Carbetocin for the prevention of post-partum hemorrhage after vaginal birth: a real-world application.

OBJECTIVE: To compare maternal outcomes using Carbetocin versus Oxytocin for the active management of the third stage of labor, given a temporary national shortage of Oxytocin. METHODS: We conducted a retrospective observational study on a cohort of 866 women with vaginal deliveries at our center, >36 weeks of gestation, between November 2018 and March 2019. During the shortage period, each woman received a single slow intravenous injection of Carbetocin 100 µg at delivery of the anterior shoulder, rather than Oxytocin 5 UI, as postpartum hemorrhage prophylaxis. 146 (16.9%) patients received Carbetocin versus 720 (83.1%) receiving Oxytocin. The outcomes were rates of postpartum hemorrhage, severe postpartum hemorrhage, and placental retention. RESULTS: Incidence rates of placental retention and postpartum hemorrhage were 4.9% and 9.4% respectively. Placenta retention was significantly more likely following Carbetocin administration (adjusted odds ratio 2.5; 95% confidence interval 1.2-5.0). Postpartum hemorrhage rates were not significantly different (adjusted odds ratio 1.1; 95% confidence interval 0.6-2.1), as were severe postpartum hemorrhage rates (adjusted odds ratio 0.7; 95% confidence interval 0.2-2.2). CONCLUSION: Carbetocin is as effective as Oxytocin for postpartum hemorrhage prevention. However, we would reserve it for use after placental delivery due to the increased retention rates.

Prevention of retained fetal membranes and improvement in subsequent fertility with oxytocin administration in cows with assisted calving.

In dairy cows, the efficacy of oxytocin treatment for preventing retained fetal membranes (RFM) is controversial. The physiological condition of cows associated with the calving process may affect the action of oxytocin. This study aimed to elucidate the difference in the efficacy of exogenous oxytocin treatment immediately after calving among cows that received various obstetric interventions. The calving ease was recorded using a score of 1-5, and assisted birth was defined as a score of 2 or more. Cows that required calving assistance (assisted, n = 28) due to delayed calving progression had a prolonged time from calving to expulsion of the fetal membrane (P < 0.01), and impaired reproductive performance compared to cows that did not receive calving assistance (unassisted, n = 78). The effect of oxytocin treatment was determined using cows that did not expel their fetal membrane within 3 h after calving. Cows were randomly divided into the control (unassisted, n = 41; assisted, n = 22) or oxytocin group (unassisted, n = 33; assisted, n = 10). Oxytocin (50 IU) was administered intramuscularly to the cows in the oxytocin group between 3 and 6 h after calving, while no treatment was administered in the control group. In cows with assisted birth, oxytocin administration accelerated placental expulsion (P < 0.05) and improved several reproductive parameters, such as the number of services until conception (P < 0.05) and the calving to conception intervals (P < 0.05) compared to the control group. On the other hand, oxytocin administration slightly accelerated placental expulsion (P < 0.05), but failed to improve fertility in cows with unassisted birth. The results indicate that the action of oxytocin varies depending on the calving situation of the cows. Oxytocin administration during the early postpartum period could prevent RFM and improve the decline in reproductive performance associated with calving assistance.

Effect of pegbovigrastim on clinical mastitis and uterine disease during a full lactation in grazing dairy cows.

In this randomized controlled trial on four commercial grazing dairy farms, we investigated whether pegbovigrastim (PEG) treatment affects clinical mastitis (CM) and uterine disease (i.e. retained placenta (RP), metritis and endometritis) occurrence during a full lactation. The association of prepartum body condition score and prepartum non-esterified fatty acid (NEFA) concentration with disease occurrence was also evaluated. Holstein cows were randomly assigned to one of two treatments: first PEG dose approximately 7 d before the expected calving date and a second dose within 24 h after calving (PEG) compared to untreated controls (Control). In total, 2,153 animals were included in the study: 733 primiparous cows (Control = 391, PEG = 342) and 1420 multiparous cows (Control = 723, PEG = 697). Treatment effects were evaluated with generalized linear mixed models and Cox's proportional hazard models. Treatment with PEG reduced the occurrence of a first case of CM during the first 30 days in milk (DIM) by 24.6% and reduced the hazard of a first case and the rate of total cases of CM during the full lactation. All PEG treatment effects were independent of parity. Prepartum body condition score interacted with PEG treatment: in over-conditioned cows, PEG reduced the occurrence of a first case of CM during the first 30 DIM by 49.5%. The hazard analysis of a first case of CM during the full lactation suggested that the preventive effect of PEG disappeared with increasing DIM. Treatment with PEG did not affect the occurrence of RP or metritis. Pegbovigrastim treated cows with metritis subsequently showed a reduced occurrence of endometritis compared to control cows with metritis. Pegbovigrastim reduces the occurrence of CM particularly in cows at risk of elevated lipid mobilization, and PEG ameliorates the uterine healing process in cows that experienced metritis.

