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VETERINARY CLINICAL SCIENCE

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REVIEW ARTICLE

Understanding patho-physiology of retained placenta and its management in cattlea review


Rooh Ul Amin1, G.R. Bhat1, Ajaz Ahmad2, Partha Sarathi Swain3 and G. Arunakumari4
1

PhD scholar, Department of Veterinary Gynaecology and Obstetrics, Guru Angad Dev Veterinary and Animal
Sciences University, Ludhiana, Punjab, India.
2
PhD scholar, Department of Veterinary Pathology, Guru Angad Dev Veterinary and Animal Sciences University,
Ludhiana, Punjab, India.
3
PhD scholar, Dairy Cattle Nutrition Division, National Dairy Research Institute, Karnal, Haryana
4
Assistant Professor, Department of Veterinary Gynaecology and Obstetrics, College of Veterinary Science
Rajendranagar, Hyderabad, India.

Abstract

*Corresponding Author:

Rooh Ul Amin
Email: dr.roohulvet@gmail.com

Received: 16/11/2013
Revised: 17/12/12013
Accepted: 18/12/2013

Retention of Placenta (ROP) in animals has adverse effects on


fertility and production. However, understanding the pathophysiology and
causes of ROP is important for managing this disease. The hormonal
processes that lead to normal placental separation are multifactorial and
begin before parturition. A variety of risk factors, including early or
induced
parturition,
dystocia,
hormonal
imbalances,
and
immunosuppression, can interrupt these normal processes and result in
retention of the placenta. Systemic administration of antibiotics can be
beneficial for treating metritis after ROP, but antibiotic administration has
not been shown to significantly improve future reproduction. Use of
immunomodulators reduces the uterine inflammation and infection but is
not used routinely. Collagenase injected into the umbilical arteries of
retained placentas specifically targets the lack of placentome proteolysis
and might enhance placental release. However, such therapy is costly and
its benefits in terms of improving subsequent reproductive function have
not been evaluated. The present review will highlight some of the effective
means of management of ROP.

Keywords: Retention of placenta, cattle, pathophysiology, management

Introduction
Fetal membranes or what is known as
placenta is an essential organ for prenatal transfer of
nutrients and oxygen from the dam to the fetus. It
normally drops within short time post partum (within 8
hrs of parturition), if it is retained up to 12 hrs then it is
called as delayed removal and if retained for more than
24 hrs of parturition then it is called as Retention of
placenta (ROP). Such retention creates a number of
problems by allowing microorganisms to grow inside
the uterus causing its inflammation, fever, weight loss,
decreased milk yield, longer calving intervals and may
result in an open cow during the next year and if the
infection is so bad the animal may actually die. Due to
retention of placenta animal may suffer from tetanus as
tetanus organism is commonly found in feaces and soil
which requires at least 1-3 months as long term
therapy. Retention of Placenta causes great economic

losses, mainly due to decreased milk yield and calf


crop.

Incidence
The incidence in cows varies from 4.0-16.1%.
However, it can be much higher in problem herds and
also increases during summer with increased parity,
milk yield in the previous seasons and following birth
of male fetus (El-Malky et al., 2010; Ahmed et al.,
1999) Abortions, stillbirths and twin calvings resulted
in increased incidence rates of 25.9, 16.4 and 43.8%,
respectively. Also El-Malky et al. (2010) demonstrated
an incidence of ROP reaching 4.6% in buffalo-cows
over three years of study.

Mechanism of fetal membrane separation

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Rooh Ul Amin et al.Understanding patho-physiology of retained placenta and its management in cattle

Three events are involved in cotyledon-caruncle


detachment (Youngquist and Threlfall, 2007):

the placentomes at the end of pregnancy (Frazer et al.,


2005).

