NEWBORN CALF VITALITY: RISK FACTORS, CHARACTERISTICS, ASSESSMENT, RESULTING OUTCOMES AND STRATEGIES FOR IMPROVEMENT Christine Murray, PhD Candidate Outline Dystocia: effects on the calf Causes of reduced newborn vitality Consequences of reduced vitality Vitality scoring Methods to improve calf vitality Study results Biomarker for calf vitality and long-term health Conclusions Dystocia: Effects on the Calf Parturition can be the most hazardous and traumatic event in the life of a calf Dystocia and subsequent health events account for up to 50% of all calf deaths In severe dystocia cases, calves have: 20.7 greater odds of stillbirth 1.7 & 1.3 greater odds of being treated for respiratory & digestive disease, respectively 6.7 greater odds of mortality (Lombard et al., 2007; Furman-Fratczak et al., 2011) Dystocia: Effects on the Calf Factors causing dystocia may include: Pelvic dimension of the dam Calf size Feto-pelvic disproportion Calf presentation Inappropriate timing of intervention or excessive force applied during delivery Maternal factors, such as weak labor, insufficient dilation of the cervix and uterine torsion (Meijering, 1984; Schuijt, 1990; Mee, 2008) Dystocia: Effects on the Calf Dystocia may have implications for calf vitality, as well as long-term health and productivity Vitality: having the capacity to live and grow with physical and mental energy and strength Physiological effects of dystocia: Inflammation, pain, injury, inability to maintain homeostasis, hypoxia and acidosis Behavioral repercussions: Reduced motivation to perform natural behaviours for survival, including standing up and suckling colostrum after birth (Breazile et al., 1988; Besser et al., 1990; Carstens, 1994; Barrier et al., 2012) Outline Dystocia: effects on the calf Causes of reduced newborn vitality Causes of Reduced Calf Vitality Pain, injury & inflammation Hypoxia/acidosis Respiratory Metabolic acidosis acidosis Impaired thermoregulation (Meyer et al., 2000; Lombard et al.,2007; Waldner and Rosengren, 2009) Pain, Injury and Inflammation Improper obstetrical assistance & excessive force: Fetal Blood loss Improper clamp timing Premature umbilical cord rupture Fractures Long bones 40% rib fractures 10% fractured vertebra Trauma Liver rupture Tracheal collapse Meningeal hemorrhages Hypoxia/Acidosis Hypoxia refers to an inadequate supply of oxygen to the cells & tissues of the body Premature umbilical cord rupture causing an inability to breath = Respiratory Acidosis Termination of blood oxygenation from the placenta Intense and prolonged labor contractions Trauma during forced extraction If severe, fetal tissues will derive O2 from anaerobic glycolysis = Metabolic Acidosis Hypoxia/Acidosis Asphyxia can cause decreased blood flow to the liver and kidneys leading to hepatic necrosis, liver dysfunction and renal tubular necrosis Other implications include aspiration pneumonia, edema, bleeding, and death Schuijt and Taverne (1994) found that calves born from a severe dystocia had more serious acidosis, took longer at achieve a normal pH (>7.2) and had a greater risk of mortality (Mulling, 1977; Ikeda et al., 2000; Poulsen and McGuirk, 2009) Hypoxia/Acidosis 7.35 7.3 pH at SR 7.25 0 people 7.2 1 person 2 people 7.15 3 people 7.1 7.05 15 30 45 60 75 90 105 Duration of Calving (Min) (Murray et al., unpublished results) 120 135 Thermoregulation Depending on the degree of stress, calving environment and season of birth, maintaining homeostasis can be challenging Decreased available energy needed for the mobilization and metabolic activity of brown adipose tissue during non-shivering thermogenesis Reduced muscle tonicity, preventing shivering Less able to withstand cold stress (Stott and Reinhard, 1978; Okamoto et al., 1986; Vermorel et al., 1989; Bellows and Lammoglia, 2000) Thermoregulation