ABSTRACT:                        A3 year old Jersey cross bred heifer was presented to the large animalobstetrics unit of teaching veterinary clinical complex, Orathanadu on January2016 and pregnancy was confirmed on November 2016 with signs of 7 monthspregnancy. Again the animal was brought for pregnancy due and confirmed on January2017 with same signs of 7 months pregnanacy and reviewed on March 2017 with nosigns of approaching parturition. On clinical observation the animal was foundto be normal with edematous vulva and pink conjuctival mucous membrane. Vaginalexamination revealed patent vaginal passage with intact cervical seal. Rectalexamination explored distended uterus, positive fremitus with normal topographyof broad ligaments.

The case was diagnosed as prolonged gestation and it wasapproached for termination of pregnancy with with injection Dexamethasone @ 32mg and injection Cloprostenol sodium @ 0.5 mg intramuscularly. Within 48 hoursof intervention a dead male calf was delivered by slight pull per vaginally. Oncareful examination of the calf along with histo-pathological evidence revealedthe pituitary abnormality. The dam was treated for 7 days and had an uneventfulrecovery. On third month of post partum, the ovarian status of the animal werefound to be normal and inseminated successfully.

                                                         INTRODUCTION:                                    Gestationlength is unique to each species. Prolonged gestation in cattle is a rarecondition that is commonly accompanied with fetal adeno-hypophyseal hypoplasia.The final diagnosis is often challenging as breeding date error remainspossible in virtually all situations.

Parturition is induced by the fetus andis initiated by the rising cortisol levels in the fetus that provoke a cascadeof endocrine activity in the dam. Fetal cortisol increases as a result ofincreased ACTH production by the maturing fetal pituitary caused by fetalstressors such as hypoxia and hypercapnia.CASEPRESENTATION:                        A 3 year old Jerseycross bred cow was presented to the Teaching veterinary clinical complex,Orthanadu with the history of mucoid discharge. The animal has been inseminatedon January 2016 and the animal was declared as pregnant around 7 months on November2016. The animal is again declared as pregnant around 7 months based on signson January 2017 also. On clinical observation, rectal examination revealedcervix on the pelvic brim and uterus in the abdominal cavity.

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The uterus wasfilled with fluid and fetal mass was palpable but not able to differentiate thefetal parts. Vaginal examination showed pink and moist mucous membrane, vaginalpassage was severely constricted and there was a mucoid discharge. The externalos the cervix has 1 finger dilatation. Ultrasonographic examination revealedhyper-echoic reflections and greyish particles in the uterus fluid which seemsto be quite abnormal.

Since it was an overdue fetus based on the clear breedinghistory, the pregnancy has been terminated with the help of dexamethasone @ 32mg and cloprostenol sodium @ 0.5 mg intramuscularly. After 48 hours oftermination rectal examination revealed fetal mass and fremitus. On vaginalexamination the fetal limb was palpable and cervix has 3 finger dilatation.Since the cervical dilatation is not sufficient for the fetus to come out, toenhance the cervical dilatation fanning and feathering of the cervix with lukewarm water was done. During this process the chorio-allontoic sac was rupturedand greenish mucoid discharge of about 30 litre was flushed out (normal volumeis around 4-8 litres).

Since there is no presentation, position and postureabnormality of the fetus by slight pull a dead male calf was delivered pervaginally. On examining the removed fetus it possess several abnormalities suchas first degree hydrocephalus, absence of hair on both the thighs and the teethwas covered by the pink spongy cartilage. As per the reference since most ofthe case of prolonged gestation has occurred because of pituitary abnormalitywe collected the pituitary from the dead calf and subjected tohisto-pathological examination. The histo-pathological result revealed thatthere is under developed pituitary. The animal was treated with oxytocin @ 40IU on first day along with ceftriaxone @ 4.5 g I/V, meloxicam @ o.5 mg I/V,chlorphenaramine maleate @ 0.5 g I/M, involon 150 ml P/O  and supportive fluid therapy for thefollowing 5 days.

After 28 days the animal showed estrus signs such asbellowing. On clinical examination all the vital parameters were normal. Rectalexamination revealed proper uterine involution.

Ultrasonographic examinationrevealed cystic corpora lutea (15.7×19.1mm) on left ovary and dominant follicle(8.8x10mm) on right ovary. It clearly indicates that the animal has beenalready ovulated results in the formation of cystic corpora lutea and now theanimal is in the stage of mid cycle estrum. In order to lyse the cystic corporalutea injection cloprostenol sodium @ 0.5 mg has been injected intramuscularly.

After 60 days the animal again showed estrus signs such as bellowing, mountingand vaginal discharge. External examination of the genitalia revealed edematousvulva and pink & moist vaginal mucous membrane. Rectal examination revealedrelaxed cervix and turgid uterus. Ultrasonographic examination revealed dominantfollicle (15.7x13mm) on the right ovary and multiple small follicles on theleft ovary. The animal was inseminated followed by GnRH @ 10 mg injection toensure the ovulation.