Morphologic events: Detachment of placenta in the


cow involves separation of the finger-like cotyledon
villi from the caruncle crypts without significant
tearing of either fetal or maternal epithelia. For the
cotyledon villi to separate from the caruncle crypt, it is
critical that the mouth of the cotyledon pouch be
opened first by proteolytic enzymes. This is achieved
by formation of the mouth of the cotyledon toward
the apex (dehiscence) or by following a concentric
band pattern in which the edge of the cotyledon
pouch is digested first.
After placental detachment is accomplished,
uterine involution is completed in an average of 39
days in normal cows and 50 days in cows with ROP.
By day 6 post partum, caruncle septa are disorganized;
by day 15, caruncles are completely sloughed as a
result of necrosis. Consequently, retained membranes
are detached by caruncle necrosis within 6 to 10 days
and not later than 17 days post partum. The surface of
the endometrium is covered by new epithelium by day
26 to 30 post partum.

Failure of cotyledon-caruncle detaching


mechanisms

Biochemical events: Postpartum uterine biochemistry


is dominated by increased collagenase and other
protease activities that correlate with different stages of
parturition, resulting in a massive breakdown of
collagen and other proteins during uterine involution.
As a result, the weight of the cows uterus decreases
from 9.0kg at parturition to 1.0kg at 30 days post
partum.
Physiologic events: Physiologic release of placenta is
accomplished in most cows between 3 and 6 hours post
partum. Cotyledon proteolysis (dehiscence) and
decreasing adhesiveness (viscosity) of the cotyledoncaruncle interface fluids seem to be key factors in the
release of placenta. Collagenases are capable of
reducing the specific viscosity of collagen. Collagenase
activity of cotyledon villi during delivery is increased
in healthy cows and decreased in cows with ROP. The
cellular sources of collagenase and proteolytic enzymes
for placental release in the cow are unknown. In
laboratory animals and humans, myometrial cells,
fibroblasts, and leukocytes have been identified as
sources of collagenase in the uterus. Lack of uterine
motility is not considered as a reason for primary
retention, because uterine motility is normal or above
normal in cows with primary ROP. The direct cause of
placental retention is uncertain, but it is related to a
deficiency of myometrial contractions and failure of
the maternal immune system to successfully degrade

The key element in the pathogenesis of retained


placenta is a failure of timely breakdown of the
cotyledon-caruncle attachment after delivering the
fetus. The most important risk factors for placental
retention are abortion, stillbirth, twining, dystocia,
induction of parturition with PGF2 and caesarean
section, metabolic disorders, especially milk fever.
Prenatal losses can be caused by infectious and non
infectious factors. Primary attention has been often
directed to infectious causes, but non infectious factors
probably account for 70% or more of the cases (Frazer
et al., 2005). The infectious causes of placental
retention are behind the scope. Non infectious causes
are often multifactorial and are difficult to diagnose
(Hanzen et al., 1999). The list of potential causes is
quite long, however, there are a number of common
causes (Ball et al., 2004).
Hereditary causes of retained placenta: Nasr et al.
(1996) reported that cows having blood group genotype
BGKOxA0 bred with sire have I genotype dropped
their placenta normally, while cows having BO3Y2
AE3GP genotype bred with sire having genotype I2
showing high incidence of ROP. On the other hand, the
most frequent alleles in serum proteins of NROP (Non
retention of placenta) cows were albumin (ALA), post
albumin (PalA) and amylase (AmB) gene markers,
while the most frequent genetic alleles in serum
proteins of ROP cows were alpha globulin (FA) and
transferrin D (TFD). Moreover, it was recommended to
use the above mentioned genetic constituents of both
dam and sire for breeding purposes In high lactating
cows, somatotropins stimulate the production of
insulin-like growth factor 1 (IGF-1) in the hepatic cells.
However, the plasma IGF-1 level was found to be quite
low, especially in the hyperketonaemic animals
Huszenicza et al. (2006) in which metabolic products
(non esterified fatty acids (NEFA) and OH-butyrate
(BHB) accumulate and impairs the migration,
phagocytic and killing activity and /or the oxidative
burst of PMNs and other leukocytes, enhancing the
susceptibility of host to invading pathogens (Reist et
al., 2003).
Mechanical causes of retained placenta: Difficult
birth (calf too large for cow, backward presentation of
calf known as breech birth, one leg or head
backwards), twins, late or premature birth, prenatal
loss, induction of parturition with PGF, cesarean

