HOW TO MANAGE THE SUBFERTILE MARE

Agalactia, Dysgalactia, and Nutrition of the Postpartum Mare

Peter R. Morresey, BVSc, MACVSc, Diplomate ACT, ACVIM (Large Animal)

Successful initiation and continuation of in the postpartum mare depends on normal hormonal activity and a lack of any inhibitory influences on the mare. Impediments to adequate lactation include underlying systemic disease of the mare, pathology of the mammary gland, malnutrition, and diminished neonatal vigor reducing normal suckling activity. Author’s ad- dress: Rood and Riddle Equine Hospital, PO Box 12070, Lexington, KY 40580; e-mail: pmorresey@ roodandriddle.com. © 2012 AAEP.

1. Introduction progressively larger ducts that converge into cis- Lactation places considerable nutritional and phys- terns above the teats. Groups of alveoli cluster to- iological demands on the mare. The nursing mare gether to form lobules. In turn, these cluster must provide sufficient to allow the foal to together to form lobes, which is collectively known achieve approximately 45% of its mature weight at as a lobuloalveolar construct. weaning.1 At the same time, to maintain a yearly The mammary gland undergoes a cycle of growth foaling interval, the mare must be sufficiently recov- and differentiation of tissue after every mating that ered from the demands of gestation to allow rebreed- results in a pregnancy. Growth of the mammary ing within the first month of lactation if so desired. gland tissue continues to some degree into the lac- Numerous management decisions and medical con- tation phase, with this being followed by a period of ditions can lead to either complete failure of lacta- involution. In most species, growth of the lobuloal- tion or insufficient milk production to meet the veolar tissue is stimulated by high levels of both needs of the growing foal. estrogen and progesterone during pregnancy, with the latter inhibiting milk production.2 2. Anatomy, Physiology, and Endocrinology of The mare differs from other species in that circu- Lactation lating progesterone levels are relatively low during The equine mammary gland is composed of four the third trimester of gestation. Progesterone en- separate functional gland units, two on either side of tering the maternal circulation from the fetoplacen- the inguinal midline. Each pair (collateral) is tal unit is metabolized to the 5␣-pregnanes.3,4 The served by a single teat; however, each of these has most bioactive metabolite is thought to be 5␣- two teat canals and cisterns, with separate duct and pregnane-3,20-dione, which is found in high concen- alveolar systems for each gland unit. Secretory ep- tration and has demonstrable affinity for the ithelial cells line the alveoli, with myoepithelial cells progesterone receptor.5 Estrogens are represented encasing the alveoli. The alveoli empty milk into by the inactive equilin and equilenin during late

