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Equine Veterinary Education - 2021 - Podico - Successful Induction of Lactation Foal Grafting and Maintenance of Pregnancy
Equine Veterinary Education - 2021 - Podico - Successful Induction of Lactation Foal Grafting and Maintenance of Pregnancy
Case Report
Successful induction of lactation, foal grafting and maintenance of
pregnancy in a nonparturient Thoroughbred mare
G. Podico , A. C. Migliorisi, P. A. Wilkins and I. F. Canisso*
Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana-
Champaign, Urbana, Illinois, USA
*Corresponding author email: canisso@illinois.edu
Keywords: horse; orphan foal; sulpiride; nurse mare; adoption
Abstract may mean that the foal is not fed throughout the night.
An 8-year-old mare was presented for induction of lactation Prematurely weaning a foal is thought to have both
and adoption of a 30-day-old twin filly. In each of the two behavioural and developmental consequences (Houpt 2000).
seasons prior to presentation, the mare had delivered a foal Hand-raised foals may become adult horses with behavioural
that died shortly after birth. The mare had been bred by live problems due to the lack of socialisation with other horses
cover ~25 days prior to presentation to the Illinois Veterinary (Houpt 2000). Thus, placement of the foal with a nurse mare
Teaching Hospital, but no pregnancy diagnosis was yet can circumvent the issues related to hand-raised and
performed. Upon arrival at the hospital, pregnancy diagnosis prematurely weaned foals. Typically, sources of nurse mares
confirmed a viable singleton gestational vesicle. Lactation include periparturient mares who had recently lost a foal;
was induced with dopamine D2 agonists. Immediately before lactating mares prematurely weaned from their own foal
grafting, the mare was started on altrenogest to provide (commercial nurse mare farms); mares with exceptional
exogenous hormonal support for the pregnancy. After two maternal behaviour that would adopt a second foal; or
consecutive days of PGF2a administration on Day 30 of mares not bred displaying inappropriate lactation or that had
gestation, the mare began to accept the foal, but by the next a hormonally induced lactation (Daels 2006; Steiner 2006).
day, the mare had insufficient milk production and began to Reported induction of lactation protocols in nonpregnant
show signs of foal rejection. The mare was treated with multiparous mares involves administration of steroid hormones
acepromazine for sedation and stimulation of lactation, with (oestrogen and progestins), dopamine D2 receptor
concurrent analgesic support provided by flunixin meglumine antagonists (domperidone and sulpiride) and PGF2a which
and butorphanol. One ovulation was confirmed on Day 40, can be administered at the end of steroid treatment to
and a second ovulation was confirmed on Day 45 of induce luteolysis (Porter et al. 2002; Daels et al. 2002;
gestation. On Day 47 of gestation, 11 days after adoption, Chavatte-Palmer et al. 2002; Daels 2006). An increase and
serum progesterone concentration was 13.2 ng/mL. As this decrease in oestrogen, followed by a rise and decline in
value was above the minimum level (≥4 ng/mL) deemed progesterone, coupled with a stimulus for prolactin
necessary to maintain pregnancy in the mare, altrenogest concentration increase, are thought to be important in the
administration was tapered and ultimately discontinued on successful induction of lactation in mares (Chavatte-Palmer
Day 50 of gestation. The pair remained at the hospital for et al. 2002).
treatment of leucopenia in the filly. On Day 61 of gestation, Ideally, foal grafting is done when a mare is in full
25 days after adoption, continued maintenance of lactation, whether induced or spontaneous. Described foal
pregnancy was confirmed in the mare, full lactation had grafting protocols include vagino-cervical stimulation,
been achieved, and strong bonding between mare and foal exposure of a lactating mare and foal to a perceived threat
was apparent. The pair was discharged from the hospital to such as another horse or dog, and hormonal manipulation
the care of the owner. (Daels et al. 2002; Porter et al. 2002; Daels 2006). Other
described ancillary methods include wrapping the mare’s
placenta on a foal to be grafted, rubbing a foal with the
Introduction mare’s faeces or using the halter from the nurse mare’s
Maternal death, foal rejection, insufficient milk production or biological foal on the new foal to be adopted (Houpt and
inability to produce milk due to maternal illness is a common Mills 2006). Additionally, some practitioners advocate
problem seen in broodmare practice. Under these conditions, collecting mare’s sweat with a towel after administering large
foals may be bottle- or bucket-fed, transferred to a nurse doses of PGF2a and rubbing the towel on the foal being
mare or weaned sooner than intended if older (Naylor and adopted.