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Rooh Ul Amin et al.Understanding patho-physiology of retained placenta and its management in cattle

section and fetal monsters or emphysematous fetus


(gas-filled fetus) are direct causes of dystocia and
consequently to ROP.
Nutritional causes of retained placenta: Cows 0-120
days postpartum are at risk of ration formulation error
and feed which leads to delivery problems.
Periparturient dairy cows (0-20 days postpartum)
undergo a transition from a relatively high fiber diet to
a lactation diet that generally is higher in energy and
lower in fiber. During this period, the amount of energy
required for maintenance of body tissues and milk
production usually exceeds the amount of energy in the
diet (Goff et al., 1997). This nutrient deficit makes the
cow susceptible to metabolic diseases such as ketosis
and milk fever, which usually occur within 3 weeks of
thereby calving slowing adaptation to the postpartum
diet. Also, prepartum heavy grain feeding may be
associated with both higher milk production and a
higher incidence of left- displaced abomasum (Lucey et
al., 1986) and increased risk of reproductive disorders
such as dystocia, retained placenta, cystic ovaries,
metritis Oetzel et al. (1995) prolapsed uterus
Markusfeld et al. (1993) and acute clinical mastitis
increasing the risk of non- parturient paresis (Gro et al.,
1989) Cows being adapted to high- energy and high
concentrate lactation rations are at risk because the
rumen papillae need time to elongate and the microbial
population needs time for adaptation. Also, lower dry
matter intake near calving can result in depressed
forage intake.It has generally been found that other
feeding-related diseases increase the risk of nonfeeding-related diseases rather than vice versa.
Vitamin and mineral deficiency conditions such
as selenium, vitamin E and vitamin A, -carotene and
disturbed C/P (1.5/1) ratio can impair general immunity
Sheldon et al. (2004) and may alter the competence of
cellular self-defence mechanism and can increase the
risk for placental retention and metritis. Ahmed et al.
(2009) reported that ROP was associated with
oxidative stress as shown by the obvious increase of
blood malondialdehyde and nitric oxide and decreases
of catalase, superoxide dismutase, ascorbic acid,
glutathione reduced and total antioxidant capacity
values with low zinc, copper, iron and selenium
concentrations.
High milking cows with a greater degree of
negative energy balance prepartum and higher NEFA
concentrations were 80% more likely to suffer from
ROP (LeBlanc et al., 2002). On the other side, overconditioned cows were shown to be more sensitive to
retained placenta and subsequent infertility than cows
with normal body condition scores (Badinand et al.,
1984). Etiological mechanism for retained placenta was
associated with dietary-conditioned liver disorders and

