4/11/2012. Incidence of diseases in early lactation dairy cows. Associations with measures of fertility

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1 NUTRITION OF DAIRY COWS TO IMPROVE REPRODUCTION José Eduardo P. Santos, Rafael S. Bisinotto, Eduardo S. Ribeiro, Leandro F. Greco, Fábio S. Lima, and Natalia Martinez Department of Animal Sciences University of Florida Scope of the Presentation Incidence of diseases in early lactation dairy cows Associations with measures of fertility Biology for the involvement of nutritional status and fertility Potential interventions 2 Postpartum Diseases and Reproduction in Confinement Herds 2 1

2 Incidence of Health Disorders in the First 60 d in Milk in High-Producing Holstein Herds Healthy Calving problem Metrits C. endometritis Fever Mastitis Ketosis Lameness Pneumonia Digestive Incidence in the first 60 days postpartum, % 5,719 postpartum dairy cows evaluated daily for health disorders from eight experiments in seven dairy farms in the US. Santos et al. (2010) Reprod. Dom. Rum. VII: Health Problems in the First 60 DIM and Resumption of Estrous Cyclicity in Dairy Cows 4 Category Cyclic, % Adjusted OR (95% CI) P Healthy case of disease ( ) 0.83 > 1 case of disease ( ) Type of health problem Calving problem ( ) < Metritis ( ) < Clinical endometritis ( ) < Fever postpartum ( ) < Mastitis ( ) 0.53 Clinical ketosis ( Lameness ( ) 0.40 Pneumonia ( ) 0.59 Digestive problem ( ) ,719 postpartum dairy cows evaluated daily for health disorders in seven dairy farms in the US. Santos et al. (2010) Reprod. Dom. Rum. VII: Health Problems in the First 60 DIM and Pregnancy in Dairy Cows Category Pregnant, % Adjusted OR (95% CI) P Healthy case of disease ( ) > 1 case of disease ( ) < Type of health problem Calving problem ( ) < Metritis ( ) < Clinical endometritis ( ) < Fever postpartum ( ) < Mastitis ( ) 0.20 Clinical ketosis ( ) < Lameness ( ) < Pneumonia ( ) 0.20 Digestive problem ( ) ,719 postpartum dairy cows evaluated daily for health disorders in seven dairy farms in the US Santos et al. (2010) Reprod. Dom. Rum. VII:

3 6 Health Problems and Pregnancy Loss in the First 60 d of Gestation in Dairy Cows Category Loss, % Adjusted OR (95% CI) P Healthy case of disease ( ) < > 1 case of disease ( ) < Type of health problem Calving problem ( ) < 0.01 Metritis ( ) 0.76 Clinical endometritis ( ) 0.03 Fever postpartum ( ) < 0.01 Mastitis ( ) < Clinical ketosis ( ) 0.22 Lameness ( ) < 0.01 Pneumonia ( ) 0.42 Digestive problem ( ) ,719 postpartum dairy cows evaluated daily for health disorders in seven dairy farms in the US. Santos et al. (2010) Reprod. Dom. Rum. VII: Feed Delivery 1x vs. 2x Daily 100 % of cows at the fe eedbunk eating Milking Milking Delivery 1 x daily Delivery 2 x daily :00 07:00 10:00 13:00 16:00 19:00 22:00 01:00 04:00 Hour DeVries et al, 2005; J. Dairy Sci. 88: Feed Delivery 4x Daily 100 eedbunk eating % of cows at the fe Milking Milking Delivery 2 x daily Delivery 4 x daily 8 0 4:00 7:00 10:00 13:00 16:00 19:00 22:00 1:00 4:00 Hour DeVries et al (2005) J. Dairy Sci. 88:

