1. Metabolic changes in transition cows – opportunities for management
Thomas R. Overton
Associate Professor of Animal Science
Director, PRO-DAIRY
Cornell University

2. The outcome challenge High milk production
Maintain/minimize loss of BCS
Low incidence of metabolic disorders
Minimize loss of immunocompetence
Control/decrease days to first ovulation and maintain/enhance fertility
Make $$

3. Risk factors for resumption of estrous cycles by 65 days postpartum and pregnancy at 1st AI in lactating dairy cows
Variable
Cyclic, % (n/n)
Adjusted OR (95% CI)
P value
BCS change from calving to 65 DIM
Lost 1 unit or more
58.7 (279/475)
Referent
Lost < 1 unit
74.6 (2,507/3,361)
1.96 (1.52, 2.52)
< 0.001
No change
80.9 (2,071/2,560)
2.39 (1.74, 3.28)
Milk yield in the first 90 DIM
Q1, 32.1 kg/d
72.7 (1,011/1,390)
------
Q2, 39.1 kg/d
77.6 (1,204/1,552)
1.34 (1.13, 1.60)
< 0.01
Q3, 43.6 kg/d
77.6 (1,350/1,739)
1.36 (1.15, 1.62)
Q4, 50.0 kg/d
75.3 (1,292/1,715)
1.21 (1.02, 1.43)
0.04
Pregnant, % (n/n)
28.9 (132/472)
37.3 (1204/3230)
1.42 (1.13, 1.79)
41.6 (1008/2422)
1.69 (1.32, 2.17)
37.2 (496/1,334)
38.9 (576/1,481)
1.06 (0.91, 1.24)
0.42
39.3 (652/1,661)
1.09 (0.93, 1.26)
0.26
37.6 (620/1,648)
1.03 (0.88, 1.21)
0.65
Santos et al. (2009) Anim. Reprod. Sci. 110: 207–221

4. Energy intake and energy balance Milk energy and energy balance
Santos et al. (2010) Reprod. Dom. Rum. VII:

5. The metabolism challenge required to meet the outcome challenge
Abrupt changes in demands for energy (and other nutrients)
High gluconeogenic rates during postcalving period
Minimize negative diet and management interactions with metabolism (esp. adipose)
Maintain sufficient DMI during precalving period and facilitate acceleration during postcalving period
Manage interactions of facility/nonnutritional management factors with metabolism?

6. Metabolic Adaptation (Schoenberg, 2010)
Increased mobilization of fatty acids
Decreased insulin response of adipose tissue
Impaired glucose disposal
Increased hepatic gluconeogenesis
Decreased uptake of glucose by peripheral tissues
Changes in intake
We are especially interested in the effects on adipose tissue
Glucose sparing for gravid uterus and eventually the mammary gland

7. Take homes
Coordination of metabolism to support late pregnancy and early lactation is extensive and exquisite
“Insulin resistance” to spare glucose for fetus and mammary gland is important for successful adaptation to lactation
Some degree of fat mobilization (and elevated NEFA) is “normal”
Excessive mobilization of fat (elevated NEFA) is associated with metabolic disorders, lower milk production, and poorer reproductive performance
“Excessive” insulin resistance in body fat likely contributes to hypermobilization of NEFA and lower DMI (cows resemble Type II diabetics)
Fat cows
Cows overfed energy during either far-off or close-up period
Impact of environmental stressors?

8. DMI and NEFA
Adapted from Smith, 2004

9. Summary of metabolic regulation work focused on insulin resistance
Glucose disposal slower and slope of NEFA decrease less following glucose challenge in prepartum cows compared to early lactation
Smith et al., J. Dairy Sci. 87(Suppl. 1):442.
Strengthening adipose tissue responses to insulin using targeted approaches in prepartum cows
Decreased NEFA spike during immediate periparturient period
Smith et al., J. Dairy Sci. 90: ;
Smith et al., J. Dairy Sci. 92:
Increased DMI during immediate periparturient period
Decreased BCS loss during early lactation and days to first ovulation

10. Excessive prepartum energy intake and insulin resistance
Mashek and Grummer (2003)
Large decreases in prepartum DMI → higher NEFA, liver TG postpartum
Holtenius et al. (2003); Agenas et al. (2003)
Prepartum overfeeding (178%) → higher glucose and insulin prepartum, higher insulin response to glucose challenge, higher postpartum NEFA, lower DMI postpartum
Dann et al. (2006)
Far-off overfeeding (150%) → higher postpartum NEFA and BHBA, lower postpartum DMI
Douglas et al. (2006)
Lower glucose and insulin prepartum, lower NEFA and higher DMI postpartum in cows fed 80% vs. 160% prepartum
Schoenberg et al. (2010)
Decreased NEFA clearance following glucose challenge in cows overfed during the dry period

