Ascending placentitis in the mare: A review
© The Author(s) 2008
Published: 1 May 2008
Ascending placentitis is a condition that occurs late in pregnancy when bacteria enter the sterile uterus from the lower reproductive tract. It leads to abortion or the birth of premature and weakened foals. Early detection and treatment of this condition is vital for ensuring the production of a viable foal.
Mares with ascending placentitis often present in late term pregnancy with signs of premature udder development and premature lactation. There may be a vulvar discharge. Early detection of placental problems is possible using trans-abdominal or trans-rectal ultrasonography. Hormones such as progesterone and relaxin may be measured as indicators of foetal stress and placental failure. Postpartum foetal membranes may be thickened and contain a fibronecrotic exudate. The region most affected is the cervical star. Definitive diagnosis of ascending placentitis is by histopathological examination of the chorioallantoic membrane.
Ideal treatment strategies are aimed at curing the infection and prolonging the pregnancy to as close to term as possible and consist of anti-microbials, anti-inflammatories and hormonal support.
Swabs are taken from affected mares to determine antibiotic sensitivity and to aid in treatment of foals born from these mares which are at risk of becoming septic. If detected early enough, the chances of producing a viable foal are greatly increased.
Ireland is the main European producer of Thoroughbred (TB) horses and is responsible for a third of worldwide TB production . There were approximately 30,000 Thoroughbred broodmares at stud in 2006 in Ireland and the UK. Of these, 23,400 were mated to Thoroughbred stallions. The conception rate, excluding mares that were exported or died, was 97%. The pregnancy failure rate was 8% . These numbers show that although few mares fail to go in foal, a considerable number will lose the foal during the pregnancy.
The failure of pregnancy can be due to foetal or maternal factors and dysfunction of the placenta . This review focuses on the loss of late term pregnancy due to infection, specifically ascending placentitis, in the mare.
Ascending placentitis is infection of the placenta by bacteria that migrate along the reproductive tract from the vagina through the cervical canal. This can lead to abortion, premature birth or the birth of a weak foal, and affected mares often have difficulties conceiving during the following breeding season [57, 56]. The condition is seen in late gestation, typically at eight to 10 months.
The current incidence of ascending placentitis in Ireland is unknown. It accounts for nearly 20% of all equine abortions, stillbirths and perinatal deaths in the USA . In the UK it is implicated in 10% of such cases . Reasons for this regional difference are unknown.
Normal anatomy and physiology
Ascending placentitis and its effect on the foetoplacental unit
The hypothalamic pituitary adrenal (HPA) axis is fundamental for the final development of the foetus in late gestation and has a function in inducing the onset of parturition [36, 35]. The HPA axis of the equine foetus matures very late in gestation compared with other species [36, 19]. Increasing levels of pro-inflammatory cytokines or prostaglandins in ascending placentitis stimulate maturation of the foetal HPA axis [19, 20, 23]. Foals from affected mares that survive premature birth may be physiologically underdeveloped but their adrenocortical function may be normal or transitional compared with those born prematurely from unaffected mares [44, 36]. These foals may survive with minimal care [20, 23]. This has implications for treatment of disease. If the length of gestation can be prolonged, the prospect of producing a viable foal can be improved .
In experimentally induced placentitis, a portion of the cervical mucus plug must be removed in order to inoculate the uterus with bacteria [27, 32]. Therefore, in naturally occurring ascending placentitis there must be a failure of the mucus plug  That is, either the plug does not form properly or it disintegrates. The reasons for failure of the mucus plug are, as yet, unknown.
Bacterial vaginosis in pregnant women is a condition similar to ascending placentitis in the mare. The vagina becomes chronically colonised by an abnormal microbial flora. These bacteria produce enzymes which are capable of degrading the cervical mucus plug, thus allowing bacteria access to the placenta . This leads to inflammation of the placenta and premature labour . A similar mode of action may apply in mares with ascending placentitis, whereby abnormal bacteria in the tract produce mucus-degrading enzymes. Certain bacterial pathogens occasionally found in the equine reproductive tract, for example Pseudomonas aeruginosa, do produce mucus degrading enzymes [24, 50].
Streptococcus equi subspecies zooepidemicus is the bacteria most often isolated from affected mares. Escherichia coli, Pseudomonas aeruginosa, Klebsiella spp., Leptospira spp., Enterobacter spp., α-haemolytic Streptococci, Staphylococci spp. and nocardioforms have also been implicated ; Hong et al., 1993). It is possible that bacteria may be responsible for the degradation of the mucus plug but are not the pathogens that affect the placenta. These organisms may be facilitatory in degrading the cervical defences, allowing commensals such as S. zooepidemicus access to the placenta.
