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Basics ⬇

Outline

BASICS

Definition!!navigator!!

Pregnancy prone to early termination, delivery of a compromised foal, and/or prolongation due to maternal, fetal, and/or placental abnormalities.

Pathophysiology!!navigator!!

  • Premature initiation of labor and/or prolonged gestation
  • Specific conditions are similar to those resulting in fetal stress, distress, and/or viability

Preexisting Maternal Disease

  • PPID
  • EMS/IR
  • Laminitis
  • Chronic, moderate to severe endometritis, endometrial periglandular fibrosis, and/or lymphatic cysts (impaired placental function)

Gestational Maternal Conditions

  • Malnutrition
  • Colic
  • Endotoxemia
  • Hyperlipemia
  • Prepubic tendon rupture
  • Uterine torsion
  • Dystocia
  • Ovarian granulosa cell tumor
  • Laminitis
  • Musculoskeletal disease
  • Ergopeptine alkaloid exposure (endophyte-infected fescue, ergotized grasses and/or grains)
  • Xenobiotic exposure
  • Abortigenic infection exposure, especially equine herpesvirus and bacterial contaminants on ETC setae

Placental Conditions

  • Placentitis; placental insufficiency, early separation
  • Umbilical cord torsion or torsion of the amnion
  • Hydropic conditions
  • MRLS
  • Placental abnormalities reported with foals resulting from SCNT cloning procedures

Fetal Conditions

  • Twins
  • Fetal abnormalities, e.g. hydrocephalus
  • IUGR
  • Fetal trauma
  • Foals resulting from SCNT cloning procedures
  • Fetal stress and distress can involve 1 or more of the following:
    • Maternal systemic disease; placental infection, insufficiency, torsion, and/or separation; fetal abnormalities, all of which impede efficient fetal gas exchange and nutrient transfer
    • With placental insufficiency, fetal growth and development are slowed, resulting in IUGR
    • Equine fescue toxicosis causes decreased maternal prolactin concentrations and impaired late-gestational 5α-pregnane secretion by the uterofetoplacental unit, resulting in prolonged gestation and fetal dysmaturity at the time of parturition

Systems Affected!!navigator!!

  • Maternal—reproductive and other organ systems, depending on the nature of maternal systemic disease and complications, e.g. dystocia, RFM
  • Fetal—all organ systems

Signs!!navigator!!

Historical Findings

1 or more of the following:
  • Maternal disease during gestation, e.g. colic, hyperlipemia, body wall or prepubic tendon rupture, uterine torsion, etc
  • Mucoid, hemorrhagic, serosanguineous, or purulent vulvar discharge
  • Premature udder development, dripping of milk
  • Complete lack of late gestational udder development
  • Previous examination indicating placentitis or fetal compromise
  • Previous abortion, high-risk pregnancy, or dystocia
  • History of delivering a small, dysmature, septicemic, and/or congenitally malformed foal
  • Preexisting maternal disease at conception, such as laminitis, PPID, EMS/IR, endometritis, fibrosis and/or cysts
  • Previous exposure to endophyte-infected fescue or ergotized grasses and/or grains
  • Previous exposure to abortigenic xenobiotics or infections

Physical Examination Findings

Maternal and Placental Signs

  • Laminitis
  • Anorexia, fever, or other signs of concurrent, systemic disease
  • Abdominal discomfort
  • Mucoid, mucopurulent, hemorrhagic, serosanguineous, or purulent vulvar discharge
  • Premature udder development and dripping of milk (except in cases of fescue toxicosis presenting with agalactia and little or no udder development)
  • Premature placental separation (red bag)
  • Placentitis, placental separation, or hydrops of fetal membranes
  • Excessive abdominal distention
  • Excessive swelling along the ventral midline, evidence of body wall weakening or rupture
  • Alterations in maternal circulating levels of progestins, estrogens, and/or relaxin, reflecting changes in fetal wellbeing and/or placental function

