Placental abnormalities, treatments, pregnancy outcome, and subsequent fertility

The decision to aggressively monitor a pregnancy with preventive ultrasound and hormonal studies will primarily be an economic one and to some degree what resources are available to you. This article makes a strong argument for such preventive work when it is economically feasible and experienced ultrasonographers are available.
DrO

Occurrence of ultrasonographic assessed placental abnormalities, treatments, pregnancy outcome, and subsequent fertility on a large warmblood stud farm: a retrospective field study
J Equine Vet Sci. 2024 Apr 30:105076. doi: 10.1016/j.jevs.2024.105076. Online ahead of print.
Authors
J Sielhorst 1 , K Koether 2 , N Volkmann 3 , M Blanco 4 , R Vicioso 4 , S Baade 5 , N Kemper 3 , A M de Mestre 6 , H Sieme 5
Affiliations

1 Clinic for Horses – Unit for Reproductive Medicine, University of Veterinary Medicine Hannover, Foundation, Buenteweg 15, 30559 Hanover, Germany; ReproTraining, Rolandstrasse 62, 33415 Verl, Germany. Electronic address: jutta.sielhorst@reprotraining.de.
2 Clinic for Horses – Unit for Reproductive Medicine, University of Veterinary Medicine Hannover, Foundation, Buenteweg 15, 30559 Hanover, Germany; Lewitz Stud, Lewitzhof, 19306 Neustadt-Glewe, Germany.
3 Institute for Animal Hygiene, Animal Welfare and Farm Animal Behavior, University of Veterinary Medicine Hannover, Foundation, Bischofsholer Damm 15, 30173 Hanover, Germany.
4 Lewitz Stud, Lewitzhof, 19306 Neustadt-Glewe, Germany.
5 Clinic for Horses – Unit for Reproductive Medicine, University of Veterinary Medicine Hannover, Foundation, Buenteweg 15, 30559 Hanover, Germany.
6 Cornell Baker Institute for Animal Health, Cornell Department of Biomedical Sciences, Equine Pregnancy Laboratory, 235 Hungerford Hill Road, Ithaca, New York 14853, USA.

PMID: 38697370
DOI: 10.1016/j.jevs.2024.105076

Highlights

• analysis of incidence of ultrasonographic assessed placental abnormalities (UPA)
• description of severity, treatments and effects on outcome and subsequent fertility
• UPA was diagnosed in 4.2% (n=177/4192) of pregnant mares
• overall abortion rate was 9.6 % of treated UPA
• early detection and treatment of UPA saved high-risk pregnancies in >90% of cases

Abstract
Little is known about the incidence and outcome of high-risk pregnancies in equine practice and clinical studies on spontaneous occurring placentitis cases and treatments are missing. Therefore, the aims of this retrospective field study were to (1) describe the incidence and severity of ultrasonographic assessed placental abnormalities (UPA) in 4,192 pregnancies on a large commercial warmblood stud farm in 2017 – 2019 and (2) characterize these UPA cases and their pregnancy outcome. UPA severity (Placental abnormality score (PSc) 1-3; low to high), nine treatment regimens (TM1-9) used in UPA cases and treatment duration as well as subsequent fertility were analyzed in the group of UPA mares. The proportion of pregnancies affected by UPA was 4.2% (n=177/4192). Placental abnormality severity was scored as PSc1 (51.4%), PSc2 (32.8%) and PSc3 (15.8%). The generalized mixed model revealed PSc was affected by mare age and mare status (own pregnancy (OP) or embryo transfer recipient (ER)) (P=0.035) with ER mares having increased PSc compared with mares having their own pregnancy. Abortion occurred in 17/177 (9.6 %) UPA pregnancies. Overall, at the end of the next season, 61.1% of UPA mares were pregnant, 32.0% barren, and 6.9% open (n=175). Pregnancy was established in 62/91(68.1%) of mares with PSc1, 31/58 (53.4%) with PSc2 and 14/26 (53.8%) with PSc3. Most pregnancies were achieved in the first 81/107 (75.7%) or second 18/107 (16.8%) inseminated cycle. In conclusion, early detection and treatment of ultrasonographic assessed placental abnormalities can save high-risk pregnancies in > 90% of cases with a satisfying subsequent fertility.