Management of the third stage of labour: (for the Optimal Intrapartum Care series edited by Mercedes Bonet, Femi Oladapo and Metin Gülmezoglu).

The physiology of the third stage of labour is described. Active management reduces the risk of postpartum haemorrhage (PPH), due to the use of a uterotonic agent. Intramuscular Oxytocin 10 IU has the highest efficacy and lowest side effect profile, although ergometrine, carbetocin and misoprostol are also effective. The appropriate uterotonic in different settings such as home birth by unskilled attendants and at caesarean section is discussed. For the latter, there is less consensus on the optimal dose/route of oxytocin, this topic remaining on the research agenda. Delayed cord clamping enables transfusion of blood to the neonate and is recommended rather than early clamping. Controlled cord traction should only be performed by skilled birth attendants and confers minimal advantage in preventing retained placenta. The importance of early recognition of PPH, and preparedness, is emphasised. An approach to medical and surgical management of PPH is presented.

Effects of recombinant bovine interleukin-8 (rbIL-8) treatment on health, metabolism, and lactation performance in Holstein cattle II: Postpartum uterine health, ketosis, and milk production.

To evaluate the effect of recombinant bovine interleukin-8 (rbIL-8) on uterine health and milk production, 2 separate studies were conducted. For study 1, postpartum Holstein cows (n = 213) were randomly allocated into 1 of 3 intrauterine treatment groups: control (CTR, 250 mL of saline solution), low dose (L-IL8, 11.25 µg of rbIL-8 diluted in 250 mL of saline solution), and high dose (H-IL8, 1,125 µg of rbIL-8 diluted in 250 mL of saline solution). Intrauterine delivery of treatments was performed within 12 h of parturition. Cows were evaluated for retained fetal membranes, puerperal metritis, and clinical endometritis. Blood samples were collected immediately before treatment and 1, 2, and 3 d in milk for assessment of IL-8, haptoglobin, fatty acids, and ß-hydroxybutyrate concentrations. Treatment with rbIL-8 reduced the incidence of puerperal metritis in multiparous cows (CTR = 34.3, L-IL8 = 8.11, and H-IL8 = 6.35%). Both the L-IL8 and H-IL8 groups produced significantly more milk, fat-corrected milk, and energy-corrected milk yields when compared with placebo-treated controls. A second study was performed to confirm the effect of rbIL-8 on milk production. In study 2, 164 primiparous cows were randomly allocated into 1 of 4 treatment groups: control (CTR, 250 mL of saline solution), low dose (L-IL8, 0.14 µg of rbIL-8), medium dose (M-IL8, 14 µg of rbIL-8), and high dose (H-IL8, 1,400 µg of rbIL-8). Treatments were prepared and administered as described for study 1. Cows in the L-IL8, M-IL8, and H-IL8 groups produced significantly more milk, fat-corrected milk, and energy-corrected milk yields when compared with control cows. In conclusion, treatment with rbIL-8 decreased the incidence of puerperal metritis in multiparous cows. The administration of rbIL-8 was repeatedly associated with a dramatic and long-lasting improvement of lactation performance.

Effects of pegbovigrastim administration on periparturient diseases, milk production, and reproductive performance of Holstein cows.