NOTES

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Orig. Op. OPERATOR: Session PROOF: PE’s: AA’s: COMMENTS ARTNO: 1st disk, 2nd beb spencers 10 3285 HOW TO MANAGE THE SUBFERTILE MARE pregnancy,6 with estradiol 17-␤ rising before preponderant in human milk.20,21 A dynamic state parturition.7,8 of immunity exists during the prepartum and the The trigger for initiation of lactation is thought to immediate postpartum periods. Prepartum, colos- be the progestagen decrease and prolactin increase tral immunoglobulin accumulates in preparation for at the end of lactation. Prolactin has a major role transfer of immunity to the neonatal foal. The in the initiation of lactation in the mare. Levels mammary gland does not produce immunoglobulin suddenly increase in the last days of gestation and G but instead concentrates it from the vascular sup- peak at parturition,9 remaining elevated for up to 3 ply. Lysozyme remains elevated in milk well after months postpartum.10 Prolactin is not required for parturition, remaining active in the foal intestine the continuation of lactation once established,11 and providing protection after cessation of macro- even though suckling raises maternal prolactin con- molecule absorption. This elevated level of ly- centrations.12 Prolactin receptors are present in sozyme may also protect the mammary gland mammary tissue and increase in number during against infection.22 gestation and after parturition. Lactation in the mare peaks 30 to 60 days post- 4. Disturbances of Lactation and Differential partum. During this time, average daily produc- Diagnoses tion of 15 L per day in Thoroughbred mares and 12 The failure to produce or milk is known as to 13 L per day in Quarter Horse mares is agalactia. This is a separate condition from lack of 13,14 achieved. Therefore, daily consumption by the milk letdown by some inexperienced primiparous foal is in the range of 21% to 25% of body weight on mares or that caused by painful mammary glands. 15 average over this period. Dysgalactia is defined as poor or inadequate milk As the demand for milk by the foal decreases, the production, this being essentially a partial failure in mammary gland undergoes a progressive involu- lactation initiation or its continuation. Devitaliza- tion. Weaning occurs at relatively high milk pro- tion of the mare due to a systemic medical condition duction, causing increased intramammary pressure or during a period of postsurgical convalescence may due to accumulation of milk. This increased pres- be responsible for diminuation or cessation of sure along with suspected inhibitors in the milk lactation. further decreases production. Secretory tissue is subsequently replaced with connective and adipose 5. Fescue Toxicosis tissue.2 The most common cause in the United States is 3. Composition of Milk ingestion of fescue pasture contaminated with the endophyte Neotyphodium coenophialum.23 This Synthesis of milk within the mammary gland of the compound is a dopamine agonist which antagonizes mare is similar to that in ruminants.16 Compo- the action of prolactin during initiation of lactation. nents are sourced from body reserves, feed materi- Placental edema and prolonged gestation also als, and de novo synthesis within the mammary result. gland epithelium. Throughout lactation, a slow de- cline occurs in energy, total solids, protein, ash, 6. Concurrent Disease Process and minerals; however, lactose concentrations increase.17 Whereas milk production is a potent driver of met- Lactose is derived from glucose absorbed from the abolic requirements, it is subservient to survival of small intestine. Fatty acids are produced from ac- the mare. In the absence of other precipitating fac- etate and 3-hydroxybutryrate sourced from carbohy- tors, systemic disease of the mare should be ruled drate digestion in the large intestine. Unsaturated out in cases of agalactia or decreased milk produc- C18 fatty acid is supplied either directly from the tion. Also, diminished suckling activity by the foal, diet or from body reserves.18 Protein in milk is failure to fully let down by the mare, or incomplete derived from the highly synthetic cells of the mam- manual (where the foal is unable to suckle mary epithelium. Most research has centered on the mare, such as with hospitalization) can lead to the effects on the foal after variations in mare pro- rapid diminution of milk production due to incom- tein intake; however, research in mares has found plete clearance of the mammary secretions, thereby that an increase in dietary crude protein up to 14% raising pressure within the mammary gland, which of the diet increased milk production.19 is deleterious to further production. Compared with human and bovine milk, mare milk is of lower fat and hence energy content. Mare 7. Malnutrition milk and human milk have a similar sugar content, The energy requirements for lactation are high. whole protein, and electrolyte content, in contrast to Lactose is sourced from glucose provided in the diet, the increased electrolyte content of cow’s milk, mak- with fatty acids produced from acetate and butyrate ing that a less suitable replacement for mare milk.16 of large intestinal origin. Adipose tissue will be Antimicrobial defense in mare’s milk seems to be mobilized during times of limited intake with the due mainly to the presence of lysozyme (as in human potential to decrease mare body condition. Protein milk) and, to a lesser degree, to lactoferrin, which is is similarly harvested from tissue stores.