11. Dry period energy formulation from herd to herd is a bit like walking a balance beam
If cows consume insufficient energy, more metabolic problems postcalving
If cows consume excessive energy, more metabolic problems postcalving
MAJOR influence of nonnutritional factors on AMOUNT and UNIFORMITY of energy intake during both the far-off and close-up periods
Dictates different approaches on different farms to achieve same goal

12. U.S. trends in last 5 to 7 years
Largely abandoned “steam up” concept advocated by 2001 Dairy NRC
Controlled energy strategies for dry cows during both far-off and close-up periods (Drackley, 2007)
0.59 to 0.62 Mcal/lb of NEL
12 to 16% starch
40 to 50% forage NDF
Appropriate for multiparous cows
Too low energy/too bulky for primiparous cows?
MP supply?? (RUP supplementation even more important)

13. Effects of far-off diet (Dann et al., 2006)
Fed far off cows to achieve
Control (100% of predicted NRC energy requirement – actual 95%)
High energy density diet
80% of energy requirements
150% (actual 160%) of energy requirements
Close-up diet to achieve
135% vs 80% of energy requirements
Cows overfed far-off had
Lower subsequent DMI and calculated energy balance
Higher NEFA and BHB during first 10 d postpartum
Close-up strategy did not affect periparturient metabolism or performance

14. Richards et al. (2009)
Controlled energy (~ 0.60 Mcal/lb) during entire dry period
High energy (~0.73 Mcal/lb) during entire dry period
Controlled energy far off followed by high energy close up
High energy for entire dry period
Gained more BCS during dry period
Lost more BCS during postpartum period
Controlled energy for entire dry period
Lower postpartum NEFA, BHB, and liver fat compared to high energy
Metabolic health for cows fed two-group more similar to controlled energy than high energy

15. Common observations with prepartum overfeeding/excessive insulin resistance
Large decreases in DMI as cows approach calving
Low/sluggish increases in DMI in fresh cows
Rapid BCS loss during postpartum period
Higher incidence of subclinical and clinical ketosis and DA
Sometimes lower colostrum yield

16. Can you go too low? Janovick and Drackley (2010)
Cows fed low energy dry cow diets (1.21 vs Mcal NEL/kg) had higher postpartum DMI, lower NEFA, better energy balance, but also yielded less milk (33.3 vs 38.9 kg/d for wk 1-8)
Silva del Rio et al. (2010)
Cows fed higher energy diet for entire dry period (1.54 Mcal/kg for 8 wk vs Mcal/kg for far-off and then 1.54 Mcal/kg diet for last 3 wk) had lower energy balance because of increased milk yield and higher postpartum NEFA

17. Overall goals for energy intake of both far-off and close-up cows
Far off cows (dry off until ~ 3 weeks precalving)
~ Mcal of NEL per day
110 to 120% of ME requirements (CNCPS 6.1)
Close-up cows (last 3 weeks before calving)
~ Mcal of NEL per day
Vary energy density of diets based upon group DMI
Which means have to know DMI to know how much to “bulk up” the diet
Almost want to achieve the above in the largest DMI package that cows will consume consistently

18. You HAVE to chop the %(*(#*@&# straw/hay
3.5 lbs straw in 26 lb DM package
6 lbs straw in 27 lb DM package

19. Potential management/facility related stressors for transition cows
Overcrowding (increased stocking density)
Commingling of cows and heifers
Excessive number of pen moves (group changes)
Heat stress
Overall cow comfort/hygiene
Very Few Data Exist for Effects of Stressors on Transition Cows
Stressors from the natural environment and deficiencies in management
Single stressor alone may not impact cows, but effects of multiple stressors may sum to have significant negative impact
Effects of multiple stressors accumulate until a breakpoint is reached and the system fails leading to periparturient disease and disorders.