Newborn calves can generate body heat through physical activity Standing up, walking and consuming colostrum may be challenging for calves with low vigor, especially in temperatures outside of their thermoneutral zone (10-25°C or 50-78°F) Energy and heat acquired through colostrum ingestion may also be delayed or reduced in calves with low vitality (Vermorel et al., 1989; Grove-White, 2000; Barrier et al., 2012) Outline Dystocia: effects on the calf Causes of reduced newborn vitality Consequences of reduced vitality Consequences of Dystocia Dystocia causing pain, injury, inflammation, hypoxia, acidosis, and impaired thermoregulation all lead to calf weakness and reduced vitality Decreased ability to perform tasks for survival Standing Walking Suckling colostrum (Schuijt and Tavern ,1994 ; Diesch et al., 2004 ; Barrier et al, 2012) Consequences of Dystocia Probability of not achieving sternal recumbency within 15 minutes of birth 0.00 0.25 0.50 Probability 0.75 1.00 Kaplan-Meier survival estimates 0 5 10 analysis time (min) calving_score = 1 calving_score = 3 (Murray et al., unpublished results) calving_score = 2 calving_score = 4 15 Consequences of Dystocia Probability of not attempting to stand within 15 minutes of birth 0.00 0.50 0.25Probability 0.75 1.00 Kaplan-Meier survival estimates 0 50 100 analysis time (min) calving_score = 1 calving_score = 3 (Murray et al., unpublished results) calving_score = 2 calving_score = 4 150 Consequences of Dystocia Suckling Response vs Calving Difficulty at 2 Hours 60% 50% % Calves 40% Unassisted 30% Easy Pull 20% Hard Pull 10% 0% Weak Medium Suckling Response (Murray et al., unpublished results) Strong Consequences of Dystocia Increased time to achieve sternal recumbency (SR), first attempt to stand and reduced suckling response Suckling reflex and time to SR have been used as objective indicators of fetal stress and vigor in newborn calves Calves forcefully extracted took significantly longer to achieve SR and had a lower overall state of vitality (Schulz et al.,1997; Schuijt and Taverne, 1994, Murray et al., unpublished results) Consequences of Low Calf Vitality Calves with low vigor have an increased risk of failure of passive transfer due to low volume of ingested colostrum Failure to get up and drink Reduced suckling reflex Up to 74% reduced colostrum intake in calves with fetal distress 12h after birth (Vermorel, 1989; Furman-Fratczak et al., 2011; Barrier et al., 2012) Consequences of Low Calf Vitality In other studies, IgG absorption is reduced in calves with dystocia induced respiratory acidosis In severely acidotic calves, a 52% decrease in colostrum intake is correlated with a 35% decrease in serum IgG concentration Significant inverse relationship between venous partial pressure of CO2 at birth and 12h post feeding serum IgG concentration (Besser et al., 1990; Boyd, 1989; Drewery et al., 1999) Consequences of Low Calf Vitality (Boyd, 1989) Long Term Health Effects Failure of passive transfer may result in: 31% of pre-weaning mortality 30% decrease in pre-pubertal growth rate 30 day increase to first insemination Produced 2,263 lbs less milk over first 2 lactations 16% decrease in survival to the end of the second lactation (DeNise et al., 1989; Faber et al., 2005; Furman-Fratczak et al., 2011) Outline Dystocia: effects on the calf Causes of reduced newborn vitality Consequences of reduced vitality Vitality scoring Human Fetal Monitoring APGAR (Virginia Apgar) 5 essential assessments: Appearance (Color) Pulse (Heart rate) Grimace (Stimulation) Activity (Muscle tone) Respiration Modified APGAR Scores Developed for piglet, foal and puppy Included variables such as heart and respiratory rate, reflexes, mobility and mucous membrane colour Pups with low vitality scores were less likely to seek the mammary gland and had