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Orig. Op. OPERATOR: Session PROOF: PE’s: AA’s: COMMENTS ARTNO: 1st disk, 2nd beb spencers 10 3285 HOW TO MANAGE THE SUBFERTILE MARE 8. Mastitis may lead to resolution of the diminished mammary Infection and inflammation of the mammary gland development and resultant agalactia. of the mare is uncommon. Most common at wean- Domperidone is the most commonly used lacto- ing, this condition may occur during lactation if the genic agent due to its ability to stimulate prolactin foal does not regularly and sufficiently suckle the secretion in situations of dopaminergic inhibition mare during periods of high production. Tail such as with fescue toxicosis. This medication will swishing, ground stomping, regional swelling, and also be administered in situations in which systemic pain, as well as curdled milk, are common signs of health of the mare or lack of appropriate suckling by mastitis. In addition, the mare may be reluctant to the foal is thought responsible. Reserpine is also in move, and fever may be present.24 Causative or- common usage, with the added benefit of behavioral ganisms have been reported to include Streptococcus modification. Reports of metoclopramide and 33–35 equi subspecies zooepidemicus, which was the most sulpiride usage also exist. common isolate, and a wide range of both Gram- The use of pergolide (a dopamine agonist and positive and Gram-negative aerobic organisms.24,25 therefore a prolactin antagonist) is not without risk Both systemic and local antimicrobial therapy, anti- of causing lactation failure in treated mares. Al- inflammatories, and regular milking have been though many mares initiate lactation without diffi- recommended and are common treatments.25 Fi- culty while on this treatment, it is the author’s brosis of untreated tissue decreases secretory mam- preference to remove this treatment in the last 30 mary mass and therefore decreases future milk days of gestation if the health of the mare is not production. endangered. Once lactation has been established postpartum, pergolide treatment can resume. 9. Mammary Pathology 12. Nutritional Requirements of Lactation Reported neoplasia of the mammary gland is rare. Invasion of mammary tissue with carcinoma,26 ad- In addition to the endocrine and medical reasons for enoma,27 ductal adenocarcinoma,28 fibrous histiocy- lactation failure, provision of inadequate nutrition toma,29 and lymphoma30 have been reported. The should not be overlooked. Total energy and protein most common presenting clinical sign in one re- requirements are composed of maintenance and lac- view24 was enlargement of the affected gland; other tation needs. Maintenance is estimated from body findings reported were increased firmness of the weight, with lactation requirements calculated from gland, heat, pain, purulent or hemorrhagic mam- milk production and composition at all stages of mary secretion, ventral abdominal edema, ipsilat- lactation, factoring in diet composition, feed intake, eral hind limb lameness, and a serous mammary conversion efficiency, and current body reserves. gland discharge. Therefore, a primary deficiency may result when insufficient calories and nutrients are offered for 10. Endocrinopathy mare maintenance and lactational demand, or a sec- ondary deficiency when consumption and utilization Diminished circulating T and T concentrations 4 3 of nutrition is diminished or uncompensated catab- have been obtained during investigation of a variety olism is occurring due to underlying disease. The of conditions in horses.31 Because of this, hypothy- energy cost and nutrient requirement of milk roidism is deduced as the cause of poor performance, production therefore exceeds available substrate weight loss, infertility, laminitis, anhydrosis, and intake. lactation failure. In the absence of thyroid stimu- lation testing demonstrating abnormal responses or 13. Requirements for the Pregnant Mare overt pathology of the gland, there is no confirma- 31 Daily energy requirements for a 200- to 600-kg mare tion possible for this diagnosis. The euthyroid 36 sick syndrome is well recognized in human medi- are calculated as follows : cine, whereby clinical signs attributable to another ϭ ͑ ͒ ϩ ͑ ͒ disease process are ascribed to the thyroid gland as DE maintenance pregnancy requirements suppression of circulating T4 levels, not thyroid DE ϭ ͑1.4 ϩ 0.03BW͒ ϩ ͑maintenance ϫ F͒ function itself, is occurring.32 where DE ϭ digestible energy (MJ); BW ϭ body 11. Management weight (kg); and F ϭ 1.11 (9 months); 1.13 (10 Key to the successful management of lactation fail- months); 1.2 (11 months). Daily protein requirements for a 200- to 600-kg ure is to diagnose and manage any underlying med- 36 ical cause of physiological stress to the mare. In mare are calculated as follows : the absence of systemic disease, causes specific to ϭ ͑ ͒ ϩ ͑ ͒ the neurohormonal lactation axis must be sought gCP/d maintenance pregnancy and addressed. gCP/d ϭ ͑10 g CP/MJDE͒ ϩ ͑11 g CP/MJDE͒ In situations in which access to the endophyte Neotyphodium coenophialum is suspected to have where CP ϭ crude protein and MJDE ϭ MJ of di- occurred, avoidance of further grazing of those areas gestible energy.