4 Changes in daily feeding pattern 80 cm/cow 100 Fresh Feed 60 cm/cow 80 Fresh Feed 40 cm/cow 20 cm/cow feeding % of cows f Milking Push Up Milking Push Up Push Up 9 0 0:00 3:00 6:00 9:00 12:00 15:00 18:00 21:00 Time (h) Huzzey et al., J. Dairy Sci. 89: Competition = Increased eating rate te (kg/min) Eating rat non No competition competitive competitive Competition :00 3:00 6:00 9:00 12:00 15:00 18:00 21:00 Hour 10 Hosseinkhani et al. (2008) J. Dairy Sci. 91: Dry Matter Intake and Uterine Disease in Dairy Cows (83 Multiparous) Metritis (n=18) Subclinical Endom. (n=47) Normal (n=18) 25 take, kg/d Dry matter int Reduction in DM intake begins prepartum Week relative to calving Hammon et al. Vet. Immunol. Immunopath. (2006) 4

5 Constant Re Grouping of Cows in the Transition Period Behavior Change with Re Grouping of Cows 1 Dry cows Reduction in feeding time by 15 min in the first hour 2 Prepartum 3 Maternity Forced displacements in the feeding area 4 Fresh cows 6 Hospital Pen Bf Before: 10 times daily dil After: 25 times daily (1 st day) 5 High Production von Keyserlingk et al. (2008) J. Dairy Sci. 12 Laying time on the stall ~ Reduction in 3 hrs 1 st day Milk yield Reduction in ~ 4 kg in the day of regrouping Effect of Cow Regrouping Prepartum All-in d 14 to 28 pre-partum All-out Calving Stable Housing Similar management postpartum Dynamic Housing Twice-weekely inclusion d 1 to 28 pre-partum Calving 13 Coonen et al. J. Dairy Sci. (2011) 94: Effect of Cow Regrouping Prepartum Housing Variables Stable Dynamic P Feed bunk displacements 1.17 ± ± DMI postpartum, kg/d 25.5 ± ± NEFA, meq/l d-3to ± ± d -9 to ± ± > d ± ± Lactation first 30 DIM Milk yield, kg/d 34.6 ± ± Fat, % 4.59 ± ± Protein, % 3.33 ± ± Coonen et al. J. Dairy Sci. (2011) 94:

6 Effect of Cow Regrouping Prepartum Study conducted in MN (6,400 lactating cow herd) 567 cows enrolled in two treatments: AIAO one group of 44 cows moved to close-up every 5 wk Conventional cows entering close-up every week to keep stocking density (44 cows/48 headlocks) Responses evaluated: Feed bunk behavior Innate immunity Metabolic parameters Health Productive parameters 15 Silva et al. (2012) J. Dairy Sci. (Abstr) Effect of Cow Regrouping Prepartum Conventional AIAO P-value Retained placenta, % Metritis, % DA, % Mastitis, % Culling within 60 DIM, % d ECM, kg/d 37.5 ± ± Pregnancy to first AI, % Silva et al. (2012) J. Dairy Sci. (Abstr) Survival analysis of exposure to a transition diet: Controlling for farm, age, calving order (mating start date) Exposure to the transition diet for > 20 d improved pregnancy rate in the subsequent lactation. In this example 78 vs 90% of cows were pregnant by 100 DIM. In this example 60% of cows were pregnant 20 days sooner 6

7 Industry Standards for Space and Comfort Oftentimes Are Inadequate for Transition Cows US Milk Production Per Cow Production has increased 13% in the last 10 years (132 kg more milk/cow/year) USA Cow, thousand 9,000 9,000 8,000 Milk/cow, kg/year 9,500 14,340 14,340 Total milk, billion kg Population, thousand 308, , ,854 Milk/person, kg/year Kg/cow Santos, J.E.P Rum. Reprod. Symp. Anchorage, AK Year Lucinda's Lactation: 67,914 lb At Peak Production: 229 lb/d -82 Mcal NEL: ~ 33 lb of body weight/d lb of MP: ~ 45.3 lb of body weight/d Kg/d Current record = 75,100 lb/lactation LA Foster Blackstar Lucy Weeks in Lactation STD Lactaion Curve Lucinda Actual Estimated NRC DM Intake 7