weaker suckling reflexes and mortality was increased Piglets with low vitality scores were slower to stand, had more difficulty breathing, had slower heart rates, decreased arterial blood pH and increased partial pressure of CO2, indicating a state of acidemia and hypercapnia (Randall, 1971; Veronesi et al., 2009) Modified APGAR Scores: Calves A modified Apgar score has been assessed in calves in several German studies Used signs of asphyxia: muscle tone, movement, reflexes, respiration and mucous membrane colour The modified Apgar score was only marginally correlated with the results of blood-gas analysis Did not accurately assess the vitality status of the calf, and calves were more appropriately classified into vitality groups based on acid–base status. (Mulling, 1977; Schafer and Arbeiter, 1995; Herfen and Bostedt, 1999a; Herfen and Bostedt, 1999b) Modified APGAR Scores: Calves Hypoxia and acidosis may be indicative of newborn calf vitality Require expensive, inconvenient and invasive lab tools A more practical assessment using visual and physical measures can be easily performed on farm Presence of meconium staining, peripheral edema, cyanosis of the mucous membranes, heart and respiration rates, muscle tone, stimulation reflexes, rectal temperature, time to SR and attempts to stand and suckle (Mee, 2008). U of G – Calf VIGOR Score Sheet Outline Dystocia: effects on the calf Causes of reduced newborn vitality Consequences of reduced vitality Vitality scoring Methods to improve calf vitality Assessment of Pain Following Dystocia Studies have shown that dystocia is one of the most painful conditions in adult cattle The severity of pain following dystocia in adult dairy cattle was 7, whereas it was only rated 4 in newborn calves Pain is a subjective experience that is not possible to measure directly (Huxley and Whay, 2006; Kielland et al., 2009; Laven et al., 2009) Assessment of Pain Following Dystocia Behaviours and physiological measures that can indicate pain in farm animals: Withdrawal reflex Movement after birth Heart and respiration rate Body temperature Are calf vitality scores directly correlated with the degree of pain experienced by a newborn calf? (Molony and Kent, 1997) Methods to Improve Vitality Vitality scores should be used as a decision making tool to assess if further intervention is needed Conventional intervention methods: Artificial respiration Respiratory stimulants Oxygen Buffer therapy for acidosis Thermal support Umbilical treatment Colostrum from esophageal feeder (Mee, 2004; Mee, 2008) Methods to Improve Vitality Administration of non-steroidal anti-inflammatory drugs (NSAIDs) for alleviation of pain and inflammation (Hudson et al., 2008) Methods to Improve Vitality Currently no published literature on NSAID use in calves 39% of dairy cattle veterinarians in the UK indicated occasional use of NSAIDs in calves following dystocia 66% reported using NSAIDs in some cows following dystocia Decisions to use analgesia to the cow and/or calf are often influenced by cost The reported use of analgesics in either cows or calves is probably greater than the actual rate of use (Huxley and Whay, 2006 ; Hudson et al., 2008; Laven et al., 2012) Methods to Improve Vitality Limited usage of NSAIDs may be due to the lack of scientific evidence of the benefits following dystocia It is clear that the physiological effects of dystocia reduce newborn calf vitality It is uncertain whether there is pain, since this cannot be directly measured NSAIDs may improve the time to standing, increase colostrum uptake, improve health, overall calf survival and welfare (Molony and Kent, 1997; Mee, 2008; Laven et al., 2012) Outline Dystocia: effects on the calf Causes of reduced newborn vitality Consequences of reduced vitality Vitality scoring Methods to improve calf vitality