2). Results are presented as the proportion of cows ever receiving medications or the proportion of total days that cows were medicated. All medications administered were recorded, and these were divided into preventive and therapeutic medica

Table 2. The effect of bST on reproductive performance during treatment period in primiparous and multiparouscows in the postapproval monitoring program.

	Primiparous			Multiparous
Paramater	Control	bST	P1	Control	bST	P
Number of cows	209	210		355	352
Days from treatment initiation to first insemination, d2	30 ± 2.4	29 ± 2.9	NS5	33 ± 2.3	31 ± 1.7	NS5
Days open, d2	135 ± 6. 2	151 ± 6.2	NS6	144 ± 5.7	148 ± 6.0	NS6
Percent pregnant, %	87 ± 8.0	87 ± 8.1	NS7	83 ± 7.4	76 ± 8.0	NS7
Fetal loss, %3	7	8	NA	9 ± 6.2	10 ± 6.6	NS7
Cystic ovaries, %	6 ± 9.4	8 ± 10.0	NS7	11 ± 7.3	9 ± 7.1	NS7
Successful calving rate,%4	96	93	NA	96	93	NA
Multiple births, %	10 ± 10.6	5 ± 9.2	NS7	7 ± 7.8	8 ± 8.3	NS7
Gestation length, d2	278 ± 0.9	276 ± 0.9	NS6	279 ± 0.5	279 ± 0.6	NS6

¹NS = nonsignificant (P > 0.05). NA = Not analyzed because <3 fetal losses, or <3 unsuccessful calvings, for each site ? treatment subclass. Results for NA are raw means.
²Calculated for animals with accurate breeding/conception information (i.e., excludes cows bred to a bull).
³Lost pregnancies as a percentage of all conceptions.
⁴Successful calving defined as cows that gave birth, lived at least seven days and calf(s) lived at least 24 hr as a percent of cows that conceived and stayed in herd until parturition.
⁵Survival analysis:log rank test. Results are reported as raw means (± SE of raw means).
⁶Linear mixed model analysis: results are reported as least squares means (± SE of least squares means).
⁷Generalized linear mixed model analyses: results are reported as least squares means (± SE of least squares means).
tions. Therapeutic medications were further subdivided into mastitis and nonmastitis medications.

In primiparous cows treated with bST, the proportion of days medicated was greater, even though days with medication were small for each group. Average percentages of days medicated were 0.59% for controls and 1.01% for bST-treated cows (P < 0.05). This was not associated with preventive treatments but was associated with use of therapeutics. Both the proportion of cows medicated at least once with therapeutics and proportion of days were increased in primiparous cowstreated with bST compared with controls. Average percentagesof cows given therapeutics at least once were36.0 and 46.8% (P < 0.05) for control and bST-treatedprimiparous cows, and these medications accounted foronly 0.54 and 0.95% (P < 0.05) of days, respectively.When subdivided into mastitis and nonmastitis medications,administration of mastitis medications was notaffected by treatments for cows or days medicated. Similarly,nonmastitis medications were unaffected for

Table 3. The effect of bST administered on clinical mastitis in primiparous and multiparous cows in thepostapproval monitoring program.

	Primiparous			Multiparous
	Control	bST	P1	Control	bST	P1
Pretreatment
Cows, no.	209	210		356	353
Total cow days	13,235	13,395		22,728	22,548
Cows with mastitis, %	2.31	2.86	NS2	5.41	4.25	NS2
Avg. cases per 100 cow days	0.04	0.04	NS2	0.1	0.07	NS2
Avg. days observed/100 cow d	0.09	0.12	NS2	0.23	0.19	NS2
Duration of cases	4.01	5.63	NS3	4.19	6.95	NS3
Treatment
Cows, no.	209	210		356	353
Total cow days	53,961	55,704		87,075	88,590
Cows with mastitis, %	14.71	18.48	NS2	22.51	28.71	NS2
Avg. cases per 100 cow days	0.09	0.11	NS2	0.15	0.2	NS2
Avg. days observed/100 cow d	0.28	0.32	NS2	0.56	0.67	NS2
Duration of cases	4.82	4.44	NS3	5.79	5.94	NS3

¹NS: nonsignficant (P > 0.05).
²Generalized linear mixed analyses: results are reported as least squares means.
³Linear mixed model analysis: results are reported as least squares means.

