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BackgroundWarmblood Fragile Foal Syndrome Type 1 (WFFS) is an autosomal recessive disorder reported previously only in warmbloods and thought to be caused by a variant in the gene procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 (PLOD1, c.2032G>A, p.Gly678Arg). Given the presentation of this Thoroughbred case, we hypothesised that a similar genetic mechanism caused this phenotype.ObjectivesTo describe the pathological and genetic findings on a foal presenting to a veterinary practice in the UK with skin lesions similar to other Ehlers-Danlos Syndromes, including those documented for warmbloods with WFFS.Study designA single case report describing a genetic investigation.MethodsA Thoroughbred foal presenting as dystocia was euthanised for multiple skin lesions and developmental abnormalities. DNA extracted from the foal was tested for the PLOD1 variant (c.2032G>A, p.Gly678Arg) using the commercially available assay. To confirm causality and further interrogate potential novel causes of Ehlers-Danlos Syndrome, 1799 functional candidate genes, including PLOD1, were analysed using whole genome sequencing data generated from DNA extracted from the foal's muscle. These data were compared to 34 control samples from at least 11 other breeds. Variants were prioritised for further evaluation based on predicted impact on protein function.ResultsPost-mortem evaluation concluded that this foal suffered from a condition of collagen dysplasia. The foal was homozygous for the c.2032G>A PLOD1 variant. Only two other missense variants identified from whole genome sequencing data were also computationally predicted to be deleterious to protein function, (NPHP3 c.1253T>C, p.Leu418Pro, EPDR1 c.154G>C, p.Glu52Gln). Neither of these genes have been linked to similar phenotypes, or Ehlers-Danlos Syndrome in humans or other species and thus further investigation of these variants as the cause of EDS was not warranted.Main limitationsThis study is a single case report in the Thoroughbred with no additional cases from this breed yet identified to replicate this finding.ConclusionsGiven the clinical presentation similar to WFFS, homozygosity for the PLOD1 variant, and absence of another more plausible causal variant from the WGS experiment, we conclude that PLOD1 c.2032G>A is the likely cause of this foal's condition. This is the first documented evidence of fragile foal syndrome caused by the PLOD1 variant in a breed outside of warmbloods, the Thoroughbred. We therefore recommend a change in the name of this disorder to fragile foal syndrome type 1 (FFS) and utilisation of genetic testing in Thoroughbreds to avoid producing affected foals.

Chromosomal abnormalities are a common cause of human miscarriage but rarely reported in any other species. As a result, there are currently inadequate animal models available to study this condition. Horses present one potential model since mares receive intense gynecological care. This allowed us to investigate the prevalence of chromosomal copy number aberrations in 256 products of conception (POC) in a naturally occurring model of pregnancy loss (PL). Triploidy (three haploid sets of chromosomes) was the most common aberration, found in 42% of POCs following PL over the embryonic period. Over the same period, trisomies and monosomies were identified in 11.6% of POCs and subchromosomal aberrations in 4.2%. Whole and subchromosomal aberrations involved 17 autosomes, with chromosomes 3, 4, and 20 having the highest number of aberrations. Triploid fetuses had clear gross developmental anomalies of the brain. Collectively, data demonstrate that alterations in chromosome number contribute to PL similarly in women and mares, with triploidy the dominant ploidy type over the key period of organogenesis. These findings, along with highly conserved synteny between human and horse chromosomes, similar gestation lengths, and the shared single greatest risk for PL being advancing maternal age, provide strong evidence for the first animal model to truly recapitulate many key features of human miscarriage arising due to chromosomal aberrations, with shared benefits for humans and equids. [ABSTRACT FROM AUTHOR]