The aim of this study was to evaluate the effects of treating Holstein cows with pegbovigrastim on periparturient diseases, milk production, and reproductive performance while exploring the mode of action of an immunomodulatory protein. Cows were randomly allocated to 1 of 2 treatments, untreated control (CTR, n = 423) and pegbovigrastim (PEG, n = 417). At 7 d from the anticipated calving date (d -7), cows allocated to PEG received a subcutaneous injection of 15 mg of pegylated recombinant bovine granulocyte colony stimulating factor (pegbovigrastim injection, Imrestor, Elanco Animal Health, Greenfield, IN). A second injection was administered within 24 h after calving (d 0). Blood samples were obtained from a subset of cows (CTR, n = 103; PEG, n = 102) at -7 and 0, 3, 7, and 14 d relative to parturition. Samples were used for hemogram and quantification of haptoglobin, nonesterified fatty acids, ß-hydroxybutyrate, and trace and macro minerals. Vaginal cytobrush was performed on the same subset cows at d 0, 7, and 14 to assess the relative neutrophil count. Additionally, colostrum samples were collected to measure IgG, IgM, IgA, and lactoferrin concentrations. Postpartum disease occurrence was recorded from calving until 30 d in milk (DIM). Weekly milk yield was recorded for the first 12 wk after calving. Cows treated with PEG had a 3- to 4-fold increase in circulating polymorphonuclear leukocyte, lymphocyte, and monocyte numbers, with a peak at 3 d after treatment followed by a gradual decline, but the counts remained significantly greater compared with CTR at 14 DIM. The administration of PEG did not affect the incidence of clinical and subclinical mastitis, retained fetal membranes, metritis, puerperal metritis, and endometritis. Primiparous cows treated with PEG tended to have lower odds of developing hyperketonemia than CTR [odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.23 to 1.42]. Cows treated with PEG had higher odds of being diagnosed with lameness within 30 DIM compared with CTR (OR = 1.79, 95% CI = 1.16 to 2.76); however, we found no significant differences by 60 DIM. Treatment with PEG increased the odds of displaced abomasum (OR = 8.27, 95% CI = 1.02 to 66.6). Cows treated with PEG had higher odds of being diagnosed with 1 or more clinical diseases compared with CTR cows (OR = 1.39, 95% CI = 1.02 to 1.90). We observed no differences in linear scores or milk composition between treatments. Furthermore, primiparous cows treated with PEG produced more milk than CTR primiparous cows during the first 12 wk postpartum (PEG = 37.51 ± 0.66; CTR = 35.91 ± 0.65 kg), but no differences were observed on energy-corrected milk. Treatment did not alter reproductive performance; additionally, cows diagnosed with metritis or puerperal metritis and treated with PEG tended to have higher proportion of neutrophils in the vaginal mucosa when compared with CTR metritic cows. Although PEG treatment increased circulating polymorphonuclear leukocyte, monocyte, and lymphocyte numbers, as expected, it was detrimental to cow health because it increased morbidity.

Conservative Management of Placenta Accreta Spectrum.

The purpose of this review was to assist obstetricians and gynecologists in considering the most appropriate conservative treatment option to manage women with placenta accreta spectrum according to their individual need and local expertise of the heath care team. The issue is challenging, as the quality of evidence with regard to efficacy is poor, and is mainly based on retrospective studies with limited sample size.

Cost of retained fetal membranes for dairy herds in the United States.

OBJECTIVE To estimate the cost of a case of retained fetal membranes (RFM) for dairy herds in the United States. DESIGN Deterministic computer-based spreadsheet analysis. SAMPLE Inputs from published studies and reports. PROCEDURES Economic losses attributable to RFM were direct (reduction in milk yield and longer interval until pregnancy) and indirect (increased risk of developing clinical disease and increased culling risk). Cost attributable to milk loss was calculated as the mean marginal loss of milk production for cows with RFM and cows with RFM complicated by metritis. Cost of the increased risk of developing clinical disease because of RFM was a product of the cost of each clinical disease and the risk of each clinical disease attributable to RFM. Cost attributable to reduced reproductive performance was a function of a longer interval until pregnancy, whereas cost for increased culling attributable to RFM was associated with the market value of cull cows and replacement heifers as well as herd turnover rate. RESULTS Cost of a case of RFM determined by use of default inputs was $386 (reduction in milk yield, $287; increased time until pregnancy, $73; increased disease risk, $25; and increased culling risk, $1). Sensitivity analysis revealed that milk and feed prices were the most influential inputs. CONCLUSIONS AND CLINICAL RELEVANCE Cost of a case of RFM, including uncomplicated cases, was substantial and comparable to that for other common clinical diseases during the transition period. Preventive measures during the nonlactating period should be considered to minimize the incidence of RFM.

