This article originally appeared in the Winter 2025 issue of EquiManagement. Sign up here for a FREE subscription to EquiManagement’s quarterly digital or print magazine and any special issues.
Equine placentitis is one of the most common causes of late-term (8-10 months gestation) pregnancy loss in horses, contributing to 20-30% of pregnancy losses worldwide. Placentitis can take one of three forms:
- Ascending from bacterial or fungal contamination.
- Diffuse or multifocal placentitis from hematogenous spread of infection elsewhere in the body.
- Nocardioform (focal mucoid) placentitis identified in Kentucky. It’s sometimes associated with Amycolatopsis spp. and/or Crossiella equi infection, but the cause remains poorly understood.
The most commonly diagnosed form is ascending placentitis due to bacterial contamination of the caudal reproductive tract—infection ascends into the vagina and cervix and into the chorioallantois to adversely affect the fetus. One of the issues with ascending placentitis is veterinarians typically don’t identify it until late in the disease process. At that point, the mare might prematurely develop mammary enlargement and/or lactation. On rare occasions, she might have a purulent discharge from the vagina that goes unrecognized as tail hairs sweep it up. Routine bloodwork is frequently unremarkable because the infection is localized to the fetal tissues.
Diagnosing and Treating Ascending Placentitis
At the 2025 VMX meeting in Orlando, Theresa Beachler, DVM, PhD, DACT, of Iowa State University, presented on causes, diagnosis, and treatment of ascending placentitis. Mares with poor perineal conformation are most at risk. A careful examination might reveal that the vulva is tilted more than 20 degrees from vertical and/or the vulvar lips do not oppose well. These mares are at risk of fecal contamination of the perineal area into the vaginal vault. Preventive techniques to counter poor perineal conformation include a Caslick’s vulvoplasty or a Gadd’s procedure for refractory cases.
Poor perineal conformation might cause a mare to windsuck, which veterinarians can confirm by parting the vulvar lips to see if air aspirates into the vagina. Abnormal vulvar position can lead to urine pooling or fecal contamination of the caudal reproductive tract. Other internal problems might include a poor vestibulovaginal seal between the vagina and the vestibule or cervical incompetence.
Common bacteria to invade the reproductive tract include Streptococcus equi subsp. zooepidemicus, E. coli, Klebsiella pneumoniae, and Pseudomonas. These bacteria can colonize and replicate in the allantoic cavity and umbilicus, and the fetus might swallow or inhale amniotic fluid. With infection, the fetus develops sepsis. A subsequent rise in inflammatory cytokines and prostaglandins increases the mare’s uterine contractility while modifying the hormonal profile and activating the hypothalamus-pituitary-adrenal axis. As the fetus becomes compromised, a pre-term rise or rapid decline in progestins and reduced estrogen levels can develop. (A mare with a normal pregnancy should have estrogen levels over 500 mg/ml.) At this point in the process, an abortion or the premature delivery of a severely compromised and sick foal will occur.
Beachler reported that with placentitis, everything starts at the cervix. Following abortion or birth, the placenta will be edematous, thick, and necrotic at the area of the cervical star. In cases of suspect placentitis, veterinarians can use transrectal ultrasound to measure the combined thickness of the uterine endometrium and placenta (CTUP). Normal CTUP measurements are as follows:
- Days 271-300 should be < 7 mm.
- Days 301-330 should be < 10 mm.
- Past Day 330 should be < 12 mm.
The cervix should not have defects visible on ultrasound and should be a solid structure with fine striations, without any surrounding air or mucus.
Another parameter for assessing fetal well-being is the fetal heart rate obtainable via transabdominal ultrasound. Because the process of rectal palpation and diagnostic ultrasound are stimulatory, the fetus is usually active with a corresponding heart rate. In addition, color Doppler can help determine fetal viability by measuring blood flow in the fetal vessels and umbilical cord.