high plasma urea and gamma-glutamyl transferase


concentrations (Lotthammer et al., 1983). Also low
plasma glucose and PGFM (the mainPGF2
metabolite) levels. Low monocyte and high red cell
counts was traced in blood of cows with retained
placenta, especially in the late gestation period
Chassagne et al. (1992) and could be connected with
the disease by means of dietary unbalanced ratio
of n-3/n-6 polyunsaturated fatty acid (PUFAs) that
would
involve reductions in synthesis of
cyclooxygenase products, impair uterine contractions,
vascular tone and platelet aggregation leading to
retained placenta (Michal et al., 2006).
Hormonal imbalances: Hormonal imbalance existing
before delivery is effective in inducing retention of
placenta. Placental separation occurs when foetal
cortisol induces the production of the enzymes, 17hydroxylase and aromatase in the placenta which
favour oestrogen synthesis at the expense of
progesterone synthesis. Maternal plasma levels of
oestradiol-17 increase suddenly, while plasma levels of
progesterone decline sharply immediately prior
toparturition. It is supposed during the week before
parturition, the level of estradiol reaches its maximum
level to help the uterus to get rid of any remnant of
fetal membranes. Therefore, a decreased level of
estrogen may be indicated as a factor enhancing ROP
(Chassagne et al., 1992).
Spontaneous myometrial contractility is
augmented by autocrine and paracrine release of PGF2
and parturition ensues. Disturbed endocrine function,
high progesterone and cortisol levels and low
oestradiol level was traced in the blood cows with ROP
(Michal et al., 2006). Increased progesterone level in
ROP may be due to failure of the placenta to produce
specific steroidal enzymes that help in progesterone
aromatization and its conversion too estrogen (Ball and
Peters, 2004). Hormone imbalances existing before
delivery are effective in inducing ROP. Progesterone,
more than estrogen, inhibits uterine collagenases and
slows uterine involution. Dexamethasone increases
synthesis and utilization of progesterone by cotyledon
tissues in the cow. These changes may contribute to
blocking
postpartum
expression
of
cotyledoncollagenases. Moreover, it has been found
that glucocorticoids down-regulate collagenases
(Youngquist and Threlfall, 2007)
Failure of maternal immune response: Maternal
immunological recognition of fetal MHC class I
proteins expressed by trophoblast cells triggers an
immune/inflammatory response that contributes
toplacental separation (De-Mouzon et al., 2006). This
lymphocytic activation was suppressed at the foeto-

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Rooh Ul Amin et al.Understanding patho-physiology of retained placenta and its management in cattle

maternal interface alongside the pregnancy course to


avoid rejection of fetal allograft (Hansen and Liu,
1996) where the trophoblast secretes interferon-tau
(IFN-) and both trophoblast and endometrium secrete
prostaglandin E and the endometrial glands secrete
serpins (uterine milk proteins), all of which inhibit
lymphocyte activation to keep on the embryo not
rejected by the dam. Furthermore, for successful nonclassical pregnancy, class-I MHC antigens expressed
by trophoblasts prevent maternal NK- mediated
cytotoxic responses (Entrican and Wheelhouse, 2006).
Strong impairment in polymorphonuclear neutrophils
(PMNs) chemotaxis was demonstrated in placentomes
from cows with retained placentas. Blood leukocytes
and neutrophils of cows with retained placenta were
less reactive to chemotactic stimuli than in cows with
normal placental separation (Gunnink, 1984).
Acyloxyacyl hydrolase (AOAH) is an enzyme of
PMNs capable of detoxifying endotoxin of the coliform
bacteria causing severe mastitis and metritis (McDermott et al., 1991). It is found that AOAH in ROP
cows is less than non-ROP cows. Decreased
myeloperoxidase activity was reported in circulating
neutrophils of cows with ROP (Tian-Quancai et al.,
1994). Furthermore, higher blood lysozyme and acid
phosphatase activities were NROP (Radostits et al.,
1994). The increased cortisol concentrations in cows
that developed ROP (Ahmed et al., 1999) has
immunosuppressive and inhibitory effects on leukocyte
migratory activity (Engler et al., 2004). Preparturient
endocrine changes are supposed to interfere with the
innate immunity of the dam (Vangroenweghe et al.,
2005). High progesterone and cortisol levels in the
blood in stressed cows (Michal et al., 2006), may
induce the accumulation of immunosuppressive
proteins in the uterine lumen which make the uterus
susceptible to infection and persistence of bacteria
(Azawi et al., 2008).
In high lactating cows, somatotropins
stimulate the production of insulin-like growth factor 1
(IGF-1) in the hepatic cells. However, the plasma IGF1 level was found to be quite low, especially in the
hyperketonaemic animals Huszenicza et al. (2006) in
which metabolic products (non esterified fatty acids
(NEFA) and OH-butyrate (BHB) accumulate and
impairs the migration, phagocytic and killing activity
and /or the oxidative burst of PMNs and other
leukocytes, enhancing the susceptibility of host to
invading pathogens (Reist et al., 2003).
Leukocytes and chemotaxis: The role of leukocytes
and chemotaxis in the etiology of ROP has been
studied. Deficient neutrophils phagocytic activity,
decreased migration, and decreased superoxide anion
production have been proposed as factors in the