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Orig. Op. OPERATOR: Session PROOF: PE’s: AA’s: COMMENTS ARTNO: 1st disk, 2nd beb spencers 10 3285 HOW TO MANAGE THE SUBFERTILE MARE 14. How Much of Common Feed Materials Is That? ered when calculating the amount of concentrate As a percentage of body weight, dry matter intake in feed required: the last trimester for the pregnant mare ranges from For example, daily amount of concentrate feed 1.5% to 2% of body weight.36 Of this, 35% to 40% is required that provides 16% CP (assume 40% of ra- suggested to be derived from concentrate. In the tion) ϭ 100/16 ϫ 0.4 ϫ 1520 g (calculated above) ϭ final stages of gestation, voluntary intake of preg- 3.8 kg. nant mares compared with nonpregnant controls decreased on average 20% due to the increase in 15. Induction of Lactation fetal size making the quality of the forage offered Lactation may be induced by hormonal methods in important to allow mares to meet their needs.37 nonparous mares. Protocols have been reviewed in Intake depends on forage quality. In a study of the literature.42,43 A combination of exogenous light breed mares fed ad libitum, daily intake of hay hormones and repeated mammary stimulation by was 11% higher in the high-quality versus the low- milking is required. Two avenues are taken to es- quality group.36 Although energy requirements tablish lactation in conjunction with repeated mam- were met in both groups, protein was only sufficient mary stimulation. As detailed by Steiner,44 the in the high-quality group. first involves the use of serial estrogen and proges- With respect to the lactating mare, little is known terone supplementation, with a dopamine antago- regarding dietary protein intake and its effect on nist (prolactin agonist) added. An alternative milk protein. Protein content of milk decreases program involves the use of a lighting program and throughout lactation, also as the energy content of a dopamine antagonist as relayed by Lyman.45 the ration increases milk volume increases, leading to dilutional effects on proteins.38 In one study, 16. Summary foals of mares fed the minimum recommended (Na- Lactation is the result of a complex interplay be- tional Research Council, 1989) total daily protein tween specialized anatomy and endocrinology were significantly decreased in size at weaning com- 39 driven by the reproductive necessities of the equine. pared with those of mares fed 160% of minimum. The mammary gland develops in response to each Protein intake is not dependent solely on the pregnancy and involutes when no longer required. amount of crude protein in the diet but the overall Milk production is tailored to the requirements of quality of the protein offered. Also, mares are able the foal but is affected by the systemic health of the to use body reserves to maintain milk production mare, nutritional status, and exogenous prolactin and composition when fed a diet deficient in pro- inhibitors. tein.40 Protein content of milk was found to be consistent and to predictably decline during lacta- References tion.17 The feeding of soybean meal to lactating 1. Martin-Rosset W, Austbo D, Coenen M. Energy and protein mares positively affected the growth of their foals in requirements and recommended allowances in lactating early life; however, the decline in protein content of mares: 3rd European Workshop in Equine Nutrition. Nutri- 41 the milk throughout lactation was not affected. tion and Feeding of the Broodmare. Campobasso, Italy: 2006; Milk production has been documented to vary 120:89–115. from 1.9% to 3.9% of body weight throughout lacta- 2. Starbuck GR. Physiology of lactation in the mare: 3rd Eu- 40 ropean Workshop in Equine Nutrition. Nutrition and Feed- tion in several studies. Using this range of pro- ing of the Broodmare. Campobasso, Italy: 2006;120:49–55. duction, calculation of protein requirements for 3. Hamon M, Clarke SW, Houghton E, et al. Production of 5 lactation can be achieved as follows: alpha-dihydroprogesterone during late pregnancy in the mare. J Reprod Fertil Suppl 1991;44:529–535. CP requirement ϭ BW ϫ 1.44 g CP/kg BW/d 4. Holtan DW, Houghton E, Silver M, et al. Plasma progesta- gens in the mare, fetus and newborn foal. J Reprod Fertil Suppl 1991;44:517–528. plus milk production (kg/d) ϫ 50 g CP/kg milk. 5. Chavatte P, Holtan D, Ousey JC, et al. Biosynthesis and This equates to, for a 500-kg mare: possible biological roles of progestagens during equine preg- nancy and in the newborn foal. Equine Vet J Suppl 1997; 500 ϫ 1.44 ϭ 720 g/d 24:89–95. 6. Pashen RL. Maternal and foetal endocrinology during late pregnancy and parturition in the mare. Equine Vet J 1984; and assuming 3.2% BW of milk (16 kg) in early 16:233–238. lactation: 7. Barnes RJ, Nathanielsz PW, Rossdale PD, et al. Plasma progestagens and oestrogens in fetus and mother in late ϫ ϭ pregnancy. J Reprod Fertil Suppl 1975;23:617–623. 16 50 800 g/d. 8. Ousey JC. Hormone profiles and treatments in the late pregnant mare. Vet Clin North Am Equine Pract 2006;22: Total daily requirement in early lactation is there- 727–747. fore 1520 g/d. 9. Worthy K, Colquhoun K, Escreet R, et al. Plasma prolactin It is therefore a straightforward calculation to concentrations in non-pregnant mares at different times of the year and in relation to events in the cycle. J Reprod determine the amount of feed material needed daily Fertil Suppl 1987;35:269–276. to provide this amount. Crude protein from all 10. Worthy K, Escreet R, Renton JP, et al. Plasma prolactin sources (grass, hay, concentrate) should be consid- concentrations and cyclic activity in pony mares during par-

