Epidemiology of Pregnancy Losses and Practical Strategies for - PowerPoint PPT Presentation

Epidemiology of Pregnancy Losses and Practical Strategies for Prevention Klibs N.A. Galvão and Jose E. P. Santos College of Veterinary Medicine University of Florida galvaok@ufl.edu

Outline • Importance of pregnancy losses • Outline the critical period for pregnancy losses • Main risk factors – Postpartum diseases – Heat stress – Anovulation/Low P4 during ovulatory follicle growth – Prolonged periods of ovulatory follicle dominance – Toxins (gossypol, mycotoxins) – Infectious diseases (Neospora, Lepto, BVD, IBR) • Conclusions

Importance of Pregnancy and Pregnancy loss • Each new pregnancy costs ~ $278 ($-14 to $551); cow 500 DIM 90 lbs • Each pregnancy lost costs ~ $555 ($-3 to $1,373)

Reproductive Failure • Fertilization failure • Pregnancy loss AI d5-7 d17-24 d 38-42 d 260 Fertilization Early Embryonic Late Embryonic Fetal Failure Loss Loss Loss Adapted from Santos et al., 2004; ARS

Fertilization and Viable Embryos Santos et al., 2004; ARS

Late Embryonic Loss Santos et al., 2004; ARS

Late Embryonic and Fetal Loss

Day Oocytes 100% 0 d Pregnancy Loss Per Period Cumulative 2 d Fertilization ~ 76% 34%; 7%/d 34% 6 d Viable embryos ~50% 20%; 0.9%/d 47% 28 d CR ~40% 13%; 0.9%/d 54% 42 d CR ~35% 9%; 0.2%/d 58% 90 d CR ~32% 6%; 0.07%/d 61% CR ~30% 180 d 7%; 0.07%/d 63% Term CR ~28% Adapted from Santos et al., 2004; ARS

Summary • Lactating dairy cows – Fertilization rate = ~ 76% (55% heat stress, ~ 80% cool weather) – Viable embryos = ~50% of oocytes (18% heat stress, ~60% cool weather) – Late embryonic loss = ~13% (43% heat stress) – Fetal losses = ~ 10% – Greatest risk in the first 42 d of gestation (0.9%/d)  With early pregnancy diagnosis (~30 d), confirmation is critical • Heifers – Fertilization rate ≥ 90% – Late embryonic and fetal mortality < 5.0%

Incidence of infectious diseases in the first 60 d postpartum • 5,719 cows from 7 dairies in the US Healthy Calving problem Metrits C. endometritis Fever Mastitis Ketosis Lameness Pneumonia Digestive 0 10 20 30 40 50 60 Incidence in the first 60 days postpartum, % (Santos et al., 2010. Soc Reprod Fertil Suppl.)

Disease and Pregnancy 35d Health status CR, % Adjusted OR (95% CI) P Healthy 51.4 1.00 0.79 (0.69 – 0.91) 43.3 0.001 1 case of disease 0.57 (0.48 – 0.69) 34.7 < 0.001 > 1 case of disease Type of health problem 0.75 (0.63 – 0.88) Calving problem 40.3 < 0.001 0.66 (0.56 – 0.78) 37.8 < 0.001 Metritis 0.62 (0.52 – 0.74) 38.7 < 0.001 Clinical endometritis 0.60 (0.48 – 0.65) 39.8 < 0.001 Fever postpartum 0.84 (0.64 – 1.10) 39.4 0.20 Mastitis 0.50 (0.36 – 0.68) 28.8 < 0.001 Clinical ketosis 0.57 (0.41 – 0.78) 33.3 < 0.001 Lameness 0.63 (0.32 – 1.27) Pneumonia 32.4 0.20 0.78 (0.46 – 1.34) Digestive problem 36.7 0.38 (Santos et al., 2010. Soc Reprod Fertil Suppl.)