pathogenesis of ROP in cattle. In fact, circulating


neutrophils from cows with ROP produced less
superoxide anion than did neutrophils from control
cows. Positive chemotaxis resulted in an ROP
incidence of 2.6%, and negative chemotaxis, 35.6%.
Moreover, leukocytes are a mobile source of
collagenases and may be involved in uterine regression
and release of placenta (Youngquist and Threlfall,
2007).
Managemental causes: Myometrium contractility is
the third component of self defence mechanisms, since
uterus contractions expel the uterine content. Lack of
exercise and hypocalcemia are the most frequent
causes of decreased myometrium contractility Sheldon
and Dobson, (2004). However, in a study by Bajcsy et
al. (2005) there was no correlation between blood
ionized calcium (Ca+2) concentrations and any of the
contractility parameters. Also, the lack of uterine
motility plays little or no role in the occurrence of
retained placenta. Moreover, cows with retained
placenta have normal or increased uterine activity in
the days after calving (Frazer et al., 2005). Stress
(Transportation, rough handling, poor feed conditions,
Isolation from group, Lameness,) results inelevated
corticosteroids and increased risk of placental
retention.

Retained fetal membranes: Living Organ


When membranes are kept in controlled
laboratory conditions, however, they are capable of
active utilization of oxygen and glucose, and more than
30% of the cells can exclude vital dye for 3 or more
days. When membranes are kept at 1 to 2C, they stay
metabolically active for 8 weeks or longer. Fetal
membranes have an outstanding potential to survive
without a live fetus. These properties suggest that ROP
may respond to ischemia, anoxia, and bacteria by
releasing biochemicals that cause inflammation, thus
predisposing the cow to metritis (Youngquist and
Threlfall, 2007).

Economic and reproductive impact of


retained placenta
Metritis: ROP and metritis are positively correlated.
Cows with ROP had a significantly higher incidence of
metritis (53%) than cows without ROP (30%); also, a
significant difference was found between conception
rates in cows with ROP and metritis (66%) and in those
with only metritis (77%) (Youngquist and Threlfall,
2007). It has been proposed that the metritis that
accompanies ROP results from the presence of
decomposing placental tissues, which provide a

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Rooh Ul Amin et al.Understanding patho-physiology of retained placenta and its management in cattle

favorable environment for bacterial colonization.


Coliform bacteria and high concentrations of
endotoxins present in lochia of cows with ROP are
potent inducers of prostaglandins and cytokines,
favoring development of uterine infections (Dohmen et
al., 2005). Bacteria found in the early postpartum
uterus or their endotoxins may interact with retained
membranes to secrete PGE2, which may further
predispose the uterus to infection.
Mastitis: Although the main economic impact of ROP
seems to be decreased milk production (more days
open, decreased milk volume, milk from treated cows
withheld), the correlation between ROP and mastitis is
controversial. Milk from cows with retained placenta is
unfit for human consumption and therefore cannot be
sold. The fertility of dairy cows is affected when most
cows in the herd suffer from retained placenta. This
causes a direct loss to the farmer due to delayed calving
leading to a lengthy period between births (calving
intervals) and hence low milk production. It is
unhygienic to milk a cow with decomposing afterbirth
hanging on it (LeBlanc et al., 2002). The financial
losses due to retained placenta in dairy cattle were due
to due to increased calving interval, increased culling
rate, loss of milk production and the costs of veterinary
treatment and drugs.