Study results Meloxicam for Calf Vitality: Field Trial A field study to evaluate of the efficacy of meloxicam NSAID therapy for improving newborn calf vigor, success of passive transfer, general health and performance Objectives: To evaluate the usefulness of pain management therapy for excessive trauma and enhancement of newborn calf vigor using meloxicam injectable solution. To determine if newborn calf vigor is associated with calving difficulty, as well as subsequent health and performance. Metacam® Non-steroidal anti-inflammatory drug (NSAID) Anti-inflammatory, anti-exudative, analgesic and fever reducing properties Approved for use in calves in Canada (20mg/mL) As an aid in improving appetite and weight gains when administered at the onset of diarrhea (Todd et al., 2010) For relief of pain following de-budding of horn buds in calves less than 3 months of age (Heinrich et al., 2010) For the symptomatic treatment of inflammation and pain associated with acute clinical mastitis (Fitzpatrick et al., 2013) Study Methods Each calf was scored at birth using calf VIGOR score sheet & a birth record was completed by the farm staff Calves were randomly assigned to receive either 1.0 cc meloxicam or placebo solution s/c by farm staff Weekly visits to herds Study Methods Blood was collected from all calves 1-7 days of age to measure success of passive transfer Assess for temperature, weight, height and health scores up to 3 weeks old and again at weaning In a subset of calves: Blood-gas analysis <2h of age 2nd VIGOR score 1-6h post Tx Suckling response Calf VIGOR Score - Results 9 8 Vigor Score 7 6 5 4 3 2 1 0 Unobserved Observed, but Easy pull unassisted Calving Difficulty Hard pull Calf VIGOR Score - Results Assistance at Calving Coefficient 95% Confidence Interval lower limit upper limit P-Value Visual Appearance Meconium staining Tongue/head 0.042 0.21 -0.047 0.11 0.13 0.30 0.35 <0.001 Initiation of Movement Calf movement 0.17 0.025 0.32 0.02 General Responsiveness Straw in nasal cavity Tongue pinch Eye reflex 0.21 0.16 0.043 0.10 0.062 0.0068 0.31 0.27 0.093 <0.001 0.002 0.09 Oxygenation Mucous membrane colour 0.16 Tongue length 0.12 0.055 -0.023 0.25 0.25 0.002 0.10 Rates Heart rate Respiration rate 0.061 0.084 0.31 0.29 0.003 <0.001 0.18 0.19 Study Results 7.38 7.36 Predicted pH at <2h 7.34 7.32 7.3 7.28 Excellent Vigor 7.26 Moderate Vigor 7.24 Low Vigor 7.22 7.2 7.18 7.16 57.1 68.55 pC02 at <2h 78.3 Study Results Effect of experimental treatment on VIGOR score n Meloxicam (Mean±SD) Placebo (Mean±SD) P-value 61 6.39±2.71 5.06±2.47 0.41 *Post-Tx VIGOR Score 61 4.71±2.34 5.12±2.37 0.091 Difference -1.68±1.94 0.06±2.66 0.023 Pre-Tx VIGOR Score 61 *1-6 h post treatment Calves who received Metacam® following birth had a significant improvement in VIGOR score from the 1st to the 2nd assessment than placebo treated calves, controlling for farm and the time after birth of VIGOR assessment (P=0.023) Study Results 9 Serum Total Protein (g/dL) 8 7 6 5 4 3 2 1 0 0 5 10 VIGOR Score 15 20 VIGOR score was not significantly associated with STP, after controlling for farm and age at blood sampling for STP (β=-0.15; 95% CI=-0.55 to 0.25; P=0.46) Study Results Effect of treatment on suckling reflex Meloxicam (Mean±SD) Placebo (Mean±SD) P-value n Finger Test (1-3) *Pre-treatment †Post-treatment 19 15 1.63±0.60 2.19±0.68 1.53±0.52 1.60±0.74 0.60 0.024 Difference 0.75±0.79 0.067±0.59 0.014 0.57±0.63 0.67±0.51 0.67 0.67±0.65 -0.0013±0.46 0.11 0.072 Manometer Suckling Pressure (psi) *Pre-treatment †Post-treatment Difference *1-2 h from birth 0.99±1.08 0.41±0.77 †1-6 h post treatment Study Results Average Milk Intake (L/d) Coefficient 95% Confidence Interval lower limit Treatment Metacam® Placebo P-value upper limit 0.03 ref 0.0016 - 0.057 - 0.039 - -0.0093 -0.016 -0.0034 0.002 Average # of