Blood Biomarkers Could Transform Diagnosis of Sick Newborn Foals

Every horse breeder dreads it: a newborn foal that seems healthy at first glance but fails to nurse, wanders aimlessly, or worse, slips into seizures within hours of birth. Neonatal maladjustment syndrome, or NMS, is one of the most perplexing conditions veterinarians face in equine medicine, striking otherwise normal foals with neurological disturbances that range from a simple lack of the nursing reflex to full-blown seizures and coma. Now, researchers at North Carolina State University have identified a suite of blood-based markers that could finally give clinicians a reliable laboratory tool for diagnosing this frustrating disease, and perhaps even point the way toward new therapies.

The study, published in the Journal of Veterinary Internal Medicine, examined how concentrations of specific neuroproteins and neurosteroids in blood serum differ between healthy foals, foals with NMS, and foals hospitalized for other illnesses such as sepsis or diarrhea. The findings suggest that molecules long used to diagnose neurological disease in humans, including conditions like Parkinson’s disease and neonatal encephalopathy, may also hold diagnostic value in newborn horses, a species in which they had never been systematically studied before.

Neonatal maladjustment syndrome is notoriously difficult to pin down. Foals with the condition typically develop neurological signs at birth or within the first 24 to 48 hours of life, according to Katarzyna Dembek, associate professor of clinical sciences at NC State and corresponding author of the research. When veterinarians can rule out physical brain damage caused by a difficult foaling, many affected foals recover fully with supportive care. But the underlying biological mechanism of the disease has remained stubbornly obscure, leaving clinicians without an objective diagnostic test. Diagnosis currently rests on clinical observation, and because the signs overlap with other neonatal diseases, distinguishing NMS from sepsis or prematurity can be challenging.

The clinical picture is variable. The most common sign is the absence of a normal nursing reflex, which sounds deceptively minor but is critical to a foal’s survival in its first hours of life. On the severe end of the spectrum, foals can seize and become comatose. Treatment is largely supportive: owners and veterinarians use feeding tubes or patiently teach the foal to drink from a bucket until normal nursing behavior returns, while more severe cases require intensive hospital care. Because most foals eventually recover, a rapid and reliable diagnostic test would help veterinarians focus resources appropriately and give owners a clearer prognosis.

Dembek’s team focused on three neuroproteins with established roles in human neurology. Brain-derived neurotrophic factor, or BDNF, is a growth factor that supports the survival and function of neurons. Glial-fibrillary-acidic protein, or GFAP, and the astrocytic protein S100B are both produced by astrocytes, the star-shaped support cells of the nervous system that maintain the chemical environment of the brain. In human medicine, these proteins serve as biomarkers of brain injury and neurological disease, rising or falling in characteristic patterns after damage. Their behavior in newborn foals, however, had never been characterized until now.

The researchers also measured a group of neurosteroids known as pregnanes, metabolites of the pregnancy hormone progesterone that are produced in the brain and can influence neuronal function. Previous work has detected high levels of these compounds in the brains of both normal foals and foals with NMS, and the study shed light on a crucial difference between the two. In healthy foals, concentrations of progesterone-derived steroids are high at birth but fall rapidly, becoming unmeasurable within 24 to 48 hours. Foals with neurological signs, by contrast, retain high concentrations for days, a persistence that the team used to help confirm NMS diagnoses in the study population.

The study design was prospective and longitudinal, following 72 foals in total: 14 healthy controls and 58 hospitalized foals under seven days of age. Among the hospitalized group, 19 were diagnosed with NMS, while the remainder presented with other diseases. Blood serum and plasma samples were collected at admission and again at days one and two of hospitalization, with biomarker concentrations measured using enzyme-linked immunosorbent assays and single-molecule-array technology. Of the 58 hospitalized foals, 48 survived, giving the researchers outcome data to correlate with the biomarker measurements.

The results revealed distinct and informative patterns. Pregnane concentrations remained significantly higher in NMS foals compared with both healthy foals and foals sick from other causes throughout the first 48 hours of hospitalization. For the neuroproteins, the picture was more nuanced. BDNF concentrations dropped over the first day of hospitalization in NMS foals, falling from a baseline median of 3.0 picograms per milliliter to 2.0 picograms per milliliter by 24 hours. Serum S100B was notably higher in septic foals that also had NMS, at 435.3 nanograms per milliliter on admission, compared with 238.9 nanograms per milliliter in septic foals without NMS. Meanwhile, GFAP concentrations were lower in both NMS foals and other sick foals than in healthy controls, a pattern that may reflect the complex physiology of the neonatal brain under stress.

The practical implications of these findings extend beyond NMS itself. According to Dembek, the central takeaway is that pregnanes and the neuroproteins, particularly BDNF and S100B, could serve as biomarkers not only of neonatal maladjustment syndrome but also of prematurity and sepsis, the leading threats to newborn foals. A blood test capable of helping clinicians distinguish between these overlapping conditions at admission would represent a meaningful advance for equine neonatal intensive care, where early, accurate decisions about treatment can determine whether a foal survives its first week of life.

The researchers caution that further work is needed before these biomarkers appear in routine clinical practice. Establishing practical applications for S100B and BDNF in veterinary settings will require additional studies to fully understand the dynamics of these molecules over time and across disease states. Still, the study marks the first systematic characterization of neuroprotein and neurosteroid profiles in foals with neurological signs, and it was supported by the Morris Animal Foundation. The research team was led by first author Javier Perez, a former NC State resident now at Veterinary Associates Equine in New Zealand, and included Kinnidy Coley of the ASPCA Adoption Center in New York, David Wong of Iowa State University, and Nimet Browne and Myriah Albrecht of the Hagyard Equine Medical Institute. For breeders and veterinarians alike, the prospect of a simple blood test to unravel the mystery of the dummy foal represents a promising step toward faster diagnosis and better outcomes.

Subject of Research: Blood neuroprotein and neurosteroid biomarkers for diagnosing neonatal maladjustment syndrome in newborn foals

Article Title: Neuroproteins are potential diagnostic tool for sick foals

Article References: Neuroproteins are potential diagnostic tool for sick foals. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: neonatal maladjustment syndrome, foals, biomarkers, neuroproteins, BDNF, S100B, GFAP, neurosteroids, pregnanes, equine medicine, veterinary diagnostics, sepsis