20. Physiological measures of stress and inflammation?
Changes in the activity and functioning of the hypothalamic-pituitary-adrenal (HPA) axis are often used to quantify an animal’s response to a potential stressor.
Plasma cortisol
Non-invasive measures of stress?
Fecal Cortisol Metabolites (Möstl and Palme)
Environmental stressors can also induce an acute phase response in cattle.
For example in cattle, cortisol concentrations increase in response to overstocking, transportation and re-penning or re-grouping . However, a limitation of using plasma cortisol as an indicator of stress is that this measurement can be easily compromised. Restraint and handling, which are required during blood sampling, can activate the HPA axis and raise circulating cortisol concentrations quickly (Cook et al., 2000). Fecal cortisol metabolites may be an alternative to plasma cortisol as a measure of the stress response in cattle, due to the feedback-free nature of the sampling method .
Stress has also been shown to induce an acute phase response in cattle and acute phase proteins such as haptoglobin have been proposed to be markers of environmental stress in cattle. During periods of inflammation, tissue damage and infection the acute phase response is activated. While there are many acute phase proteins, haptoglobin has been of particular interest for the detection of sick animals due to its virtual absence in the blood of healthy animals. There is also some evidence that increased levels of haptoglobin can be identified prior to the onset of clinical signs of metritis.
Haptoglobin

21. Prepartum haptoglobin is not associated with postpartum disease
Haptoglobin is a non-specific marker of inflammation, infection or injury
No differences in prepartum Haptoglobin between health categories.
(Huzzey et al., Submitted for review 2010)

22. Fecal cortisol during wk -2 and -1 were higher in cows that developed more than one health disorder or died by 30 DIM
(Huzzey et al., Submitted for review 2010)

23. Haptoglobin and milk production (Huzzey et al., 2010)
wk wk wk wk+1
∆ 305ME (kg milk) † * †
*** **
Cutpoint: >1.1 g/L
% Cows Above Cutpoint:
wk wk wk wk+1
Multiparous
Primiparous

24. Fecal cortisol and milk production (Huzzey et al., 2010)
wk wk wk wk+1
∆ 305ME (kg milk) * **
***
Cutpoint: ng/g fecal DM ng/g fecal DM
% Cows Above Cutpoint:
wk wk wk wk+1
Multiparous
Primiparous

25. Overstocking affects behavior
Increased aggression
Reduced feeding times
Increased feeding rate
Increased inactive standing time
Reduced lying time
Little work has evaluated how these behavioral changes influence subsequent health
3 X more displacements in displacements in competatively fed transition cows
Changes in feeding times have been reported at stocking densities of 113% or higher cows at the bunk during peak feeding times. Peak feeding periods are most affected.
Increases in feeding rate are dramatic. Proudfood: Cows in competition 20g/min faster during wk-1 and +1… wk+2 rate increases to 40g/min (no differences in the heifers)
DMI does not change… due to rate?
At higher stocking densities there are are less cows resting during peak lying times (0-4am) and more cows standing inactively. (Tendency for more % eating during this time).

26. Overstocking and metabolism
Treatments (6 cows and 4 springers per group)
Control:
Full access to feed bunk (~2 ft/cow) and lying stalls (10stalls/10cow)
Overcrowded:
50% less feed bunk space (~1 ft/cow) and lying stalls (5 stalls /10 cows)
Huzzey, Nydam, Grant, and Overton, 2010 Cornell Nutrition Conference

27. Competition for feed Standard Overstocked
Huzzey, Nydam, Grant, and Overton, 2010 Cornell Nutrition Conference

28. Pattern of feeding activity
In the overstocked group fewer cows were at the feed bunk following fresh feed delivery while more cows were at the bunk at night
There is a positive correlation between the time it takes to approach the bunk following FD and daily NEFA (r=0.30) and glucose (r=0.24) concentration (P≤0.02).
% of cows at the feed bunk
Feed Delivery
Hour of the Day
Huzzey, Nydam, Grant, and Overton, 2010 Cornell Nutrition Conference

29. DMI & feeding time Feeding rate was greater in overstocked cows
Cows in the overstocked group had a greater DMI (33 vs 31 lb/d)
Feeding time was not different between overstocked and control groups (242 vs. 241 min/cow/d)
Feeding rate was greater in overstocked cows
DMI (kg/cow)
Treatment Day
Huzzey, Nydam, Grant, and Overton, 2010 Cornell Nutrition Conference

30. Daily metabolite concentrations
NEFA
Glucose
uEQ/L
mg/dL
trt day
Insulin
Fecal Cortisol Met.
NEFA, glucose, and fecal cortisol metabolite concentrations were negatively correlated with daily feeding time ( r = -0.54, -0.32, and respectively; P≤0.003)
ng/g fecal DM
uIU/mL
Huzzey, Nydam, Grant, and Overton, 2010 Cornell Nutrition Conference

31. Challenges with assessing energy metabolism and inflammation-related opportunities in transition cows
Most of dairy industry works on averages
Challenges related to energy/grouping mgt/nonnutritional factors cause increases in variation in DMI/performance
Almost impossible to detect some of these on farms
Potential tools for use in monitoring variation in transition cow management
NEFA (best marker for negative energy balance)
BHB (“gold standard” blood ketone)
Haptoglobin and/or fecal cortisol? (not ready for prime time)
Variation in early lactation milk yield