Table 4. The effect of bST on the odds ratio of an animal having mastitis and expected mastitis cases duringthe pretreatment and treatment periods of the post-approval monitoring program.

	Odds ratio1,2		Expected mastitis cases in period
Parity handling	Estimate	95% CI	Control	bST	P5
Primiparous
Pretreatment3	1	(0.46,3.39)	0.03	0.03	NS
Treatment4	1.31	(0.71,2.43)	0.23	0.28	NS
Multiparous
Pretreatment	0.78	(0.40,1.50)	0.06	0.04	NS
Treatment	1.39	(0.98,1.96)	0.38	0.5	NS

¹Odds ratio is the antilog of the difference between least square means from Linear Mixed Model Analysis of logits. 95% CI = 95% Confidence Interval of the odds ratio.
²Expressed as percentage of cows that contracted mastitis.
³14-d pretreatment period.
⁴Assumes a 252-d standardized treatment period.
⁵Probability of a significance from generalized mixed model analysis. NS: Nonsignificant (P > 0.05).cows; however, the proportion of days medicated was small but was greater for primiparous cows treated with bST. These medications were given 0.33% of days for control primiparous cows and 0.65% of days for bSTtreated cows. These therapies were associated primarily with feet and hock medications (see section on musculoskeletal system).

The percentage of multiparous cows that were given at least one medication was greater for those treated with bST compared with controls, but the percentage of days cows were treated was not affected (Table 5).Average percentages of cows and days treated were 48.2 and 59.6% (P < 0.05) and 1.14 and 1.15% for control and bST-treated cows, respectively. This increase was associated with therapeutic medications, which was further associated with nonmastitis therapies (Table 5). There were 31.5% of control cows and 40.1% of cows treated with bST that received at least one nonmastitis therapy during the entire treatment period (P < 0.05); however, the proportions of days medicated during this period were 0.55 and 0.48%, respectively, which were not significantly different. These treatments were asso-

Table 5. Effect of bST on proportions of cows and days medicated in primiparous and multiparous cows.

	Primiparous			Multiparous
	Control	bST	P1	Control	bST	P
No. cows	209	210		356	353
Total cows days2	53,961	55,704		87,075	88,590
All
% Cows affected	43.6	53.3	NS1	48.2	59.6	*
% Days affected	0.59	1.01	*	1.14	1.15	NS
Preventive medications3
% Cows affected	2	4.5	*	3.4	2.9	NS
% Days affected	0.01	0.01	NS	0.01	0.01	NS
Therapies4
% Cows affected	36	46.8	*	41.7	52.3	*
% Days affected	0.54	0.95	*	1.07	1.08	NS
Mastitis therapies
% Cows affected	15.3	20	NS5	21.6	27.2	NS
% Days affected	0.23	0.33	NS	0.51	0.61	NS
Non-Mastitis therapies
% Cows affected	29.8	39.4	NS	31.5	40.1	*
% Days affected	0.33	0.65	*	0.55	0.48	NS

¹NS = Nonsignificant (P > 0.05).²Estimates are proportion of total cow treatment days - generalized linear mixed model analysis unless otherwise noted.
³Includes vaccinations or any medication administered for prevention of a condition that was not observed.
⁴Medication administered for a condition that was observed.
⁵Exact test. Values are raw means.
*P = 0.05.

Table 6. Effect of bST on digestive disorders in primiparous and multiparous cows in the postapproval monitoring program.

	Primiparous			Multiparous
	Control	bST	P1	Control	bST	P
No. cows	209	210		356	353
Total cow treatment days	53,961	55,704		87,075	88,590
Diarrhea
% Cows affected (no.)	3.3 (7)	4.3 (9)	NA	2.2 (8)	2.5 (9)	NS3
% Days observed (no.)	0.01 (31)	0.01 (11)	NS2	0.01 (13)	0.02 (14)	NS3
Bloat
% Cows affected (no.)	0.5 (1)	0.5 (1)	NA	0.0 (0)	0.6 (2)	NA
% Days observed (no.)	<0.01 (1)	<0.01 (1)	NA	0.00 (0)	<0.01 (3)	NS3
Off-feed
% Cows affected (no.)	0.2 (2)	0.8 (6)	NA	0.3 (1)	2.8 (10)	*3
% Days observed (no.)	<0.01 (4)	0.01 (20)	NS2	<0.01 (1)	0.01 (22)	*2

¹NS = Non significant (P > 0.05). NA = Not analyzed because <3 recorded for each site ?? treatment subclass.
²Generalized linear mixed model analysis. Values are least squares means.
³Exact test. Values presented are raw means.
*P ?? 0.05.
>**P ?? 0.01.ciated primarily with medications for feet and hocks, which was similar to primiparous cows.