Influence of the duration of calving and obstetric assistance on the placental retention index in Holstein dairy cows.

The aim of this study is to evaluate the influence of duration of calving and obstetric assistance on retained placenta incidence of high milk production Holstein cows. Experimental groups were determined according to the duration of the expulsive phase of calving: 2 h (n = 16), 2-4 h (n = 16) and >4 h (n = 12), and additionally allocated in two sub-groups: spontaneous calving (n = 22) and intervention calving (n = 22). Diagnosis of retained placenta was considered with a threshold of 8 h after the expulsive phase. Cows without obstetric intervention, with labor duration of 2 h, presented reduced time needed for placental release, in comparison to those with obstetric assistance. In the 2-4 h group and >4 h, there was no statistical difference. The 2 h and 2-4 h groups with intervention and the spontaneous >4 h group were considered retained placenta groups. On the other hand, performing obstetric intervention when calving period was superior to 4 h nulled the occurrence of retention of fetal membranes. As a conclusion, obstetric assistance predisposes placental retention to calving with <2 h of duration in dairy cows. Conversely, when calving is more than 4 h, performing fetal extraction has a beneficial influence on preventing retained placenta.

Intravenous carbetocin shot is superior to oxytocin infusion for placental delivery in second trimester abortion: a pilot randomized controlled trial.

OBJECTIVE: To study the efficacy of 100 µg intravenous shot of carbetocin compared to 20 IU oxytocin intravenous infusion to prevent placental retention in second trimester medical termination of pregnancy. METHODS: A double-blinded randomized controlled trial was conducted at Ain Shams University Maternity Hospital from 1 April 2013 to 30 November 2013. A total of 132 women between 14 and 24 weeks gestation indicated for termination were randomized to receive either 20 IU oxytocin infusion (n = 66) or 100 µg carbetocin shot (n = 66) after fetal expulsion. Patients were observed for time elapsed between fetal and placental expulsion, presence of placental retention and blood loss. RESULTS: Third stage was 33.4 ± 20.4 min in oxytocin group & 23.1 ± 16.8 min in carbetocin group (p = 0.002). Eight patients (12.1%) in oxytocin group had complete placental retention versus two patients (3.0%) in carbetocin group (p = 0.05). Eight patients (13.8%) received oxytocin had remnants of placenta compared to four patients (6.2%) received carbetocin (p = 0.04). Sixteen patients (24.2%) received oxytocin and six patients (9%) received carbetocin needed surgical curettage (p = 0.04). Third stage blood loss was 87.2 ± 33.7 ml in carbetocin and 206.9 ± 35.2 ml in oxytocin groups (p = 0.001). CONCLUSION: Carbetocin is superior to oxytocin infusion for management of placental delivery in second trimester abortion.

Periparturient stress and immune suppression as a potential cause of retained placenta in highly productive dairy cows: examples of prevention.

The immune system during the periparturient period is impaired. At this time the most important factor causing immune-suppression in highly productive cows is metabolic stress resulting from hormonal and metabolic fluctuations, a negative energy balance, shortage of proteins, minerals and vitamins which are required to meet the demands of the fetus as well as the onset of lactation. This stress can activate the hypothalamic-pituitary-adrenocortical axis (HPA), which results in increase plasma corticosteroids. As a result, the cortisol concentration during the periparturient period increases by several folds particularly on the day of calving. Cortisol is a powerful immune-suppressive agent. During stress, this hormone causes depression of the leukocyte proliferation and their functions. Decreased phagocytosis of neutrophils, decreased cytotoxic ability of lymphocytes, as well as depressed activity of their cytokines, make it impossible for the normal, efficient maternal immune recognition and rejection of fetal membranes (as a foreign, allogeneic tissue expressed fetal antigens-MHC class I proteins by trophoblast cells) and finally results in their retention in cows. The metabolic periparturient stress also activates production of catecholamines, especially adrenalin. Adrenalin activates adrenoreceptors of the myometrium and then causes hypotony or atony of the uterus. Thus, cortisol and adrenalin inhibit rejection and expulsion of fetal membranes and cause their retention. These mechanisms of retained placenta (RP) often have a metabolic etiology and occur in herds, where important infectious diseases causing placentitis are absent or prevented. The aim of this article is to show the fundamental mechanisms occurring during periparturient stress and the accompanied immune-suppression in cows, as well as their consequences in relation to RP. The paper also gives examples of the symptomatic prevention of RP in cows caused by metabolic and immune suppressive factors. The prevention of RP was carried out using drugs which inhibit the activity of cortisol or adrenalin in dairy cows during calving.

