Obstetric and fetal outcomes in dystocic and eutocic sows to an injection of exogenous oxytocin during farrowing

Abstract

Sixty hybrid Yorkshire-Landrace penned sows, 30 with eutocic farrowing and 30 experiencing a dystocic parturition, were studied to evaluate the obstetric and neonatal outcomes to low doses of oxytocin administered at advanced stages of parturition. Animals in each group were randomly subdivided into 2 subgroups: 15 eutocic and 15 dystocic sows received oxytocin 0.083 IU/kg (equivalent to 1 IU/12 kg body weight), administered intramuscularly after the delivery of the 5th piglet; the other 15 eutocic and 15 dystocic sows received saline solution intramuscularly at the same time. Oxytocin decreased the number of intrapartum deaths by approximately 50% (P = 0.002). No piglet was born dead from the saline- and oxytocin-treated eutocic sows. The highest viability score was observed among piglets born to eutocic sows treated with oxytocin. In summary, this dose schedule would help to decrease the number of stillbirths in both eutocic and dystocic farrowing sows.

Introduction

Stillbirths remain a major problem in intensive pig farming. According to the 2002 records of the commercial swine database program produced by the University of Minnesota (PigCHAMP), there are 0.56 stillbirths per litter in Mexico, 0.7 in Canada, and 0.98 in the USA (1). Prolonged farrowing could explain these mortality rates (2). Oxytocin is involved in the maintenance and reinforcement of spontaneous labor (3) and, in humans, exogenous administration of oxytocin appears to have been used extensively for some time to induce or augment uterine contractions, especially to facilitate the 3rd stage of labor (4–8). Probably, as a consequence, oxytocin is used in more than 80% of United States’ swine farms for complementing normal parturition in sows (9). In humans, it has been proposed that fetal injuries and sudden infant death syndrome may increase after oxytocin administration in labor (10,11), but in pigs, while oxytocin administration may decrease the duration of farrowing in sows, the mortality rate in their offspring remains unchanged (12–14).

We recently demonstrated a dose-dependent relationship between oxytocin administration and adverse obstetric events in parturient sows (15). For example, the rate of intrapartum deaths was minimal at an oxytocin dose level of 1 IU/12 kg (0.083 IU/kg body weight (BW) in comparison with the rate at levels of 1 IU/9 kg (0.111 IU/kg BW) and 1 IU/6 kg (0.167 IU/kg BW). In addition, the mortality rate of piglets born to sows exposed to oxytocin during parturition was also modified by the time at which the hormone was administered during parturition; the mortality rate was higher when it was administered after the birth of the 1st piglet than after that of the 4th or the 8th piglet (16). However, the potential influence of dystocia in the response of farrowing sows to oxytocin was not considered, and sows having a dystocic farrowing may have a higher susceptibility to the adverse effects of oxytocin than those with an eutocic labor, limiting its efficacy. The purpose of this study was to evaluate the obstetric and neonatal outcomes to oxytocin 1 IU/12 kg BW administered at advanced stages of parturition to sows with eutocic and dystocic farrowing, with a view to clarifying the clinical criteria when considering oxytocin administration in farrowing sows.

Materials and methods

Population

The animal welfare aspects and the methodology of the study were approved by the Postgraduate Committee of Production Science and Animal Health, Faculty of Veterinary Medicine and Zootechnics at the Universidad Nacional Autónoma de Mexico, Mexico DF. The study was performed in a commercial swine farm located in the State of México, Mexico, in accordance with the guidelines of the ethical use of animals in applied ethologic studies described elsewhere (17).

Sixty hybrid Yorkshire-Landrace penned sows that weighed from 201 to 291 kg and were in their 2nd to 5th pregnancy were included in the study; 30 with eutocic farrowing and 30 experiencing a dystocic parturition.

Fetal dystocia was considered as present if any of the first 4 piglets delivered by the sows were stillborn or in acute fetal distress, secondary to asphyxia, including meconium-stained skin, hyperglycemia (glucose > 80 mg/L), severe damage of the umbilical cord (edema, congestion, or hemorrhage), lactate > 8.8 mmol/L, pCO₂ > 108 mmHg, or metabolic acidosis (umbilical blood pH < 7.2). Maternal dystocia was defined as a 40-min period of uterine quiescence after the delivery of any of the first 4 piglets. Parturition was manually assisted by 2 of the investigators when the interval between delivery of piglets was more than 1 h.

During the experimental phase, the animals were housed in individual farrowing pens in accordance with the Mexican standards on the use and care of experimental animals NOM-062-ZOO-1999 (18). The farrowing rooms had an electronic ventilation system and natural lighting. Air conditioning was set at 26°C, relative humidity 60%, and zero wind speed.