The average number of days with at least one milking discarded due to medication withdrawals was calculated using appropriate withdrawal times for every time a medication was administered. There was no effect of bST administration on the average days of discarded milk for primiparous cows, but there were more (P < 0.05) days with discarded milk for multiparous cows. Mean days with discarded milk during the entire treatment period for primiparous cows were 2.1 ± 0.50 and 2.9 ± 0.50 d for control and bST groups, respectively. Mean days with discarded milk for multiparous cows were 2.4 ± 0.54 and 3.7 ± 0.54 d, respectively.

Body Temperature

The incidences of elevated rectal temperatures were analyzed as the numbers of cows or numbers of days during which a temperature of ??39.4??C was recorded and were not affected by administration of bST.

Feed Intake and Digestive Disorders

Episodes of high feed refusal or reduced feed intake were part of the daily observation dataset and are shown in Table 6. Notations of off-feed were rare and were based on observations, not on actual measurements of feed consumption as cows in these herds were group-fed. In multiparous cows, the percentage of control cows with reduced feed intake was 0.3% and bSTtreated cows were 2.8%, which were different (P < 0.05). Similarly, days affected were very low but occurred only 1 d (< 0.01% of d) in controls and 22 d (0.01% of d) inbST-treated multiparous cows, which was different (P< 0.05). There was no association (P > 0.05) betweenuse of bST and diarrhea or digestive disorders in multiparouscows. In primiparous cows, neither number ofcows affected nor days observed for episodes of reducedfeed intake was affected by use of bST. Similar to multiparouscows, the incidences of diarrhea and digestivedisorders were not different between primiparous controlcows and cows treated with bST.

Musculoskeletal System

The effect of bST on musculoskeletal disorders is presented in Table 7. In primiparous cows, there were no significant effects of treatment with bST on musculoskeletal observations or the categories that comprise this system, except for observations of the foot. Percentages of days with foot observations were 0.08% for controls and 0.17% for bST-treated primiparous cows (P < 0.05). These foot observations did not result in an increase in cows or days affected for altered gait or lameness.

For multiparous cows (Table 7), musculoskeletal disorders were observed at least 1 d in 50 control cows and 88 bST-treated cows, which was different (P < 0.01). However, total days observed were only 0.25 and 0.31% of total treatment period days and these values were not affected by treatment. Although significant, days with disorders of the hock occurred less than 0.01% of the total cow-days for both treatment groups (P < 0.05). Percentages of cows with foot observations were 5.6 and 14.3% (P < 0.001) for the control and bST groups, and this accounted for 0.11 and 0.22% of days (P < 0.05). There were more cows treated with bST that had at least 1 d with an altered gait observation during the treatment period, but numerically there were fewer total days in which altered gait was observed for cows treated with bST. These were observed in 5.4 and 9.2% (P < 0.05) of control and bST-treated cows, which accounted for 0.09 and 0.07% of total days, respectively, and cases were of short duration.

Culling

Cows remained on study until dry-off for pregnant cows and 400 d of lactation for open cows. Cows removed before these times were classified as removed from study, and these data are summarized in Table 8. There was no effect of bST use on numbers of animals that died or were removed from the study due to mastitis, lameness, foot problems, digestive problems, other health problems, or low body condition. No control multiparous animals were removed from study due to poor body condition, and four bST-treated multiparous cows were removed for this reason, which accounted for 1.1% of cows. These cows were removed from study but remained in the herd to hasten body condition repletion at the herd owners’ discretion. Three of these animals were removed within the first 100 d of treatment and had other clinical signs, suggesting that body condition was only a secondary reason for removal.

DISCUSSION

An axiom of production animal agriculture is that the health and well being of domestic animals have direct and indirect relationships to their productive ef- ficiency (Collier et al., 1992; Comens-Keller et al., 1995). High-producing dairy cows must be healthy to achieve sustained levels of above-average performance. Herds utilized in this study were all above average in levels of milk yield, management, and performance. Overall, cows in these herds treated with bST remained as healthy as their herd mates despite greater levels of milk production.

