Prolonged gestation generally exceeds normal gestation by between 3 weeks and 3 months. Underlying anatomic or functional abnormalities in the fetal hypothalamic-pituitary-adrenal axis prevent the initiation of parturition and hence the end of gestation. The most commonly documented causes are genetic, but other causes include fetal mummification, infections, phytogenous toxins, and iatrogenic causes. Cases are diagnosed by going beyond full-term gestation. The fetus may be viable or nonviable depending on the cause of prolonged gestation. Treatment involves induction of parturition and, often, cesarean section.
Definitions of "normal" and "prolonged" gestation length are not established and so are arbitrarily defined. Normal gestation length may be defined as the mean length of gestation of a population (eg, 279 days for Holstein-Friesian cattle) ± 3 standard deviations (SD), (eg, SD = 7 days × 3 = 21 days; 260–300 days), which includes at least 99.7% of gestations. Statistically, those above and below this range are considered outliers.
Prolonged gestation length may thus be defined as more than 3 SDs longer than normal gestation (eg, >300 days in this example). This is congruent with adding an estrus cycle length (21 days) to the normal gestation length before calling it true prolonged gestation due to the problem of inaccurate service date recording, assuming the cow conceived at the last recorded service, and hence inaccurate gestation length calculation. Although pregnancies carried beyond 300 days may be considered prolonged in Holstein-Friesians, statistically, some of these will be physiologic (outliers) and some will be pathologic. The former tend to be slightly prolonged (by days) whereas the latter can be grossly prolonged (by months). Prolonged gestation is independent of, but may be a cause of, prolonged parturition. The focus of this chapter is on true pathologic prolonged gestation, which in cattle commonly exceeds 11 months and can reach 15 months (6 months post-term).
Etiology of Prolonged Gestation in Cattle and Sheep
The underlying pathophysiology of prolonged gestation is a defective hypothalamic-pituitary-adrenal (HPA) axis, which prevents the initiation of parturition and hence the end of gestation. In many cases, the cause of the anatomic or functional abnormalities in the pituitary and/or adrenal glands may go undetected.
The commonly diagnosed causes of prolonged gestation may be classified as:
The most commonly documented causes are genetic, but mummification occurs more commonly but is often not recorded. In cases of mummification-associated prolonged gestation, the cause of the prolongation is a nonfunctioning HPA axis in a retained dead fetus, whereas in other cases the fetus may be alive but the HPA is malfunctioning.
Note that fetal gigantism may occur occasionally after normal gestation length (spontaneous large offspring syndrome), with calves of 60–80 kg reported, without abnormalities of the HPA axis detected. The cause(s) of some of these large-for-gestational-age calves has not yet been determined, although epigenetic conditions are suspected. In other cases, normal gestational age fetal macrosomia (large for gestational age) is associated with congenital defects. In a small percentage of pregnancies (< 0.3%), gestation is technically prolonged by a short period (eg, >300 days in Holstein-Friesian cows) but the fetus is not oversized and the dam calves normally. Such cases appear to be physiologically, but not pathologically, prolonged gestations, (ie, normal statistical outliers).
Pathogenesis of Prolonged Gestation in Cattle and Sheep
Factors Influencing Gestation Length
The most important factors influencing gestation length are the sire breed, genotype, gender, and plurality of the fetus; the parity, age, and milk yield of the dam, and the individual sire (sire-within-breed genetic effects). Environmental factors, including nutrition, ambient temperature, and the season of the year, have a lesser influence.
Breed has the greatest influence on gestation length. In European cattle of the Bos taurus species, considerable breed variation is recognized, with dairy breeds having shorter gestation lengths than beef breeds (eg, 279 days mean gestation in Holstein-Friesian vs 287 days in Charolais). In breeds of the Bos indicus species, a slightly longer gestation length is often seen (eg, Zebu cattle have a mean gestation length of 296 days).
Within breeds, wide variation exists between individual bulls in offspring gestation length. The sire genome and epigenome can influence gestation length via regulation of embryonic development. Gestation length is a moderately heritable trait (h2 for service sire 30%–50%) and is included in some modern multifunctional genetic indices for sire selection (mainly in seasonal breeding cattle industries) to reduce sequelae associated with prolonged gestation.
