Review of Prognostic Studies of Neonatal Foals: Making Sense of the Noise

Estimating the prognosis of the sick neonate has profound clinical, economic, and client-relationship implications. A plethora of information is available; however, inconsistency between study location and methodology has led to disparate results, and research center diagnostic capabilities are largely unavailable in field settings. However, in some study populations readily observable parameters have been found to be good indicators of prognosis, reinforcing the utility of a comprehensive clinical examination. 

1. Introduction

Central to the viability of the equine breeding industry is live foal production. This is consistent between various locations at approximately 80% of mares bred.^1,2  Economic modeling has determined that to maintain financial viability for the individual broodmare, six foals must be produced over a 7-year period and remain viable so as to be sold at auction.³  Survival of each foal delivered is therefore critical to the health of the overall equine industry.

A number of studies have investigated the prognostic value of clinical and laboratory findings in neonatal foals at time of admission to intensive care units. From these values mathematical models have been created to assist decision making and prognosticate on survival.^{4 –7}  However, repeatability between different locations or between different groups of foals from the same location where the model was created but in different years was found to be poor. Mathematical model accuracy was lessened for conditions that developed after the initial assessment.⁷  It has been suggested that sepsis scoring should not be used to define sepsis in clinical study situations unless the score has been previously validated for the particular study center.⁸  However, when compared with a regression model derived from objective clinical data, the modified sepsis score performed favorably.⁹  

In field clinical settings utility of such prognostic models is complicated as parameters available in academic settings are likely not measurable in the field. Also, if important values are measurable, results are typically not available in a reasonable timeframe that would allow meaningful application of the information. Even with readily available information, prolonged delay in hospital referral may alter both clinical and laboratory findings sufficient to affect prognosis.¹⁰ 

2. History and Initial Evaluation

Readiness for birth of the neonatal foal is intuitively likely to have a bearing on prognosis, yet in one study prematurity or dysmaturity of the neonate (as indicated by gestational age) did not differ between survivors and nonsurvivors.⁷ Likewise, age of the neonate at admission did not affect survival.^7,11 However, duration of clinical signs prior to admission was found to significantly negatively affect outcome.⁷ In one study a 5.8-fold increase in the risk of death for each 24-hour period of delay was demonstrated.¹¹

Among physical parameters determined at the time of admission, a heart rate ≥ 70 beats per minute, a respiratory rate ≥ 60 breaths per minute, a rectal temperature greater than 99°F, a normal appearance of mucous membranes, and the ability to stand at admission positively affected survival in one study.⁷ In contradiction to these findings, in foals presented for respiratory disease the majority of clinical examination variables at initial evaluation were unassociated with case outcome.¹² With respect to septic foals, fever was found to be an inconsistent finding in one study.¹³

Maternal disease (both systemic and placental) was found to be higher among nonsurviving than surviving foals.⁷ Events at parturition, particularly dystocia, have been suggested to be associated with negative outcomes.^12,14

3. Signs of Sepsis

Signs suggestive of sepsis have been a negative prognostic indicator in many neonatal studies. Sepsis was identified as the most common problem in both survivors and nonsurvivors in one study.¹⁵ Diagnosis was assisted by sepsis scoring, this being considered more reliable that any individual parameter.⁴ Bacteremia in one study was most consistently due to Escherichia coli, although mixed infections were also found.¹⁶ Of 423 bacteremic foals in this study 254 survived, this being affected by a number of historical and clinical findings. A positive blood culture is associated with nonsurvival.¹⁷

4. Hematology and Clinical Chemistry

Hematological and clinical chemistry values have been integral in many neonatal foal prognostic models. A low segmented neutrophil count,^4,6,7,11 low total erythrocyte count,⁶ and elevated fibrinogen concentration⁶ were significant indicators of mortality in a number of studies. Immunoglobulin G (IgG) concentration also factored in a number of studies involving survival and prevention of infection.^18,19 A recent study found odds of nonsurvival increasing proportionally with lower IgG concentrations, with higher total protein associated with a decreased likelihood of low IgG, and increased albumin associated with an increased likelihood of low IgG.²⁰

Blood glucose has been shown in other species to be indicative of survival. Hyperglycemia, both degree and duration, has been associated with nonsurvival in human medicine.^21-23 Hypoglycemia also is problematic, and although critical glucose levels have not been determined, prolonged human neonatal hypoglycemia is associated with negative outcomes, both neurological and survival.²⁴ In neonatal foals, hypoglycemia has been associated variably with survival, being associated with nonsurvival in septic foals¹¹ but not overall foal admissions.⁶ Hypoglycemia at admission has been associated with sepsis, bacteremia, and the systemic inflammatory response syndrome, with blood glucose outside the range of 50 to 180 mg/dL associated with decreased survival.²⁵ In another study blood glucose > 120 mg/dL was associated with increased likelihood of survival.¹¹ It remains uncertain whether derangements in blood glucose are the cause of, or merely reflective of, the pathophysiological processes decreasing survival.

5. Lactate

Lactate is widely reported in the assessment of health and prognosis. Lactate is considered a marker of circulatory competence, with the rate of clearance predicting survival in some studies.^26,27 In human sepsis cases, serial blood lactate is considered to predict development of multiple organ failure.²⁸ In sick human neonates blood lactate elevations are associated with increased mortality, with increasing levels preceding clinical indicators of deterioration.²⁹

In neonatal foals, admission arterial blood lactate has been shown to be associated with survival and occurrence of systemic inflammatory response syndrome.³⁰ Venous blood lactate elevation, and persistent hyperlactatemia, has been shown associated with survival and severity of illness.^31,32 The highest admission lactate concentrations were present in hemorrhagic shock, sepsis, and complicated perinatal asphyxia in one study,³¹ but in younger, premature, or encephalopathic foals in another.³² Regardless of initial diagnosis, lactate is significantly increased in nonsurvivors vs survivers.¹⁷

6. Metabolic and Endocrinological Pathways

Academic studies regarding the prognosis for neonatal survival have advanced to involve variables difficult to measure at point of care in routine clinical practice. Septic nonsurvivors have been shown to have elevated arginine vasopressin and adrenocorticotrophic hormone, with a subcategory of neonates having concurrent normal to decreased cortisol implying a relative adrenal insufficiency.^33,34 Hypoperfusion of critically ill foals, with the attendant clinically evident signs of poor peripheral perfusion, has been associated with elevated levels of both arginine vasopressin and aldosterone.³⁵ Anion gap elevation and decreased venous pO₂ were also associated significantly with nonsurvival.¹⁵ Associated with sepsis in humans, plasma adrenomedullin has been shown elevated in critically ill foals but lacks the specific association with sepsis seen in other species.³⁶ [...]