Table 7. Effect of bST on musculoskeletal observations in primiparous and multiparous cows in the postapproval monitoring program.

	Primiparous			Multiparous
	Control	bST	P1	Control	bST	P
No. cows	209	210		356	353
Total cow treatment days	53,961	55,704		87,075	88,590
Musculoskeletal system
% Cows affected (no.)	13.1 (29)	19.5 (42)	NS2	11.7 (50)	22.1 (88)	***2
% Days observed (no.)	0.19 (100)	0.27 (148)	NS2	0.25 (253)	0.31 (322)	NS2
Neck/Shoulder/Rib/Back
% Cows affected (no.)	0.0 (0)	0.0 (0)	NA	2.0 (7)	0.8 (3)	NA2
% Days observed (no.)	0.00 (0) )	0.00 (0	NA	0.02 (18)	0.01 (5)	NS2
Hip/Thigh/Hook/Gluteal/Pinbone
% Cows affected (no.)	0.5 (1)	0.5 (1)	NA	0.0 (0)	0.6 (2)	NA
% Days observed (no.)	<0.01 (1)	<0.01 (1)	NA	0.00 (0)	<0.01 (2)	NA
Leg
% Cows affected (no.)	1.4 (3)	0.5 (1)	NA	0.8 (3 )	0.6 (2)	NA
% Days observed (no.)	0.06 (33)	<0.01 (2)	NS2	<0.01 (13)	<0.01 (5)	NS2
Hock
% Cows affected (no.)	0.0 (0)	0.5 (1)	NA	0.3 (1)	1.1 (4)	NA
% Days observed (no.)	0.00 (0)	<0.01 (1)	NA	<0.01 (1)	<0.01 (10)	*3
Stifle
% Cows affected (no.)	0.0 (0)	0.0 (0)	NA	0.3 (1)	0.0 (0)	NA
% Days observed (no.)	0.00 (0)	0.00 (0)	NA	<0.01 (1)	0.00 (0)	NA
Foot/Hoof/Dew Claw/Fetlock
% Cows affected (no.)	10.7 (25)	14.9 (34)	NS2	5.6 (31)	14.3 (68)	***2
% Days observed (no.)	0.08 (49)	0.17 (117)	*2	0.11 (117)	0.22 (247)	*2
Gait
% Cows affected (no.)	6.2 (13)	9.0 (19)	NS3	5.4 (24)	9.2 (41)	*2
% Days observed (no.)	0.05 (26)	0.07 (40)	NS2	0.09 (123)	0.07 (83)	NS2

¹NS = nonsignificant (P > 0.05). NA = Not analyzed because <3 recorded for each site ?? treatment subclass.
²Generalized linear mixed model analysis. Values are least squares means.
³Exact test. Values are actual means.
*P ?? 0.05.
***P ?? 0.001.Table 8. Effect of bST treatment for a full lactation on removal from study for primiparous and multiparouscows in the postapproval monitoring program.

	Primiparous			Multiparous
	Control	bST	P1	Control	bST	P
No. cows	209	210		356	353
% Died (no.)2	1.4 (3)	1.4 (3)	NA	1.4 (5)	1.4 (5)	NA
% Removed due to mastitis (no.)	1.9 (4)	1.0 (2)	NA	2.8 (10 )	3.7 (13)	NS3
% Removed due to lameness (no.)	0.0 (0)	0.0 (0)	NA	1.1 (4)	2.0 (7)	NS3
% Removed due to foot problems (no.)	1.0 (2)	0.5 (1)	NA	1.1 (4)	2.3 (8)	NA
% Removed due to digestive problems (no.)	1.4 (3)	2.4 (5)	NA	0.6 (2)	1.1 (4)	NA
% Removed due to other health (no.)	0.5 (1)	1.0 (2)	NA	2.5 (9)	4.0 (14)	NS3
% Removed due to misinjection (no.)	1.0 (2)	0.5 (1)	NA	1.1 (4)	1.7 (6)	NS3
% Removed due to poor body condition (no.)	0.0 (0)	0.0 (0)	NA	0.0 (0)	1.1 (4)	NA

¹NS = nonsignificant (P > 0.05). NA = Not analyzed because <3 recorded for each site ? treatment subclass.
²Individual cows can be represented in more than one removal category if multiple reasons given at time of removal.
³Exact test.In a previous study, the use of bST was associated with increased days open for primiparous cows and reduced pregnancy rate for multiparous cows (Cole et al., 1991). In this study, days open and percent pregnant for primiparous and multiparous cows treated with bST were similar to control cows. Also, there were no changes in incidences of abortion, fetal loss, cystic ovaries, or twinning in primiparous or multiparous cows treated with bST. Cole et al. (1991) reported on reproductive performance of 814 cows treated with bST in preclinical trials, where doses and routes of injection varied considerably. They indicated that length of the breeding period and level of milk production had a greater influence on reproductive performance than bST.