Treatment for ROP


Objectives: The treatment objectives for ROP are to
cause early detachment of the membranes in order to
reduce the occurrence of metritis, decrease milk losses,
reduce reproductive inefficiency, and decrease
veterinary expenses.
Managemental aspects: As the non infectious causes
of placental retention is multi-factorial and difficult to
be diagnosed, so special care should be paid for control
measures rather than treatment protocols. The genetic
aspect should be put in consideration to select animals
having the minimal probability for the occurrence of
ROP (Ahmed and Zaabal, 2009). Selection of bulls
with suitable birth weight for the breed is essential to
protect the herd from calving problem (Skidmore and
Loskutoff, 1999).
Nutrition: Supplementation with balanced vitamin and
mineral mixture in prepartum period is considered a
prophylactic step to avoid fetal membrane retention.
Prepartum supplementation with antioxidants, vitamin
E (DL -tocopherol acetate, 1100 IU) and Se (sodium
selenite, 30 mg) by single I/M injection, at 3 week
prepartum, is used as a prophylactic dose to avoid
placental retention in cows (Gupta et al., 2005).

Manual removal: Manual removal of retained


membranes is contraindicated because uterine
infections are more frequent and more severe after this
form of intervention. Bolinder et al. (1988) found that
manual removal prolonged the interval from calving to
1st functioning CL by 20 days. The removal of an
attached placenta causes damage to the endometrium
and suppresses uterine leukocyte phagocytosis,
Vandeplassche et al. (1982) both of which encourage
bacterial invasion (Peters and Laven, 1996). It is also
not easy to properly remove a retained placenta; 62%
can be removed completely, 27% partially, and 11%
are non-removable. Often, attempts at removal during
the first 48 hours after calving are unsuccessful because
the placenta is too firmly attached and the apical part of
the gravid horn is beyond the reach. It is also strictly
prohibited to remove the retained placenta manually at
high temperature.
Hormones: Hormones are not effective in either
detaching the placenta in primary ROP or preventing
early postpartum metritis in cows with ROP. Induced
labor associated with the incidence of ROP was also
reduced when relaxin was administered along with
dexamethasone or cloprostenol Musah et al. (1986)
presumably because of relaxin promoting collagenase
activity that could counteract the inhibitory effects of
dexamethasone. But some of the hormones are used for
contraction of uterus thereby, expulsion of fetal
membranes. The commonly used hormones are:
Prostaglandin: PGF2 does not cause detachment of
retained membranes, but can improve reproductive
performance in the early postpartum cow due to
uterokinetic effect (Youngquist and Threlfall, 2007).
Induction of labor with dexamethasone, with or without
prostaglandin, is an established risk factor for ROP in
cattle, although the exact mechanism for this is unclear
(Gross et al., 1985). It has been suggested that
glucocorticoids could have a direct inhibitory effect on
collagenase activity (Guerin et al., 2004). Also,
dexamethasone inhibits PGF2 synthesis within
cotyledon cells, Gross et al. (1986) and administering
prostaglandin along with dexamethasone reduces but
does not eliminate the occurrence of ROP (Gross et al.,
1985 and 1986).
Oxytocin: Oxytocin is the uterokinetic hormone of
choice in the early postpartum cow. 20 IU three to four
times daily have been used for ROP (Youngquist and
Threlfall, 2007).
Antibiotics: The use of antimicrobial therapy in the
treatment of ROP has demonstrated conflicting results
(Peters and Laven, 1996). Postpartum metritis is a

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Rooh Ul Amin et al.Understanding patho-physiology of retained placenta and its management in cattle