Treatments

F2-alfa prostaglandin (dinoprost tromethamine 10 mg; Lutalyse, Pfizer, Mexico) was administered, IM, to pregnant sows in the morning (from ~ 0700 to 0800 h) of day 113 gestation. Clinical monitoring of animals was initiated 12 h later. Sows during parturition and piglets at birth were assisted by 2 of the investigators. By means of a table of random numbers, the 30 dystocic and 30 eutocic sows were randomly divided into 2 groups: 15 sows from each group received oxytocin (Oxipar; Boehringer Ingelheim, Mexico) 0.083 IU/kg (equivalent to 1 IU/12 kg BW; 0.05 mL = 1 IU), as previously reported by Mota-Rojas et al (15). The other 15 sows received saline solution (0.05 mL/12 kg BW); a volume similar to that of the oxytocin dose. Treatments were administered, IM, after the delivery of the 5th piglet.

Study outcomes

Litter size, live-born piglets, meconium-stained newborns, and intrapartum deaths were recorded. Fetal deaths were classified as antepartum (type I) or intrapartum (type II), according to criteria previously described (12,14). Briefly, type I stillbirths had a rather characteristic edematous and hemorrhagic appearance and may had a grayish-brown discoloration because of beginning mummification; if the process was advanced, the fetuses were dehydrated and had started to lose hair. Type II stillbirths appeared exactly like their normal littermates, with the exception that they did not breathe; these fetuses had died of oxygen starvation during parturition.

The viability score of the piglets was obtained according to the scale described by Zaleski and Hacker (19) and modified by Mota-Rojas et al (20). Briefly, the heart rate (< 110, between 121 and 160, or > 161 beats/min), the time interval between birth and 1st breath (< 15 s, between 16 s and 1 min, or > 1 min), the snout skin color (pale, cyanotic, or pink), time interval between birth and 1st stand (> 5 min, between 1 and 5 min, or < 1 min), and the skin staining with meconium (severe, mild, or absent) were rated from 0 (the worst) to 2 (the best); a resulting total score ranging from 1 to 10 was obtained for each piglet.

The heart rate was obtained by 1 of the investigators, using a stethoscope. The 1st breath was recorded as when thoracic movements were noticed accompanied by air exhalation from the muzzle. Time to stand was recorded as when the piglet reached the stand position supported by its 4 legs. Meconium staining was considered as severe when more than 40% of the body surface was stained. In addition to the observations made for the scale, the time to 1st udder contact was registered. Since piglets were handled by investigators to obtain a blood sample and tympanic membrane temperature, both the time to stand and the time to 1st udder contact were registered starting from the time at which the piglets were returned to the mother close to the vulva to allow the piglets to try and find the maternal teat by themselves.

Blood samples were obtained from the cranial vena cava of piglets immediately after birth, according to the Mexican regulation (18). The blood samples were placed in glass tubes containing lithium heparin. Glucose (mmol/L), electrolytes [Na⁺, K⁺, and Ca⁺ (mmol/L)], and lactate (mmol/L) levels, and partial pressure of carbon dioxide [pCO₂ (mm Hg)] and oxygen [pO₂ (mmHg)], were obtained by means of an automatic blood gas and electrolytes analyzer (GEM Premier 3000; Instrumentation Laboratory Diagnostics S. A. de C. V., Mexico DF, Mexico).

Immediately after blood samples had been obtained, piglets were weighed in a digital bascule (Salter Weight-Tronix, West Bromwich, United Kingdom) and their temperature was obtained by means of a tympanic membrane thermometer (ThermoScan Braun GMBH, Kronberg, Germany).

Statistical analysis

Data were stored in an electronic form that had been specially designed for the management of swine production and development at the farm. Continuous data were summarized as mean ± standard deviation (s) and compared among the 4 subgroups by means of a general linear model (GLM) for a mixed-effects model, followed by a post-hoc Tukey test for comparisons between different combinations of pairs of subgroups. Categorical data were compared among the 4 subgroups by means of a ‘2-by-k’ X ² test. If the P < 0.05, a ‘2-by-2’ X ² test was performed for comparisons between different combinations of pairs of subgroups. Statistical analyses were performed with statistical software (SPSS v. 16.0; SPSS, Chicago, Illinois, USA). A two-tailed P < 0.05 was considered to be the significance level for each test.

Results

In dystocic sows, the number of intrapartum deaths was approximately 50% less in those receiving oxytocin than in those receiving saline (Table 1). No piglet was born dead from the saline- or oxytocin-treated eutocic sows. Piglets born to eutocic sows treated with oxytocin had the highest viability score (8.5, s = 0.7) (Table 1); in fact, in each group (eutocic, dystocic) the piglets born in the 2 oxytocin-treated subgroups had significantly better viability scores than did those in the corresponding saline-treated subgroups.