The ovary is a target organ for somatotropin (Lucy et al., 1993, 1994), and somatotropin may have beneficial effects on reproductive performance (Lucy et al., 1994; Stanisiewski et al., 1992). Moreira et al. (2000) demonstrated that when estrus detection is eliminated by use of a timed AI program, bST-treated cows had improved reproductive performance compared with control cows. Lucy et al. (1994) found that treatment with 25 mg/d of bST extended the life of normal corpus luteal function. Additionally, the initiation of the second follicular wave was earlier. Kirby et al. (1997) found that bST (500 mg/ 14 d) increased the incidence of undetected estrus. They suggested that while differences in steroid concentrations were not a causative factor in lack of estrus, changes in energy dynamics with increased milk production may have been involved. In support of this concept, low doses of bST, with concomitantly lowered milk production responses, improved reproductive performance (Stanisiewski et al., 1992). Taken together, these findings suggest that nutritional management to minimize shifts in energy balance and improved methods of estrus detection are important management practices that can result in no effects of increased milk production due to bST on reproductive performance.

Use of bST was associated with a greater incidence of twinning (Cole et al., 1991) in a previous clinical study in which bST was administered intramuscularly. But, in a second clinical trial, where bST was administered SC, there was no effect of bST treatment on twinning (Cole et al., 1991). In the current study, twinning was also unaffected by bST use. Data from these studies indicate that when bST was used according to the product label, there was no affect of bST treatment on the incidence of twinning. Whether the increased incidence of twinning observed in the first study was due specifi- cally to intramuscular administration of bST cannot be determined conclusively.

Although not significantly different, the days open obtained in this study would result in a calving interval of 420 d or 14.0 mo compared with an average of 410 d or 13.7 mo in control cows. The additional 10 d of lactation for bST-treated cows was more than compensated for by an average of 932 kg of additional milk per cow per lactation across the 28 herds.

Mastitis incidence was unaffected in either parity group treated with bST in this study. Overall, the odds ratio for mastitis (controlled for parity) in bST-treated animals was 1.23. This ratio is lower than the odds ratios estimated from previous studies (Collier, 1993). In those studies, the risk of mastitis was estimated to be approximately one additional case per cow every 10 lactations. Thus, under actual conditions of use, the incidence of mastitis was lower than had been predicted from the preclinical studies in university herds. There was no significant effect of bST use on the incidence of mastitis. Even though mastitis incidence in cows treated with bST was not corrected for greater days at risk or increased milk yields compared with control cows (White et al., 1994), these data are in agreement with results from a study conducted at four commercial farms where mastitis incidence was unaffected by bST (Judge et al., 1997).

Increased use of medications for nonmastitis-associated treatments was detected in cows treated with bST. As indicated earlier, mastitis medications were associated with therapeutics and not preventive medications. Further examination of these data indicated that the majority of medications used for therapies were not associated with mastitis. These medications included both nonmicrobial (foot baths) as well as microbial (antibiotic) treatments of acute foot disorders.

Digestive disorders were minimal in cows treated with bST. Days bST-treated multiparous cows were recorded as off-feed slightly increased, but days for primiparous cows were not affected. These days were not associated with major digestive problems such as displaced abomasum or metabolic diseases.

An analysis of daily observations and veterinary observations for the musculoskeletal system were in agreement and indicated an increase in foot and hock problems for cows treated with bST (Table 7). Foot and hock disorders included abrasions, ulcers, abscesses, and sores. Although the incidence of these events was increased in both primiparous and multiparous cows, there was no associated increase in laminitis for either parity group.

