Maximum Dose Rate of Intrapartum Oxytocin Infusion and Associated Obstetric and Perinatal Outcomes.

OBJECTIVE: Despite lack of evidence for a safety threshold for oxytocin dose rate, many hospital protocols specify a maximum rate. We investigated whether exceeding 20 milliunits/min of oxytocin was associated with adverse outcomes. METHODS: This is a secondary analysis of a double-blind, single-center, randomized controlled trial of nulliparous patients with singleton gestations at 36 weeks of gestation or later who presented in spontaneous labor randomized 1:1 to either a high-dose oxytocin titration regimen (initial-incremental rate of 6 milliunits/min) or standard-dose titration regimen (initial-incremental rate of 2 milliunits/min) for labor augmentation. A maximum oxytocin dose rate limit was not specified in the study protocol. For this secondary analysis, outcomes of participants who received oxytocin and exceeded a dose rate of 20 milliunits/min at any point in labor were compared with those whose rate remained at 20 milliunits/min or less. In addition, the cumulative proportions of labor and birth outcomes were calculated for each maximum dose rate of oxytocin reached among this study cohort. RESULTS: Of the 1,003 participants in the parent trial, 955 (95.2%) received oxytocin, as planned, and were included, with 190 (19.9%) exceeding a maximum dose rate of 20 milliunits/min. Those who exceeded 20 milliunits/min were older and were more likely to have rupture of membranes as their trial entry indication, have hypertensive disorders of pregnancy, receive intrapartum magnesium sulfate infusion, and receive oxytocin for longer. Those whose maximum rates exceeded 20 milliunits/min underwent cesarean delivery more frequently, but the majority (74%) still delivered vaginally. In multivariable analyses, there were no significant associations between maximum oxytocin dose rates greater than 20 milliunits/min and cesarean delivery (adjusted odds ratio [aOR] 1.57, 95% CI 1.00-2.46), peripartum infection (aOR 0.69, 95% CI 0.41-1.19), postpartum hemorrhage (aOR 1.37, 95% CI 0.70-2.71), or neonatal intensive care unit (NICU) admission (aOR 1.72, 95% CI 0.89-3.31). Although 85% of spontaneous vaginal deliveries occurred at maximum oxytocin dose rates of 20 milliunits/min or less, vaginal deliveries continued to occur at higher maximum dose rates. The cumulative proportions of NICU admissions and composite severe neonatal morbidity and mortality cases increased with increasing oxytocin dose rates even with maximum oxytocin dose rates at 20 milliunits/min or less. CONCLUSION: In multivariable analyses, there are no significant differences in maternal or perinatal adverse outcomes based on exceeding 20 milliunits/min of oxytocin. These data suggest that oxytocin dosing should be individualized to each patient and not be based on arbitrary thresholds. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02487797.

Administration of carbetocin after the first piglet was born reduced farrowing duration but compromised colostrum intake in newborn piglets.

