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Objective To determine, from the best available evidence, the effectiveness and safety of misoprostol administered vaginally or orally for third trimester cervical ripening or induction of labour. Methods Clinical trials of misoprostol used for cervical ripening or labour induction in the third trimester were identified from the register of randomised trials maintained by the Cochrane Pregnancy and Childbirth Group. All identified trials were considered for inclusion in the review according to a prespecified protocol. Primary outcomes were chosen to address clinical effectiveness (delivery within 24 hours) and safety (uterine hyperstimulation, caesarean section, serious maternal and neonatal morbidity) and were determined a priori. All meta-analyses were based on the intentionto-treat principle. In the absence of heterogeneity the summary statistics have been expressed as typical relative risk (RR) and 95% confidence interval (CI). Results Vaginal misoprosrol: one small study showed that the use of misoprostol results in more effective cervical ripening and reduced need for oxytocin when compared with placebo. When compared with oxytocin, vaginal misoprostol was more effective for labour induction. The relative risk of failure to achieve vaginal delivery within 24 hours was 0.48 (95% CI 0.35 to 0.66). However, the relative risks for uterine hyperstimulation with and without fetal heart rate abnormalities were 2.54 (95% CI 1.12 to 5.77) and 2.96 (95% CI 2.11 to 4.14), respectively. In three out of four trials which studied women with intact membranes and unfavourable cervices, failure to achieve vaginal delivery within 24 hours was reduced with misoprostol when compared with other prostaglandins (RR 0.71,95% CI 0.62 to 0.81). Vaginal misoprostol was associated with increased uterine hyperstimulation both without fetal heart rate changes (RR 1.67, 95% CI 1.30 to 2.14) and with associated fetal heart rate changes (RR 1.45, 95% CI 1.04 to 2.04). There was also an increase in meconium stained amniotic fluid following vaginal misoprostol (RR 1.38,95% CI 1.06 to 1.79). Oral misoprostol: one small trial suggests that, when compared with placebo, oral misoprostol reduces the need for oxytocin and shortens the time between induction and delivery. Compared with other prostaglandins one small trial showed a reduced need for oxytocin with oral misoprostol. No trials compared oral with vaginal misoprostol using different doses. No significant differences were evident. Conclusions Overall, misoprostol appears to be more effective than conventional methods of cervical ripening and labour induction. Although no differences in perinatal outcome were shown, the studies were not sufficiently large to exclude the possibility of uncommon serious adverse effects. In particular the increase in uterine hyperstimulation with fetal heart rate changes following misoprostol is a matter for concern. It is possible that, if sufficient numbers are studied, an unacceptably high number of serious adverse events including uterine rupture and asphyxia1 fetal deaths may occur. The data at present are not robust enough to address the issue of safety. Thus, though misoprostol shows promise as a highly effective, inexpensive and convenient agent for labour induction, it cannot be recommended for routine use at this stage. Lower dose misoprostol regimens should be investigated further.

OBJECTIVE: To assess the effect of three different partograms on caesarean section and maternal satisfaction. DESIGN: Prospective randomised clinical trial. SETTING: Regional teaching hospital in North West of England. PARTICIPANTS: Nine hundred and twenty-eight primigravid women with uncomplicated pregnancies who presented in spontaneous labour at term. INTERVENTIONS: The women were randomised to have their progress of labour recorded on a partogram with an action line 2, 3 or 4 hours to the right of the alert line. If the progress reached the action line, a diagnosis of prolonged labour was made. Prolonged labour was managed according to the standard ward protocol. MAIN OUTCOME MEASURES: Primary: Caesarean section rate and maternal satisfaction; secondary: need for augmentation, duration of labour, analgesia, cord blood gas analysis, postpartum haemorrhage, number of vaginal examinations, Apgar score and admission to special care baby unit. RESULTS: Caesarean section rate was lowest when labour was managed using a partogram with a 4-hour action line. The difference between the 3- and 4-hour partograms was statistically significant (OR 1 8, 95% CI 1.1-3.2), but the difference between 2 and 4 hours was not (OR 1.4, 95% CI 0.8-2.4). The women in the 2-hour arm were more satisfied with their labour when compared to the women in the 3-hour (P < 00001) and 4-hour (P