Background: Excessive inbreeding increases the probability of uncovering homozygous recessive genotypes and has been associated with an increased risk of retained placenta and lower semen quality. No genomic analysis has investigated the association between inbreeding levels and pregnancy loss. Objectives: To compare genetic inbreeding coefficients (F) of naturally occurring Thoroughbred Early Pregnancy Loss (EPLs), Mid and Late term Pregnancy Loss (MLPL) and Controls. The F value was hypothesised to be higher in cases of pregnancy loss (EPLs and MLPLs) than Controls. Study design: Observational case–control study. Methods: Allantochorion and fetal DNA from EPL (n = 37, gestation age 14–65 days), MLPL (n = 94, gestational age 70 days–24 h post parturition) and Controls (n = 58) were genotyped on the Axiom Equine 670K SNP Genotyping Array. Inbreeding coefficients using Runs of Homozygosity (FROH) were calculated using PLINK software. ROHs were split into size categories to investigate the recency of inbreeding. Results: MLPLs had significantly higher median number of ROH (188 interquartile range [IQR], 180.8–197.3), length of ROH (3.10, IQR 2.93–3.33), and total number of ROH (590.8, IQR 537.3–632.3), and FROH (0.26, IQR 0.24–0.28) when compared with the Controls and the EPLs (p < 0.05). There was no significant difference in any of the inbreeding indices between the EPLs and Controls. The MLPLs had a significantly higher proportion of long (>10 Mb) ROH (2.5%, IQR 1.6–3.6) than the Controls (1.7%, IQR 0.6–2.5), p = 0.001. No unique ROHs were found in the EPL or MLPL populations. Main limitations: SNP‐array data does not allow analysis of every base in the sequence. Conclusions: This first study of the effect of genomic inbreeding levels on pregnancy loss showed that inbreeding is a contributor to MLPL, but not EPL in the UK Thoroughbred population. Mating choices remain critical, because inbreeding may predispose to MLPL by increasing the risk of homozygosity for specific lethal allele(s). [ABSTRACT FROM AUTHOR]

Background: Excessive umbilical cord length (UCL) is associated with equine pregnancy loss. However, a lack of UCL reference values makes it difficult to define excessive UCL. Further, factors associated with differences in UCL are poorly understood. Objectives: To (i) report the total, allantoic and amniotic UCL in healthy term pregnancies in Thoroughbreds, (ii) describe the relationship between gestational age and UCL, fetal weight and crown rump length (CRL) using clinically normal pregnancies (CNPs) from mares dying during gestation, and (iii) identify associations between UCL and maternal age and parity, paternal age, and fetal sex. Study design: Cross‐sectional. Methods: Data including UCLs, fetal weight, CRL and maternal age, parity, paternal age and fetal sex were taken from CNPs from Thoroughbred mares dying during gestation (n = 32), and placentas from HTPs (n = 34) in England. Correlations were assessed using Spearman's rank with significant correlations estimated by locally weighted scatter plot smoothing (LOWESS). Regression plots were fitted to highly correlated variables to further assess and quantify relationships. Differences in UCL between categorical variables were assessed using Kruskall Wallis and Mann–Whitney U tests. Results: The median total, amniotic and allantoic HTP UCLs were 53.5 cm (interquartile range [IQR] 16), 29.5 cm (IQR 7) and 25.0 cm (IQR 8) respectively. Gestational age and amniotic UCL were moderately correlated (rho = 0.53, p = 0.04), with LOWESS estimating an exponential increase followed by plateauing at around Day 200. Nonlinear associations were observed between fetal weight and gestational age and CRL (adjusted r2 = 0.98 and 0.95 respectively). A linear association was observed between gestational age and CRL: predicted CRL = −17.60 + 0.38 × gestational age, p < 0.001. Main limitations: Limited availability of CNPs from mares dying during gestation. Estimated relationships can only approximate growth. Conclusions: This study provides important UCL and fetal size reference values, which may aid in assessing abnormalities. For the first time, associations between UCL and gestational age have been described. [ABSTRACT FROM AUTHOR]

Embryonic and foetal loss remain one of the greatest challenges in equine reproductive health with 5–10% of established day 15 pregnancies and a further 5–10% of day 70 pregnancies failing to produce a viable foal. The underlying reason for these losses is variable but ultimately most cases will be attributed to pathologies of the environment of the developing embryo and later foetus, or a defect intrinsic to the embryo itself that leads to lethality at any stage of gestation right up to birth. Historically, much research has focused on the maternal endometrium, endocrine and immune responses in pregnancy and pregnancy loss, as well as infectious agents such as pathogens, and until recently very little was known about the both small and large genetic variants associated with reduced foetal viability in the horse. In this review, we first introduce key aspects of equine placental and foetal development. We then discuss incidence, risk factors and causes of pregnancy loss, with the latter focusing on genetic variants described to date that can impact equine foetal viability. Pregnancy loss is hugely problematic for the majority of mammalian species, and the horse is no exception. However, research in this area is lacking. In this review, we first provide a summary of features of equine pregnancy. We then discuss risk factors and finally delve into the complex genetic contributors to this problem. This research can help horse breeders worldwide make breeding choices and the findings may also pave the way for discoveries to aid women in their quest for successful pregnancies. [ABSTRACT FROM AUTHOR]