Carbetocin is an oxytocin-like compound with long acting properties that has recently been introduced to both human and domestic animal obstetrics. The aims of the present study were to evaluate the effects of carbetocin administration after the first piglet was born on farrowing duration, birth interval, colostrum consumption and vitality index in newborn piglets. In total, 186 sows and their offspring (n = 2611 piglets) were distributed into three groups: 1) CONTROL: sows were allowed to farrow naturally (n = 66); 2) OXY: sows were administered oxytocin 20 IU intramuscularly after the first piglet was born (n = 62); and 3) CARBE: sows were administered carbetocin 0.6 µg/kg intramuscularly after the first piglet was born (n = 58). The reproductive data of sows including farrowing duration, total number of piglets born per litter (TB), number of piglets born alive per litter (BA), proportion of stillborn piglets per litter (SB) and proportion of mummified fetuses per litter (MF) were recorded. Piglet vitality index including skin colour, integrity of the umbilical cord, heart rate, blood oxygen saturation, screaming score, udder stimulation score, movement capacity and number of completed circles around enclosure were determined. Birth weights of the piglets were measured immediately at birth and again at 24 h thereafter to determine the individual colostrum intake of the piglets. On average, the farrowing duration, birth interval and BA were 188.0 ±â€¯95.7 min, 12.5 ±â€¯18.3 min, and 12.3 ±â€¯2.9 piglets per litter, respectively. The farrowing duration of the sows was reduced in CARBE group (151.2 ±â€¯11.9 min) compared to OXY (180.2 ±â€¯11.5 min, P = 0.003) and CONTROL (227.7 ±â€¯11.2 min, P < 0.001) groups. Birth interval of piglets in all categories of birth weight in the CARBE group was shorter than those in the CONTROL group (P < 0.05). However, the colostrum yield of sows in CARBE group (2398 ±â€¯133 g) was lower than CONTROL and OXY groups (3371 ±â€¯125 g and 3549 ±â€¯128 g, respectively; P < 0.001). Similarly, colostrum intake of piglets in the CONTROL and OXY groups was higher than in the CARBE group (276.4 ±â€¯11.0 g, 286.4 ±â€¯13.6 g and 225.3 ±â€¯14.0 g, respectively; P < 0.05). The percentage of stillborn piglets in CARBE was higher than OXY (8.7 ±â€¯1.1% vs 5.3 ±â€¯1.1%, P < 0.05) but did not differ significantly compared to CONTROL (7.5 ±â€¯1.1%, P > 0.05). The piglet movement capacity in CONTROL was lower than CARBE group (1.36 vs 1.48, P < 0.05) but was not different compared to OXY group (1.40, P > 0.05). In conclusion, administration of carbetocin after the birth of the first piglet reduced the farrowing duration of sows, but increased the number of stillborn piglets and reduced the colostrum yield of sows.

Active versus expectant management for women in the third stage of labour.

BACKGROUND: Active management of the third stage of labour involves giving a prophylactic uterotonic, early cord clamping and controlled cord traction to deliver the placenta. With expectant management, signs of placental separation are awaited and the placenta is delivered spontaneously. Active management was introduced to try to reduce haemorrhage, a major contributor to maternal mortality in low-income countries. This is an update of a review last published in 2015. OBJECTIVES: To compare the effects of active versus expectant management of the third stage of labour on severe primary postpartum haemorrhage (PPH) and other maternal and infant outcomes.To compare the effects of variations in the packages of active and expectant management of the third stage of labour on severe primary PPH and other maternal and infant outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the World health Organization International Clinical Trials Registry Platform (ICTRP), on 22 January 2018, and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing active versus expectant management of the third stage of labour. Cluster-randomised trials were eligible for inclusion, but none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias, carried out data extraction and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included eight studies, involving analysis of data from 8892 women. The studies were all undertaken in hospitals, seven in higher-income countries and one in a lower-income country. Four studies compared active versus expectant management, and four compared active versus a mixture of managements. We used a random-effects model in the analyses because of clinical heterogeneity. Of the eight studies included, we considered three studies as having low risk of bias in the main aspects of sequence generation, allocation concealment and completeness of data collection. There was an absence of high-quality evidence according to GRADE assessments for our primary outcomes, which is reflected in the cautious language below.The evidence suggested that, for women at mixed levels of risk of bleeding, it is uncertain whether active management reduces the average risk of maternal severe primary PPH (more than 1000 mL) at time of birth (average risk ratio (RR) 0.34, 95% confidence interval (CI) 0.14 to 0.87, 3 studies, 4636 women, I2 = 60%; GRADE: very low quality). For incidence of maternal haemoglobin (Hb) less than 9 g/dL following birth, active management of the third stage may reduce the number of women with anaemia after birth (average RR 0.50, 95% CI 0.30 to 0.83, 2 studies, 1572 women; GRADE: low quality). We also found that active management of the third stage may make little or no difference to the number of babies admitted to neonatal units (average RR 0.81, 95% CI 0.60 to 1.11, 2 studies, 3207 infants; GRADE: low quality). It is uncertain whether active management of the third stage reduces the number of babies with jaundice requiring treatment (RR 0.96, 95% CI 0.55 to 1.68, 2 studies, 3142 infants, I2 = 66%; GRADE: very low quality). There were no data on our other primary outcomes of very severe PPH at the time of birth (more than 2500 mL), maternal mortality, or neonatal polycythaemia needing treatment.Active management reduces mean maternal blood loss at birth and probably reduces the rate of primary blood loss greater than 500 mL, and the use of therapeutic uterotonics. Active management also probably reduces the mean birthweight of the baby, reflecting the lower blood volume from interference with placental transfusion. In addition, it may reduce the need for maternal blood transfusion. However, active management may increase maternal diastolic blood pressure, vomiting after birth, afterpains, use of analgesia from birth up to discharge from the labour ward, and more women returning to hospital with bleeding (outcome not pre-specified).In the comparison of women at low risk of excessive bleeding, there were similar findings, except it was uncertain whether there was a difference identified between groups for severe primary PPH (average RR 0.31, 95% CI 0.05 to 2.17; 2 studies, 2941 women, I2 = 71%), maternal Hb less than 9 g/dL at 24 to 72 hours (average RR 0.17, 95% CI 0.02 to 1.47; 1 study, 193 women) or the need for neonatal admission (average RR 1.02, 95% CI 0.55 to 1.88; 1 study, 1512 women). In this group, active management may make little difference to the rate of neonatal jaundice requiring phototherapy (average RR 1.31, 95% CI 0.78 to 2.18; 1 study, 1447 women).Hypertension and interference with placental transfusion might be avoided by using modifications to the active management package, for example, omitting ergot and deferring cord clamping, but we have no direct evidence of this here. AUTHORS' CONCLUSIONS: Although the data appeared to show that active management reduced the risk of severe primary PPH greater than 1000 mL at the time of birth, we are uncertain of this finding because of the very low-quality evidence. Active management may reduce the incidence of maternal anaemia (Hb less than 9 g/dL) following birth, but harms such as postnatal hypertension, pain and return to hospital due to bleeding were identified.In women at low risk of excessive bleeding, it is uncertain whether there was a difference between active and expectant management for severe PPH or maternal Hb less than 9 g/dL (at 24 to 72 hours). Women could be given information on the benefits and harms of both methods to support informed choice. Given the concerns about early cord clamping and the potential adverse effects of some uterotonics, it is critical now to look at the individual components of third-stage management. Data are also required from low-income countries.It must be emphasised that this review includes only a small number of studies with relatively small numbers of participants, and the quality of evidence for primary outcomes is low or very low.