Bell 1985; Cymbaluk et al. 1993; Paradis 2012; Stoneham et al. Vagino-cervical stimulation consists of restraining the mare
2017). Despite the availability of commercial equine milk in stocks, performing vigorous stimulations in the birth canal to
replacers, there are concerns that these products can lead emulate parturition, eliciting the Ferguson reflex and then
to diarrhoea or constipation (Paradis 2012). Additionally, supervising suckling with the mare restrained in stocks for
feeding an orphan with milk replacers is relatively expensive, several days until the full maternal–foal bond is attained
given the cost of quality milk replacers, and a laborious task (Porter et al. 2002). Pharmacological protocols entail
requiring frequent attention (e.g. q. 2–4 h up to 60 days) administering oxytocin and/or extremely high doses of PGF2a
(Paradis 2012). In some farm settings, personnel limitations or its analogs; the latter is presumably given to stimulate the
release of oxytocin in the central nervous system (Fuchs 25 days, consistent with the breeding history provided by the
1987). Administration of oxytocin alone to induce foal grafting owner. Visual examination and manual palpation of the
should be discouraged as it is thought to be ineffective, as udder were performed. There was no mammary gland
oxytocin does not cross the blood–brain barrier in several development, nor were secretions, signs of mastitis or fibrosis
species such as sheep, rat, guinea pig and humans present.
(Meisenberg and Simmons 1983; Ermisch et al. 1985).
While PGF2a and its analogs are thought to be effective in
Diagnosis
promoting foal grafting, they are known to be abortifacient in
mares during the first trimester of pregnancy, particularly Apparently healthy mare carrying a singleton ~25-day-old
when given up to 35 days of gestation (Ginther 1985; Daels pregnancy.
et al. 1996; Podico et al. 2020). For this reason, induction of
lactation and subsequent foal grafting is typically performed
Treatments
in nonpregnant mares. However, while not ideal, in some
specific situations, using a pregnant mare for foal grafting Induction of lactation
could be both practical and financially beneficial when the The mare was started on a course of a labelled dose of
foal on the ground is prioritised over the pregnancy in utero. domperidone (Equidoneâ, 1.1 mg/kg bwt, per os, q. 24 h)1
This report aimed to describe the successful induction of treatment for 4 days (Table 1). Milk stripping was started on
lactation in a pregnant mare starting at ~25 days of gestation the second day of domperidone and continued two times a
with subsequent foal grafting at ~35 days of gestation. This is day for the first 5 days, with average milk production of 45 mL
the first report of successful induction of lactation and foal per day (Table 2). On Day 5, the domperidone treatment
grafting in a pregnant mare to the authors’ knowledge. was discontinued, and sulpiride treatment was initiated with
compounded injectable sulpiride (50 mg/mL, dissolved in 85%
cottonseed oil and 10% benzyl alcohol, 1 mg/kg bwt, i.m., q.
Case history
12 h)2. At the IVTH and elsewhere (Daels et al. 2002; Porter
An 8-year-old multiparous Thoroughbred broodmare was et al. 2002), sulpiride is the preferred benzamide over
presented to the Illinois Veterinary Teaching Hospital for domperidone for induction of lactation in mares. It has been
induction of lactation and subsequent adoption of a 30-day- suggested by other authors (Chavatte-Palmer et al. 2002;
old orphan Thoroughbred filly owned by the same breeder. Daels 2006), and it is the authors’ clinical impression that
The filly and its twin colt had been delivered in the field by sulpiride results in a more consistent clinical response when
the referring veterinarian via terminal caesarean section compared to domperidone. However, herein the treatment
necessitated by dystocia. The twin colt died after 12 h of with sulpiride was delayed due to a nationwide shortage
hospitalisation; the filly required 4 weeks of intensive care immediately prior to the initiation of treatment of the present
before withstanding the adoption procedure. The mare had case. On Day 9, after 5 days of sulpiride treatment initiation,
been bred by live cover ~25 days prior to presentation to the milk production progressively increased in volume (Table 2).