Fetal Signs

  • Fetal stress and/or distress might first be recognized upon premature delivery of a live or dead foal; the late delivery of a severely compromised foal, unable to stand and suckle
  • Fetal hyperactivity or inactivity (concurrent with maternal or placental abnormalities) may suggest a less-than-ideal fetal environment and/or fetal compromise
  • Can be assessed by visual inspection or by TRP of the mare
  • Parameters are assessed using transrectal or transabdominal US:
    • Fetal activity and normal muscle tone:
      • <330 days of gestation, the normal FHR is ≤100 bpm after activity and ≥60 bpm at rest
      • >330 days of gestation, the normal FHR is ≥50 bpm at rest and difference between resting and active rates is ≤40 bpm
      • Normal fetal heart rhythm, as assessed by US and/or ECG
      • Normal fetal breathing movements
    • Increased volumes of amniotic fluid reflect hydrops amnion (hydramnios); low volumes indicate fetal distress, longstanding chronic hypoxia
    • Sudden changes in the echogenicity of the amniotic fluid in late gestation can indicate meconium expulsion and fetal distress
    • Appropriately sized fetus for gestational stage
      • Fetal aortic diameter ≈ 2.1 cm at 300 days of gestation and 2.7 cm at 330 days of gestation
      • Record length and width of fetal orbit

Placental Health

  • Normal CTUP, by transabdominal US—12.6 ± 3.3 mm
    • Uteroplacental thickness >19.2 mm indicative of placentitis
  • Normal CTUP by transrectal US:
    • 271–300 days of gestation ≤8 mm
    • 300–330 days of gestation ≤10 mm
    • >330 days of gestation ≤12 mm
  • Look for evidence of absence or very small areas of uteroplacental detachment
  • Increased echogenicity of allantoic fluid >44 days prior to anticipated foaling date may reflect fetal distress; floating particulate matter becomes gradually larger 10–36 days prior to foaling; sudden increases in the echogenicity of the allantoic fluid may indicate fetal and/or placental abnormalities
  • The mean vertical distance of allantoic fluid in uncomplicated pregnancies from <300 days to term is generally 19 ± 9 mm

Risk Factors!!navigator!!

  • May be nonspecific
  • Thoroughbreds, Standardbreds, draft, and American Miniature Horse mares, and related breeds predisposed to twinning
  • >15 years of age
  • Other organ system involvement depends on the presence of placentitis, stage of gestation, presence of maternal disease, infection, and/or toxemia
  • Hyperlipidemia is of special concern for overconditioned American Miniature Horses, ponies, and donkeys

Preexisting Maternal Disease

  • PPID
  • EMS/IR
  • Laminitis
  • Chronic, moderate to severe endometritis, endometrial periglandular fibrosis, and/or lymphatic cysts, leading to impaired placental function

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

Normal, uncomplicated pregnancy with an active, normal fetus as assessed by TRP, transrectal or transabdominal US, and/or various laboratory tests.

Diagnostic Procedures!!navigator!!

Maternal Assessment

  • Complete physical examination
  • CBC/differential serum biochemistry for inflammatory or stress leukocyte response, evidence of other organ system involvement
  • Specific tests to confirm suspected predisposing cause (see Preexisting Maternal Disease)
  • Test for EMS/IR, including basal glucose and insulin analyses, oral sugar test, and combined glucose and insulin test
  • ELISA or RIA analyses for maternal P4 useful at <80 days of gestation (normal levels vary from >1 to >4 ng/mL, depending on reference laboratory). At >100 days, RIA detects both P4 (very low >day 150) and cross-reacting 5α-pregnanes of uterofetoplacental origin. Acceptable levels of progestins, including 5α-pregnanes, vary with stage of gestation and laboratory used. Decreased maternal 5α-pregnane concentrations during late gestation are associated with fescue toxicosis and ergotism and are reflected in RIA analyses for progestagens
  • Maternal estrogen concentrations can reflect fetal estrogen production and viability, especially conjugated estrogens, e.g. estrone sulfate
  • Decreased maternal relaxin concentration may be associated with abnormal placental function
  • Decreased maternal prolactin secretion during late gestation is associated with fescue toxicosis and ergotism