8 Polar Expedition or Iditarod Energy requirements increase to 6 to 8 Mcal/day Therefore working at between 2.5 and 3.5 times maintenance 21 Courtesy J. Huxley, University of Nottingham Holstein Cows at Peak Production Average cow at 100 lb/day Maintenance energy required: 15 Mcal/d of ME Energy for milk synthesis 55 Mcal of ME/d Total energy needed = 70 Mcal of ME/d Therefore, consuming at 46ti 4.6 times maintenance Lucinda produced 229 lb/day Maintenance energy required: 15 Mcal/d of ME Energy for milk synthesis 113 Mcal of ME/d Total energy needed = 128 Mcal of ME/d Therefore, consuming at 8.5 times maintenance 22 Santos et al. (2010) Reprod. Dom. Rum. VII: If Energy Balance is a Major Drive of Reproductive Success in the Dairy Cow, then the Focus Should be on Intake and not Milk Yield r 2 = 0.07 r 2 = 0.57 r 2 = 0.03 Santos et al. (2010) Reprod. Dom. Rum. VII:

9 Risk factors for resumption of estrous cycles by 65 days postpartum and pregnancy at 1 st 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) < 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) Referent 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, kg/d 75.3 (1,292/1,715) 121( (1.02, 143) 1.43) Variable Pregnant, % (n/n) Adjusted OR (95% CI) P value BCS change from calving to 65 DIM Lost 1 unit or more 28.9 (132/472) Referent Lost < 1 unit 37.3 (1204/3230) 1.42 (1.13, 1.79) < 0.01 No change 41.6 (1008/2422) 1.69 (1.32, 2.17) < Milk yield in the first 90 DIM Q1, 32.1 kg/d 37.2 (496/1,334) Referent Q2, 39.1 kg/d 38.9 (576/1,481) 1.06 (0.91, 1.24) 0.42 Q3, 43.6 kg/d 39.3 (652/1,661) 1.09 (0.93, 1.26) 0.26 Q4, 50.0 kg/d 37.6 (620/1,648) 1.03 (0.88, 1.21) Santos et al. (2009) Anim. Reprod. Sci. 110: Nutrient Partitioning in Dairy Cows Early Lactation/High Production Growth Hormone GHR Adipose LH Liver Insulin NEFA + F F Ovarian IGF I F + Blood IGF I (Endocrine) Lactose Milk fat + Mammary Courtesy of M.C. Lucy Ovary 26 Milk Nutrient Partitioning in Dairy Cows Early Lactation/High Production Growth Hormone GHR Adipose LH Liver Insulin NEFA + F F Ovarian IGF I F + Blood IGF I (Endocrine) Lactose Milk fat + Mammary Courtesy of M.C. Lucy 20 Ovary 27 Milk 9

10 Nutrient Partitioning in Dairy Cows Late Lactation/Low Production Growth Hormone GHR Adipose LH Liver Insulin NEFA + F F F Ovarian IGF I + Blood IGF I (Endocrine) Lactose Milk fat + Mammary Courtesy of M.C. Lucy Ovary 28 Milk Changes in mrna for Hepatic GH Receptors and IGF 1 Plasma Concentrations of Total and Free IGF1 r control Control Insulin Control Insulin fold increase ove Total, ng/ml Free, ng/ml 0 GHR1A IGF1 Total GHR 0 Total IGF1 Free IGF1 0.4 Butler et al. (2003) J. Endocrinology 176:

11 Highly Fermentable Diets Cause Satiety Sooner in High Starch Diets (31%) Corn Type High Moisture Dry ground DMI, kg/d 20.8 b 22.5 a Rumen fermentable OM, kg/d Meal size, kg 1.9 b 2.3 a Intermeal interval, min Oba and Allen J. Dairy Sci. 86: (2003) 31 Nutrition Programs to Enhance Fertility Focus: Assure feed available at all times and increased frequency of feed delivery Minimize competition in the feedbunk Diets should be designed to prevent postparturient diseases Adequate forage fiber content Prepartum cow should consume daily ~ Mcal of NE L and 1.1 kg of metabolizable protein Fresh cow programs should be designed for prompt diagnosis and treatment of sick cows 27 Metritis and Serum Ca Concentrations Calcium m, mg/dl Effect of metritis: P < P < 0.05 Effect of metritis : P < Healthy 7.9 Metritis Day posptartum 28 Martinez-Patino et al. (2011) AABP Abstr. 11