Illinois Veterinary Teaching Hospital (IVTH) but had not yet The mare was then milked more frequently (q. 4 h).
been examined to diagnose pregnancy. The mare delivered
two live foals in consecutive pregnancies, but both foals died Foal adoption
shortly after birth due to unknown causes. Acquisition of a On the day of adoption, the orphan filly was 30 days old,
lactating mare from a specialised nursing mare farm or weighed 32 kg and had a withers height of 76 cm. The
induction of lactation in a different mare and then adoption was carried out at this age because the filly had
performing a foal adoption were offered but declined by the been intensively treated for immature bone and lung
owner. Instead, the owner wanted to use one of his development until this point. Until this time, the filly had been
nonparturient broodmares for the induction of lactation and unable to stand for an extended period of time and required
foal grafting. The owner was informed about potential risks for intensive treatments, which precluded grafting efforts. Prior to
abortion after the administration of PGF2a in the presence of the onset of adoption, the filly was being fed from a pan with
pregnancy but elected to pursue the adoption with this 500 mL of equine milk replacer (Mare’s Match foal milk
particular mare. replacer)3 every 3 h. To facilitate the adoption, the milk
replacer was withheld for 4 h before the onset of the grafting.
Right before the procedure, transrectal palpation and
Clinical findings
ultrasonographic examination of the mare revealed a
The mare weighed 636 kg and was bright, alert and singleton gestational vesicle with an embryo displaying
responsive. Physical examination was performed at admission, apparently normal heartbeats, staged as ~35 days old, and a
and findings were unremarkable. The reproductive corpus luteum in each ovary (Fig 1, Table 3).
examination revealed poor perineal conformation (vulva To prevent pregnancy loss, the mare was administered
slightly tilted horizontally with the majority of the vulva altrenogest (Regu-Mateâ, 0.088 mg/kg bwt, per os., q. 24 h)4
located above the pelvic brim), and there was no Caslick’s beginning 6 h before the first grafting attempt. Dinoprost
vulvoplasty in place. Transrectal palpation and tromethamine (Lutalyseâ, 25 mg, 5 mL, i.m.)5 was
ultrasonography revealed a singleton gestational vesicle administered, and the introduction of the orphan filly was
(30 mm 9 35 mm) with an embryo displaying apparently attempted, after ~20 min, when the mare was showing signs
normal heartbeats. In addition, one corpus luteum was of discomfort, which included mild sweating, restlessness and
visualised on each ovary associated with multiple small soft manure due to hyperperistalsis (Coffman and Pinto 2016).
follicles (<20 mm). Based on the clinical findings, the The filly was carefully restrained when presented to the mare;
gestational age was determined as approximately 23– an experienced handler held the mare to allow a controlled
TABLE 1: Summary of drugs used to induce and maintain lactation, to perform foal adoption and maintain pregnancy
Gestation Duration
days (d) Drugs and dosing Reason(s) for performing
TABLE 2: Milk production of an early pregnant Thoroughbred related to the high dose of PGF2a analogs and to mimic the
mare treated with domperidone (1.1 mg/kg bwt, per os, q. 24 h)
physiological release of opioids occurring during suckling.