Efficacy and safety of motherwort injection add-on therapy to carboprost tromethamine for prevention of post-partum blood loss: A meta-analysis of randomized controlled trials.

Motherwort (YiMuCao), a traditional Chinese herb, has been shown beneficial effects for women's diseases. This meta-analysis aimed to evaluate the efficacy and safety of motherwort injection add-on therapy to carboprost tromethamine for prevention of post-partum blood loss. A systematic literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang from their inception to December 2017. Randomized controlled trials that determined the add-on effects of motherwort injection to carboprost for prevention of post-partum blood loss were eligible. Pooled risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were used to summarize the effect sizes. Eight trials including 1276 pregnant women fulfilled the inclusion criteria. Prophylactic use of motherwort injection add-on therapy significantly reduced the post-partum 2 h (MD -127.5 mL; 95% CI -149.13 to -105.88) and 24 h (MD -146.85 mL; 95% CI -179.77 to -113.94) blood loss and incidence of post-partum hemorrhage (RR 0.28; 95% CI 0.17-0.45) than carboprost. Moreover, adjunctive treatment with motherwort injection significantly decreased the length of the third stage of labor (MD -3.41 min; 95% CI -4.33 to -2.49) and duration of lochia (MD -7.13 days; 95% CI -8.49 to -5.76). There was no statistical significant difference in the incidence of adverse events (RR 0.76; 95% CI 0.50-1.16). Prophylactic use of motherwort injection add-on therapy to carboprost tromethamine could reduce post-partum blood loss. However, more well-designed trials are necessary to confirm the findings of this study due to the methodological flaws of the included trials.

Effectiveness and safety of herbal medicines for induction of labour: a systematic review and meta-analysis.