33. Question: Which of the following do you think are the most important effects/associations of elevated NEFA and/or BHB in transition cows?
Increased incidence of health disorders
Poorer reproductive performance
Decreased milk production

36. Herd-level impacts of elevated NEFA/BHB
Metabolite level
Herd Alarm
Associated with:
PRE-Partum
NEFA > 0.3 mEq/L
15%
+3.6% Disease incidence
-1.2% Pregnancy rate
- 529 lbs ME305 milk (both heifers and cows)
POST-Partum
NEFA > 0.6a - 0.7b mEq/L
+1.7% Disease incidenceb
- 0.9% Pregnancy ratea
Heifers: lbs, Cows: - 1,272 lbs
BHB > 10a-12b* mg/dL
*20%
+1.8% Disease incidenceb
-0.8% Pregnancy rateb
Heifers: -1,179 lbs*, Cows: lbsa
*15% of 15 = 2-3 animals
Ospina et al., 2010

37. Approach for monitoring energy-related blood analytes in transition cows
Sample size:
>12 cows
Cows to sample
Pre-partum: 14 to 2 days before calving
Post-partum: 3 to 14 DIM
Sample to take
Serum (red top tubes)
Don’t shake, keep cool
What to do with sample?
BHB: Lab or Precision Extra Meter
NEFA: Lab
What to do with results
Interpret % above cut-point
More than 15% above cut-point indicates herd-level problem

38. Interpretation of metabolites to assess herd-level opportunities
Scenario 1 – High prepartum NEFA, High postpartum NEFA and/or BHB
Likely starting with low DMI in close-up cows
Too low energy in prefresh diet, facility and/or management issues (grouping, stocking, heat stress)?
Scenario 2 – High prepartum NEFA, low postpartum NEFA and/or BHB
Likely low DMI in close-up cows
Are you sampling the survivors in the fresh pen?
Is the herd outmanaging or putting band-aids on fresh cow issues?
Scenario 3 – Low prepartum NEFA, high postpartum NEFA and/or BHB
Is herd overfeeding energy either far-off or close-up?
Diet or facility/management issues specific to maternity/fresh cow group

39. Ways to evaluate variation in early lactation performance
Milk yield/ME projection and index of variability at test days following calving
Standard deviation
+/- 1 SD accounts for 67% of observations
Coefficient of variation (CV)
SD divided by mean
1st Test day milk yield (n=48)
Mean SD = 25.2 lb (range 10.5 to 30.4)
Mean CV = 0.35 (range 0.25 to 0.62)
1st ME projected milk yield (n=48)
Mean SD = 5166 lbs (range 4192 to 6822)
Mean CV = 0.20 (range 0.16 to 0.24)

40. Herd-level pregnancy rate vs
Herd-level pregnancy rate vs. CV (index of variation) of ME milk yield projected at the first test day after calving

41. Fresh cow cull/dead first 60 DIM – 6.9%

42. 17/20 prepartum animals > 0.3 mEq/L NEFA!!
Date Drawn
ID#
NEFA
BHB
10/6/2006
334
0.32
346
0.39
1712
0.43
2012
0.62
2292
0.51
2327
0.37
2394
0.82
2456
0.34
2582
0.77
2589
0.53
2647
0.29
2651
2776
0.48
3094
0.58
3095
0.45
3102
0.59
3106
0.44
3113
0.49
3116
0.85
303
0.35 23
313
0.27 6
330
0.2
347 5
2385
0.55
2408
0.33
2491
2.07 22
2619
0.38
2659
0.22
2681
0.42 8
2730
0.13
2836
0.6 10
3076
3080 4
3085
1.11 30
3089
1.4 15
3093 57
3099
0.3
3105
0.52
3110
0.36
17/20 prepartum animals > 0.3 mEq/L NEFA!!
5/20 postpartum animals > 0.7 mEq/L NEFA
5/20 postpartum animals > 12 mg/dL BHBA

43. Monthly snapshot of herd milk production at test day
120
100 80 60 40
Days in milk at test day

44. The outcome challenge High milk production
Maintain/minimize loss of BCS
Low incidence of metabolic disorders
Minimize loss of immunocompetence
Control/decrease days to first ovulation and maintain/enhance fertility
Make $$

45. The transition management challenge
Putting systems into place (nutritional strategies, facilities, grouping strategies) that decrease individual variability or counter inherent animal to animal variation
Remember, it’s about milk and reproductive performance; disorders/disease should not drive the transition opportunity discussion