Fetal Assessment

  • Transrectal and transabdominal US useful in diagnosing twins, assessing fetal stress, distress, and/or viability, monitoring fetal development, evaluating placental health and diagnosing other gestational abnormalities
  • In barren, older mares, mares with history of high-risk pregnancy (placentitis, abortion, EED, conception failure, or endometritis), transrectal or transabdominal US should be performed on a routine basis during the entire pregnancy to assess fetal stress and viability
  • Confirmation of pregnancy and diagnosis of twins should be performed any time serious maternal disease occurs
  • Twin pregnancy is confirmed by 2 fetuses (transrectal US when gestational age is <90 days) or ruled out by presence of a nonpregnant uterine horn (transabdominal US during late gestation)
  • Fetal stress, distress, and/or viability can best be determined by transabdominal US during late gestation. View fetus in both active and resting states for at least 30 min. Note abnormal fetal presentation and position
  • Fetal ECG can detect twins and assess fetal viability and distress, but largely has been replaced by transabdominal US with ECG capabilities
  • While a higher risk technique in horses than in humans, US-guided amniocentesis and/or allantocentesis and analysis of the collected fluids might become a future means to assess fetal karyotype, pulmonary maturity, and to measure fetal proteins
    • Samples might reveal bacteria, meconium, or inflammatory cells

Pathologic Findings!!navigator!!

  • Evidence of villous atrophy or hypoplasia on the chorionic surface of the fetal membranes
  • Thickening and edema of the chorioallantois
  • Various placental abnormalities reported with foals resulting from SCNT/cloning procedures
  • An endometrial biopsy can demonstrate the presence of moderate to severe, chronic endometritis, endometrial periglandular fibrosis with decreased normal glandular architecture, and/or lymphatic lacunae

Treatment ⬆ ⬇

Outline

TREATMENT

Appropriate Health Care!!navigator!!

Depending on the circumstances, monitoring/managing high-risk pregnancies (especially close to anticipated foaling date), including prolonged examination times required for complete serial transabdominal fetal assessments, is best performed at a facility prepared to manage these types of pregnancies, especially if distress is severe and parturition (induction or cesarean section) is imminent.

  • Early diagnosis of at-risk pregnancies is essential for successful treatment. Do not underestimate the impact of maternal disease on fetal and placental health
  • Foal survival is improved with maternal body wall tears, when circumstances allow conservative management, without induction of parturition or elective cesarean section
  • With prolonged fetal stress and/or distress, maintenance of pregnancy must be balanced with the need to induce parturition (with or without cesarean section), if necessary to stabilize the mare's health
  • Parturition requires close supervision in cases of fetal stress and distress. The neonatal foal will likely require intensive care
  • Foal resuscitation during delivery or immediately postpartum; pay close attention to airways, breathing, circulation
  • Consider individual circumstances/their sequelae to determine nature and timing of treatment:
    • PE
    • CBC/biochemistry profile
    • Stage of gestation
    • Nature of maternal disease
    • Hydrops
    • Evidence of fetal stress, distress, or impending demise
    • Maternal mammary development
    • Maternal health risks and/or impending maternal demise
    • Occurrence of complications such as dystocia, RFM, FTPI (necessitating a plasma transfusion), and/or fetal dysmaturity, with or without septicemia
    • Financial—relative value of mare and foal

Nursing Care!!navigator!!

Depending on maternal disease, fetal stress/distress, the necessity for surgical intervention, intensive nursing care might very well be required for the neonatal foal and mare.

Activity!!navigator!!

  • For most cases, exercise will be somewhat limited and supervised. However, for EMS/IR exercise may an important part of the therapeutic regimen
  • Body wall tears, prepubic tendon rupture, laminitis, and/or fetal hydrops may necessitate severe restrictions or complete elimination of exercise

Diet!!navigator!!

Feed the mare an adequate, late gestational diet with proper levels of energy, protein, vitamins, and minerals, unless contraindicated by concurrent maternal disease, e.g. EMS/IR.

Client Education!!navigator!!

  • Early diagnosis is essential for fetal survival
  • Correct/manage predisposing conditions to improve outcomes
  • Induction of parturition and cesarean section also have inherent risks

Surgical Considerations!!navigator!!

  • Cesarean section may be indicated when vaginal delivery is not possible or if dystocia is not amenable to resolution by manipulation alone
  • Surgical intervention might be indicated for future repair of anatomic defects predisposing mares to endometritis and placentitis

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

See recommendations for specific conditions associated with high-risk pregnancies. Oxygen, epinephrine, vasopressin (argipressin), and atropine may be necessary for foal resuscitation