OBJECTIVE: The use of herbal medicines for induction of labour (IOL) is common globally and yet its effects are not well understood. We assessed the efficacy and safety of herbal medicines for IOL. DESIGN: Systematic review and meta-analysis of published literature. DATA SOURCES: We searched in MEDLINE, AMED and CINAHL in April 2017, updated in June 2018. ELIGIBILITY CRITERIA: We considered experimental and non-experimental studies that compared relevant pregnancy outcomes between users and non-user of herbal medicines for IOL. DATA EXTRACTION AND SYNTHESIS: Data were extracted by two reviewers using a standardised form. A random-effects model was used to synthesise effects sizes and heterogeneity was explored through I2 statistic. The risk of bias was assessed using 'John Hopkins Nursing School Critical Appraisal Tool' and 'Cochrane Risk of Bias Tool'. RESULTS: A total of 1421 papers were identified through the searches, but only 10 were retained after eligibility and risk of bias assessments. The users of herbal medicine for IOL were significantly more likely to give birth within 24 hours than non-users (Risk Ratio (RR) 4.48; 95% CI 1.75 to 11.44). No significant difference in the incidence of caesarean section (RR 1.19; 95% CI 0.76 to 1.86), assisted vaginal delivery (RR 0.73; 95% CI 0.47 to 1.14), haemorrhage (RR 0.84; 95% CI 0.44 to 1.60), meconium-stained liquor (RR 1.20; 95% CI 0.65 to 2.23) and admission to nursery (RR 1.08; 95% CI 0.49 to 2.38) was found between users and non-users of herbal medicines for IOL. CONCLUSIONS: The findings suggest that herbal medicines for IOL are effective, but there is inconclusive evidence of safety due to lack of good quality data. Thus, the use of herbal medicines for IOL should be avoided until safety issues are clarified. More studies are recommended to establish the safety of herbal medicines.

Motherwort injection for preventing postpartum hemorrhage in pregnant women with cesarean section: A systematic review and meta-analysis.

OBJECTIVE: To assess the impact of motherwort injection alone or combined with oxytocin for preventing postpartum hemorrhage in pregnant women with caesarean section. METHODS: A systematic review and meta-analysis of randomized trials were performed. PubMed, EMbase, The Cochrane Central Register of Controlled Trials (CENTRAL), Chinese database Sino-Med, Chinese National Knowledge Infrastructure Database (CNKI), VIP Chinese Science and Technique Journals Database, WanFang, and ClinicalTrials.gov were searched. Randomized controlled trials (RCTs) that compared motherwort injection alone or motherwort injection combined with oxytocin in pregnant women receiving cesarean section were included. Paired reviewers independently screened abstracts and full texts for eligibility, assessed risk of bias, and extracted data. We performed random-effects meta-analyses of RCTs along with a limited number of prespecified subgroup hypotheses, and sensitivity analyses were carried out with other statistical approaches. RESULTS: Forty-six RCTs (n = 7359) proved eligible. Compared with oxytocin, both motherwort injection and motherwort injection combined with oxytocin had a significantly lower blood loss within 2 hours (MD = -21.81, 95% CI -37.05 to -6.58 and MD = -53.04, 95% CI -61.68 to -44.39); lower blood loss within 24 hours (MD = -25.44, 95% CI -39.38 to -11.51 and MD = -67.81, 95% CI -78.02 to -57.60); and lower the risk of adverse events (ORPeto 0.40, 95% CI 0.16 to 0.96 and ORPeto 0.50, 95% CI 0.35 to 0.71). Motherwort injection combined with oxytocin also decreased the risk of postpartum hemorrhage (OR 0.22, 95% CI 0.14 to 0.35.) CONCLUSIONS: In pregnant women with cesarean section, motherwort injection suggests an obvious benefit and less adverse event.

An exploration of village-level uterotonic practices in Fenerive-Est, Madagascar.

BACKGROUND: Pharmaceutical uterotonics are effective for preventing postpartum hemorrhage and complications related to unsafe abortion. In Madagascar, however, traditional birth attendants (Matrones) commonly administer medicinal teas for uterotonic purposes. Little is known about Matrone practices and how they might coincide with efforts to increase uterotonic coverage. The aims of this study were to: 1) identify indications for presumed uterotonic plant use by Matrones, 2) explore uterotonic practices at the village level, and 3) describe the response of health practitioners to village-level uterotonic practices. METHODS: Twelve in-depth interviews with health practitioners, Matrones and community agents were conducted in local dialect. All interviews were audio-recorded, transcribed, and translated into English for analysis using Atlas.ti. Medicinal plant specimens were also collected and analyzed for the presence of uterotonic peptides. RESULTS: While Matrones reported to offer specific teas for uterotonic purposes, health practitioners discussed providing emergency care for women with complications associated with use of specific teas. Complications included retained placenta, hypertonic uterus, hemorrhage and sepsis. Chemical analysis indicated the presence of cysteine-rich peptides in the Dantoroa/Denturus plant used in some Matrones' teas. CONCLUSIONS: The presence of uterotonic peptides in one plant used by Matrones may indicate that Matrones intend to administer uterotonics for safer childbirth. This finding, combined with practitioner reports of complications related to some medicinal teas, points to a need for availability of an evidence-based uterotonic at the village level, namely, misoprostol pills or oxytocin in the form of uniject.