In the search for a more potent alternative to a single i.m. injection of methotrexate for ectopic pregnancy, a randomized trial was organized. The efficacy of a combination of methotrexate and mifepristone was compared with methotrexate alone in the treatment of unruptured tubal pregnancies. The diagnosis of an unruptured tubal pregnancy was confirmed laparoscopically in 50 patients during a 2 year period. Women were randomized to receive a single i.m. injection of 50 mg/m2 methotrexate alone or a single dose of 600 mg oral mifepristone in combination with the same dose of methotrexate. Both treatment protocols were successful in achieving the resolution of unruptured ectopic pregnancy (18/25 in the methotrexate group and 22/25 in the combination group) following the initial intervention. A second injection was needed in four (16%) cases in the methotrexate group and in one (4%) case in the combination group. Overall, a complete resolution was achieved in 22/25 and 23/25 cases respectively. Unruptured ectopic pregnancy resolved faster in women given the combination of methotrexate and mifepristone compared to women given methotrexate only (P = 0.01). The effect of the methotrexate and mifepristone combination was more pronounced in women with higher human chorionic gonadotrophin concentrations.

Objective: To evaluate the ability of intraumbilical oxytocin injection as a treatment for retained placenta after vaginal delivery to reduce the incidence of manual removal and postpartum hemorrhage. Methods: A randomized controlled trial was set up in a university and a district general hospital. We recruited 81 women with singleton pregnancies who underwent vaginal delivery and who failed to deliver the placenta after 20 minutes of active management of the third stage of labor. Study subjects were randomized to receive either 1) an intraumbilical injection of oxytocin (20 IU in 20 mL of saline); 2) an intraumbilical injection of saline (20 mL); or 3) no treatment. Outcome measures were expulsion of the placenta within 45 minutes of delivery, need for manual removal of the placenta under anesthesia, and postpartum hemorrhage (defined as a blood loss greater than 500 mL). Results: Women given an intraumbilical injection of oxytocin had a significant increase in spontaneous expulsion of the placenta within 45 minutes of delivery and fewer manual removals of the placenta, compared with women without treatment (odds ratio [OR] 11.6, 99% confidence interval [CI] 1.4, 272.8; and OR 7.4, 99% CI 1.1, 86.5; respectively). When women given intraumbilical oxytocin were compared with women given only intraumbilical saline, the difference was not statistically significant (OR 6.6, 99% CI 0.9, 77.2 for spontaneous expulsion of the placenta; and OR 4.7, 99% CI 0.8, 39.5 for manual removal). There was no significant difference in the incidence of spontaneous expulsion and manual removal of the placenta between women given intraumbilical saline injection and women without treatment (OR 1.8, 99% CI 0.1, 53.9; and OR 1.6, 99% CI 0.1, 22.4; respectively). Conclusion: The results of our study suggest a clinically important beneficial effect of intraumbilical oxytocin injection in the management of retained placenta.

Sixty-one women making slow progress in the active phase of spontaneous labour with intact membranes were randomised to oxytocin and amniotomy, amniotomy only or expectant management. The data show that oxytocin significantly increases the rate of cervical dilatation and shortens prolonged labour, when compared with amniotomy alone and expectant management (P = 0.0144 and 0.0006, respectively). The impact on the operative delivery rate and neonatal outcome is difficult to assess due to the small number of relevant adverse outcomes. Women reported higher satisfaction score in the two groups where intervention followed the diagnosis of dysfunctional labour.