Altrenogest

  • Depending on clinical circumstances, risk factors, and clinician preferences, administration can start at various stages of pregnancy, continue until near term or at parturition, be used for only short periods (based on maternal progestin concentrations), and/or be decreased over time or discontinued abruptly
  • History of endometritis/previously aborted mare (without active infectious component) and/or mare with fibrosis—0.044–0.088 mg/kg PO daily; commence 2–3 days after ovulation or upon diagnosis of pregnancy; continue to ≥100 days of gestation; can decrease dose over 14 days at end of treatment period
  • Endotoxic/Gram-negative septicemic mares <80 days of gestation—0.088 mg/kg PO daily, initially, then 0.044 mg/kg daily to ≥100 days of gestation; can decrease dose over 14 days at end of treatment period
  • To prevent premature parturition and promote uterine quiescence, following diagnosis of maternal disease, placentitis, or late gestational twins—0.088 mg/kg PO daily, initially, then 0.044 mg/kg daily
  • Near term, discontinue 7–14 days before expected foaling date, unless otherwise indicated by assessment of fetal maturity/viability, questions regarding accuracy of gestational age, and/or clinician preference

Antibiotic or Antibacterial Therapy

  • Indicated with a diagnosis of or potential for diagnosis of maternal, placental, and/or fetal infection
  • The specific antibiotics used depend on clinical circumstances, suspect organisms, therapeutic goals, clinician preferences, and, potentially, financial considerations

Domperidone

  • Indicated for agalactia and late gestational fetal maturation
  • When fescue toxicosis is diagnosed or when there is confirmation of prolonged gestation, based on breeding records—1.1 mg/kg PO daily
  • Continue domperidone to parturition, with anticipated normal mammary development and lactation

Flunixin Meglumine

  • Prophylaxis if endotoxin release is anticipated—0.25 mg/kg IM (potential for injection reactions) or, preferably, IV or PO (daily to QID)
  • Dose can be doubled for analgesia and anti-inflammatory effect
  • May help decrease premature uterine contractions

Pentoxifylline

  • Anti-inflammatory and anticytokine effects, especially during endotoxemia
  • Dosing regimens used vary from 4.4 mg/kg PO every 8 h for laminitis to 8.5 mg/kg PO twice daily to reduce cytokine effects in endotoxemia

Precautions, Possible Interactions!!navigator!!

Altrenogest

  • Only to prevent abortion or premature delivery in confirmed pregnancies, where a live fetus is present in utero
  • Not recommended to prevent spontaneous, infectious abortion other than those caused by placentitis and endotoxemia
  • Initially, weekly monitoring of fetal viability—retention of dead fetuses has been reported to result from continued treatment with supplemental progestins
  • Altrenogest is absorbed across skin; wear nitrile or rubber gloves and wash hands
  • Dependent on the etiology of the high-risk pregnancy, progestin supplementation might be unsuccessful

Antibiotic or Antibacterial Therapy

  • Depends on the specific drug
  • Some are potentially teratogenic

Domperidone

Premature lactation; loss of colostrum—can generally be addressed by adjusting the treatment regimen.

Flunixin Meglumine

Can cause gastric ulcers and kidney problems.

Pentoxifylline

Potentially, adverse GI, CNS, and cardiovascular effects.

Alternative Drugs!!navigator!!

  • Injectable P4 (150–500 mg/day, oil base) can be administered IM daily, instead of the oral formulation. Variations, contraindications, and precautions are similar to those associated with altrenogest
  • Other injectable and implantable progestin preparations are available commercially for use in other species. Any use in horses of these products is off-label, and few scientific data are available regarding their efficacy
  • Newer, repository forms of P4 are occasionally introduced; however, some evidence of efficacy should be provided prior to use
  • See recommendations for specific conditions, e.g. dystocia, fescue toxicosis, high-risk pregnancy, induction of parturition, prepubic tendon rupture, RFM, hydrops
  • Phenylbutazone can be used as an alternative to flunixin meglumine. Variations, contraindications, and precautions are similar to those associated with flunixin meglumine
  • Thyroxine supplementation has been successful (anecdotally) for treating mares with histories of subfertility and high-risk pregnancy, especially obese mares with EMS; its use remains controversial; considered deleterious by some clinicians. Few clinical data available, metformin has been suggested for mares with IR, where exercise and diet are insufficient for successful management
  • Medications for other maternal diseases—potential risks are dependent on the specific drug. Pergolide is currently the drug of choice for treating PPID. However, its effects will mimic those of fescue toxicosis, with agalactia/dysgalactia and possibly prolonged gestation. It may be appropriate to consider treating these mares as for fescue toxicosis

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Monitor mare and fetus until termination of pregnancy
  • Monitor for premature or inadequate udder development
  • Within no more than 24 h after delivery, the foal should be assessed; if necessary, treat for FTPI
  • Vaginal speculum examination, uterine cytology, and culture (as indicated) can be performed 7–10 days postpartum
  • Endometrial biopsy may be indicated as part of the postpartum examination; a prognostic tool for future reproduction

Prevention/Avoidance!!navigator!!

