Eye on the prize: pregnancy maintenance in late gestation

The closer you get, the more you worry about the risk of losing.  Regrettably, even with all the best intentions there is an inherent rate of pregnancy loss.  Bosh et al. 1 demonstrated a 12.9% pregnancy loss between day 40 of gestation and foaling.1  In a review of 3,527 aborted fetuses and placentas, stillborn foals or foals that died <24 hours after birth, 34% were due to feto-placental infection or placentitis of unidentified etiology.2  Bacterial infection caused 628 (17.8%) of these losses.  Complications of birth led to the demise of 679 (19%), congenital anomalies including contracted foals counted for 348 (10%), and no diagnosis was identified in 585 (17%) of these cases.  Other causes included placental edema, premature placental separation, twins, umbilical cord anomalies, placental villous atrophy, body pregnancy, fetal diarrhea, and neoplasia.  Some things you can change, some you can’t.  I’ll talk about many of these at a later time, for now let’s go over attempts to maintain a troubled pregnancy regardless of the cause.

In early pregnancy, synthetic progestins seem to be able to stand in for ovarian progesterone and prevent endotoxin or prostaglandin induced abortion.  In later gestation when, in the mare, numerous pregnancy supportive (progestogen) hormones are usually present, the mechanism may include myometrial quiescence.  In two similar induced placentitis models where mares were treated with trimethoprim sulfa and pentoxifylline with and without altrenogest, twice as many mares delivered live foals with altrenogest treatment compared to without altrenogest treatment.3  During the first trimester, altrenogest prevented abortion in 8/8 mares treated with cloprostenol, whereas control mares and 3/8 mares receiving progesterone aborted.4  Since progestogen concentrations can be elevated in mares with compromised pregnancy it is uncertain whether progestogen administration should be recommended in all cases.  Also, in one study stage II parturition was prolonged in altrenogest treated mares, with effects on neonatal viability.5

Inflammation is a significant driver of pregnancy loss.  Non-steroidal anti-inflammatory agents such as flunixin meglumine and firocoxib are commonly used as part of pregnancy maintenance therapy.  However, flunixin meglumine was not effective at preventing cloprostenol-induced abortion between 80 and 150 days gestation.4  Pentoxifylline can decrease uterine activity and down regulates pro-inflammatory cytokines such as TNF-a, IL-6 and interferon-g.  This drug also increases erythrocyte flexibility, is fibrinolytic, and inhibits platelet adhesion.6  Pentoxifylline has been shown to reach the allantoic fluid in normal pregnancy and in experimental placentitis models.7  Acetylsalicylic acid improves uterine and ovarian perfusion which appears to be supportive of pregnancy.8

Antimicrobials are a critical component of bacterial placentitis treatment, and are often used without proof of bacterial involvement as the risk of unaddressed infection is high.  Antimicrobials that have been demonstrated to reach allantoic fluid include penicillin G, gentamicin, and trimethoprim sulfamethoxazole.9, 10  Other antimicrobials are anecdotally used with effect.  Antimicrobial therapy in pregnant mares with placentitis may need to be prolonged.  The combination of altrenogest, pentoxifylline, and antimicrobials resulted in an increased number of live foals in an induced placentitis study.3

Adjunctive treatments can also be attempted in more controlled situations or during hospitalization.  Oxygen therapy (10 -15 L/min nasal insufflation) can be utilized in pregnant mares with compromised placental function to improve oxygen delivery to the fetus.11  There are anecdotal reports regarding the efficacy of acupuncture for pregnancy maintenance, however there are few controlled studies.  Many studies focus on reduction in uterine tone, in one study in rats acupuncture at LI-4 was found to suppress myometrial contractility in the face of oxytocin infusion.12  Cervical cerclage involves placement of a suture within the musculature of the cervix that is tightened to obliterate the cervical lumen.13  This procedure is typically used in cases of cervical incompetence that jeopardizes the pregnancy and is not sufficiently improved with progestogen therapy.  Great care is necessary in case selection and monitoring as foaling with suture in place would be catastrophic.

Things go right most of the time, but you have to keep your eyes open.  Coming up later: a deeper dive into placentitis.  The water is deep and murky.  Hope you can swim.

 

1.   Bosh KA, Powell D, Shelton B et al. Reproductive performance measures among Thoroughbred mares in central Kentucky, during the 2004 mating season. Equine Vet J 2009;41:883-888.

2.   Giles RC, Donahue JM, Hong CB et al. Causes of abortion, stillbirth, and perinatal death in horses: 3,527 cases (1986-1991). J Am Vet Med Assoc 1993;203:1170-1175.

3.   Bailey CS, Macpherson ML, Pozor MA et al. Treatment efficacy of trimethoprim sulfamethoxazole, pentoxifylline and altrenogest in experimentally induced equine placentitis. Theriogenology 2010;74:402-412.

4.   Daels PF, Besognet B, Hansen B et al. Effect of progesterone on prostaglandin F2 alpha secretion and outcome of pregnancy during cloprostenol-induced abortion in mares. Am J Vet Res 1996;57:1331-1337.

5.   Neuhauser S, Palm F, Ambuehl F et al. Effect of altrenogest-treatment of mares in late gestation on adrenocortical function, blood count and plasma electrolytes in their foals. Equine Vet J 2009;41:572-577.

6.   Lauterbach R, Rytlewski K, Pawlik D et al. Effect of Pentoxifylline, administered in Preterm Labour, on the Foetal-Placental Circulation and Neonatal Outcome: A Randomized, Prospective Pilot Study. Basic Clin Pharmacol Toxicol 2012;110:342-346.

7.   Rebello S, Macpherson ML, Murchie TA et al. Placental transfer of trimethoprim sulfamethoxazole and pentoxifylline in pony mares. Anim Reprod Sci 2006;94:432-433.

8.   Bollwein H, Weber F, Steffen S et al. The effect of acetylsalicylic acid and captopril on uterine and ovarian blood flow during the estrous cycle in mares. Theriogenology 2004;61:301-309.

9.   Murchie TA, Macpherson ML, LeBlanc MM et al. Continuous monitoring of penicillin G and gentamicin in allantoic fluid of pregnant pony mares by in vivo microdialysis. Equine Vet J 2006;38:520-525.

10. Macpherson ML. Treatment strategies for mares with placentitis. Theriogenology 2005;64:528-534.

11. Wilkins P. Monitoring the pregnant mare in the ICU. Clinical Techniques in Equine Practice 2003;2:212-219.

12. Farooki MA. Observations on the epidemiology and pathology of human infertility in the Peshawar region of West Pakistan. Int Surg 1968;50:252-268.

13. Bucca S. How to Manage Cervical Incompetence by Application of a Cervical Cerclage Suture in the Pregnant Mare.    American Association of Equine Practitioners 2013,59:28-33.

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