(Days 1–4) and sulpiride (1 mg/kg bwt, i.m., q. 12 h) (Days 5–10)
Overnight, the pair was kept in the same stall, divided by
Milking Estimated production in a built-in pen. The filly was exposed to the mare overnight
Days frequency 24 h (mL) and encouraged to nurse at 4-h intervals. When no successful
latching was achieved, the filly was fed 500 mL equine milk
Domperidone 1 0 0 replacer (Mare’s Match Foal Milk Replacer) in a pan held
2 q. 12 h 40
under the mare. The mare was handheld during all the pan
3 q. 12 h 40
feedings. While she did not display aggressive behaviour,
4 q. 12 h 40
Sulpiride 5 q. 12 h 60 interest for the foal progressively declined throughout the
6 q. 8h 100 night. The next day, the mare showed no maternal
7 q. 8h 300 behaviour, and the procedure was repeated as previously;
8 q. 8h 600 the filly had feeding withheld for 4 h before the procedure.
9 q. 4h 1500 The mare did not show any maternal behaviour after 15–
10 q. 4h 2400 20 min from the injection of dinoprost (25mg, 5mL, i.m.)5;
therefore, she received an injection of cloprostenol sodium
(500 lg, 2 mL, i.m.)4. Within 5–10 min from the second
injection, the mare began to display excellent maternal
behaviour, and the filly was encouraged to nurse (Fig 2a).
and safe interaction. The filly’s nose, ribs, flank and perineal The mare started vocalising and licking the foal; she did not
area were presented to the mare. After 10–15 min of react at any attempt of the filly to nurse; indeed, she was
exposure, the mare did not show overt signs of aggression gently stimulating the filly to nurse while touching her back.
towards the filly, but did not display maternal behaviour like In contrast with the previous day, the filly had a strong
nickering, licking or sniffing the foal. The mare was then sucking reflex, which greatly facilitated grafting. Each
administered cloprostenol sodium (Estrumateâ, 500 lg, 2 mL, latching lasted for 2–5 min, whereas the filly would not fully
i.m.)4. The mare started showing stronger maternal behaviour latch in the previous day and only kept her mouth on the
after 10 min, such as licking, sniffing and nickering to the foal. udder for a few seconds. The mare was administered
The filly was assisted while trying to nurse; unfortunately, butorphanol tartrate (10 mg, 1 mL, i.v.)5 to alleviate pain and
her sucking reflex was not vigorous enough to fully latch on to further mimic the physiological release of endogenous
the udder. In addition, the filly seemed intimidated by the opioids during suckling. Thereafter, the filly was allowed to
mare as this was her first close exposure to another horse. nurse on the mare every 2 h under close supervision: one
After four unsuccessful attempts to assist the filly in nursing person holding the mare and a second person holding the
over approximately 2 h, with breaks of 20 min between foal with care to not allow the foal to cross beyond the
attempts, the nursing assistance was discontinued until the mare’s flank. After 6 h of successful foal–mare interaction,
next day. A dose of butorphanol tartrate (Torbugesicâ, 10 mL, they were kept together and monitored by having a person
1 mL, i.v.)5 was administered to the mare to alleviate the pain standing in front of the stall and watching on a wall-mounted
D 35 D 36 D 37 D 40 D 47
* * *
* * * * * *
* * *
*
a) b) c) d) e)
Fig 1: Representative images of ovarian structures and pregnancy development of a pregnant mare before a) and after b-e) the foal
grafting with PGF2a analogs. Images were obtained with a 5 MHz linear transducer. * denotes luteal structure; ▲ denotes the embryo a-
d) or fetus e).