Retained placenta: will medical treatment ever be possible?

The standard treatment for retained placenta is manual removal whatever its subtype (adherens, trapped or partial accreta). Although medical treatment should reduce the risk of anesthetic and surgical complications, they have not been found to be effective. This may be due to the contrasting uterotonic needs of the different underlying pathologies. In placenta adherens, oxytocics have been used to contract the retro-placental myometrium. However, if injected locally through the umbilical vein, they bypass the myometrium and perfuse directly into the venous system. Intravenous injection is an alternative but exacerbates a trapped placenta. Conversely, for trapped placentas, a relaxant could help by resolving cervical constriction, but would worsen the situation for placenta adherens. This confusion over medical treatment will continue unless we can find a way to diagnose the underlying pathology. This will allow us to stop treating the retained placenta as a single entity and to deliver targeted treatments.

Oxytocin via Uniject (a prefilled single-use injection) versus oral misoprostol for prevention of postpartum haemorrhage at the community level: a cluster-randomised controlled trial.

BACKGROUND: Access to injectable uterotonics for management of postpartum haemorrhage remains limited in Senegal outside health facilities, and misoprostol and oxytocin delivered via Uniject have been deemed viable alternatives in community settings. We aimed to compare the efficacy of these drugs when delivered by auxiliary midwives at maternity huts. METHODS: We did an unmasked cluster-randomised controlled trial at maternity huts in three districts in Senegal. Maternity huts with auxiliary midwives located 3-21 km from the closest referral centre were randomly assigned (1:1; via a computer-generated random allocation overseen by Gynuity Health Projects) to either 600 µg oral misoprostol or 10 IU oxytocin in Uniject (intramuscular), stratified by reported previous year clinic volume (deliveries) and geographical location (inland or coastal). Maternity huts that had been included in a previous study of misoprostol for prevention of postpartum haemorrhage were excluded to prevent contamination. Pregnant women in their third trimester were screened for eligibility either during community outreach or at home-based prenatal visits. Only women delivered by the auxiliary midwives in the maternity huts were eligible for the study. Women with known allergies to prostaglandins or pregnancy complications were excluded. The primary outcome was mean change in haemoglobin concentration measured during the third trimester and after delivery. This study was registered with ClinicalTrials.gov, number NCT01713153. FINDINGS: 28 maternity hut clusters were randomly assigned-14 to the misoprostol group and 14 to the oxytocin group. Between June 6, 2012, and Sept 21, 2013, 1820 women were recruited. 647 women in the misoprostol group and 402 in the oxytocin group received study drug and had recorded pre-delivery and post-delivery haemoglobin concentrations, and overall 1412 women delivered in the study maternity huts. The mean change in haemoglobin concentrations was 3·5 g/L (SD 16·1) in the misoprostol group and 2·7 g/L (SD 17·8) in the oxytocin group. When adjusted for cluster design, the mean difference in haemoglobin decreases between groups was not significant (0·3 g/L, 95% CI -8·26 to 8·92, p=0·71). Both drugs were well tolerated. Shivering was common in the misoprostol group, and nausea in the oxytocin group. Postpartum haemorrhage was diagnosed in one woman allocated to oxytocin, who was referred and transferred to a higher-level facility for additional care, and fully recovered. No other women were transferred. INTERPRETATION: In terms of effects on haemoglobin concentrations, neither oxytocin nor misoprostol was significantly better than the other, and both drugs were safe and efficacious when delivered by auxiliary midwives. The programmatic limitations of oxytocin, including short shelf life outside the cold chain, mean that misoprostol could be more appropriate for community-level prophylaxis of postpartum haemorrhage. FUNDING: Bill & Melinda Gates Foundation.