On next day of GnRH injection ultrasonographicexamination showed ovulatory site on the right ovary and the animal has beeninseminated successfully second time to improve the chance of fertilisation.Hence a successful case of prolonged gestation and its therapeutic managementwas reported.DISCUSSION:                      Prolonged gestation due to adenohypophyseal hypoplasia is a well known disorder in many cattle breeds(Jackson 2005). In cattle, gestation length is influenced by factors such asthe breed of the cow and bull, calf gender, single vs. multiple birth, theparity of the cow, and the fetal genotype. Environmental factors, includingnutrition, ambient temperature, and the season of the year, have a smallerinfluence. The breed of cattle has the greatest influence on gestation length.

In European cattle of the Bos taurus species, considerablebreed variation is recognized (eg, 279 days mean gestation in Holstein-Friesianto 287 days in Charolais). In breeds of the Bos indicus species,a slightly longer gestation length is often seen (eg, Zebu cattle have a meangestation length of 296 days). Within breeds, individual bulls may sire calveswith longer gestation length than normal, leading to a higher incidence ofdystocia. The fetal pituitary gland plays an important rolein the induction of parturition at the end of gestation, and its importance inthe physiological mechanism of parturition has been extensively studied in thesheep (Liggins and others 1967, Nathanielsz 1993, Wood 2005). In the finalstage of gestation, the maturing fetal hypothalamic-pituitary-adrenal axis isable to respond to chronic stimuli and acute stressors such as hypoxia andhypercapnea with the production of corticotropin-releasing hormone (CRH) in thepara ventricular nuclei of the hypothalamus (Nathanielsz 1993, Jackson 2005,Wood 2005). This hormone causes the release of high levels of ACTH from theadenohypophysis into the bloodstream.

The fetal adrenal glands in sheep respondto this ACTH stimulus with the production of high amounts of cortisol; fetalcortisol induces the activition of cytochrome P450c17 (CYP17) in the placenta,through up regulation of prostaglandin-2 synthethase activity and production ofprostaglandins. CYP17 is essential in the conversion of placental progesteroneand pregnenolone to oestrogens (oestradiol). This oestradiol has a positivefeedback on the production of CRH in the fetal hypothalamus; thereby furtherstimulating this initial sequence of the birth process (Wood 2005).In cattle,the initiation of parturition includes an additional step, which is necessaryto reduce the plasma progesterone concentration in the dam. Unlike in sheep,the corpus luteum of the bovine ovary is the main source of progesterone duringalmost the entire pregnancy (Hoffmann and Schuler 2002). An abrupt drop inplasma progesterone levels during the two to three days before parturition iscaused by luteolysis induced by prostaglandins, especially prostaglandin F2?,released from the fetal membranes, the placenta and the maternal endometrium atthe end of gestation (Kindahl and others 2004).

The increased oestrogen-to-progesteroneratio enhances the activity of the myometrium, leading to the onset of labourand delivery contractions (Wood 2005). Oxytocin is released from theneurohypophysis to further stimulate uterine contractions. In a positivefeed-forward mechanism, known as the Ferguson reflex, stretching of the uterinecervix stimulates the release of more oxytocin by the maternal pituitary gland.

This chain of events is impossible to reverse and very difficult to stop,making delivery inevitable (Nathanielsz 1993).The lack of any crucial elementin this whole sequence, such as the adenohypophysis in the two calves, disablesthe entire chain of events and parturition fails to occur. Maternal ACTH isunable to cross the placental barrier and although maternal cortisol is able todiffuse through the placenta, the plasma cortisol levels in the mother neverreach the required concentration of 25 to 100 ng/ml, as seen in the fetalplasma approaching delivery. The dam is therefore unable to take over the initiationof the birth process from the fetus (Nathanielsz 1993).The differential diagnosis in cases of prolongedgestation in cattle consists of threemajor elements. First and mostcommonly, human error, such as miscalculation ofthe prospective calving date or failure to record a subsequent service isinvolved, leading to an incorrect diagnosis of prolonged gestation (Jackson2005). Double checking the breeding records, eliminating all possibilities of asubsequent service and a good rectal examination (palpation and/or ultrasonography)to estimate the fetal age is mandatory before taking other possible causes intoconsideration.

Secondly, intrauterine death and fetal mummification can alsoresult in indefinite continuation of the pregnancy. These dams do not showabdominal enlargement as expected in late pregnancy. A dead fetal mass withoutfetal fluids can be palpated in an irregularly shaped, contracted uterus(Jackson 2005).True prolonged gestation of a living fetus is relatively rareand is due to a defective hypothalamic-pituitary-adrenal axis (Jackson 2005).This third type of prolonged gestation in cattle is sometimes associated with aprimary adrenal insufficiency (Stabenfeldt and others 1975) or, more commonly,with defects of the brain in general and of the pituitary gland in particular. Infectious, toxic and genetic causes have beenassociated with brain or pituitary defects, resulting in prolonged gestationsin cattle (Hanzen 2005). Bovine viral diarrhoea, Akabane or bluetongue virusinfections can cause severe brain damage in the fetus, including anencephaly,hydrencephaly or porencephaly, resulting in rupture of the hypothalamus and/orhypophysis (Hanzen 2005, Jackson 2005).