TABLE 3: Ultrasonographic findings from 25 to 61 days of pregnancy in a Thoroughbred mare submitted to induction of lactation and
foal grafting with PGF2a at ~ 35 days of gestation
Gestational age Follicles Luteal structures (no, size Follicles Luteal structures (no, size Fetal heart rate (beats/
(days) (mm) mm) (mm) mm) min)
25 20 1 20 1 n/a
35 40 1 (27.4 9 34.0) 15 1 (31.9 9 33.0) 128
36 40 1 (27.8 9 26.5) 15 1 (26.0 9 26.7) 124
37 40 1 (25.1 9 26.5) 30 1 (23.0 9 25.4) 118
40 15 1 40 2 120
47 15 2 15 2 112
61 15 2 15 2 120
camera. After no signs of rejection, they were left stimulate prolactin production to promote lactation for 2 days
unsupervised. Administration of the equine milk replacer to (Bryant et al. 1968). In addition, butorphanol tartrate (10 mg,
the filly was discontinued that night. Flunixin meglumine 1 mL, i.m., q. 8 h for 2 days)4 was also administered for its
(PrevailTM, 1.1 mg/kg bwt, i.v., q. 24 h)6 was administered for 4 analgesic and sedative properties and its potential ability to
days to prevent and treat pain derived from a potentially also stimulate prolactin release (Knight et al. 1986; Baumann
sore udder due to the now vigorous nursing behaviour of the and Rabii, 1991). The filly gained 2.5 kg over the next 2 days,
foal. considered appropriate weight gain, and milk replacer was
Approximately 18–24 h after the filly’s apparently then offered at 12-h intervals (Knight and Tyznik 1985). After 4
successful introduction, the mare demonstrated mild to days of continued weight gain, milk replacer was
moderate signs of foal rejection, including stall walking, not discontinued, and there were no further signs of rejection.
standing for the foal to nurse and minimal interest in the filly. Ultrasound examinations were performed daily for the first
This behaviour was thought to be due to insufficient milk 6 days, then every 48 h for four more days and then weekly
production and subsequent discomfort caused by vigorous until discharge (35–41, 43, 45, 47, 55 and 61 days of
suckling attempts in the absence of sufficient milk by the gestation). The ultrasound examinations on the mare were
mare. The filly was then offered 500 mL of the same brand of carried out with a linear probe 5 MHz coupled with an
equine milk replacer fed previously every 8 h to decrease the ultrasound machine (IBEX EVO II)8 using the manufacturer’s
burden on the mare. In addition, the mare received settings for equine reproduction. During each examination,
acepromazine maleate (AceproJectâ, 30 mg, 3 mL, i.m., q. 8 ovarian structures (number and size of follicles and corpora
h for 2 days)7 for its tranquilising properties and its ability to lutea) and pregnancy features (size of the gestational
a) b) c) d)
Fig 2: Representative images of excellent maternal behaviour of the broodmare during a-b) and after c) the grafting procedure.
vesicle, stage of development, embryonic/fetal heart rates) achieved. The filly was treated with chloramphenicol
were assessed (Fig 1, Table 3). The follicles and corpora lutea (Vicetonâ, 1 g/tablet, 20 mg/kg bwt, per os, q. 6 h)10 until
were measured at two of the major diameters of each the white blood cell count returned to within normal limits. At
structure and reported in Table 3. One clinician manually the time of discharge from the hospital, the mare was
counted the embryonic/fetal heart rates, and the mean value confirmed pregnant at 61 days of gestation (Fig 4a-b), and
of two assessments was reported (Table 3). The pregnancy the foal was apparently healthy. The pair was reported to be
continued developing after the treatments with PGF2a; the clinically well 3 months after discharge; they were successfully
chorioallantoic cavity increased in size. No abnormalities were reintroduced into their herd, and the filly appeared in good
noted in the pregnancy fluids, embryonic and fetal structures, general systemic health (Fig 5). No objective follow-up (e.g.
or embryonic and fetal heart rates. The two primary corpora physical examination, bloodwork) was performed. Per
lutea decreased in size after PGF2a administration (Table 3). communication with the referring veterinarian and farm
Two large follicles developed on Days 38 and 40 of gestation; manager, 6 months after discharge from the hospital, the filly
one dose of deslorelin acetate (SucroMateTM, 1.8 mg, 1 mL, i. (weighing 180 kg) and mare were reported to be apparently
m.)9 was administered on Day 38 of gestation to induce healthy (Fig 6), and the mare remained pregnant. The stud
ovulation. Two new corpora lutea were visualised on Days 40 farm planned to wean off the filly within days after our last
and 45 of gestation. The peripheral progesterone communication.