common sequele of ROP, and the rationale behind


antibiotics for ROP is to prevent or treat metritis and its
subsequent negative effects on fertility. One opinion is
that antibiotics should not be used to treat ROP because
they may delay the release of retained membranes by
inhibiting
the
putrefaction
process.
Local
antimicrobials, typically given as uterine infusions or
boluses, have not been shown to reduce the incidence
of metritis or improve fertility (Peters and Laven,
1996).
In one study (Youngquist and Threlfall, 2007),
despite intrauterine treatment with 5g of tetracycline
powder on day 1 and 10.5 million U of procaine
penicillin G IM on days 1, 2, and 3, 76% of the cows
developed metritis. The reason for the lack of
effectiveness of antibiotics has been attributed to the
use of inadequate dosages, because it is difficult to
attain adequate tissue concentrations of antibiotics in
the uterus by using uterine infusions. Intrauterine
tetracycline has been reported to have a negative effect
on subsequent fertility. A possible explanation for this
effect is that tetracycline may cause irritation of the
endometrium and perhaps also of the metabolically
active retained membranes. Chemical inflammation
may override the beneficial effects of the antibiotic.
Another complicating factor with infusion of
antibiotics into the uterus is the extreme pH of the
antibiotic solutions used, which may contribute to
damage of the uterus. For example, tetracycline
solutions can be strongly acidic (with a pH of 1.83.0)
or alkaline (for Oxytetracycline for IV injections, pH is
8.08.5). Nevertheless, there is consistent support for
the use of antibiotics, especially in severe cases of
metritis, provided that adequate dosage and route of
administration are used.
Systemic antibiotics are believed to be
beneficial in ROP cases where fever was also present
(Drillich et al., 2006 and LeBlanc et al., 2008).
Systemic antibiotics alone were just as effective as
systemic antibiotics combined with intrauterine
treatment (Drillich et al., 2006). However, because all
febrile cows were treated systemically, it is unclear
whether the resolution of fever was caused by the
antibiotics or to the cows own immune defense
mechanisms. There are currently no known trials in
which cows with ROP and fever were left untreated
(LeBlanc et al., 2008). Treating all ROP cows with
systemic ceftiofur regardless of temperature was not
superior, in terms of occurrence of fever, shedding of
retained fetal membranes, or subsequent reproductive
parameters, to selective antibiotic treatment of only
febrile cows (Drillich et al., 2006). Treating RFM for 5
days with 2.2mg/kg of systemically administered
ceftiofur was superior in preventing metritis when
compared with estradiol or no treatment, although no

significant improvements in reproductive performance


were found (Nadja et al., 2007). LeBlanc, (2008)
stressed that at present it seems economically
preferable to selectively treat metritis cases rather than
automatically treat all cows with retained placenta with
antibiotics.
Immunomodulators: E Coli LPS plus oxytocin
effectively reduced the uterine inflammation and
infection, thus increasing the overall reproductive
efficiency in chronically sub fertile mares. LPS is a
potent secretagogue for a variety of inflammatory
mediators and immuneregulatory cytokines from
endometrial cells andleukocytes. The failure to produce
any systemic endotoxic responses after intrauterine
infusion of E coli endotoxin confirms that E coli LPS
can be used safely without producing any adverse
reaction in mares (Nadja et al., 2007). Recombinant
human interleukin 8 (rhIL-8) was effective in attracting
PMNs into the uterus within 6 hours after
administration in cattle and horses (Zerbe et al., 2003).
Antiseptics: A variety of antiseptics, including
chlorhexidine and dilute iodine, have been used in the
treatment and prevention of ROP. In most cases, their
efficacy remains to be demonstrated. These compounds
should be used with caution, especially iodine
preparations, some of which can be extremely
irritating.
Collagenase: A new approach for the treatment of
ROP is the injection of collagenase into the umbilical
arteries retrieved from ROP. Bacterial collagenase
from Clostridium histolyticum is used because it can
degrade several types of collagen, it is commercially
available, it is affordable, and it does not cause residual
blood clotting in placenta. Collagenase therapy shows
promise as a means of treating retained placenta in a
variety of species (Eiler et al., 1993, and Haffner et al.,
1998).