Clinical signs of ascending placentitis in the mare
Clinical signs of ascending placentitis
Premature udder development
Softening of the cervix
Live foals born to mares affected with ascending placentitis may be premature, weak and/or unthrifty and may develop sepsis . Alternately, they may present as a 'dummy' foal, as a result of chronic in utero transplacental oxygen deprivation [58, 1]. High creatinine concentrations in the neonatal foal that resolve rapidly over the first day or two suggest placental insufficiency, as the placenta functions as the excretory organ of the foetal foal [58, 1, 31].
Early diagnosis of ascending placentitis is essential to increasing the likelihood of producing a viable foal. This condition should be considered as a possible cause in a mare with premature lactation.
Mares that have a vulvar discharge should be carefully examined using a sterile speculum. If the speculum passes easily into the vagina, the cervix can be evaluated for competency, presence of the mucus plug and/or discharge. Care should be taken not to stimulate the cervix during the examination as this can induce premature parturition . If the speculum does not pass easily, it is likely that the normal thick vaginal mucus is still in place and this should not be disturbed.
Ultrasonography can be used to detect or confirm cases of ascending placentitis in suspect cases showing the classical clinical signs and also in subclinical mares [40, 17, 2, 32, 55]. Ultrasound scanning can be performed trans-rectally or trans-abdominally. Measurements of the uterine wall and attached chorioallantois may be used to identify mares at risk of ascending placentitis. This measurement is known as the combined thickness of the uterus and placenta (CTUP). If the CTUP is increased, placental insufficiency is likely present and abortion may ensue [41, 57, 56, 17]. Measurement of the CTUP can be taken at the placento-cervical junction when scanning trans-rectally or at the uterine body or uterine horns when scanned trans-abdominally .
Upper limits for the combined thickness of the uterus and placenta (CTUP) by transrectal ultrasonography during late gestation (adapted from Renaudin et al., 1997)
Day of gestation
Normal CTUP (mm)
Another disadvantage of trans-abdominal scanning is that focal areas of abnormal placenta may be missed as the only parts of the uterus and placenta that can be evaluated are those which are closest to the abdominal wall [2, 55]. The cervical pole of the placenta, which is the region most affected in ascending placentitis, can be easily evaluated trans-rectally. Examination may reveal separation of the chorioallantois from the endometrium and the presence of pus [57, 23, 55]. This may lead to identification of ascending placentitis in mares not yet showing clinical signs . Rectal ultrasound is a routine procedure used to diagnose problems in late term pregnancy. In a study by Renaudin et al.  there were no reports of adverse effects of using rectal ultrasound in late term mares.
Indicators of placental failure, detectable by ultrasound, in late gestation of the mare (adapted from Reimer, 1997 and Troedsson and Macpheron, 2006)
Anomalies detectable by ultrasound
Noticeable abnormality of foetus, foetal position or foetal activity
Increases or decreases in foetal heart rate
Accumulation of fluid between chorioallantoic membrane and endometrium - leads to placental separation
Abnormalities of the umbilical cord
Greatly increased or reduced allantoic or amniotic fluids
Increased echogenicity of the allantoic and amniotic fluids
Foetal heart rate during pregnancy (adapted from )
Month of gestation
Heart rate - beats per minute
Plasma progesterone levels during pregnancy of the normal mare (adapted from )
Day of gestation
Plasma progesterone level
(ng per ml)
Relaxin concentrations could potentially be useful in diagnosing insufficiency of the placenta. Relaxin is primarily produced by the placenta . Subnormal levels of relaxin may be present in mares with compromised pregnancies [45, 53, 56]. However, measurement of relaxin concentration is not routinely available at most equine diagnostic centres.
Postpartum examination of the placenta in these cases may reveal thickening and discolouration of the chorioallantoic surface primarily in the region of the cervical star . There may also be a purulent exudate [57, 30, 47]. The cervical star is the area of the chorioallantoic membrane that ruptures during normal delivery. If there has been premature detachment of the chorioallantois from the endometrium the rupture may occur in another area [30, 31, 47] and may result in a 'red bag' delivery. The chorioallantoic membrane may appear normal on gross examination; however, microscopically, it may be severely inflamed. Therefore, the foetal membranes including the umbilical cord should be submitted for histopathological investigation to confirm the diagnosis .