In sheep, although the normal gestation length is 144–150 days, the exact gestation length is seldom known unless ewes were served in hand or by artificial insemination. In most flocks, the ewes run with rams and, when served, receive a raddle crayon mark on their rumps to indicate that service has occurred. Crayon color is changed at 14- to 17-day intervals, and after later pregnancy confirmation (via transabdominal ultrasonography), a lambing date within a 14- to 17-day period is calculated. Gestation length is unique to each fetus, but approximate gestation lengths can be ascribed to each species and, more importantly, to breeds within species ().
Sequelae of Prolonged Gestation
Prolonged gestation is associated with significantly increased risk of morbidity, mortality, and reduced productivity. There is an increased incidence of both dystocia and stillbirth and their sequelae (eg, retained fetal membranes, metritis) due to the relationship between gestation length and fetal birthweight (nonlinear), and increased days open and calving interval (linear) and lower milk yield. Prolonged gestation (postmaturity) commonly (though not necessarily) results in relative fetal oversize (leading to macrosomia/gigantism; >60 kg calves). In cattle, the fetus grows at approximately 350 g/day in the last trimester of gestation. Additionally, calves born following prolonged gestation have greater postweaning mortality, lower pregnancy rate, and a higher risk of being culled, (ie, carry-over effects).
End of Gestation
The fetus determines the length of gestation (day of birth) in cattle and sheep whereas the dam determines the timing of parturition (time of birth). Fetal stressors such as hypoxia and hypercapnia in association with maturation and activation of the fetal pituitary gland induce increased ACTH production, resulting in increased cortisol secretion. Increasing fetal cortisol concentration provokes a maternal hormonal cascade, resulting in the initiation of parturition. Insufficient production of fetal cortisol and consequent failure of placental conversion of progesterone and pregnenolone to estrogens in ewes and maternal prostaglandin-induced luteolysis of the corpus luteum in cows (malfunction of the HPA axis) leads to prolonged gestation.
Diagnosis of Prolonged Gestation in Cattle and Sheep
Deviation from the known length of gestation
Appearance of the fetus
Cattle and sheep are typically diagnosed with prolonged gestation when owners notice that external signs of late pregnancy, including abdominal enlargement, mammary gland development, vulvar edema, and sacrosciatic ligament relaxation, are less obvious than in other members of a group.
True prolonged gestation must be differentiated from false prolonged gestation. When artificial insemination (AI) is used, calculation of gestation length can confirm prolonged gestation. Once pregnancy is detected, it can be positively dated (eg, by ultrasonography), However, when natural service is used, (eg, sheep, beef cows, and dairy cows after the end of the AI period, and often heifers) and pregnancy is not detected or dated, prolonged gestation can be misdiagnosed. Other common errors that can lead to a false diagnosis of prolonged gestation include failure to record a subsequent service (thus erroneously miscalculating gestation length by >21 days), faulty pregnancy diagnosis (missing nonpregnancy, twins, incorrect dating of a fetus), and incorrect identification of animals. Thus, the most common causes of a cow failing to calve at term are nonpregnancy and an error in breeding or identification records, not true prolonged gestation.
Given the varied causes of prolonged gestation, the appearance of the affected fetuses can be highly variable, from undersized, mummified fetuses and dysmature, small fetuses to gigantic, morphometrically normal or abnormal fetuses.
The three steps to investigate a case of suspected prolonged gestation are:
establish whether it is a true prolonged gestation
examine the pregnant dam and her fetus
necropsy the affected calf, if dead
Followup investigations are only warranted when a true case of prolonged gestation has been established. True prolonged gestation is uncommon in all species though most commonly reported in cattle (estimated < 1%). Most cases are investigated as a result of a cow or ewe not calving/lambing when expected, at term.
The first step in investigating such cases is to confirm gestation length using breeding data and pregnancy dating records, if available. Once the true length of gestation is established, a full clinical examination of the dam should be conducted. In cattle, fetal body parts may be palpable transrectally, identifying the approximate size of the fetus (very small—mummified; oversized—gigantism) and possibility its status (live/dead).In some cases it is possible to detect an abnormal cranium and to assess the volume of fetal fluids (reduced—mummification; excess—hydrops). Ultrasonography may confirm the presence of fetal abnormalities, including a thin-walled, fluid-filled cranium. However, the weight of an overdue fetus may cause it to pass under the rumen while still within the uterus, preventing it from being palpated per rectum.