The African Pitocin - a midwife's dilemma: the perception of women on the use of herbs in pregnancy and labour in Zimbabwe, Gweru.

INTRODUCTION: The use of natural health products is gradually increasing all over the world with up to 50% of the general population having tried at least one herbal product. This becomes a dilemma to the midwife who has limited or no knowledge on their effects in pregnancy, hence the need to explore the perceptions of women on the use herbs in pregnancy and labour. METHODS: The research, which was a case study of a Claybank Private Hospital in Gweru, Zimbabwe, adopted a qualitative approach with a triangulation of data from interviews, observations and analysis of maternal records. A sample of 20 women, admitted to using herbs, was purposively selected from the labour and post natal wards. RESULTS: A variety of substances, but mainly the elephant's dung, was used. The family, (mother) prescribed the herbs. The women did not have knowledge on how the substances work but believed in them, as they have stood the test of time. CONCLUSION: The African women in Zimbabwe cannot be stopped from taking herbs as it is engraved in their culture and have absolute faith in them. Whilst the herbs are assumed by the women to be effective, their safety is questionable, especially in women with underlying obstetric complications. It is therefore recommended to scientifically explore the safety and effectiveness of the most commonly used herbs if pregnancy is to be safe. Whilst the women can not be stopped from taking these herbs, it is important to build a trusting relationship between the midwife and the mother so that communication about the use of herbs can be done freely without fear or judgement.

Large doses of uterotonic drugs caused type II second degree sinoatrial block during cesarean section.

In China, it is a routine procedure to inject 250 µg of hemabate (sterile solution, an oxytocic, contains the tromethamine salt of the (I5S)-15 methyl analogue of naturally occurring prostaglandin F2α in a solution suitable for intramuscular injection) into the myometrium of patients experiencing uterine inertia after delivery, with an additional dose given in the event that the efficacy is not obvious. Although hemabate is prohibited from being used in patients with active liver disease, there are no restrictions regarding the application of hemabate in positive hepatitis B surface antigen (HbsAg)-positive subjects with normal liver function. Here we report adverse effects of hemabate in 1 HbsAg-positive subject with normal liver function. This subject experienced increased blood pressure, chest tightness, and type II second degree sinoatrial block 25 minutes after an additional injection of hemabate. Thus, special attention should be paid when applying hemabate in HbsAgpositive subjects with normal liver function.

Advance distribution of misoprostol for prevention of postpartum hemorrhage (PPH) at home births in two districts of Liberia.

BACKGROUND: A postpartum hemorrhage prevention program to increase uterotonic coverage for home and facility births was introduced in two districts of Liberia. Advance distribution of misoprostol was offered during antenatal care (ANC) and home visits. Feasibility, acceptability, effectiveness of distribution mechanisms and uterotonic coverage were evaluated. METHODS: Eight facilities were strengthened to provide PPH prevention with oxytocin, PPH management and advance distribution of misoprostol during ANC. Trained traditional midwives (TTMs) as volunteer community health workers (CHWs) provided education to pregnant women, and district reproductive health supervisors (DRHSs) distributed misoprostol during home visits. Data were collected through facility and DRHS registers. Postpartum interviews were conducted with a sample of 550 women who received advance distribution of misoprostol on place of delivery, knowledge, misoprostol use, and satisfaction. RESULTS: There were 1826 estimated deliveries during the seven-month implementation period. A total of 980 women (53.7%) were enrolled and provided misoprostol, primarily through ANC (78.2%). Uterotonic coverage rate of all deliveries was 53.5%, based on 97.7% oxytocin use at recorded facility vaginal births and 24.9% misoprostol use at home births. Among 550 women interviewed postpartum, 87.7% of those who received misoprostol and had a home birth took the drug. Sixty-three percent (63.0%) took it at the correct time, and 54.0% experienced at least one minor side effect. No serious adverse events reported among enrolled women. Facility-based deliveries appeared to increase during the program. CONCLUSIONS: The program was moderately effective at achieving high uterotonic coverage of all births. Coverage of home births was low despite the use of two channels of advance distribution of misoprostol. Although ANC reached a greater proportion of women in late pregnancy than home visits, 46.3% of expected deliveries did not receive education or advance distribution of misoprostol. A revised community-based strategy is needed to increase advance distribution rates and misoprostol coverage rates for home births. Misoprostol for PPH prevention appears acceptable to women in Liberia. Correct timing of misoprostol self-administration needs improved emphasis during counseling and education.