Background: Thoroughbred breeders aim to have foals born early in the season, but scientific evidence on the advantages for race performance is scarce and contradictory. Methods: The association between date of birth and purchase price as foal/yearling, with race performance by the end of the second and third years of life of Thoroughbreds racing in flat races in the United Kingdom (UK) and Ireland (IRE) was assessed using negative binomial and zero-inflated negative binomial models on the entire 2014-2015 UK/IRE foal crops (n = 28,282). Results: In total, 6666 and 9456 horses raced in UK/IRE flat racing by the end of their second and third years of life. Prize money and prize money per start decreased with each additional day beyond 1 January that the foal was born. Purchase price as foal and yearling was negatively associated with the number of races run, while it was positively associated with prize money and prizemoney per start by the end of the third year of life. Conclusions: Foals born early in the season had higher earnings by the end of their second and third years of life than foals born later. Differences were more marked among males than females. The most expensive horses sold as foals or yearlings ran fewer races but earned more prize money and prize money per start than less expensive horses. Results fromthis population-based analyses may informstrategies and management practices aiming to maximise horses' racing performance potential and increase financial returns. [ABSTRACT FROM AUTHOR]

Responsibility for the provision of veterinary care and services is increasingly shared between veterinary surgeons/veterinarians and registered veterinary nurses/veterinary technicians. Interprofessional education of these clinical professionals is not widespread but is growing. Understanding students' perceptions of veterinary interprofessional education and working is therefore important; however, no validated scale exists to assess this. This study aimed to create and test the psychometric properties of a 'Student perceptions of veterinary interprofessional education and work scale' (SP-VIEWS). A scale was built using scales previously validated in other contexts, plus statements informed by veterinary interprofessional research, and sent to veterinary and veterinary nursing students at six UK institutions. Exploratory Factor Analysis (EFA) on a randomly-selected half of the responses (n = 260) suggested a model with 16 items grouped within three factors: 'Benefits of learning with the other profession', 'Leadership and speaking up' and 'Teams and benefits of teamwork'. Confirmatory Factor Analysis (CFA) on the remaining 260 responses demonstrated appropriate fit based on conventional parameters, such as goodness of fit index. Overall internal consistency was good (Cronbach's alpha 0.82). CFA demonstrated that SP-VIEWS showed adequate, though not excellent, fit to the data. Future research should evaluate SP-VIEWS in other universities and countries. [ABSTRACT FROM AUTHOR]

Background: Pregnancy loss after Day 70 of gestation manifests as abortion, stillbirth or perinatal death. While previous studies have reported the diagnoses of laboratory submissions, none have quantified the incidence and causes of abortions, stillbirths and perinatal mortality at a population level. Objectives: To report the incidence and causes of pregnancy loss after Day 70 of gestation in a cohort of Thoroughbreds. Study design: Retrospective cohort study. Methods: Outcomes of Day 70 pregnancies were collected from eight Thoroughbred farms over the 2013‐2017 breeding seasons. Stud, veterinary and laboratory records were supplemented with publicly available data. Cause of loss was categorised using custom criteria. Results: Data were collected on 3,586 pregnancies from 1,802 mares. The incidence risk of a pregnancy failing to produce a live foal at 24 hours post parturition was 7.3% (95% confidence interval (CI) 6.5‐8.2, equating to 7.3 cases per 100 Day‐70 pregnancies). The incidence of pregnancy loss between Day 70 and 300 of gestation, Day 301‐315 and stillbirth/perinatal death was 4.0% (95% CI 3.4‐4.7), 0.3% (95% CI 0.2‐0.6) and 1.4% (95% CI 1.1‐1.9) respectively. Of the pregnancy losses where tissue was available, 61.1% were submitted for post‐mortem examination. The incidence risk of loss due to umbilical cord‐related pathologies was 1.5% (95% CI 1.1‐1.9), 0.4% (95% CI 0.2‐0.6) for noninfectious placental disease and 0.3% (95% CI 0.2‐0.6) for both infectious placentitis and Equine Herpesvirus infection. No primary diagnosis was made in 11.2% of the cases which underwent full post‐mortem examination. Main limitations: It was not possible to differentiate between intra‐partum stillbirth and early post‐partum death. Conclusion: Pregnancy loss after Day 70 of gestation is a significant source of loss in the Thoroughbred with umbilical cord‐related pathologies being the most commonly diagnosed cause. Reporting the incidence of pregnancy loss at a population level with clear case definitions will allow for accurate global comparisons. [ABSTRACT FROM AUTHOR]