Research is underway to identify early biomarkers, because once changes are evident on transrectal ultrasound, the mare is far along in the disease process. Potential biomarkers include a severe increase in the progesterone metabolite 20α-DHP as well as a low ratio of comprehensive hormone panel to 20α-DHP. Serum amyloid A, lactate, haptoglobin, and alpha-fetoprotein are also being evaluated. Researchers are investigating metabolomics and proteomics for gene alterations, transcription and protein expression, and metabolism. Another biomarker—eIL-1-β—can also be significantly elevated with compromised foals, but it might not be specific for placentitis.
Beachler urged vets to follow the Three Pillars of Treatment—antimicrobials, anti-inflammatories, and tocolytics—at least until the mare delivers.
1. Antimicrobial drugs. Ideally, first obtain culture and sensitivity from vaginal or cervical discharge.
- a. Systemic trimethoprim/sulfa methoxazole (TMS) and/or procaine penicillin G (PPG) + gentamycin (pen/gen). TMS is only effective in about 49% of cases.
- b. Doxycycline might have a role.
- c. Ceftiofur achieves insufficient concentration in allantoic fluids.
- d. Local antibiotics with transcervical administration of pen/gen: In one study of intrauterine PPG + gentamicin given between Days 280 and 295 of gestation in normal mares, all foaled without complications 12-58 days after the antibiotic infusion. The combination antibiotic was administered at a mean gestational age of 322.7 (+/- 12.7 days). Intrauterine infusion during pregnancy needs further study for safety and efficacy.
2. Anti-inflammatory medications to downregulate the inflammatory cascade and block the production of cytokines and prostaglandins:
- a. Flunixin meglumine.
- b. Firocoxib.
- c. Aspirin might help improve uterine blood flow, act as an anti-platelet drug, and inhibit COX-1 and -2 to some degree.
- d. Pentoxifylline.
- e. Dexamethasone.
- f. Estradiol cypionate to help with placental blood flow.
3. Tocolytics such as altrenogest.
Preventing Abortion in Affected Mares
At a 2025 Gluck Center Equine Veterinary Seminar in Kentucky, Hossam El-Sheikh Ali, DVM, MVSC, PhD, DACT, of the Martin-Gatton College of Agriculture, Food and Environment, said studies have shown that just 1 million bacteria are enough to induce placentitis. All efforts to prevent contamination of the caudal reproductive tract should be taken prior to breeding.
Ali suggested methods to encourage myometrial quiescence and help mitigate abortion in mares with placentitis. Besides altrenogest, he said isoxsuprene or clenbuterol have been considered for their effects on relaxing smooth muscle. However, he reported a lack of evidence to support using them to treat placentitis.
Studies suggest selective COX-2 inhibitors like firocoxib could slow myometrial activation. Also, an antagonist in humans is being investigated in horses for its Toll-like receptor 4 inhibition of inflammation from lipopolysaccharide-induced, pre-term uterine contractility. Amitriptyline is both a receptor 2 and 4 antagonist.
Ali said uterine quiescence depends on progestin availability, which inflammation alters. However, he noted that progestin supplementation might not be effective for treating placentitis because the condition is associated with functional withdrawal of progestins in the myometrium. He suggested a combination of treatments based on favorable study results: “Trimethoprim-sulfamethoxazole, altrenogest, and firocoxib suppress inflammatory cytokines and prostaglandins in amniotic fluid and improve foal survival in mares with placentitis.”
References
- Macpherson ML, et al. Evidence for anti-inflammatory effects of firocoxib administered to mares with experimentally induced placentitis. Am J Reprod Immuno 2021.
- Adams-Waldorf KM, et al. Pretreatment with toll-like receptor 4 antagonist inhibits lipopolysaccharide-induced preterm uterine contractility, cytokines, and prostaglandins in rhesus monkeys. Reprod Sci 2008.
- Varner J, et al. Effects of Firocoxib, Trimethoprim Sulfamethoxazole, and Altrenogest on Inflammation and Foal Survival After Administration to Mares with Experimentally-Induced Placentitis. AAEP Proceedings 2019.
Related Reading
- Managing Pregnant Mares From Conception to Parturition
- Diagnosing Causes of Equine Abortion
- Daily Vet Life: Breeding an Older Barren Mare
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