Analysis of data on removal of cows from the study and from the herd indicated that bST had no effect on reasons for removal of animals from the herd or from the study. Since adoption of bST for commercial use in the United States, analyses of DHIA data for 340 commercial dairy herds in the northeastern United States indicate that herds that adopted bST for 4 yr of continuous use did not differ in culling compared with herds that never used bST (Bauman et al., 1999). Similarly, in a study of 32 Midwest dairy herds, culling was not affected by use of bST (Ruegg et al., 1998).

In summary, health problems detected in cows treated with bST under commercial conditions were typical health events that normally occur in dairy herds. All of the conditions noted are managed routinely by accepted management practices within high-producing herds. Mastitis incidence was less than estimated from preclinical studies (Collier, 1993) and reproductive performance was improved compared with preclinical studies (Cole et al., 1991). Supplemented cows had a slight increase in foot disorders, resulting in more medications, but these disorders were minor and not associated with lameness. Thus, there was no indication that health problems were exacerbated in cows treated with bST under commercial conditions.

ACKNOWLEDGMENTS

We wish to thank the following people for their invaluable assistance in data collection and analysis: R. Hoffman, P. Olsson, M. Aubuchon, S. Piazza, S. Bettis, E. Plunkett, M. McCrate, T. Loesch, T. Curran and R. Sorbet. Additionally, appreciation is extended to the herd veterinarians that contributed to the health observations in this study.

REFERENCES

Adriaens, F. A.,D. L.Hard, M. A. Miller, R. H. Phipps, R. H. Sorbet, R. L. Hintz, and R. J. Collier. 1995. Pituitary response to thyrotropin, corticotropin, and gonadotropin-releasing hormones in lactating cows treated with sometribove for a fourth consecutive lactation. Domest. Anim. Endocrinol. 12:301–316.

Adriaens, F. A., M. A. Miller, D. L. Hard, R. F. Weller, M. D. Hale, and R. J. Collier. 1992. Long-term effects of sometribove in lactating cows during a fourth consecutive lactation of treatment: insulin and somatotropin responses to glucose infusion. J. Dairy Sci. 75:472–480.

Bauman, D. E. 1992. Bovine somatotropin: review of an emerging animal technology. J. Dairy Sci. 75:3432–3451.

Bauman, D. E., R. W. Everett, W. H. Weiland, and R. J. Collier. 1999. Production responses to bovine somatotropin in northeast dairy herds. J. Dairy Sci. 82:2564–2573.

Cole, W. J., P. J. Eppard, B. G. Boysen, K. S. Madsen, R. H. Sorbet, M. A. Miller, R. L. Hintz, T. C. White, W. E. Ribelin, B. G. Hammond, R. J. Collier, and G. M. Lanza. 1992. Response of dairy cows to high doses of a sustained-release bovine somatotropin administered during two lactations. 2. Health and reproduction. J. Dairy Sci. 75:111–123.

Cole, W. J., K. S. Madsen, R. L. Hintz, and R. J. Collier. 1991. Effect of recombinantly-derived bovine somatotropin on reproductive performance of dairy cattle. Theriogenology 36:573–595.

Collier, R. J. 1993. Presentation: U. S. Food and Drug Administration Veterinary Medicine Advisory Committee hearing on bovine somatotropin (sometribove). Gaithersburg, MD; March 31.

Collier, R. J., J. L. Vicini, C. D. Knight, C. L. McLaughlin, and C. A. Baile. 1992. Impact of somatotropins on nutrient requirements in domestic animals. J. Nutr. 122:855–860.

Comens-Keller, P. G., P. J.Eppard, and R. J. Collier. 1995. Evaluation of somatotropin as a homeorhetic regulator of immunity. Pages 79–94 in Animal Science Research and Development Moving Toward a New Century. M. Ivan, ed. Centre for Food and Animal Research, Agriculture and Agri-Food Canada, Ottawa. Eppard. P. J., S. Hudson, W. J. Cole, R. L. Hintz, G. F. Hartnell, T. W. Hunter, L. E. Metzger, A. R. Torkelson, B. G. Hammond, R. J. Collier, and G. M. Lanza. 1991. Response of dairy cows to high doses of a sustained-release bovine somatotropin administered during two lactations. 1. Production response. J. Dairy Sci. 74:3807–3821.

Hartnell, G. F., S. E. Franson, D. E. Bauman, H. H. Head, J. T. Huber, R. C. Lamb, K. S. Madsen, W. A. Samuels, C. J. Peel, and G. A. Green. 1991. Evaluation of sometribove in a prolonged release system in lactating dairy cows-production response. J. Dairy Sci. 74:2645–2663.