Technique
The umbilical cord is located and is recognized
by two firm arteries and two veins. Once the cord is
located, a second hand is introduced into the vagina
and the cord is retracted by alternating hands in the
vagina. Once the umbilical cord is in the vulva, the
arteries are clamped with forceps. Collagenase solution
(200,000U, plus 40mg calcium chloride and 40mg
sodium bicarbonate dissolved in1L saline) is injected
rapidly. Injection of collagenase solution can be
accomplished easily by using a hand-pressurized 1000ml saline bag attached to an intravenous administration
set. The needle tip of the set is directly inserted into the
artery (and ligated) without using a catheter. To ensure

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Rooh Ul Amin et al.Understanding patho-physiology of retained placenta and its management in cattle

perfusion of the entire placenta, a volume of 1L is


injected. Oxytetracycline (100mg total dose, which is
approximately 30mg/kg fetal membranes) for
intravenous injection can be added to 1L of collagenase
solution if an antibiotic is desired; however, final pH of
the solution should be adjusted to approximately 7.5.
Five hundred ml of collagenase solution is injected into
each artery or 1000ml into one artery if only one is
available. Because of arterial anastomosis, it is
unnecessary to inject the two arteries in single births or
the two umbilical cords in twin births. Thirty-six hours
later, the retained membranes are easily extracted by
gentle traction if they have not been expelled
spontaneously (Eiler et al., 1993). This treatment is
safe and has no side effects. It can be applied between
12 hours (best) and 96 hours after calving. After 48
hours of retention, there is a tendency for the residual
blood in the placenta to clot and for anastomoses to
close, which limits the perfusion of retained
membranes with collagenase solution. The technique is
simple, and the procedure can be completed in 25
minutes by a skilled veterinarian without an assistant.
Oxytetracycline plus collagenase constitutes a useful,
therapeutic combination, owing to the advantage of
loosening retained membranes while preventing
infection. Antibiotic collagenase combinations should
be used with caution, however, to avoid inactivation of
collagenase by the antibiotic.
Herbs and herbal preparations:
Garlic: It has cleansing action and helps in
expulsion of retained fetal membranes.
Feeding of bamboo leaves mixed with oil bran
or bajra.
Feeding of parched chick pea floor (1 kg) mixed
with butter milk (rabri).
Feeding of electuary prepared from liquid
extract of ergot (8 ml), Quinine sulphate (4g)
Magnesium sulphate (200g), pulv.Gentian (16g)
and molasses.
Herbal preparations like Replanta Powder,
Utrefit, and Utretone can also be used for
treatment of ROP.

Prevention of retained placenta

Current recommendations for prevention of


RFM in cattle include cow comfort, reducing stress
around parturition, and careful nutritional management,
particularly during the transition period. Due to
metabolic diseases uterine immunity is impaired Zerbe
et al. (2001) so proper nutrition in prepartum period is
provided to avoid metabolic diseases. Vitamin and
mineral deficiencies can impair general immunity, to
avoid this Vitamin E and Selenium supplementation
should be given Bourne et al. (2007) and of Ca:P ratio
of 1.5:1.0 should be maintained and P should be
supplemented. The infectious diseases can be
prevented by proper immunization against specific
infection

Conclusion
Placental detachment and expulsion are
complex processes that begin with prepartum hormonal
and biochemical changes. Disturbances in any of these
normal processes may result in placental retention. An
understanding of the physiology of placental retention
allows discussions about the link of risk factors to
specific causes that will aid in the critical appraisal of
treatment protocols and prevention of bovine ROP.
Thus, ROP can be thought of more as a syndrome with
possibly multifactorial causes as well as reflecting herd
management. Many common therapies for ROP have
not been shown to be effective, and some could
actually have a negative impact on future reproduction.
Manual removal, local antibiotics, and prostaglandins
are used treatments, although current evidence does not
support their use. When cows become febrile, systemic
ceftiofur has been the most widely evaluated antibiotic,
and appears to be beneficial in reducing disease and
aiding in the return to normal reproductive function.
Collagenase might prove to be valuable in achieving
faster release, although cost prohibitive in many cases.
New therapies should be aimed at correcting specific
causes of ROP. The limited availability of effective
treatment options emphasizes the importance of
prevention. Current recommendations for prevention of
ROP in cattle include cow comfort, reducing stress
around parturition, and careful nutritional management,
particularly during the transition period. Supplementing
vitamin E and selenium may be an effective preventive
measure.

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