Effect of injectable vitamin E on incidence of retained fetal membranes and reproductive performance of dairy cows.

The objectives were to evaluate the effects of injectable vitamin E during the last 3 wk prepartum on the incidence of retained fetal membranes (RFM) and reproductive performance. Dairy cows (n=890), 390 Holsteins (132 nulliparous and 258 parous) and 500 crossbred Holstein × Gyr (199 nulliparous and 301 parous), from 3 dairy farms in Brazil were assigned to the study. In all 3 farms, from October to March, prepartum cows grazed tropical grasses and received 2 kg/d of a mixture of finely ground corn, soybean meal, and minerals and vitamins. From April to September prepartum cows received a total mixed ration composed of corn silage, finely ground corn, soybean meal, and minerals and vitamins. During the prepartum period, cows were fed 280 (farm 1), 390 (farm 2), and 480 IU (farm 3) of supplemental vitamin E per day, and throughout postpartum, cows were fed 370 (farm 1), 500 (farm 2), and 600 (farm 3) IU of supplemental vitamin E. Within each farm, cows were randomly assigned to remain as untreated controls or to receive 3 i.m. injections of 1,000 IU each of dl-α-tocopherol administered at 19.2 ± 4.3, 12.9 ± 3.3, and 6.2 ± 2.9 d before calving (VitE). Blood was sampled from 141 cows immediately before enrollment to determine the α-tocopherol and cholesterol statuses. Blood was also sampled and analyzed for concentrations of cortisol and nonesterified fatty acids in the last 3 wk of gestation. The serum concentration of α-tocopherol or α-tocopherol:cholesterol ratio did not differ between treatments and averaged 2.97 ± 0.10 µg/mL and 4.46 ± 0.16 × 10(-3), respectively. In total, 53.2% of the cows had an inadequate concentration of serum α-tocopherol based on the 3.0 µg/mL cut-off for adequacy. The risk of RFM decreased as serum α-tocopherol increased. Milk production did not differ between controls and VitE cows. Treatment with injectable α-tocopherol decreased RFM from 20.1 to 13.5%, decreased incidence of stillbirth from 14.9 to 6.8%, and tended to decrease death by 200 d postpartum. VitE cows tended to have improved pregnancy per insemination at first AI (36.7 vs. 30.1%) because of decreased pregnancy loss from 31 to 62 d of gestation (12.5 vs. 20.5%). Despite a similar insemination rate, VitE cows had 22% greater pregnancy rate than control cows. Cows receiving vitamin E had decreased circulating cortisol and nonesterified fatty acids around calving. In summary, when cows were fed limited amounts of supplemental vitamin E, 28 to 48% of the recommendations, prepartum supplementation with injectable α-tocopherol decreased incidence of RFM and improved reproduction.

Effects of folic acid and vitamin B12 supplementation on culling rate, diseases, and reproduction in commercial dairy herds.