concentrations were assessed in serum samples at 35, 36, 37,
40 and 47 days of gestation (Fig 3). After a rapid decline,
Discussion
progesterone’s serum concentration increased after the
detection of one corpus luteum on Day 40 and another one on The present report described a clinical case in which the
Day 45 of gestation (Fig 3). The administration of altrenogest induction of lactation and foal grafting were successfully
(0.044–0.088 mg/kg, per os, q. 24 h) was adjusted based on the carried out in a nonparturient early pregnant mare. Induction
serum progesterone concentrations and perceived proximity of lactation has been successfully carried out in mares and
of abortifacient side effects of PGF2a. The mare received a other species involving a combination of ovarian steroids,
supratherapeutic dose of altrenogest (0.088 mg/kg, per os, q. PGF2a and benzamide dopamine D2 antagonists (Chakriyarat
24 h) for 4 days (35–38 days of gestation), then a standard et al. 1978; Head et al. 1980, 1982; Daels et al. 2002; Porter
therapeutic dose (0.044 mg/kg, per os, q. 24 h) from 39 to et al. 2002; Chavatte-Palmer et al. 2002). The combination of
46 days of gestation. The concentration of progesterone at these hormones provides satisfactory induction of lactation in
47 days of gestation was 13.2 ng/mL, and the altrenogest dose multiparous mares but unsatisfactory lactation in nulliparous
was tapered off by 2–3 mL/day until none was administered at mares (Chavatte-Palmer et al. 2002). In the present case, the
50 days of gestation. The minimum threshold of serum mare was a multiparous Thoroughbred mare that had never
progesterone concentration for maintenance of pregnancy in raised foals for a full lactation, so while her udder was
the first trimester has been suggested as ≥4 ng/mL (Shideler developed enough up to delivery, she never came into the
et al. 1982). Once it became clear that the mare was peak of an entire lactation. This history implies that,
maintaining the pregnancy, Caslick’s vulvoplasty was potentially, the udder was never fully developed before this
performed at 45 days of gestation to correct the poor vulvar case. This may explain the relatively slow response of the
conformation. The client declined to have it performed initially mare to produce milk in response to ten days of benzamide
as the mare could have experienced early pregnancy loss dopamine D2 antagonists and milking.
during the foal grafting with the PGF2a administrations. An early Widely used protocols for induction of lactation involve
pregnancy loss would have implied transvaginal procedures administration of oestrogen, progesterone and PGF2a; this last
and the removal the Caslick’s procedure; therefore, the client hormone is typically given at the end, after a few days of
elected to postpone it to not incur additional costs. ovarian steroid administration (Daels et al. 2002; Daels 2006).
Due to progesterone’s negative feedback on prolactin
secretions, it is desirable to induce luteolysis early in the
Outcome
protocol for induction of lactation (Shand et al. 2000;
The pair was kept in the hospital for 26 days after the foal Chavatte-Palmer et al. 2002; Guillaume et al. 2003). A
grafting onset due to the foal’s concurrent leucopenia. A retrospective study found that Arabian mares, a breed
definitive diagnosis of the cause of leucopenia was not known for having a high incidence of abnormal maternal
14
PGF2α Ovulation
*
12
Ovulation
10 *
Progesterone (ng/mL)
0
35 36 37 38 39 40 41 42 43 44 45 46 47
Day of gestation
Fig 3: Serum progesterone concentrations before and after the administration of PGF2a. The mare was administered 0.088 mg/kg, per
os of altrenogest at 35–38 days, and then 0.044 mg/kg, per os from 39 to 50 days of gestation.
D 61
*
*
* *
a) b)
Fig 4: Representative images of the accessory corpora lutea a) and fetal appearance b) of a 61-day pregnancy of a mare after
induction of lactation and adoption of an orphan foal. Images were obtained with a 5 MHz transrectal sectorial convex transducer.
*denotes luteal structure; ▲denotes fetus.
behaviour (Juarbe-Diaz et al. 1998), had high peripheral domesticated animals, progesterone is known to have a
concentrations of progesterone and low prolactin the day direct inhibitory effect on prolactin release (Chamley et al.
after parturition when rejecting their foals (Berlin et al. 2018). 1973; Erb et al. 1976). Interestingly, a study involving dioestrous
This finding, coupled with the present clinical case, suggests mares receiving PGF2a demonstrated that prolactin pulses
that progesterone may play an important role in maternal frequency and amplitude peaked at the nadir of
behaviour in mares. progesterone concentrations following luteolysis (Shand et al.