Disease and Pregnancy Loss 35-70d Health status Loss, % Adjusted OR (95% CI) P Healthy 8.9 1.00 --- 1.73 (1.25 – 2.39) 13.9 < 0.001 1 case of disease 2.08 (1.36 – 3.17) > 1 case of disease 15.8 < 0.001 Type of health problem 1.67 (1.16 – 2.40) 15.9 < 0.01 Calving problem 1.01 (0.71 – 1.60) Metritis 11.3 0.76 1.55 (1.04 – 2.32) 15.1 0.03 Clinical endometritis 2.00 (1.24 – 3.14) Fever postpartum 18.0 < 0.01 2.62 (1.48 – 4.64) Mastitis 19.8 < 0.001 1.64 (0.75 – 3.59) 14.6 0.22 Clinical ketosis 2.67 (1.38 – 5.12) Lameness 26.4 < 0.01 1.87 (0.40 – 8.69) 16.7 0.42 Pneumonia 1.81 (0.52 – 6.32) Digestive problem 15.8 0.35 (Santos et al., 2010. Soc Reprod Fertil Suppl.)

Incidence of infectious diseases in the first 60 d postpartum Calving problem 8.2 Metritis 5.7 Clinical endometritis 14.7 NEFA > 0.7 mEq/L Lipidose 20.0 Subclinical ketosis Ketosis 35.4 Mastitis 15.5 Lameness 3.2 Pneumonia 2.5 Digestive problem 4.3 0 5 10 15 20 25 30 35 40 Incidence until First Insemination (%) N = 957 cows Ribeiro et al., 2013; JDS

Disease and Pregnancy 30d Category Pregnant, % Adjusted OR (95% CI) P Healthy 70.9 1.00 --- 0.67 (0.47 – 0.94) 61.4 0.02 1 case of disease 0.42 (0.29 – 0.60) 48.5 < 0.01 > 1 case of disease Type of health problem 0.51 (0.29 – 0.91) 44.8 0.02 Calving problem 0.36 (0.19 – 0.67) 38.6 < 0.01 Metritis 0.72 (0.48 – 1.07) 54.1 0.10 Clinical endometritis 0.47 (0.32 – 0.70) 45.6 < 0.01 NEFA > 0.7 mEq/L 0.70 (0.51 – 0.96) 56.8 0.03 Subclinical ketosis 0.66 (0.45 – 0.98) Mastitis 54.4 0.04 0.52 (0.23 – 1.17) Lameness 45.8 0.11 0.59 (0.24 – 1.45) Pneumonia 45.0 0.25 0.30 (0.13 – 0.70) Digestive problem 32.0 <0.01 Ribeiro et al., 2013; JDS

Disease and Pregnancy Loss 30-65d Health status Loss, % Adjusted OR (95% CI) P Healthy 10.4 1.00 --- 0.91 (0.46 – 1.82) 1 case of disease 9.0 0.80 1.71 (0.86 – 3.39) 15.0 0.13 > 1 case of disease Type of health problem 3.89 (1.53 – 9.93) 26.9 < 0.01 Calving problem 4.06 (1.34 – 12.29) Metritis 31.2 0.01 2.55 (1.28 – 5.07) Clinical endometritis 20.6 < 0.01 0.67 (0.23 – 1.99) 6.6 0.48 NEFA > 0.7 mEq/L 0.92 (0.44 – 1.92) Subclinical ketosis 8.3 0.82 1.02 (0.45 – 2.31) 12.3 0.96 Mastitis Lameness 0.0 --- --- 2.93 (0.58 – 14.90) Pneumonia 22.2 0.20 1.28 (0.15 – 10.72) 12.5 0.82 Digestive problem Ribeiro et al., 2013; JDS

Endometritis and Pregnancy Loss 35 a, A 30 Pregnancy loss 32-60d, % 25 20 Healthy CE 15 CE+SCE B 10 b, B 5 0 Lima et al., 2013; JDS