This study was undertaken to determine the effect of a combined folic acid and vitamin B12 supplement given in early lactation on culling rate, metabolic disorders and other diseases, and reproduction in commercial dairy herds. A total of 805 cows (271 primiparous and 534 multiparous cows) in 15 commercial dairy herds were involved. Every 2mo from February to December 2010 and within each herd, cows were assigned according to parity, previous 305-d milk production, and calving interval to 5mL of either (1) saline 0.9% NaCl (control group) or (2) 320mg of folic acid + 10mg of vitamin B12 (vitamin group). Treatments were administered weekly by intramuscular injections starting 3wk before the expected calving date until 8wk after parturition. A total of 221 cows were culled before the next dry period. Culling rate was not affected by treatment and was 27.5%; culling rate was greater for multiparous (32.2%) than for primiparous cows (18.8%). Within the first 60d in milk (DIM), 47 cows were culled, representing 21.3% of total culling, and no treatment effect was noted. Ketosis incidence based on a threshold ≥100µmol/L of ß-hydroxybutyrate in milk was 38.3±2.9% for the vitamin group and 41.8±3.0% for the control group and was not affected by treatment. The combined supplement of folic acid and vitamin B12 did not decrease incidence of retained placenta, displaced abomasum, milk fever, metritis, or mastitis. However, the incidence of dystocia decreased by 50% in multiparous cows receiving the vitamin supplement, although no effect was observed in primiparous cows. The first breeding postpartum for multiparous cows occurred 3.8d earlier with the vitamin supplement compared with controls, whereas no treatment effect was seen for primiparous cows. Days open, first- and second-breeding conception rates, number of breedings per conception, and percentage of cows pregnant at 150 DIM were not affected by treatment. The reduced percentage of dystocia combined with the earlier DIM at first breeding for multiparous cows receiving the combined supplementation in folic acid and vitamin B12 indicates that the vitamin supplement had a positive effect in older cows.

The administration of Sheng Hua Tang immediately after delivery to reduce the incidence of retained placenta in Holstein dairy cows.

Sheng Hua Tang, a classical herbal formula consisting of Radix Angelicae sinensis, Ligustici rhizoma, Semen persicae, Zingiberis rhizoma, and Radix glycyrrhizae, is known to be beneficial in alleviating postpartum diseases and facilitating a return to normal reproductive function. This study investigated whether the administration of Sheng Hua Tang within 2 to 4 hours after delivery was effective as a preventive treatment for reducing the risk of retained placenta in Holstein dairy cows. A total of 357 cows, each of which had delivered its calf spontaneously, were randomly allocated to one of two groups. In the treatment group, the cows (n = 175) received Sheng Hua Tang with an oral dose of 0.36 g crude herb per kg·body weight once daily for three consecutive days. The controls (n = 182) received no treatment. The placental retention proportion was 4.0% and 17.0% within 12 hours after delivery in the treated and control animals, respectively (P < 0.01). We found decreases in the calving-to-first-service interval (73.2 ± 25.1 vs. 81.9 ± 32.8 days; P < 0.01), calving-to-conception interval (93.4 ± 38.8 vs. 114.6 ± 42.9 days; P < 0.01), and service per conception (1.5 ± 0.8 vs. 1.9 ± 1.0 days; P < 0.01) in the treatment group compared with the control group. The first artificial insemination conception proportion was higher in the treatment group than in the control group (60.4% vs. 41.1%; P = 0.01). Moreover, the between-group difference in the proportion of cows that were pregnant within 180 days postpartum approached statistical significance (88.2% vs. 80.6%; P = 0.07). Sheng Hua Tang showed beneficial effects in reducing the incidence of retained placenta and improving subsequent reproductive performance in cows. This preventive treatment strategy would be effective in improving the management of puerperal health. The potential benefits of Sheng Hua Tang warrant further investigation to determine whether this preventive treatment strategy can be endorsed as a general preventive approach in postpartum cows.

Effect of intraumbilical vein oxytocin injection on third stage of labor.

OBJECTIVE: Manual removal of placenta is performed in 1-3% of cases, and although it is a well-established and relatively safe procedure, it is not without complications. We carried out this study to determine whether intraumbilical vein oxytocin injection reduces the need for manual removal of placenta and shortens the third stage of labor, in comparison with placebo. MATERIALS AND METHODS: In this randomized clinical trial, 178 women with singleton pregnancy and normal delivery were studied in 1 year. Immediately after fetus delivery, oxytocin infusion (20 IU/L) was started in both groups. Moreover, 10 IU oxytocin and 1 mL normal saline were injected into the umbilical vein of women in the experimental and control groups, respectively. The duration of third-stage labor, need for manual delivery of placenta, and drug side effects were evaluated in both groups. With regard to the mean level of hemoglobin before and after delivery, the two groups were compared using the Levene test and independent t test, and other qualitative variables of the two groups were compared using the χ(2) test. RESULTS: The women who received intraumbilical vein oxytocin had a shorter third stage of labor as compared with the placebo group (4.24 ± 3.27 min vs. 10.66 ± 7.41) (p < 0.001) and there was less need for manual delivery of placenta in the experiment group (1.1% vs. 5.1%) (p = 0.024). CONCLUSION: It was concluded that intraumbilical vein administration of 10 IU (1 mL) oxytocin immediately after fetus delivery was clinically effective in shortening the third stage of labor.