  • Early recognition of at-risk mares and potential high-risk pregnancies
  • Correction of perineal conformation; prevent placentitis
  • Management of preexisting endometritis before breeding
  • Early monitoring of mares with a history of fetal stress, distress, and/or viability concerns
  • Complete breeding records, especially for double ovulations, early diagnosis of twins (<25 days; ideally, days 14–15); selective embryonic or fetal reduction
  • Careful monitoring of pregnant mares for vaginal discharge and premature mammary secretion
  • Removal of pregnant mares from fescue pasture or ergotized grasses or grains during last trimester (60 days optimal, especially if bred on multiple cycles, with no US confirmation of pregnancy; minimum of 30 days prepartum, with adequate breeding dates and confirmation of pregnancy using US)
  • Use ET procedures with mares predisposed to EED or high-risk pregnancies
  • Avoid breeding or using ET procedures in mares that have produced multiple stressed, distressed, or dead foals due to congenital and potentially inheritable conditions
  • Prudent use of medications in pregnant mares
  • Avoid exposure to known toxicants
  • Management of ETCs for prevention of MRLS
  • If history of abortion, evidence of moderate to severe endometritis and/or fibrosis, evaluate and treat before breeding

Possible Complications!!navigator!!

  • Abortion, dystocia, RFM, endometritis, metritis, laminitis, septicemia, reproductive tract trauma, and/or impaired fertility, which will all affect the mare's wellbeing and reproductive value
  • Fetal stress and/or distress; fetal death; stillbirth; neonatal death
  • Neonatal foals from high-risk pregnancies have potentially been compromised during gestation and are more likely to be dysmature, septicemic, and subject to FTPI, and/or angular limb deformities than foals from normal pregnancies

Expected Course and Prognosis!!navigator!!

  • The ability to prevent and treat the conditions associated with high-risk pregnancies has improved dramatically. Successful management requires rigorous monitoring of mare, fetus, and neonatal foal. Address treatable health concerns as soon as possible during the pregnancy and to avoid and/or minimize challenges to maternal, fetal, and placental health
  • If the predisposing conditions can be treated and/or managed, pregnancies in which fetal stress has been diagnosed have a guarded prognosis for successful completion
  • If there is evidence of fetal stress progressing to distress and the distress continues in the face of treatment, fetal viability and maternal health become major concerns and the prognosis for a healthy, term gestation under these circumstances is guarded to poor

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Synonyms!!navigator!!

  • Abortions, spontaneous infectious and noninfectious
  • Fetal stress, distress, and viability
  • Placental insufficiency
  • Twins

Abbreviations!!navigator!!

  • CNS = central nervous system
  • CTUP = combined thickness of uterus and placenta
  • EED = early embryonic death
  • ELISA = enzyme-linked immunosorbent assay
  • EMS = equine metabolic syndrome
  • ET = embryo transfer
  • ETC = eastern tent caterpillar
  • FHR = fetal heart rate
  • FTPI = failure of transfer of passive immunity
  • GI = gastrointestinal
  • IR = insulin resistance
  • IUGR = intrauterine growth retardation
  • MRLS = mare reproductive loss syndrome
  • P4 = progesterone
  • PPID = pituitary pars intermedia dysfunction
  • RIA = radioimmunoassay
  • RFM = retained fetal membranes
  • SCNT = somatic cell nuclear transfer
  • TRP = transrectal palpation
  • US = ultrasonography, ultrasound

Suggested Reading ⬆ ⬇

Vaala WE. Monitoring the high risk pregnancy. In: McKinnon AO, Squires EL, Vaala WE, Varner DD, eds. Equine Reproduction, 2e. Ames, IA: Wiley Blackwell, 2011:16–38.

Author(s) ⬆

Author: Tim J. Evans

Consulting Editor: Carla L. Carleton