Castor oil, bath and/or enema for cervical priming and induction of labour.

BACKGROUND: Castor oil, a potent cathartic, is derived from the bean of the castor plant. Anecdotal reports, which date back to ancient Egypt have suggested the use of castor oil to stimulate labour. Castor oil has been widely used as a traditional method of initiating labour in midwifery practice. Its role in the initiation of labour is poorly understood and data examining its efficacy within a clinical trial are limited. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. OBJECTIVES: To determine the effects of castor oil or enemas for third trimester cervical ripening or induction of labour in comparison with other methods of cervical ripening or induction of labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013) and bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials comparing castor oil, bath or enemas used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. DATA COLLECTION AND ANALYSIS: A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. MAIN RESULTS: Three trials, involving 233 women, are included. There was no evidence of differences in caesarean section rates between the two interventions in the two trials reporting this outcome (risk ratio (RR) 2.04, 95% confidence interval (CI) 0.92 to 4.55). There were no data presented on neonatal or maternal mortality or morbidity.There was no evidence of a difference between castor oil and placebo/no treatment for the rate of instrumental delivery, meconium-stained liquor, or Apgar score less than seven at five minutes. The number of participants was too small to detect all but large differences in outcome. All women who ingested castor oil felt nauseous (RR 59.92, 95% CI 8.46 to 424.52). AUTHORS' CONCLUSIONS: The three trials included in the review contain small numbers of women. All three studies used single doses of castor oil. The results from these studies should be interpreted with caution due to the risk of bias introduced due to poor methodological quality. Further research is needed to attempt to quantify the efficacy of castor oil as an cervical priming and induction agent.

Misoprostol for postpartum hemorrhage prevention at home birth: an integrative review of global implementation experience to date.

BACKGROUND: Hemorrhage continues to be a leading cause of maternal death in developing countries. The 2012 World Health Organization guidelines for the prevention and management of postpartum hemorrhage (PPH) recommend oral administration of misoprostol by community health workers (CHWs). However, there are several outstanding questions about distribution of misoprostol for PPH prevention at home births. METHODS: We conducted an integrative review of published research studies and evaluation reports from programs that distributed misoprostol at the community level for prevention of PPH at home births. We reviewed methods and cadres involved in education of end-users, drug administration, distribution, and coverage, correct and incorrect usage, and serious adverse events. RESULTS: Eighteen programs were identified; only seven reported all data of interest. Programs utilized a range of strategies and timings for distributing misoprostol. Distribution rates were higher when misoprostol was distributed at a home visit during late pregnancy (54.5-96.9%) or at birth (22.5-83.6%), compared to antenatal care (ANC) distribution at any ANC visit (22.5-49.1%) or late ANC visit (21.0-26.7%). Coverage rates were highest when CHWs and traditional birth attendants distributed misoprostol and lower when health workers/ANC providers distributed the medication. The highest distribution and coverage rates were achieved by programs that allowed self-administration. Seven women took misoprostol prior to delivery out of more than 12,000 women who were followed-up. Facility birth rates increased in the three programs for which this information was available. Fifty-one (51) maternal deaths were reported among 86,732 women taking misoprostol: 24 were attributed to perceived PPH; none were directly attributed to use of misoprostol. Even if all deaths were attributable to PPH, the equivalent ratio (59 maternal deaths/100,000 live births) is substantially lower than the reported maternal mortality ratio in any of these countries. CONCLUSIONS: Community-based programs for prevention of PPH at home birth using misoprostol can achieve high distribution and use of the medication, using diverse program strategies. Coverage was greatest when misoprostol was distributed by community health agents at home visits. Programs appear to be safe, with an extremely low rate of ante- or intrapartum administration of the medication.

Community mobilization to reduce postpartum hemorrhage in home births in northern Nigeria.