In the authors’ experience, mares displaying regular 2000). However, the relationship between progesterone and
ovarian cyclic activity during the breeding season have no prolactin concentrations and maternal behaviour remains to
need for exogenous ovarian steroid administration as oestrus be better studied in horses.
and dioestrus produce physiological changes in oestrogen It has been recommended that mares are producing 3–5 L
(oestrus) progesterone (dioestrus and luteolysis) of milk in 24 h before foal adoption (Daels et al. 2002),
concentrations. In the present case, the mare was pregnant, however, as this mare was not progressing as typical in our
and the administration of PGF2a alone could have resulted in practice (1.5 L and 2.4 L in 24 h, 2 days before and the day
pregnancy loss (Ginther 1985; Podico et al. 2020). It is possible before adoption). The authors elected to carry on with the
that high progesterone concentrations from double adoption and supplement the foal as needed. The presence
ovulations between 25 and 35 days of gestation, followed by of offspring (visual, tactile and olfactory stimuli) is thought to
altrenogest supplementation from 35 to 47 days of gestation, play a role in stimulating lactation in sheep (Kendrick et al.
and coupled with the fact that the mare had never fully 1986; Poindron et al. 1988); a similar mechanism likely occurs
lactated slowed the initial milk production. In other in horses (Wolski et al. 1980). In addition, foals are more
maintenance of pregnancy is entirely dependent on the The adoption protocol used here has been commonly
progesterone produced by the primary corpus luteum and used at the University of Illinois for the past 5 years (>30 mares
abrupt luteolysis induced by PGF2a administration generally treated). After 15–20 min of dinoprost, if the mare does not
leads to pregnancy loss (Ginther 1985). If the mare in the show signs of maternal behaviour, cloprostenol is added to
present case had lost her pregnancy between foal grafting the protocol. The authors have tried administering a larger
(35 days of gestation) and discharge (61 days of gestation) dose of dinoprost, and mares become extremely
from the hospital, it would have been difficult to differentiate uncomfortable, and the adoption protocol does not seem
between an expected pregnancy loss of 6% between 15 and effective. The authors also have attempted to use large
42 days of gestation in Thoroughbreds for various causes not doses of cloprostenol, such as 1000–1250 lg, and mares do
related to exogenous PGF2a administration (Rose et al. 2018). not respond satisfactorily to it, and foal adoption is not
Due to the high odds for pregnancy loss in mares receiving successful. Vagino-cervical stimulation is routinely performed
exogenous PGF2a analogs (Daels et al. 1995; Daels et al. if the mare fails to respond to the combination of dinoprost
1996), the use of pregnant mares for foal grafting should be and cloprostenol. Oxytocin is not administered to the mare
restricted to select cases where the orphan foal is prioritised unless it needs to be used as an ecbolic to treat intrauterine
over the ongoing pregnancy in utero. Luteolysis was fluid accumulation.
documented to occur shortly after initial PGF2a administration. The authors routinely administer butorphanol tartrate once
Progesterone concentrations were 10.2 ng/mL on Day 35 and the foal latches on the mare. This drug is included for its
then 2.76 ng/mL on Day 36 of gestation, and it was 0.54 ng/ analgesic properties and for presumably mimicking
mL on Day 39 of gestation. Interestingly, since the mare had endogenous release of opioids in the brain during suckling.