In cases of abortion, the foetus and the foetal membranes should be submitted. Uterine swabs should be taken from all mares that deliver prematurely to eliminate bacterial infection as the cause and, if infection is found, to aid treatment of the foal with appropriate antibiotics .
Management of ascending placentitis is aimed at fighting the infection, reducing the inflammatory response and supporting the pregnancy (LeBlanc, 2004d)[25, 55]. There is a correlation between chronic placentitis and accelerated foetal maturation [44, 20, 23]. If the pregnancy can be prolonged for a few weeks after the clinical signs of ascending placentitis are first seen, then a premature foal may be born with an improved likelihood of survival . In other words, the dam is a better incubator for a compromised foal than a neonatal intensive care unit. Broad spectrum antibiotics are used to treat the infection in ascending placentitis . Potentiated sulphonamides (trimethoprim sulfamethoxazole, 30 mg/kg, BID PO) and penicillin (procaine penicillin 22,000 IU/kg BID IM or crystalline penicillin 22,000 IU/kg QID IV) have been shown to cross the placenta and so are useful where organisms are susceptible to these drugs [33, 25, 55]. Gentamicin (6.6 mg/kg SID IV) has not been shown to achieve a high enough concentration in the allantoic fluid to inhibit Streptococcus equi . However, it may achieve concentrations adequate to be effective against E. coli and Klebsiella spp. [33, 25]. A swab of the vulvar discharge should be taken to identify organisms and determine antibiotic sensitivity.
Inflammation and the increased level of prostaglandins are initiating factors in preterm parturition . Anti-inflammatories which block inflammatory cytokines may be useful in treating this (LeBlanc, 2004d). It has not yet been determined if flunixin meglumine (1.1 mg/kg IV or IM) can transfer across the equine placenta to reach adequate concentrations . Mares affected with ascending placentitis may be treated with pentoxifylline (8.5 mg/kg, BID PO), a member of the methylxanthine class of drugs. Pentoxifylline inhibits the transcription of the tumour necrosis factor-a (TNF) gene and suppresses the production of this proinflammatory cytokine [7, 51, 19] (2004d),. It is also a rheologic agent which is thought to improve microcirculatory blood flow .
Tocolytics are given to women in premature labour. These drugs can interrupt the premature uterine contractions and therefore delay impending parturition . Efficacy in extending gestation has not been proven when these drugs are used alone [25, 55]. Clenbuterol has been demonstrated to cause uterine relaxation during late gestation, for up to two hours . However, studies have shown that it may cause relaxation of the cervix and treated mares may, in fact, give birth earlier than untreated mares [4, 38, 25, 55]. Therefore, it cannot be recommended that mares suffering from ascending placentitis be treated with clenbuterol.
The synthetic progesterone analogue, altrenogest, is thought to have an anti-prostaglandin effect [6, 23]. This can help to maintain the quiescence of the uterus [21, 23, 25]. Although the mechanisms are not fully understood, it is often given to mares showing clinical signs of placentitis. Trials on the efficacy of this approach have not yet been undertaken. However, some veterinary practitioners recommend double the normal dose, (0.088 mg/kg, SID PO) [21, 35]. Treatment is maintained throughout the remainder of the pregnancy.
Ascending placentitis is an important cause of late term foetal loss in the mare. Affected mares exhibit premature lactation and may have a vulvar discharge. Early detection of the ascending placentitis and implementation of treatment is critical in increasing the possibility of survival of the neonate.
Diagnosis may be assisted by prepartum ultrasonographic evaluation of the foetoplacental unit and treatment is aimed at prolonging the pregnancy to produce a viable foal. Combined therapy of long-term antibiotics, anti-inflammatories and synthetic progestagens is used to increase possibility of producing live, viable foals. In addition to the obvious economic consequences of the loss of a viable foal, there is also a decrease in the fertility of the mare for the following breeding season [57, 56].
There are still many unanswered questions regarding the pathogenesis of ascending placentitis and the most appropriate treatment strategies. Current research is aimed at determining the predisposing factors, discovering a method of early detection and validating appropriate treatments.
The authors' research is funded by a Marie Curie Individual Fellowship (International re-Integration Programme Proposal N° 041304-ChAirDis) to Vivienne Duggan, which funds Carolyn Cummins. The authors would like to thank Mary Gallagher, Tommy McGeady and Eva Maischberger for their help.
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