Introduction
Placentitis is among the leading infectious causes of abortion in the mare. It is assumed that placentitis is affecting approximately 3-7 % of pregnancies worldwide. However, data about the incidence and outcome of placentitis in the field is limited [1]. In North America, Australia, Brazil, France and Germany 10-34 % of abortions, stillbirth and perinatal losses examined by a pathologist have been reported to be caused by placentitis [[2], [3], [4], [5], [6], [7], [8], [9]]. However, in the United Kingdom umbilical cord pathology is the leading cause of abortion [10] and in a recent Danish study umbilical cord torsion accounted for the highest prevalence of abortions (37/72, 51 %) [11]. Infectious placentitis was diagnosed in 10.3% (n = 12) of pregnancy loss cases, with a population incidence risk of 0.3% in a large-scale UK survey, equating to 0.3 cases per 100 Day 70 pregnancies [12].

Early detection of placentitis and management to prevent pregnancy loss are essential in equine practice. Some practitioners still question the intensive management and the chance to receive a healthy, successful athlete from a mare which suffered placentitis. However, a study reported that racing performance of Thoroughbreds from 190 early detected and treated placentitis pregnancies are comparable to the matched foals in the control group [13].

The most common clinical signs of placentitis in mares are premature udder development and vulvar discharge. The mammary development reflects the endocrine changes similar to the increase and drop in progestogens close to delivery when there is a general decline in the concentrations 2 or 3 days before foaling in parturient mares. Data from a clinical study showed that early detection of disease by daily examination of the mammary gland and perineal area as well as ultrasonographic monitoring allowed for early treatment of mares and an over 30% reduction in prematurely delivered foals [14]. Transrectal ultrasonography in late pregnancy allows evaluation of placental integrity, fetal viability, allantoic and amniotic fluid character and cervical dimensions. Measuring the combined thickness of the uterus and placenta (CTUP) at the cervical star region has been used as the major diagnostic tool to assess placental integrity in the last two decades [15,16]. However, one study could not find correlations between CTUP and histo-pathological diagnosed ascending placentitis in 333 mares [17]. A single evaluation of Thoroughbred mares in mid-gestation (day 84–232) was not sufficient to foresee placental failure and impending abortion; however, in that study the odds ratio to have an abortion for mares with free floating particles in placental fluids was 6.3 times higher than for mares without increased echogenity[18]. Although the assumption persists in equine practice that an increased CTUP correlates with ascending placentitis it is questionable if these ultrasonographic assessed placental abnormalities (UPA) are limited to infectious disease or can be caused by different pathophysiology e.g. abnormalities in placental blood flow or degenerative changes in the mare’s endometrium leading to placental insufficiency. The limitation in sensitivity and specificity of clinical and ultrasonographic parameters in rapid diagnosis of equine placentitis have led to evaluation of laboratory-based tests to improve diagnosis. In recent studies the focus lays on hormonal assays [[19], [20], [21], [22]] and biomarkers [[22], [23], [24], [25], [26], [27], [28]]. Identifying non-invasive sampling procedures and assays to predict natural occurring high-risk pregnancy is the aim of on-going research to support an objective and effective detection of mares at risk for pregnancy loss.

The placentitis treatment strategy is aimed at controlling the infection, reducing the inflammation, and promoting myometrial quiescence. Experimentally induced placentitis studies support a combined therapy. Common treatments include antibiotics [[29], [30], [31]], non-steroidal anti-inflammatory drugs [32], pentoxifylline [33,34] and progestins [34]. Treated mares should be evaluated on a regular base to ensure that the fetus has not died in utero. Based on current available evidence, the length of antibiotic, non-steroidal and altrenogest treatment is controversial.

Despite intensive research in the field of equine placentitis, some questions are remaining including the incidence of placentitis in other breeds (including Warmbloods) and geographic areas. Further, questions remain as to how key clinical parameters used in the field to measure and treat placentitis are associated with short term and long-term outcomes. The current parameters used by clinicians, in combination with high economic pressure in the breeding industry, have the potential to lead to “overdiagnosing” and “overtreating” of mares at risk. This needs to be evaluated critically due to antimicrobial stewardship and costs. Furthermore, it is still unclear to what extent experimentally induced placentitis mirrors spontaneous infections in the field and therefore if such experiments inform optimal treatment strategies in the field. As far as we know subsequent mare fertility has not been evaluated in a large population of (UPA) mares.

Therefore, the aim of this retrospective field study was to describe the incidence and severity of UPA (based on increase in CTUP with or without further clinical signs of placentitis) in a large cohort of mares on a commercial warmblood stud farm. Moreover, the study aimed to further describe treatments utilized, including their duration, in UPA cases and the association between severity, treatment and treatment duration on pregnancy outcome and to analyze subsequent fertility.

Keywords: Abortion; Equine; Fertility; Foal weight; High-risk pregnancy; Placental abnormalities; Treatment.