Objective To compare the impact of two different ultrasound methods for assessing amniotic fluid volume on the incidence of obstetric interventions in post-term pregnancies. Design A prospective randomised controlled trial. Setting Liverpool Women's Hospital. Participants Five hundred women with singleton, uncomplicated pregnancies with gestational age 290 days. Interventions Random allocation to fetal monitoring by either: 1. amniotic fluid index and computerised cardiotocography, or 2. maximum pool depth and computerised cardiotocography. Main outcome measures Primary: caesarean section. Secondary: the number of abnormal monitoring tests, induction of labour, intrapartum management and neonatal outcome. Results The number of abnormal amniotic fluid indices was significantly higher than the number of abnormal maximum pool depths (10%vs 2.4%; OR 4.51, 95% CI 1.82–11.21; P= 0.0008) which resulted in more inductions for abnormal post-term monitoring in the amniotic fluid index group (14.8%vs 8.4%; OR 1.89; 95% CI 1.07–3.33; P= 0.0362) and more intrapartum electronic fetal monitoring (94.4%vs 88.4%; OR 2.21; 95% CI 1.13–4.29; P= 0.0255). There were no other statistically significant differences in outcomes related to labour and delivery, but there was a trend towards more caesarean sections in the amniotic fluid index group (18.8%vs 13.2%), in particular caesarean sections for fetal distress (8%vs 4%). There were no perinatal deaths and no statistically significant differences in perinatal outcome between the two groups. Conclusions Published reference ranges for amniotic fluid index overestimate the number of abnormal results in post-term pregnancies. Their use, when compared with maximum pool depth, is likely to increase the number of obstetric interventions with, as yet, an uncertain impact on perinatal mortality and morbidity. It is possible that antepartum fetal assessment in pregnancies where the risk of adverse perinatal outcome is very low may cause, rather than prevent morbidity.

To determine the long-term outcome of infants born with cord pH ≤ 7.0 and no clinical evidence of asphyxia at birth.Tertiary Referral Centre. A prospective matched cohort study was conducted. 51 term infants were recruited following singleton birth with venous cord pH ≤ 7.0. For each recruited baby a healthy baby with normal cord pH ≥ 7.20 was recruited matched for gestation, gender and mode of delivery. Ages and Stages Questionnaires (ASQ)(TM) and Health Screening Questionnaires (HSQ) were sent out at 24 months of age. Two independent assessors, blinded to the case assignment, reviewed intrapartum and neonatal events to look for clinical evidence of birth asphyxia among the cases.From 102 infants recruited, 62 questionnaires (24 cases, 38 controls) were returned. 20 matched pairs with no clinical evidence of birth asphyxia were available for analysis. The groups were similar except in terms of birth weight; the pH ≥ 7.0 group had mean birth weight 584 g lower than controls (p = 0.005). The ASQ motor scores were lower in children born with low cord pH (p = 0.019); however, once adjusted for birth weight, the difference was not significant (p = 0.289).It is unlikely that abnormal cord pH in otherwise healthy neonates leads to a substantially increased risk of abnormal neurodevelopmental outcome or severe health problems by 2 years of age.

Objective To identify the current status of specialist preterm labour (PTL) clinic provision and management within the UK. Design Postal survey of clinical practice. Setting UK Population All consultant-led obstetric units within the UK. Methods A questionnaire was sent by post to all 210 NHS consultant-led obstetric units within the UK. Units that had a specialist PTL clinic were asked to complete a further 20 questions defining their protocol for risk stratification and management. Main outcome measures Current practice in specialist preterm labour clinics.. Results We have identified 23 specialist clinics; the most common indications for attendance were previous PTL (100%), preterm prelabour rupture of membranes (95%), two large loop excisions of the transformation zone (95%) or cone biopsy (95%). There was significant heterogeneity in the indications for and method of primary treatment for short cervix, with cervical cerclage used in 45% of units, progesterone in 18% of units and Arabin cervical pessary in 5%. A further 23% used multiple treatment modalities in combination. Conclusions A significant heterogeneity in all topics surveyed suggests an urgent need for networking, more evidence-based guidelines and prospective comparative audits to ascertain the real impact of specialist PTL clinics on the reduction in preterm birth and its sequelae.