Differences in apoptotic status in the bovine placentome between spontaneous and induced parturition.

We conducted this study to analyze apoptotic changes in the bovine placentome at spontaneous and induced parturition. Cows delivered i) after the administration of dexamethasone followed by prostaglandin F(2α) and estriol, ii) after the administration of prostaglandin F(2α) and estriol or iii) spontaneously. Prepartum changes in plasma progesterone and estradiol-17ß concentrations were similar between spontaneous and induced parturition. Messenger RNA of BCL2-related protein A1 (BCL2A1), an antiapoptotic gene, was expressed by trophoblast binucleate cells and caruncular epithelial cells. Quantitative RT-PCR showed that the expression of BCL2A1 mRNA in cotyledonary and caruncular portions was significantly lower in spontaneous parturition than induced parturition. The expression of BCL2-associated X protein (BAX) mRNA, a proapoptotic gene, was significantly higher in cotyledons at spontaneous parturition than parturition induced without dexamethasone. Caspase-3 (CASP3) mRNA and pre-activated CASP3 protein were predominantly detected in caruncular epithelial cells regardless of how parturition proceeded. Activated CASP3 protein was found in trophoblast uninucleate cells and binucleate cells rather than caruncular epithelial cells. In spontaneous parturition, intense staining of activated CASP3 was detected in caruncular epithelial cells. Spontaneous and dexamethasone-induced parturition increased apoptotic cells in the placentome compared with parturition induced without dexamethasone. The number of binucleate cells was significantly decreased in spontaneous parturition. The present results suggest that although the clinical dose of dexamethasone induces apoptosis in the placentome at term, neither dexamethasone nor prostaglandin F(2α) evoke normal physiological changes in the placentome during delivery such as a change in the balance of apoptosis-related genes and disappearance of binucleate cells.

Placental cord drainage after vaginal delivery as part of the management of the third stage of labour.

BACKGROUND: Cord drainage in the third stage of labour involves unclamping the previously clamped and divided umbilical cord and allowing the blood from the placenta to drain freely into an appropriate receptacle. OBJECTIVES: The objective of this review was to assess the specific effects of placental cord drainage on the third stage of labour following vaginal birth, with or without prophylactic use of uterotonics in the management of the third stage of labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (February 2010). SELECTION CRITERIA: Randomised controlled trials comparing placental cord draining with no placental cord drainage as part of the management of the third stage of labour. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the quality of trials and extracted data. This was then verified by the third review author who then entered the agreed outcomes to the review. MAIN RESULTS: Three studies involving 1257 women met our inclusion criteria. Cord drainage reduced the length of the third stage of labour (mean difference (MD) -2.85 minutes, 95% confidence interval (CI) -4.04 to -1.66; three trials, 1257 women (heterogeneity: T² = 0.87; Chi²P=17.19, I² = 88%)) and reduced the average amount of blood loss (MD -77.00 ml, 95% CI -113.73 to -40.27; one trial, 200 women).No incidence of retained placenta at 30 minutes after birth was observed in the included studies, therefore, it was not possible to compare this outcome. The differences between the cord drainage and the control group were not statistically significant for postpartum haemorrhage or manual removal of the placenta. None of the included studies reported fetomaternal transfusion outcomes and there were no data relating to maternal pain or discomfort during the third stage of labour. AUTHORS' CONCLUSIONS: There was a small reduction in the length of the third stage of labour and also in the amount of blood loss when cord drainage was applied compared with no cord drainage. The clinical importance of such observed statistically significant reductions, is open to debate. There is no clear difference in the need for manual removal of placenta, blood transfusion or the risk of postpartum haemorrhage. Due to small trials with medium risk of bias, the results should be interpreted with caution.