Ingestion of Veratrum californicum orVeratrum album has also been associated with prolonged gestation due to severecranial deformities and brain defects in the bovine fetus (Jackson 2005).Casesof primary hypophyseal anomalies and prolonged gestation with a possiblegenetic background have been reported in different cattle breeds such asAyrshire (Wilson and Young 1958), German Fleckvieh (Hafner and others 1991),Guernsey (McEntee and others 1952, Kennedy and others 1957), Holstein-Friesian(Graves and others 1991), Jersey (Blood and others 1957) and Meuse-Rhine-Yssel(Matthijsen and Borst 1983); gestational lengths of up to 469 days have beenreported (Hafner and others 1991). In Holstein-Friesian cows, hypophysealhypoplasia has been identified as resulting from an autosomal recessive genedefect (Jackson 2005). In the Holstein-Friesian, Ayrshire and Guernsey breeds,adeno-hypophyseal hypoplasia is associated with fetal gigantism, hirsutism,retarded ossification and hypoplasia of the thyroid and adrenal glands. Anotherautosomal recessive genetic defect resulting in prolonged gestation has beendescribed in Guernsey and red-white Swedish cattle, and is associated withhydrencephaly, fetal growth retardation, delayed ossification, hypotrichosisand atresia jejunalis (Hanzen 2005)In a case of suspected prolonged gestation, the dam’sbreeding records, if available, should be checked to ensure that parturitiontruly is overdue. Treatment of a case in which gestation is not genuinelyprolonged may result in the delivery of a premature fetus that is unlikelyto survive. Once the true length of gestation is established, a full clinicalexamination of the dam should be conducted.

In cattle; rectal examination ofthe uterus and its contents is an important diagnostic aid. Fetal parts may bepalpable, and in some cases it is possible to detect an abnormal cranium. Anultrasonographic scan may confirm the presence of fetal abnormalities,including a thin-walled, fluid-filled cranium. The weight of an overdue fetusmay cause it to pass under the rumen while still within the uterus, so that itcannot be palpated per rectum. In some animals, prolonged gestation isaccompanied by development of excessive amounts of fetal fluid.

The origin ofexcessive fetal fluid can be assessed by analysis of sodium and chloride levelsin an aspirated sample. Amniotic fluid contains sodium at ~120 mmol/L andchloride at ~90 mmol/L. Allantoic fluid contains sodium at 50 mmol/L andchloride at 20 mmol/L. The correlation between hydrops amnion and hydropsallantois and prolonged gestation is tenuous, however.

Most fetal giants sufferfrom oligoamnios.In true prolonged gestation; the fetus is unlikely to beof any economic value. Treatment should be aimed at fetal delivery with minimaldamage to the dam. In cases of fetal giantism, the dam may be distressed by theweight of the fetus and its associated fluids. Painful edema in front of theudder may indicate rupture or impending rupture of the prepubic tendon. Acanvas sling support can be placed around the abdomen to prevent further damageuntil the pregnancy is terminated.

General health of the dam should be assessedand economic considerations discussed with the owner before treatment isattempted. Milk production may be compromised. Successful induction ofparturition requires an intact fetal hypothalamic-pituitary-adrenal axis.Pregnancy is maintained in cases of prolonged gestation chiefly by continuedproduction of progesterone bythe corpus luteum. Spontaneous induction of birth in cases of prolongedgestation fails as a result of insufficient production of fetal cortisol andthe failure of luteolysis to occur.

Birth in both cows and sheep can besuccessfully induced by administering both prostaglandin F2? (andits synthetic analogue cloprostenol) and the corticosteroid dexamethasone by IM injection. Luteolysisis induced by the prostaglandin, and the maternal hormone cascade thatprecedes parturition is initiated by the corticosteroid. In cows, 500 mcgcloprostenol and 20 mg dexamethasone aregiven; in sheep 125 mcg cloprostenol and 16 mg dexamethasone are recommended.

A single doseof these two drugs is normally effective. Parturition should begin in 24–72 hr.Induced parturition should be monitored carefully. Assistance may be requiredif there is evidence of uterine inertia or damage to the abdominal wall, eitherof which might make expulsive efforts ineffective. Fetal malposition requiringobstetric assistance may occur once birth begins. If the fetus is verylarge, dystocia due to fetal-pelvic disproportion may occur, and assisteddelivery by careful traction may be attempted.

If this is not possible,cesarean section may be required. If the dam is seriously ill but consideredwell enough to withstand surgery, an elective cesarean without an attempt atvaginal delivery may be considered. Fetal dysmaturity can be a problem,especially in very valuable cloned offspring, and intensive care facilities maybe needed. After fetal delivery, uterine involution may be encouraged byadministration of oxytocin. Fluidtherapy, antibiotics, and treatment with NSAIDs such as flunixin meglumine mayaid recovery and provide analgesia.