BACKGROUND: Planned caesarean delivery for women thought be in preterm labour may be protective for baby, but could also be quite traumatic for both mother and baby. The optimal mode of delivery of preterm babies for both cephalic and breech presentation remains, therefore, controversial. OBJECTIVES: To assess the effects of a policy of planned immediate caesarean delivery versus planned vaginal birth for women in preterm labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (5 August 2013). SELECTION CRITERIA: Randomised trials comparing a policy of planned immediate caesarean delivery versus planned vaginal delivery for preterm birth. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion. Two review authors independently extracted data and assessed risk of bias. Data were checked for accuracy. MAIN RESULTS: We included six studies (involving 122 women) but only four studies (involving only 116 women) contributed data to the analyses. Infant There were very little data of relevance to the three main (primary) outcomes considered in this review: There was no significant difference between planned immediate caesarean section and planned vaginal delivery with respect to birth injury to infant (risk ratio (RR) 0.56, 95%, confidence interval (CI) 0.05 to 5.62; one trial, 38 women) or birth asphyxia (RR 1.63, 95% CI 0.84 to 3.14; one trial, 12 women). The only cases of birth trauma were a laceration of the buttock in a baby who was delivered by caesarean section and mild bruising in another allocated to the group delivered vaginally. The difference between the two groups with regard to perinatal deaths was not significant (0.29, 95% CI 0.07 to 1.14; three trials, 89 women) and there were no data specifically relating to neonatal admission to special care and/or intensive care unit. There was also no difference between the caesarean or vaginal delivery groups in terms of markers of possible birth asphyxia (RR 1.63, 95% CI 0.84 to 3.14; one trial, 12 women) or Apgar score less than seven at five minutes (RR 0.83, 95% CI 0.43 to 1.60; four trials, 115 women) and no difference in attempts at breastfeeding (RR 1.40, 95% 0.11 to 17.45; one trial, 12 women). There was also no difference in neonatal fitting/seizures (RR 0.22, 95% CI 0.01 to 4.32; three trials, 77 women), hypoxic ischaemic encephalopathy (RR 4.00, 95% CI 0.20 to 82.01;one trial, 12 women) or respiratory distress syndrome (RR 0.55, 95% CI 0.27 to 1.10; three trials, 103 women). There were no data reported in the trials specifically relating to meconium aspiration. There was also no significant difference between the two groups for abnormal follow‐up in childhood (RR 0.65, 95% CI 0.19 to 2.22; one trial, 38 women) or delivery less than seven days after entry (RR 0.95, 95% CI 0.73 to 1.24; two trials, 51 women). Mother There were no data reported on maternal admissions to intensive care. However, there were seven cases of major maternal postpartum complications in the group allocated to planned immediate caesarean section and none in the group randomised to vaginal delivery (RR 7.21, 95% CI 1.37 to 38.08; four trials, 116 women). There were no data reported in the trials specifically relating to maternal satisfaction (postnatal). There was no significant difference between the two groups with regard to postpartum haemorrhage. A number of non‐prespecified secondary outcomes were also considered in the analyses. There was a significant advantage for women in the vaginal delivery group with respect to maternal puerperal pyrexia (RR 2.98, 95% CI 1.18 to 7.53; three trials, 89 women) and other maternal infection (RR 2.63, 95% CI 1.02 to 6.78; three trials, 103 women), but no significant differences in wound infection (RR 1.16, 95% CI 0.18 to 7.70; three trials, 103 women), maternal stay more than 10 days (RR 1.27, 95% CI 0.35 to 4.65; three trials, 78 women) or the need for blood transfusion (results not estimable). AUTHORS' CONCLUSIONS: There is not enough evidence to evaluate the use of a policy of planned immediate caesarean delivery for preterm babies. Further studies are needed in this area, but recruitment is proving difficult.

This Review describes the rationale for the use of cervical pessaries to prevent spontaneous preterm birth and their gradual introduction into clinical practice, discusses technical aspects of the more commonly used designs and provides guidance for their use and future evaluation. Possible advantages of cervical pessaries include the easy, 'one-off' application, good side-effect profile, good patient tolerance and relatively low cost compared with current alternatives. Use of transvaginal sonography to assess cervical length in the second trimester allows much better selection of patients who may benefit from the use of a cervical pessary, but future clinical trials are needed to establish clearly the role of pessaries as a preterm birth prevention strategy worldwide.