Table 1.

Effects of oxytocin (0.083 IU/kg BW) in the outcome of piglets born to eutocic and dystocic sows

	Eutocic	Eutocic + Oxytocin	Dystocic	Dystocic + Oxytocin
Sows (n)	15	15	15	15
Number of piglets (n)a	165	162	203	204
Intrapartum deaths [n (%)]	—	—	41 (20.2)	19 (9.3)b
Piglets born with asphyxia [n (%)]c	21 (12.7)	9 (5.6)e	31 (15.3)g	16 (7.8)j
Viability scored	7.9, s = 1.2	8.5, s = 0.7e	5.8, s = 3.1f,h	7.2, s = 2.5g,i,j
Latency to first udder contact (min)d	28.8, s = 11.6	23.9, s = 7.0e	35.1, s = 13.8f,h	26.5, s = 8.7g,i,j

The latency to first udder contact was not recorded for intrapartum death piglets.

^aThe number of piglets were similar in the 2 eutocic subgroups and in the 2 dystocic subgroups; however, the number of piglets in the eutocic and dystocic groups was different.

^b2-by-2 X ² test, P < 0.0001.

^d2-by-k X ² test: P < 0.05, followed by a post-hoc 2-by-2 X ² test; or

^cGeneral linear model for mixed effects: P < 0.05, followed by a post-hoc Tukey test. Significant differences (P < 0.05) in the post-hoc analysis were observed between:

^eeutocic versus eutocic with oxytocin

^feutocic versus dystocic

^geutocic versus dystocic with oxytocin

^heutocic with oxytocin versus dystocic

ⁱeutocic with oxytocin versus dystocic with oxytocin

^jdystocic versus dystocic with oxytocin

s = standard deviation

The piglets’ birth weight and hematocrit levels were similar in the 4 study subgroups (Table 2). As expected, the parameters of asphyxia were significantly more evident among piglets born to dystocic sows. However, oxytocin administered to dystocic sows prevented such changes. For example, in piglets born to dystocic sows, lactate levels were approximately 2.5 mmol/L higher than those observed in piglets born to eutocic sows. However, in the group of dystocic sows that received oxytocin, the levels were only 0.6 mmol/L higher (P > 0.05) (Table 2). Furthermore, blood glucose levels in piglets born to saline-treated dystocic sows were, on average, 0.88 mmol/L higher than those in saline-treated eutocic animals. Oxytocin administration did not modify the glucose levels in piglets born to eutocic sows, whereas it decreased the glucose levels in piglets born to dystocic sows to almost similar values to those in piglets born to eutocic sows.

Table 2.

Effects of oxytocin (0.083 IU/kg BW) on blood gases, electrolytes, and glucose levels in live-born piglets of dystocic and eutocic sows

	Eutocic (n = 165)	Eutocic + Oxytocin (n = 162)	Dystocic (n = 203)	Dystocic + Oxytocin (n = 204)
Weight (g)	1415.4, s = 196.5	1411.3, s = 177.0	1441.8, s = 240.1	1440.9, s = 201.5
Temperature (°C)a	37.5, s = 0.6	37.7, s = 0.7a	37.3, s = 0.7b,d	37.3, s = 0.7c,e
Hematocrit (L/L)	0.37, s = 0.04	0.38, s = 0.04	0.37, s = 0.05	0.37, s = 0.04
Glucose (mmol/L)a	3.6, s = 0.5	3.6, s = 1.1	4.5, s = 2.4b,d	3.9, s = 1.4f
Na+ (mmol/L)	135.1, s = 3.4	136.08, s = 3.7	135.7, s = 3.7	135.7, s = 3.6
K+ (mmol/L)a	6.5, s = 0.5	6.6, s = 0.5	7.2, s = 1.5	6.9, s = 1.1
Ca2+ (mmol/L)a	0.23, s = 0.1	0.20, s = 0.06	0.35, s = 0.2b,d	0.26, s = 0.1e,f
pH	7.2, s = 0.1	7.3, s = 0.1	7.1, s = 0.2	7.2, s = 0.1
Lactate (mmol/L)a	4.6, s = 1.9	4.3, s = 1.3	7.0, s = 4.5b,d	5.2, s = 3.3e,f
HCO3− (mmol/L)	22.0, s = 2.1	22.2, s = 2.1	21.7, s = 2.3	21.9, s = 2.1
PaO2 (mmHg)	24.7, s = 5.7	25.9, s = 5.4	21.8, s = 8.3	24.0, s = 6.9
PaCO2 (mmHg)	55.8, s = 14.3	54.7, s = 12.4	77.5, s = 40.6	64.04, s = 29.6

Bicarbonate (HCO₃⁻) was not measured in intrapartum-death piglets. Data represent mean 3 standard deviation (s).