Rewarded Visits to Milk Feeder 2 ref - - - 4 0.080 0.050 0.11 <0.001 5 0.055 0.0093 0.10 0.019 2 0.61 0.53 0.69 <0.001 1 ref - - - Total 8 Week Health Score Farm Study Results 7 Milk Intake (L/d) 6.5 6 5.5 5 4.5 4 N=124 Meloxicam N=124 Placebo Study Results 5 Weight Gain in Week 1 (kg) 4.5 4 3.5 n=63 3 n=166 2.5 2 n=92 Metacam n=150 Placebo n=55 1.5 n=100 1 0.5 0 Observed but Unassisted Unobserved Calving Assistance Assisted Study Results Total Health Score Treatment Metacam® Placebo Coefficient 95% Confidence Interval lower limit upper limit P-value -0.36 ref -0.64 - -0.073 - 0.014 - Season of Birth Spring Summer Winter Fall 1.21 -0.16 1.40 ref 0.082 -0.57 1.06 - 2.34 0.25 1.74 - 0.036 0.44 <0.001 - Time colostrum fed after birth <2hrs 3-4 h 5-6 h 7-12 h ref -0.15 -0.27 1.20 -0.54 -0.98 0.21 0.25 0.45 2.10 0.43 0.46 0.018 Outline Dystocia: effects on the calf Causes of reduced newborn vitality Consequences of reduced vitality Vitality scoring Methods to improve calf vitality Study results Biomarker for calf vitality and long-term health Haptoglobin Major bovine acute phase protein Produced in response to a bacterial or viral challenge Works by binding free hemoglobin in plasma to reduce the pro-oxidative and pro-inflammatory stress associated with hemolysis Can be used as a quantifiable indicator of tissue damage, including infection, neoplasia or trauma (Gruys et al., 1994; Murata et al., 2004; Petersen et al., 2004) Haptoglobin – Indicator of Inflammation at calving Mean Haptoglobin (g/L) 0.25 0.2 0.15 0.1 0.05 0 Observed but Unobserved Unassisted (N=533) (N=146) Easy Pull (N=356) Hard Pull (N=44) Assistance at Birth Malpresented Surgery (N=23) (N=7) Haptoglobin – Indicator of Health P<0.001, accounting for farm as a random effect Mean Haptoglobin (g/L) 0.25 0.2 0.15 0.1 0.05 0 0 (N=186) 1 (N=629) 2 3 (N=227) (N=65) Event 1 Health Score ≥4 (N=43) Haptoglobin – Predictor of Health P<0.05, accounting for farm as a random effect 0.18 Mean Haptoglobin (g/L) 0.16 0.14 0.12 0.1 0.08 0.06 0.04 0.02 0 No (N=890) Yes (N=312) Treated for BRD in 1st 4 Months Haptoglobin – Predictor of Health P<0.001, accounting for farm as a random effect Mean Haptoglobin (g/L) 0.25 0.2 0.15 0.1 0.05 0 No (N=1070) Yes (N=132) Treated for Diarrhea in the 1st 4 Months Haptoglobin –Predictor of Mortality P=0.001, accounting for farm as a random effect Mean Haptoglobin (g/L) 0.25 0.2 0.15 0.1 0.05 0 No (N=1158) Yes (N=55) Dead Haptoglobin –Predictor of Mortality Mortality Odds Ratio Hp (g/L) 4.29 95% CI P-value Lower Limit Upper Limit 1.07 17.18 0.04 Passive Transfer Pass (>5.4g/dl) Intermediate (5.2-5.4g/dl) Fail (<5.2g/dl) Ref 0.43 2.22 0.13 1.2 1.47 4.11 0.18 0.01 Treated for BRD once or more during study period No Yes Ref 2.77 1.56 4.92 0.001 Treated for scours once or more during study period No Ref Yes 3.26 1.72 6.18 <0.001 Treated for other disease once or more during the study period No Yes 1 4.22 0.049 Ref 2.06 Conclusions Effects of dystocia: pain, fractures, trauma, hypoxia & impaired thermoregulation lead to reduced calf vigor & failure of passive transfer Newborn calf vitality assessed through modified APGAR scores are well correlated to the degree of calving assistance using practical on farm measures NSAIDs following dystocia my improve calf vitality, health and growth Haptoglobin may be a biomarker for inflammation at calving and subsequent risk of morbidity and mortality Acknowledgements Advisory committee: Ken Leslie – Professor Emeritus Todd Duffield – Professor, Dairy Health Management Derek Haley – Assistant Professor, Animal Welfare David Pearl – Associate Professor, Epidemiology Doug Veira – Senior Scientist, AAFC, Agassiz BC Kathleen Shore – Nutritionist, Grober/New-Life Mills Funding & support provided by: Questions?
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