Study question Is it feasible to screen women with idiopathic recurrent miscarriage (RM) for high uterine natural killer (uNK) cell density and then randomize them to prednisolone or placebo when pregnant? Summary answer It was feasible to recruit women with idiopathic RM into a 'screen and treat' trial despite their desire for active medication. What is known already Clinical trials of immunotherapy in women with idiopathic RM have failed to substantiate efficacy in preventing miscarriage. Preimplantation uNK cell density is higher in women with RM and can be reduced with prednisolone. Study design, size, duration In a pilot RCT, 160 eligible women were screened with an endometrial biopsy and those with high uNK cell density were invited to return when pregnant for randomization to prednisolone (20 mg for 6 weeks, 10 mg for 1 week, 5 mg for 1 week) or identical placebo tablets. Randomization was by random number generation and patients, clinicians and outcome assessors were blinded to allocation. The study size and duration was determined by funding, which was for a feasibility trial, for 2 years, sufficient to screen 150 women and randomize 40 women. The outcome measures were recruitment rate, women's perspectives, compliance, live birth and miscarriage rates and pregnancy complications. Participants/materials, setting, methods The trial was advertised nationally in the UK. Women who attended research clinics run by one consultant (SQ) with three or more consecutive idiopathic miscarriages were included. Women's perspectives of the trial were sought through a questionnaire. The endometrium was sampled 5-9 days after the LH surge, stained using immunohistochemistry for CD56 and the sub-epithelial region analysed with image analysis. Women with a high uNK cell density (>5%) were invited to contact the clinic at 4-6 weeks gestation for randomization. Compliance with medication was assessed using a daily log, and side effects recorded by the women in a diary and on a structured proforma completed in the clinic at the end of the first trimester. All women had ultrasound scans every 2 weeks until 14 weeks' gestation and growth scans at 28 and 34 weeks' gestation in addition to routine antenatal care and a follow-up in person or by telephone 6 weeks after delivery. Main results and the role of chance Despite the fact that 85% of women said they would prefer the active treatment, the trial recruitment occurred at the planned rate. Eligible women (n = 160) attended the research clinics and had the uNK test, 72 were screen positive and 40 returned when pregnant for randomization. Compliance with medication was reported to be 100%. The active treatment was associated with side effects of insomnia and flushing. The live birth rate was 12/20 (60%) with prednisolone and 8/20 (40%) with placebo (Risk Ratio 1.5, 95% confidence interval (CI) 0.79-2.86, absolute difference 20% CI-10%, +50%), and hence, this was not significant. There were no pregnancy complications or serious adverse fetal outcomes. Limitations, reasons for caution This was a feasibility trial so of insufficient size to assess efficacy or safety. There was inconsistency in the start date of the trial medication and this may have affected the outcome in the active treatment group. Wider implications for the findings It was feasible to recruit women with idiopathic RM into a 'screen and treat' trial despite their desire for active medication. Our data also suggest that in future trials the primary outcome measure is live birth rate after 24 weeks gestation.