Timing of prophylactic uterotonics for the third stage of labour after vaginal birth.

BACKGROUND: Administration of the uterotonic drugs is one of the main components of the active management of the third stage of labour. The timing of uterotonics varies considerably across the globe and it may have significant implications on the well-being of the mothers and their babies. OBJECTIVES: To assess the effect of the timing of administration of prophylactic uterotonics (before compared to after placental delivery) on the outcomes related to the third stage of labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009). SELECTION CRITERIA: Randomised controlled trials examining the timing of prophylactic uterotonic drugs in the third stage of labour. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked MAIN RESULTS: We included three trials involving 1671 participants; oxytocin was the only uterotonic drug that was used. The dose and route of administration of oxytocin varied among the included studies. Administration of oxytocin before and after the expulsion of placenta does not significantly influence the incidence of postpartum haemorrhage (blood loss greater than 500 ml) (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.62 to 1.04; n = 1667, three trials); retained placenta (RR 1.54, 95% CI 0.76 to 3.11; n = 1667, three trials); length of third stage of labour (minutes) (mean difference (MD) -0.30, 95% CI -0.95 to 0.36; n = 1667, three trials); postpartum blood loss (ml) (MD 22.32, 95% CI -58.21 to 102.86; n = 181, two trials); changes in haemoglobin (g/dL) (MD 0.06, 95% CI -0.60 to 0.72; n = 51, one trial); blood transfusion (RR 0.79, 95% CI 0.23 to 2.73; n = 1667, three trials); the use of additional uterotonics (RR 1.10, 95% CI 0.80 to 1.52; n = 1667, three trials); the incidence of maternal hypotension (RR 2.48, 95% CI 0.23 to 26.70; n = 130, one trial) and the incidence of severe postpartum haemorrhage (blood loss 1000 ml or more) (RR 0.98, 95% CI 0.48 to 1.98; n = 130, one trial). No data on other maternal or neonatal outcome measures were available. AUTHORS' CONCLUSIONS: Administration of oxytocin before and after the expulsion of placenta did not have any significant influence on many clinically important outcomes such as the incidence of postpartum haemorrhage, rate of placental retention and the length of the third stage of labour. However, the number of available studies were limited. The only uterotonic drug used was oxytocin, mainly through intravenous infusion, therefore its extrapolation to other routes of administration should be interpreted cautiously. More studies are required to examine other maternal and neonatal outcomes using consistent approaches.

Using intraumbilical vein injection of oxytocin in routine practice with active management of the third stage of labor: a randomized controlled trial.

OBJECTIVE: To estimate the efficacy of the routine use of intraumbilical vein injection of oxytocin with active management of the third stage of labor in reducing blood loss and length of the third stage. METHODS: In this prospective, randomized, double-blind trial, 412 women undergoing vaginal delivery who did not have risk factors for postpartum hemorrhage were randomly allocated to receive either 20 international units oxytocin diluted with 26 mL saline (n=207) or 30 mL saline (n=205) by intraumbilical vein injection. Active management of the third stage of labor (prophylactic injection of 10 international units oxytocin within 2 minutes of birth, early clamping of the umbilical cord, and controlled cord traction) was used in both groups. The primary outcome was mean blood loss during the third and fourth stages of labor. RESULTS: The mean estimated blood loss was significantly lower in women treated with oxytocin compared with women in the placebo group (195.3+/-81.0 mL compared with 288.3+/-134.1 mL, respectively; P<.001). The third stage of labor was significantly shorter in the oxytocin group than in the placebo group (4.5+/-1.6 minutes compared with 7.9+/-3.4 minutes, respectively; P<.001). The percentages of placentas remaining undelivered beyond 15 minutes were 0% in the oxytocin group and 4.4% in the placebo group (P=.002). CONCLUSION: The use of intraumbilical injection of oxytocin with the active management of the third stage of labor significantly reduced postpartum blood loss and the duration of the third stage. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01094028. LEVEL OF EVIDENCE: I.