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turition and early lactation. J Reprod Fertil 1986;77:569– 30. Mendes LCN, de Araujo MA, Bovino F, et al. Clinical, his- 574. tological and immunophenotypic findings in a mare with a 11. Deichsel K, Aurich J. Lactation and lactational effects on mammary lymphoma associated with anaemia and pruritus. metabolism and reproduction in the horse mare. Livestock Equine Vet Educ 2011;23:177–183. Product Sci 2005;98:25–30. 31. Breuhaus BA. Thyroid-stimulating hormone in adult euthy- 12. Wiest J, Thompson D Jr. Plasma prolactin, LH and FSH roid and hypothyroid horses. J Vet Intern Med 2002;16: concentrations after suckling in post-partum mares. J Re- 109–115. prod Fertil Suppl 1987;35:731–732. 32. Docter R, Krenning EP, de Jong M, et al. The sick euthyroid 13. Chavatte P. Lactation in the mare. Equine Vet Educ 1997; syndrome: changes in thyroid hormone serum parameters 9:62–67. and hormone metabolism. Clin Endocrinol 1993;39:499– 14. Doreau M, Boulot S. 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Mammary adenoma Induced lactation with a dopamine antagonist in mares: dif- in a mare: clinical, histopathological and immunohisto- ferent responses between ovariectomized and intact mares. chemical findings. Equine Vet Educ 2008;20:4–7. Reprod Domest Anim 2003;38:394–400. 28. Reppas GP, McClintock SA, Canfield PJ, et al. Papillary 44. Steiner JV. How to induce lactation in non-pregnant mares, ductal adenocarcinoma in the mammary glands of two in Proceedings. Am Assoc Equine Pract: 2006;52:259–260. horses. Vet Rec 1996;138:518–519. 45. Lyman J. Induced lactation nurse mares used to raise Stan- 29. Reesink HL, Parente EJ, Sertich PL, et al. Malignant fi- dardbred sale yearlings. Proceedings of the Annual Con- brous histiocytoma of the mammary gland in a ference of the Society for Theriogenology. Seattle: 2010:344– mare. Equine Vet Educ 2009;21:467–472. 347.

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