12 Serum NEFA and BHBA Concentrations According to Calcium Subclinical Hypocalcemia NEFA, ueq/l NEFA, ueq/l Healthy Metritis Metritis BHBA, mg/dl Healthy Metritis Effect of metritis: P > 0.60 Day postpartum Day postpartum P < 0.05 Calcium Status BHBA, mg/dl P < Normocalcemia 6 Normocalcemia Sub-hypocalcemia 5 Sub-hypocalcemia Day postpartum Day postpartum Effect of sub-hypocalcemia: P < Subclinical Hypocalcemia and Neutrophil Function Phagocytosis Oxidative Burst Phagocytos sis, % neutrophils * Subhypocalcemia Normocalcemic Normocalcemia Sub hypocalcemia Oxidative burst, % neutrophils * Normocalcemic Sub hypocalcemia * Day postpartum Day postpartum Interaction between subclinical hypocalcemia and day P < 0.05 Within a day, * P < 0.05 Effect of subclinical hypocalcemia: P < 0.05 Within a day, * P Martinez et al. (2011) AABP Abstr. Incidence of Metritis According to Calcium Status and Risk Group Subclinical hypocalcemia 1 Normocalcemia Low Risk High Risk Low Risk High Risk Metritis, % *, 40.7 (11/27) 77.8 (35/45) 14.3 (4/28) 20.0 (2/10) Puerperal metritis, % *, 29.6 (8/27) 53.5 (24/45) 0 (0/28) 10.0 (1/10) *Effect of hypocalcemia (P < 0.05), Effect of metritis risk (P < 0.05). 1 Serum Ca 8.59 mg/dl in the first 3 d postpartum. 2 Puerperal metritis was defined as metritis with presence of fever ( 39.5 C). Population Attributable Risk for metritis due to subclinical hypocalcemia PAR = Incidence of metritis in the study population Incidence of metritis in normocalcemic cows Incidence of metritis in the study population = = 66.6% 31 Martinez et al. (2011) AABP Abstr. 12

13 Probability of Metritis Relative to the Change in Serum Calcium Probability of metritis, % Drop in Ca Increase in Ca Change in serum Ca in the first 3 d postpartum (mg/dl) 1.5 Effect of change in serum calcium: P < 0.05 AOR = 0.38 (95% CI = 0.16 to 0.90) Martinez et al. (2011) AABP Abstr. 37 Milk Production and Fertility Milk Yield, Kg Normocalcemia Sub-hypocalcemia Month postpartum Effect of subclinical hypocalcemia: P = 0.47 Subclinical Normocalcemia hypocalcemia P Clinical endometritis, % 82.6 (57/69) 68.4 (26/38) 0.04 Subclinical endometritis, % 46.2 (30/65) 21.1 (8/38) 0.07 Cyclicity at 38 DIM, % 48.6 (35/72) 57.9 (22/38) 0.70 Pregnant at 1 st service, % 31.3 (20/64) 37.1 (13/35) Martinez et al. (2011) AABP Abstr. Proposed Mechanism Cow undergoes parturition Decline in serum Ca Excess of Ca loss in colostrum + Inadequate Ca intake/absorption Insufficient Ca mobilization Subclinical hypocalcemia ( [Ca] < 8.59 mg/dl) Reduced [Ca +2 ] i for neutrophil activation Develops Metritis Compromises innate Immunity cell function 39 Adapted form Nunez and Demaurex, Journal of Leukocyte Biology,