In some animals, prolonged gestation is accompanied by development of excessive amounts of fetal fluid. The origin of excessive fetal fluid can be assessed by analysis of sodium and chloride concentrations in an aspirated sample. Amniotic fluid contains sodium at ~120 mmol/L and chloride at ~90 mmol/L. Allantoic fluid contains sodium at 50 mmol/L and chloride at 20 mmol/L. The correlation between hydrops amnion and hydrops allantois and prolonged gestation is tenuous, however. Most fetal giants have oligoamnios (amniotic fluid volume < expected for gestational age).
Necropsy examination of the fetus may determine the characteristic features of fetal gigantism (macrosomia, overlong hair coat [hirsutism], long hooves, and large teeth) and possible pituitary or adrenal abnormalities. However, prolonged gestation fetuses can have a heterogeneous phenotype depending on the cause. After a prolonged gestation has been established, followup investigations may include investigation of possible exposure to toxic plants, maternal tests for evidence of exposure to or presence of fetopathogens, and pedigree analysis or fetal karyotyping to detect possible genetic causes. In many cases, the cause of prolonged gestation remains unknown, because thorough investigations are rarely conducted in the field by breeders or their veterinarians.
Treatment of Prolonged Gestation in Cattle and Sheep
Supportive care with appropriate perinatal management of the dam
Induction of parturition
In most cases of true prolonged gestation, the fetus is unlikely to be of any economic value, but in cases of cloned calves, the calf has an extremely high economic value. Treatment should be aimed at fetal delivery with minimal injury to the dam. In cases of fetal gigantism, the dam may be distressed by the weight of the fetus and its associated fluids. Painful edema in front of the udder may indicate rupture or impending rupture of the prepubic tendon. A canvas sling support can be placed around the abdomen to prevent further injury until the pregnancy is terminated. General health of the dam should be assessed and economic considerations discussed with the owner before treatment is attempted, noting that milk production may be compromised.
Prolonged gestation persists in cows due to insufficient production of fetal cortisol and the consequent failure of maternal prostaglandin-induced luteolysis to occur. This results in maintenance of pregnancy chiefly by means of continued production of progesterone by the corpus luteum, irrespective of whether the fetus is alive or dead. Thus, treatment of prolonged gestation involves induction of parturition using exogenous corticosteroid (with a live fetus/viable placenta only) and prostaglandin (live or dead fetus) to mimic spontaneous induction of parturition.
Birth in both cows and sheep can be successfully induced by administering a corticosteroid (eg, dexamethasone) followed by prostaglandin F2alpha (or one of its synthetic analogs, eg, cloprostenol) by IM injection. The maternal hormonal cascade that precedes parturition is initiated by the corticosteroid, and luteolysis is induced by the prostaglandin. In cows, 20 mg dexamethasone followed by 500 mcg cloprostenol can be given; in sheep, 16 mg dexamethasone and 125 mcg cloprostenol are recommended. A single dose of these two drugs is normally effective. Parturition should begin in 24–72 hours.
Induced parturition should be monitored carefully. Assistance may be required if there is evidence of uterine inertia or damage to the abdominal wall, either of which might make expulsive efforts ineffective or if the birth canal is not sufficiently dilated. Fetal malposition, requiring obstetric assistance, may occur once birth begins. If the fetus is very large, dystocia due to fetal-pelvic disproportion may occur, and assisted delivery by careful traction may be attempted (though not usually in valuable calves). If this is not possible, cesarean section may be required. If the dam is seriously ill but considered well enough to withstand surgery, or if a cloned calf is involved, an elective cesarean without an attempt at vaginal delivery may be considered. Fetal dysmaturity can be a problem, especially in very valuable cloned offspring; intensive neonatal care facilities may be needed. After fetal delivery, uterine involution may be encouraged by administration of oxytocin. Retention of fetal membranes is managed in the usual way. Fluid therapy, antibiotics, and treatment with NSAIDs such as flunixin meglumine may aid recovery and provide analgesia.
Key Points on Prolonged Gestation in Cattle and Sheep
Functional or anatomic abnormalities of the fetal HPA axis lead to prolonged gestation in cattle and sheep.
Genetic factors and fetal mummification are the most common causes of prolonged gestation.
Treatment includes induction of parturition and often requires cesarean section.