General linear model for mixed effects: P < 0.05, followed by a Tukey test significantly different (P < 0.05) between:

^aeutocic versus eutocic with oxytocin

^beutocic versus dystocic

^ceutocic versus dystocic with oxytocin

^deutocic with oxytocin versus dystocic

^eeutocic with oxytocin versus dystocic with oxytocin

^fdystocic versus dystocic with oxytocin

Discussion

Response to hypoxia in neonates is influenced by factors that include fetal metabolic reserves and growth and maturity at birth (21). The piglets’ birth weight and hematocrit levels were similar in the 4 subgroups (Table 2), ruling out the possibility that the differences in the mortality rates among the 4 subgroups was secondary to differences in maturity and growth. The finding that blood glucose levels in piglets born to saline-treated dystocic sows were higher than those in saline-treated eutocic animals and that oxytocin administration only modified the glucose levels in piglets born to dystocic sows supports the conclusion that dystocia, but not oxytocin, favored hyperglycemia as a metabolic response to intrapartum fetal distress (22).

The viability score results support our previous observations in a dose-response study of oxytocin in farrowing sows (15) and in a study of oxytocin administered at different periods of parturition (16), so that, altogether, these studies support the view that oxytocin, when administered after approximately half the piglets have been delivered, may not only decrease the mortality rate of piglets at birth but also favor better neonatal outcomes.

The optimum time period at which oxytocin should be administered for labor induction had not previously been clearly defined. In humans, in a recent small clinical trial, it was observed that the administration of oxytocin throughout labor could increase certain unplanned pregnancy outcomes, such as cesarean sections, vacuum extraction, and uterine hyperstimulation, compared with discontinuing its administration when cervical dilation reached 5 cm (23). Oxytocin administered in the 3rd stage of labor has proven benefits (4–6,8,9). At early stages of parturition, the uterus has a good responsiveness to either endogenous or exogenous oxytocin. Due to the proliferation of oxytocin receptors, this responsiveness may not be saturated by endogenous oxytocin; therefore, the administration of exogenous hormone may enhance the uterine activity, potentially to levels dangerous for the offspring. For example, uterine hyperstimulation can decrease the uterine blood supply, which subsequently may result in fetal distress (17). However, oxytocin administered in advanced stages of parturition can produce a low level of uterine stimulation, sufficient to stimulate the fatigued muscles to a level enough to deliver the remaining piglets (16).

In human neonates, hypoxia and, therefore, metabolic acidosis are associated with significant mortality rates and sequelae in the long term. In piglets, the major cause of fetal death is hypoxia, mainly secondary to prolonged intervals between the expulsion of piglets (24). Normally, the elimination of CO₂ (and therefore carbonic acid) and fetal blood lactate depends almost completely on the placenta helping to compensate for the deficit of fetal oxygen (25). Although oxygen is the substrate that cells use in large quantities in the aerobic metabolism and cellular integrity, tissues do not have an oxygen storage system, thus they must be supplied continuously at a rate that meets the metabolic requirements. If this supply is diminished, hypoxemia can occur, resulting in anaerobic metabolism and lactate production. Hypoxia resulting from a diminished blood flow secondary to enhanced uterine contractions, as may occur at high doses of oxytocin or when oxytocin is administered early during parturition or during dystocia, can be prevented by administering oxytocin at low doses and at advanced stages of parturition, as was observed in the biochemical evaluations, including electrolyte and blood gases levels, performed in the present studies. Prolonged hypoxia during parturition could lead to the development of acidosis (21,26), even if compensating mechanisms are present (25).

The effects of oxytocin would have been affected by the number of piglets born in the different groups. However, a similar number of piglets were born in the saline-treated and oxytocin-treated eutocic subgroups and in the saline-treated and oxytocin-treated dystocic subgroups, and in both groups (eutocic and dystocic) the effects of oxytocin administered after the 50% of the litter had been delivered were significantly beneficial. Furthermore, in our view, the use of a GLM, considering sows as a fixed effect, since treatment has been made to them, and the study outcomes as random effects, was sufficient to account for any potential deleterious effects of the number of piglets to the mother, which, subsequently, could affect the differences among the subgroups.

In summary, oxytocin 0.083 IU/kg (1 IU/12 kg BW) administered to farrowing sows decreased the number of stillbirths in dystocic farrowing sows when administered after 50% of the litter had been delivered and increased viability score in both eutocic and dystocic farrowing sows.