Premature and immature newborn foals could experience lasting consequences from their challenging starts, affecting their health, training, and the way they cope with various kinds of stress—even if they appear normal—according to recent study results.

“There may be a subclinical issue that affects these foals at a later date, in terms of their innate responses to stressors,” said Jane Clothier, PhD, owner of Equine Healthworks, in Armidale, New South Wales, Australia.

“It’s important that breeders recognize this underlying physiological difference may only emerge later, when the horse responds poorly to environmental, health, or training pressures,” said Clothier, who carried out her work in association with the University of New England and the Commonwealth Scientific and Industrial Research Organisation (CSIRO), also in Armidale. “As a result, some horses may not be suited to their intended careers. Dysmature foals (those born full-term but still not fully mature), in particular, fly under the radar in this regard, because their weight and musculoskeletal issues appear to rapidly resolve, and then they’re believed to have ‘caught up.’ They haven’t necessarily done so.”

‘They React Differently’: Investigating a Hunch About Former Preemies

As an equine musculoskeletal therapist, Clothier had noticed differences in the health and behavior of some of her adult patients that had been born premature, she said. For instance, it appeared these horses often reacted differently when touched.

“It was different to a pain response, which usually comes down as an issue is resolved,” she explained. “Every time I visited these horses, it was like the first time all over again. Then I learned that humans born prematurely can have a lasting difficulty in differentiating between harmless and harmful touch and be more sensitive … generally. That’s when I began to get really interested.”

Curious about whether those horses might still suffer the consequences of a difficult start in life, she began investigating scientific studies and found that certain endocrinological disorders are known problems in premature humans and animals alike.

A specific issue seems to be related to poor development of the hypothalamic-pituitary-adrenal (HPA) axis. These three glands are found in the hypothalamus, a part of the brain that operates the autonomic nervous system, which controls body processes that individuals do not consciously direct. The HPA axis is a complex set of interactions among these three glands that regulates the secretion of cortisol, the “stress hormone” that spreads throughout the body, leading to the classic physiological features of stress.

In horses the HPA rapidly develops toward maturity at a very late stage of fetal growth—essentially over the last five days before birth, Clothier said. That could make horses particularly vulnerable to HPA-related effects of immaturity, as even a matter of days in this species can make a big difference, she explained.

Dramatically Higher—or Lower—Cortisol Responses to ACTH

To test their theories Clothier and her fellow researchers studied 10 adult horses, ranging from 4 to 8 years old, that had been born either premature—younger than 315 days of gestation—or full-term but with clear signs of immaturity, including weakness, small size, and poor suckling. All the horses were still living with their breeder, and none had been hospitalized as foals. For the sake of comparison, the scientists also selected 12 closely related horses living on the same farm and, in one case, a similarly bred horse within the same area that essentially matched the age, sex, and breed of the case horse.

Clothier and her teammates injected all the case horses and seven of the control horses with a low dose (0.1 ug/kg) of synthetic adrenocorticotropic hormone (ACTH) to stimulate cortisol release. Then they took saliva samples from all the horses immediately and every 30 minutes for the next two and a half hours.

Without the ACTH stimulation, all the horses had about the same basic cortisol level in their saliva, she said.

But after the injection, cortisol rates changed dramatically. The five control horses that did not receive the injection continued to maintain their basic cortisol levels, and the other seven control horses had a gradual rise in cortisol over the next two and a half hours—as expected.

But the horses that had been born premature or dysmature responded significantly different than the controls, said Clothier. Some of the horses’ cortisol rates shot up higher than the controls; others rose at a remarkably lower rate.

“I’d expected elevated responses to be present, as that’s what I was associating with the reactive behavior we sometimes see,” she said. “But I was surprised that some horses had adrenocortical responses so depressed as to be nearly nonexistent.”

Surviving dysmature and premature foals in hospital settings often have very high or very low cortisol responses to ACTH stimulation in the days and weeks after birth, she said. But some studies had indicated these issues would resolve over time.

That’s not what this new study appears to show, however, said Clothier. “These results suggest that the effects of an underdeveloped adrenal cortex can persist for a long time on a subclinical level,” she said.

Managing the Dysmature Foal’s Adult Life Challenges

While this was only a pilot study involving a handful of horses, the findings point to long-term consequences of immaturity at birth that merit owners’ attention, said Clothier. “Not much is established yet in terms of equine research but, speaking subjectively, some of these affected horses are having a really hard time in life because their responses to stressors are so different,” she said.

That’s worth keeping in mind for breeders as they raise, train, and market their horses, she said. It’s also important knowledge for potential buyers, who should look well beyond pedigrees and the farm’s history.

“Some horses still show signs of their gestational deficit on a musculoskeletal level—especially the former prematures,” she said. “I’d advise buyers to specifically inquire about the foaling background and how long the gestation was, with first week-of-life photos if possible. Viewed alongside a prepurchase examination report, it may answer a few questions.”

The current study was part of a much larger project looking into what Clothier refers to as “a wider syndrome of effects linked to immaturity at birth,” she explained.

“My research only scratched the surface, yet I found strong associations with pathologies and conditions (such as equine metabolic syndrome) that are already published in scientific literature,” she said. “I really hope some longitudinal studies are set up to investigate this area further.”

The study, “Perinatal Stress in Immature Foals May Lead to Subclinical Adrenocortical Dysregulation in Adult Horses: Pilot Study,” appeared in the April 2022 issue of the Journal of Equine Veterinary Science.