14 Nutrition Programs to Enhance Fertility Focus: Minimize subclinical hypocalcemia Mineral composition of prepartum diets to avoid hypocalcemia Additional Ca postpartum for the first 2 to 3 DIM might be needed to reduce the risk of uterine diseases 32 Effects of Fat Supplementation on Energy Status in Studies Reporting Benefits to Fertility Reference Nebraska, 1996 Israel, 1991 Wisconsin, 1995 Florida, 1998 Israel, 1988 Israel, 1989 Penn, 1990 DMI, kg/day NR NR NR FCM, kg/day +0.7 a BW/Energ Status +1.7 a Loss of BW More neg ES +1.3 a No difference +1.6 a No difference +2.9 a No difference +1.4 a Loss or gain BW +0.9 a Not reported a Significant increase for cows fed supplemental fat. Courtesy of C.R. Staples, University of Florida 41 Fat supplementation on pregnancy at first postpartum AI in lactating dairy cows (Studies > 99 cows) Pregnancy per AI, % Reference Cows Fat source and amount 1 Control Fat Ferguson et al. (1990) kg of saturated free FA * McNamara et al. (2003) to 0.36 kg of FA from Ca-LCFA * Schingoethe et al(1991) 153 Oilseeds Schneider et al. (1988) kg of Ca-LCFA Scott et al. (1995) kg of Ca-LCFA Sklan et al. (1991) % of ration as Ca-LCFA Sklan et al. (1994) % of ration as Ca-LCFA Primiparous Multiparous 73.7 * Overall effect * Within a row, effect of supplemental fat (P < 0.05). Santos et al. Reprod Dom Anim 43: (2008) 1 FA = fatty acid; Ca LCFA = Ca salts of long chain fatty acids from palm oil. 14

15 Fat Feeding Influences Ovarian Function in Dairy Cows Supplemental fat on the diameter of the dominant ovarian follicle of lactating dairy cows Experimental diets Reference Fat source1 Control Fat mm Ambrose et al. (2006) Rolled flaxseeds Beam and Butler (1997) Tallow, yellow grease Bilby et al. (2006a) Ca-LCFA or flaxseed oil Lucy et al. (1991) Ca-LCFA Lucy et al. (1993) Ca-LCFA Oldick et al. (1997) Yellow grease Robinson et al. (2002) Protected soybeans Staples et al. (2000) Soybean oil, fish oil Average Ca LCFA = Ca salts of long chain fatty acids from palm oil or a blend of palm and soybean oils. Control vs fat was P < 0.10 for each study. Effect of supplemental fat on plasma progesterone concentrations in dairy and beef cattle Control Fat Measurement Progesterone, ng/ml P < Reference Dairy cows Peak concentration Garcia-Bojalil et al. (1998) Wk 2 to 12 postpartum Son et al. (1996) Wk 5 to 12 posptartum Spicer et al. (1993) D1to12ofestrouscycle Lucy et al. (1993) D 9 to 15 of estrous cycle Carroll et al. (1992) Beef cows and heifers Peak concentration NS1 De Fries et al. (1998) Days 12 to 13 of the EC Hawkins et al. (1995) Day 5 of the second EC < 2.6 > Lammoglia et al. (1997) Weekly samples Lammoglia et al. (1996) Day 5 of -induced EC NS Thomas and Williams, (1996) Santos et al. Reprod Dom Anim 43: (2008) 1 NS: not significant; EC: estrous cycle. 43 Some Fatty Acids are Essential Mammalian cells do not express the genes for desaturases beyond the C 9 Carboxyl end HO O O Linoleic acid C 18:2 ω 6 ω 6 ω 3 ω 1 ω 1 Methyl end HO α Linolenic acid C 18:3 ω 3 44 Polyunsaturated fatty acids synthesis derived from diet linoleic acid (LA) 18:2 n 6 linolenic acid (LNA) 18:3 n 3 Elongases and desaturases dihomo linolenic acid (DGLA) 20:3 n 6 COX 1 / 2 Series 1 prostaglandins eicosapentaenoic acid (EPA) 20:5 n 3 COX 1 / 2 Series 3 prostaglandins arachidonic acid (AA) 20:4 n 6 COX 1 / 2 Series 2 prostaglandins docosahexaenoic acid (DHA) 22:6 n

16 Gatekeepers of Cell Regulation Phospholipids of Cell Membranes 62/lect/lect_06/4_18.GIF Reproductive Effects of Unsaturated Fatty Acids May Be Mediated by PPARs Somoza (2006) Hepatic gene expression Venn diagram 13,142 genes expressed in the hepatic tissue Upregulated (P < 0.05) Control SFA+EFA SFA EFA , , Control : 135 had at least a 2 fold change SFA+EFA: 68 had at least a 2 fold change SFA: 82 had at least a 2 fold change EFA: 69 had at least a 2 fold change Greco et al. (2012) J. Dairy Sci. (Abstr.) 48 16