Time to Pregnancy Dubuc et al., 2011; JDS

Effect of Cyclicity Status Prior to Insemination on Late Embryonic Losses in Dairy Cows, % (No. Pregnancies) Status Reference Cyclic Anovular P = Bisinotto et al. (2010) 13.2 (1,780) 15.0 (374) 0.17 Cartmill et al. (2001) 24.0 (223) 33.0 (33) NS Cartmill et al. (2001) 36.8 (95) 80.0 (15) 0.05 Cerri et al. (2003) 10.8 (204) 14.6 (48) NS Chebel et al. (2010) 8.7 (207) 13.3 (60) 0.30 Gumen et al. (2003) 12.3 (81) 20.0 (5) NS McDougall et al. (2005) 5.0 (1,470) 9.0 (534) 0.007 Pursley et al. (2001) 15.1 (186) 35.0 (46) --- Santos et al. (2004) 10.4 (270) 17.5 (40) NS Santos et al. (2004) 10.2 (186) 7.7 (26) NS Stevenson et al. (2006) 16.0 (208) 31.0 (81) < 0.05 Overall 11.3 (4,910) 15.3 (1,262) < 0.001 Anovular vs. Cyclic: Relative Risk = 1.35 (95% CI = 1.16-1.58)

Proportion of Cows Classified as Cyclic (o) and Anestrus ( ▲ ) Remaining Pregnant N = 2,004 cows Proportion remaining pregnant 10 dairy herds McDougall et al. N. Zeal. Vet. J. (2005)

What Factors Affect Cyclicity? Vercouteren et al., 2014; JDS

Combined effect of Anovulation and CTE Vieira-Neto et al., 2014; JDS

Summary • There is no good disease!!! 23

What leads to disease? • Disease is multifactorial 24

Infection and the Immune System Kuby Immunology, 6 th ed.

Metabolic State Peripartum Vazquez-Añon et al., 1994; JDS

NEB in Early Lactation Courtesy of Dr. WR Butler

DMI and Uterine Disease ___ Healthy ----- Metritis ….. SCE Hammon et al., 2006; Vet. Imm. Immunop.

NEFA and Immune Function Hammon et al., 2006; Vet. Imm. Immunopath.

Immunosuppression PMN function ___ Healthy SMN function 160 ----- Metritis ….. SCE 140 Immnune Function, % Controls 120 100 80 60 40 20 -6 -4 -2 0 2 4 6 Week Around Calving Kehrli et al., 1989; JDS Hammon et al., 2006; Vet Im Im

NEFA & BHBA & Immune Function Ster et al., 2012; JDS

BHBA and Immune Function Grinberg et al., 2008; Infec. Immun. Papayannopoulos et al. 2010. J. Cell Biol.

DMI and Uterine Disease • Each kg decrease in DMI the last week prepartum increased the odds of severe metritis by 187% (OR = 2.87; P = 0.02) • Each 10 min decrease in feeding time during the last week prepartum increased the odds of severe metritis by 72% (OR = 1.72; P = 0.02) Huzzey et al., 2007; JDS

DMI Pre- and Postpartum Disease Disease 18 25 16 20 14 12 DMI (Kg) 15 DMI (Kg) 10 8 10 6 5 4 2 0 -14 -12 -10 -8 -6 -4 -2 0 0 5 10 15 20 25 30 Time (days) Time (days) No Disease No Disease Disease Disease • Disease = RP, metritis, mastitis, ketosis or DA (n = 167; 57%) • Each kg decrease in DMI the last week prepartum increased the odds of postpartum disease by 18% (OR = 1.18; P < 0.01) Perez et al., 2014; unpublished

Calcium during transition Kimura et al., 2006; JDS

Calcium Activates Leukocytes Nunez and Demaurex, Journal of Leukocyte Biology, 2010

SCHCa and Immune Function Martinez et al., 2012; JDS

Calcium and Metritis P < 0.05 10.0 9.7 9.4 Calcium, mg/dL 9.1 8.8 8.5 Healthy 8.2 Metritis 7.9 7.6 0 1 2 3 4 7 12 Day postpartum Martinez et al., 2012; JDS

Metritis and Immune Function 85.0 60.0 Phagocytosis, % neutrophils Healthy Oxidative burst, % neutrophils 80.0 * 55.0 Metritis 50.0 75.0 * 45.0 70.0 * 40.0 65.0 35.0 60.0 30.0 Healthy 55.0 25.0 Metritis 50.0 20.0 0 1 3 0 1 3 Day postpartum Day postpartum Martinez et al., 2012; JDS