two large pre-ovulatory follicles on Days 39 and 44, ovulation Studies in rodents and sheep have shown that endogenous
was induced on Day 39, and two corpora lutea were and exogenous opioids cause hyperprolactinaemia (Knight
identified on Days 40 and 45 of gestation. These two et al. 1986; Baumann and Rabii 1991). Specifically, in
ovulations raised progesterone concentrations to 13.2 ng/mL, mammals, suckling results in a release of endogenous opioids,
which was deemed enough (≥4 ng/mL) to maintain which bind to mu and kappa receptors, causing a release of
pregnancy in this mare (Shideler et al. 1982). prolactin and inhibition of LH secretion (Baumann and Rabii
Once exogenous PGF2a is administered, the mare 1991). While single doses of butorphanol were shown to
responds by producing more endogenous PGF2a, as increase prolactin concentrations in humans (Franceschini
evidenced by an increase in PGFM, an inactive metabolite et al. 1989), it is unknown whether butorphanol increases
of PGF2a (Daels et al. 1996). Interestingly, PGFM was reduced prolactin in horses. Opioid receptors (mu, kappa and delta)
in pregnant mares challenged with the administration of are G-protein-coupled receptors that are once activated by
cloprostenol sodium (250 lg, i.m., q. 24 h) but also an agonist or a competitive antagonist, resulting in
supplemented with altrenogest (0.044 mg/kg per os q. 24 h) decreased cAMP production and downregulation of
when compared to mares treated with cloprostenol but not adenylate cyclase (Kukanich and Wiese 2015). The analgesic
treated with altrenogest (Daels et al. 1996). In addition, none effect is produced by reduced excitatory molecules of
of the mares (8/8) treated with cloprostenol and altrenogest nociceptors and elevation of the activation threshold.
aborted, whereas all mares aborted (6/7) when treated with Specifically, butorphanol interacts with mu receptors, as a
cloprostenol alone, with one out of seven not aborting when competitive antagonist and partial agonist, and with kappa
treated with cloprostenol and flunixin meglumine (500 mg i.v. receptors as an agonist (Kukanich and Wiese 2015). Its
q. 8 h) (Daels et al. 1995, 1996). While the concentration of analgesic properties are somewhat dose-dependent and do
PGFM was not assessed in the present case report, the not increase after a specific dose (Kukanich and Wiese 2015).
amount of PGF2a administered was certainly enough to In the present case, the pain level was low, and the need for
cause abortion should this mare have not been both sedation and mild analgesia led us to use butorphanol
supplemented with altrenogest. (Kukanich and Wiese 2015). Antagonist properties of
Sulpiride is preferred over domperidone to induce butorphanol with mu receptors prevent the hyperexcitement
lactation in mares. While one study reported similar total milk associated with the opioid administration in horses (Gozalo-
production in mares treated with either product, studies Marcilla et al. 2015). This represented a desirable feature for
overwhelmingly recommend using sulpiride over the present case (Gozalo-Marcilla et al. 2015).
domperidone (Daels et al. 2002; Chavatte-Palmer et al. 2002; If the mare fails to accept the foal or does not display
Guillaume et al. 2003). One huge disadvantage is that the fully satisfactory maternal behaviour, the authors elect to
oral product has low bioavailability (~20%), thus requiring repeat PGF2a administrations 2–3 days in a row. In our clinic,
parenteral administration (Giorgi et al. 2013). Each injection mare and foal are only put together after adoption if the
involves a large volume of product (i.e. 14 mL twice a day, in mare shows strong maternal behaviour over 6–12 h of careful
the present case), which is administered intramuscularly. The observation. The mare in the present case could have given
half-life (~9 h) of sulpiride is rather short, requiring the false idea that it was safe to house the foal with her after
administration twice a day to maintain adequate blood the first attempt. While the mare showed positive maternal
concentrations (Giorgi et al. 2013). Commonly, serial behaviour after the first round, the foal’s lack of a strong suck
injections of large volume of compounded medication cause reflex resulted in the mare losing interest in the foal overnight.
local swelling and tenderness. In the authors’ experience, Though the maternal behaviour after the first round of
mares could become sensitised to repeated injections after dinoprost could have discouraged some practitioners, a
initial treatments. Surprisingly, the mare of the present case second round was necessary. It is possible that altrenogest
did not develop an excessive local reaction or display supplementation given to prevent pregnancy loss could have
behavioural changes. been the reason for the need for a second treatment. It
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experimental induction by ovariectomy or prostaglandin F2alpha.
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