Judge, L. J., R. J. Erskine, and P. C. Bartlett. 1997. Recombinant bovine somatotropin and clinical mastitis: incidence, discarded milk following therapy, and culling. J. Dairy Sci. 80:3212–3218.

Kirby, C. J., S. J. Wilson, and M. C. Lucy. 1997. Response of dairy cows treated with bovine somatotropin to a luteolytic dose of prostaglandin F2. J. Dairy Sci. 80:286–294.

Littell, R. C., G. A. Milliken, W. W. Stroup, and R. D. Wolfinger. 1996. SASSystem for Mixed Models.SAS Institute Inc., Cary, NC.

Lucy, M. C., R. J. Collier, M. L. Kitchell, J. J. Dibner, S. D. Hauser, and G. G. Krivi. 1993. Immunohistochemical and nucleic acid analysis of somatotropin receptor populations in the bovine ovary. Biol. Reprod. 48:1219–1227.

Lucy, M. C., T. L. Curran, R. J. Collier, and W. J. Cole. 1994. Extended function of the corpus luteum and earlier development of the second follicular wave in heifers treated with bovine somatotropin. Theriogenology 41:561–572.

Marcek, J. J., W. J. Seaman, and J. L. Nappier. 1989. Effects of repeated high dose administration of recombinant bovine somatotropin in lactating dairy cows. Vet. Hum. Toxicol. 31:455–460.

Mehta, C., and N. Patel. 1996. StatXact 3 for Windows: Statistical Software for Exact Nonparametric Inference. Cytel Software Corp., Cambridge, MA.

Moreira, F., C. A. Risco, M.F.A. Pires, J. D. Ambrose, M. Drost, and W. W. Thatcher. 2000. Use of bovine somatotropin in lactating dairy cows receiving timed artificial insemination. J. Dairy Sci. 83:1245–1255.

Ruegg, P. L., A. Fabellar, and R. L. Hintz. 1998. Effect of the use of bovine somatotropin on culling practices in thirty-two dairy herds in Indiana, Michigan, and Ohio. J. Dairy Sci. 81:1262–1266. SAS Institute Inc. 1997.

SAS/STAT Software: Changes and Enhancements Through Release 6.12, SAS Inst., Cary, NC.

Stanisiewski, E. P., F. Krabill, and J. W. Lauderdale. 1992. Milk yield, health, and reproduction of dairy cows given somatotropin (somavubove) beginning early postpartum. J. Dairy Sci. 75:2149–2164.

Thomas. J. W., R. A. Erdman, D. M. Galton, R. C. Lamb,M. J. Armbel, J. D. Olson, K. S. Madsen, W. A. Samuels, C. J. Peel, and G. A. Green. 1991. Responses by lactating cows in commercial dairy herds to recombinant bovine somatotropin. J. Dairy Sci. 74:945–964.

Vicini, J. L., S. Hudson, W. J. Cole, M. A. Miller, P. J. Eppard, T. C. White, and R. J. Collier. 1990. Effect of acute challenge with an extreme dose of somatotropin in a prolonged-release formulation on milk production and health of dairy cattle. J. Dairy Sci 73:2093–2102.

Wells, S. J., A. M. Trent, R. J. Collier, and W. J. Cole. 1995. Effect of long-term administration of a prolonged release formulation of bovine somatotropin (Sometribove) on clinical lameness in dairy cows. Am. J. Vet. Res. 56:992–996.

White, T. C., K. S. Madsen, R. L. Hintz, R. H. Sorbet, R. J. Collier, D. L. Hard, G. F. Hartnell, W. A. Samuels, G. de Kerchove, F. Adriaens, N. Craven, D. E. Bauman, G. Bertrand, Ph. Bruneau, G. O. Gravert, H. H. Head, J. T. Huber, R. C. Lamb, C. Palmer, A. N. Pell, R. Phipps, R. Weller, G. Piva, Y. Rijpkema, J. Skarda, F. Vedeau, and C. Wollny. 1994. Clinical Mastitis in cows treated with sometribove (recombinant bovine somatotropin) and its relationship to milk yield. J. Dairy Sci. 77:2249–2260.

Source: Journal of Dairy Science
Author: Monsanto Dairy Group