The purpose of this study is to demonstrate the importance of community mobilization in the uptake of a health intervention, namely, community-based distribution of misoprostol to prevent postpartum hemorrhage. Community mobilization to increase access to misoprostol for postpartum hemorrhage prevention was implemented in northwestern Nigeria in 2009. Theories of community participation and the current near-epidemic maternal mortality conditions underpin an approach using modest levels of community involvement. The study was undertaken in five communities around Zaria, Nigeria. Community leaders and selected community members participated in a series of dialogs. Additionally, community education, information and dramas sessions were held. Twenty nine community oriented resource persons (CORPs), 27 drug keepers and 41 traditional birth attendants (TBAs) were involved in the intervention. Postpartum interviews were used to assess the impact of community mobilization efforts and to track use of misoprostol. Multiple logistic regression was used to examine the association between correct use and receiving information regarding misoprostol from TBAs or CORPs. A total of 1875 women were enrolled in the study in 2009. Most women delivered at home (95%) and skilled attendance at delivery was low (7%). Community mobilization efforts reached most women with information about postpartum hemorrhage and misoprostol (88%), resulting in high comprehension of intervention messages. Women identified TBAs and CORPs as the single most important source of information about misoprostol 41% and 31% of the time, respectively. Availability of misoprostol at the community level gave 79% of enrolled women some protection against postpartum hemorrhage which they otherwise would not have had. Although high level community participation in health care interventions is the ideal, this study suggests that even in circumstances where only modest levels of participation can realistically be achieved, community mobilization can have a significant impact on the successful distribution and uptake of a potentially life-saving health intervention, in turn helping promote policy change.

Clinical trials during pregnancy: what has been done.

OBJECTIVE: We describe clinical trials conducted in pregnant women. METHODS: We searched PubMed database for articles related to clinical trials between 01/01/2000 and 31/12/2009 involving pregnant women by using the preferred terms "pregnancy", "human", and "clinical trials". RESULTS: Of 1,264 retrieved publications, 762 (60%) were excluded, leaving 502 for analysis: 53% were preventive studies in maternal or fetal conditions; 47% were therapeutic trials, mostly focused on acute obstetric diseases; 66% were assigned a pharmacological intervention. The studied drugs were 16% for labour induction and 15% for abortive procedures, followed by multivitamins and micronutrients, labour analgesia and anesthesia, antibiotics, tocolytics, and antimalarial drugs. The main objectives of the studies were focused on efficacy (54%) and efficacy and safety (26%); 81% of the studies were controlled, randomized and parallel-design trials; 19% were blinded. CONCLUSION: Clinical trials in pregnant women are mainly conducted with an efficacy objective regarding maternal-fetal prevention and in obstetric diseases to study labor induction and abortive measures. This is in line with the type of intervention and drugs involved.

The evolving management of the third stage of labour.

The immediate postpartum period is a risky period because life-threatening events can occur unexpectedly, and lead to death if they are not managed promptly. Appropriate management of the third stage of labour can reduce severe postpartum haemorrhage and death. This commentary summarizes how various management techniques of third stage of labour evolved to date and the evidence base for current international recommendations.

Castor oil for induction of labour: not harmful, not helpful.

BACKGROUND: Castor oil is one of the most popular drugs for induction of labour in a non-medical setting; however, published data on safety and effectiveness of this compound to induce labour remain sparse. AIM: To assess the safety and effectiveness of castor oil for induction of labour in pregnancies with an ultrasound estimated gestational at birth of more than 40 weeks. METHODS: Data were extracted from hospital-based records of all pregnant women who attended antenatal clinics on the Thai-Burmese border and who were more than 40 weeks pregnant. The effectiveness of castor oil to induce labour was expressed as time to birth and analysed with a Cox proportional hazards regression model. Measures associated with safety were fetal distress, meconium-stained amniotic fluid, tachysystole of the uterus, uterine rupture, abnormal maternal blood pressure during labour, Apgar scores, neonatal resuscitation, stillbirth, post-partum haemorrhage, severe diarrhoea and maternal death. Proportions were compared using Fisher's exact test. RESULTS: Of 612 women with a gestation of more than 40 weeks, 205 received castor oil for induction and 407 did not. The time to birth was not significantly different between the two groups (hazard ratio 0.99 (95% confidence interval: 0.81 to 1.20; n = 509)). Castor oil use was not associated with any harmful effects on the mother or fetus. CONCLUSIONS: Castor oil for induction of labour had no effect on time to birth nor were there any harmful effects observed in this large series. Our findings leave no justification for recommending castor oil for this purpose.