IN-DEPTH: CONDITIONS AND MANAGEMENT OF THE PERIPARTUM MARE
Table 3. Endocrine Findings Consistent with Fetoplacental Compro- mise Due to Placentitis or Other Disease Between 240 and 320 Days of Gestation
Gestational Age, days
240–260 260–280 280–300 300–320
Progesterone, ng/mL
5 5
7.5 10
Estradiol-17, pg/mL
153 192 171 70
susceptible to both overinterpretation and over- sight.44 Lastly, physical alterations of the utero- placental unit and fetus may not occur until the disease process is well underway. Thus, in order to increase diagnostic sensitivity and specificity, he- matologic parameters are frequently included in screening and diagnostic protocols. A complete blood count, serum chemistry and lac-
tate may provide immediate information regarding maternal systemic health, whereas serum proges- terone or estrogen concentrations may provide in- sight into fetoplacental wellbeing.23,45,46 Ousey and colleagues22 proposed that an early
rise in the progestin concentration may be seen in cases of chronic placentitis prior to the normally expected rise 2–3 weeks prior to parturition in response to placental insufficiency (twins), pathol- ogy, and/or fetal stress. Alternately, in cases of acute placentitis or fetal sepsis, a premature rapid decline in progestogens generally precedes fetal de- mise. When present, the premature rise may be associated with activation of the hypothalamic-pitu- itary-adrenal axis, which may suggest precocious maturation and potential improved viability of the foal.22,47,48 Large quantities of plasma estrogens are also
found in maternal circulation after mid gestation due to hypertrophy of the fetal gonads. Dehydroepi- androsterone (DHEA) and 7-dehydroepiandrosterone (7-dehydro-DHEA) produced in large amounts in mid pregnancy by the fetal gonads serve as precursors for synthesis of estrogens by the placenta. These include estrone, 17-estradiol, 17-estradiol, and their sulfo-
conjugates as well as the unsaturated -ring steroids equilin and equilenin and their derivatives 17-dihy- roequilin, 17-dihyroequilenin, 17-dihyroequilin and 17-dihyroequilenin.49,50 Normally, estrogens re- main elevated for the majority of pregnancy until they gradually decline over the final 1–2 months of gesta- tion. In compromised pregnancies prior to day 280 and the hormone’s natural decline, a reduction in plasma estrogens likely indicates severe fetal compro- mise and potential demise. Therefore, concentra- tions of total estrogens above 1000 ng/mL between days 150 and 280 are typically assumed to be normal while concentrations of less than 500 ng/mL are asso- ciated with severely compromised or deceased foals.18 Recent work in a large population of mares described cutoff values, diagnostic sensitivity and specificity for both progesterone and estradiol-17.48 Cutoff values for progesterone and estrogen with potential clinical utility are summarized in Table 3. Other serologic markers of disease, including se-
rum amyloid A, lactate and -fetoprotein, mi- croRNA, and metabolomic variations have all been proposed as measures of fetal health.19–21,51 In the authors’ laboratory, we have identified 12 serum metabolites that differ between mares with experi- mentally induced placentitis and healthy pregnant mares. As early as 4 hours post inoculation, a sig- nificant increase was detected in the metabolites alanine, phenylalanine, histidine, pyruvate, citrate, glucose, creatine, glycolate, lactate, and hydroxy- isobutyrate. In contrast, on day 4, a significant reduction in the metabolites alanine, histidine, phenylalanine, tyrosine, pyruvate, citrate, glyco- late, lactate, and dimethylsulfone was detected in infected mares compared to healthy controls (Beachler, unpublished data). However, to date, none of the serologic parameters
are known to be specific to placentitis or any partic- ular disease, nor are they predictive of fetal out- come. Consequently, veterinarians must depend on regular screening, ultrasonographic appearance of the fetus, uterus, and placenta as well as the complete clinical picture of the mare to guide ther- apeutic decisions and gauge clinical response.
Table 4. Common Diagnostic Findings in Cases of Infectious Late-Term Pregnancy Loss Ascending Placentitis
Diffuse Placentitis Physical exam
Fetal heart rate Fetal fluids
Serum progesterone concentration
Serum estrogen concentration
No change
Ultrasound exam Increase in peri-cervical CTUP
Bradycardia
Fever, uveitis, hematuria, sepsis, inappetance
Increased CTUP, renal edema
No change
Focal Placentitis No change
Increased CTUP ventrally
Bradycardia Increased echogenicity Increased echogenicity No change
Viral Disease
Variable, fever No change No change
No change
Increase progesterone Decreased progesterone Increase progesterone No change Decrease estradiol 17 Decrease estradiol 17 Decrease estradiol 17 Decrease estradiol 17
CTUP, combined thickness of the uterus and placenta. 130 2019 Vol. 65 AAEP PROCEEDINGS
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