17 Immune Responses to Differential FA Feeding: Ca Salts of Palm Oil vs. Safflower Oil Silvestre et al. (2011) J. Dairy Sci. 94: Pro-Inflammatory Cytokine Production by Neutrophils According to Fatty Acid Feeding Silvestre et al. (2011) J. Dairy Sci. 94: Uterine Health of Dairy Cows Fed Diets Differing in FA Fat Feeding and Postpartum Uterine Health Profile Prepartum C18:2 n6 in Supplemental Fat Low High P Reference % (number of cows) Retained placenta 6.5 (246) 6.7 (255) 0.96 Juchem et al. (2010) 9.8 (579) 10.4 (588) NS Silvestre et al. (2011) Metritis 22.3 (246) 24.4 (255) 0.68 Juchem et al. (2010) 16.8 (579) 18.0 (588) NS Silvestre et al. (2011) Puerperal metritis 15.5 (246) 8.8 (255) 0.08 Juchem et al. (2010) Periparturient problem* 42.9 (35) 8.3 (12) 0.05 Cullens et al. (2004) * Includes retained placenta, metritis and mastitis Santos et al. Reprod Dom Anim 43: (2008) 17

18 Effect of Source of FA on Fertilization and Embryo Development (n = 154 cows) Fatty Acid Saturated n-6 FA P value Fertilization rate, % Accessory spermatozoa, n Excellent and good embryos % Embryos % Embryos-ova Viable blastomeres, % Cerri et al. (2009) J. Dairy Sci. 92: Source of Fatty Acids and Pregnancy at 1 st Postpartum AI P = te (%) Pregnancy Rat N = 178 N = N = 178 N = 166 Sat. Palm FA oil n 6 LTFA FA d 41d Juchem et al. Reprod. Dom. Anim. (2010) 45:55 62 Effects of Fatty Acid Supplementation During the Transition and Breeding Periods on Fertility of Dairy Cows 54 % Transition diets = 30 to 30 DIM (saturated vs. n6 FA) Breeding diets = 30 to 160 DIM (saturated vs. n3 FA) 60 Pregnancy on Day 60 Pregnancy Loss (32 to 60 d) Sat vs. n3: P < 0.01 Interaction: P = Sat vs. n3: P < N = N = 268 N = 270 Sat-Sat n6-sat Sat-n3 n6-n3 Silvestre et al. (2011) J. Dairy Sci. 94 : N = 258 % N = 146 N = N = N = 153 Sat-Sat n6-sat Sat-n3 n6-n3 18

19 How these fatty acids might be working Priming cows with n-6 fatty acids can induce a pro-inflammatory state in which cellular (neutrophils) and systemic innate immunity are more prone to respond to pathogen challenges. Phagocytized pathogen n-6 Fatty Acids HOCl.OH O 2 O 2 O O 2 2-.OH H 2 O 2 HOCl PGF 2α LTB 4 Liver Acute Phase Response Silvestre et al. (2011) J. Dairy Sci. 94 : Cytokines 55 ENVIROLMENTA AL CHALLENGES PGF 2α CYTOKINES Omega-3 Fatty acids Threshold for triggering inflammation - immune response PGF 2α CYTOKINES NEUTROPHIL FUNCTION ACUTE PHASE RESPONSE Follicle Corpus Luteum EMBRYO PRE-IMPLANTATION IMPLANTATION PREPARATION OF UTERUS 56 Omega-6 Fatty acids POSTPARTUM BREEDING Silvestre et al. (2011) J. Dairy Sci. 94 : Fat Feeding For Lactating Dairy Cows Feeding fat improves reproduction in dairy cows Follicle development, luteal function, immune response, uterine health, and oocyte and embryo quality Fertility responses to fat feeding are best when moderate amounts of unsaturated fatty acids of the n-6 and n-3 families are fed Sources rich in n-6 FA improve pregnancy because of increased fertilization and embryo quality Sources rich in n-3 FA increase pregnancy by improving embryo survival 57 19

20 THANK YOU José Eduardo P. Santos Department of Animal Sciences University i of Florida Jepsantos@ufl.edu 20