Background Chorionic villus sampling (CVS) is the method of choice for obtaining fetal tissue for prenatal diagnosis before 15 weeks of pregnancy. CVS can be performed using either a transabdominal or transcervical approach. The type of instrument and technique used could have a significant impact on the outcome of the procedure. An ability to manoeuvre the instrument within the uterine cavity without puncturing the gestational sac, to see the tip of the instrument on ultrasound scanning and to minimise the number of instrument passes into the uterus are particularly important. Objectives To compare the efficacy and safety of different instruments and techniques used to obtain chorionic tissue in early pregnancy by the transabdominal or transcervical route. Primary outcomes included failure to obtain an adequate sample (greater than 5 mg of chorionic villi), need for reinsertion of the instrument, pain, and miscarriage following the procedure. Secondary outcomes included mean weight of tissue obtained, successful culture, difficult instrument insertion, poor visualisation of instrument, vaginal bleeding following the procedure and cost per procedure. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2012). Selection criteria Randomised trials comparing different instruments (forceps, cannula, needle) or techniques for CVS using either transabdominal or transcervical approach. Data collection and analysis Two review authors assessed eligibility and trial quality. Main results For transcervical CVS, forceps and cannulae were evaluated in five trials involving 472 women. When a cannula was used, operators failed to obtain an adequate sample (greater than 5 mg of chorionic villi) more often (average risk ratio (RR) 3.81; 95% confidence interval (CI) 1.52 to 9.56). There was no difference in the need for reinsertion of instruments (average RR 2.44; 95% CI 0.83 to 7.20). However, inserting a cannula was more painful (RR 1.93; 95% CI 1.11 to 3.37). There was no difference in spontaneous miscarriage when the use of a cannula was compared with biopsy forceps (RR 1.00; 95% CI 0.14 to 6.96). One study reported the cost of the procedures and found CVS with a cannula to be more expensive (mean difference (MD) $183.7; 95% CI 152.62 to 214.78). When different types of cannulae for transcervical CVS were compared, a Portex cannula was more likely to result in an inadequate sample (RR 2.23; 95% CI 1.25 to 3.98) compared with the silver cannula and to result in a difficult (RR 3.26; 95% CI 1.38 to 7.67) or painful (RR 5.81; 95% CI 1.41 to 23.88) procedure when compared with the aluminium cannula. For transabdominal CVS, two trials comparing different needle techniques were included involving 285 women. One study using an ex vivo system of term placentae was excluded. The included trials compared different continuous negative pressure aspiration techniques with a discontinuous negative pressure system created by a syringe attached to a 20 gauge needle. The studies produced discrepant results. One study found there was no significant difference between groups in the mean weight of chorionic villi obtained (MD 0.40; 95% CI -2.25 to 3.05) or in failure to obtain an adequate sample (more than 5 mg of chorionic villi) on the first attempt (RR 1.02; 95% CI 0.54 to 1.93), whereas the other study found both of these outcomes to be significantly less favourable with the standard discontinuous technique using a syringe (mean weight of chorionic villi obtained: MD -14.80; 95% CI -21.71 to -7.89; failure to obtain an adequate sample on the first attempt: RR 2.73; 95% CI 1.08 to 6.92). There was no difference in rate of miscarriage following the procedure in either study (RR 7.15; 95% CI 0.37 to 136.50; RR 2.93; 95% CI 0.12 to 70.00). Perceived pain by the patient was similar between groups (MD 0.00; 95% CI -0.04 to 0.04) as was success of culture (no failed cases). Authors' conclusions For transcervical CVS, although there is some evidence to support the use of small forceps instead of cannulae, the evidence is not strong enough to support change in practice for clinicians who have become familiar with a particular technique. For transabdominal CVS, based on current evidence, there is no difference in clinically important outcomes with the use of a continuous compared with a discontinuous negative pressure needle aspiration system.

Major postpartum hemorrhage (PPH) remains a common cause of maternal morbidity and death worldwide. Using criteria of blood loss exceeding 1500 ml, a fall in hemoglobin of at least 40 g/liter, and/or transfusion of 4 or more units of blood, close to 5000 cases of severe PPH are expected to have occurred in the United Kingdom in the years 1997 and 1998. A postal survey was sent to 258 maternity units in the United Kingdom to determine the frequency of major PPH and how it is managed. Among the 199 units that responded, there was a lack of agreement about what constitutes major PPH. Blood loss criteria ranged from 1 to 2.5 liters. A few units diagnosed major PPH from the patient's condition and the need for blood transfusion. A majority of units reported commonly using oxytocin, ergometrine, and carboprost to treat PPH. Surgical interventions varied, but hysterectomy was the commonest procedure reported. There is substantial variation in how major PPH is defined and treated in the United Kingdom, and this has important implications in view of the fact that this is a life-threatening emergency demanding rapid intervention. Evidence-based guidelines are needed, and randomized, controlled trials will have to be performed to determine how best to manage women with intractable postpartum bleeding. Whether randomization is ethical is a question that will have to be addressed since it is not practical to expect to obtain fully informed consent.

Objective To determine the most effective tocolytic agent at delaying delivery. Design Systematic review and network meta-analysis. Data sources Cochrane Central Register of Controlled Trials, Medline, Medline In-Process, Embase, and CINAHL up to 17 February 2012. Study selection Randomised controlled trials of tocolytic therapy in women at risk of preterm delivery. Data extraction At least two reviewers extracted data on study design, characteristics, number of participants, and outcomes reported (neonatal and maternal). A network meta-analysis was done using a random effects model with drug class effect. Two sensitivity analyses were carried out for the primary outcome; restricted to studies at low risk of bias and restricted to studies excluding women at high risk of preterm delivery (those with multiple gestation and ruptured membranes). Results Of the 3263 titles initially identified, 95 randomized controlled trials of tocolytic therapy were reviewed. Compared with placebo, the probability of delivery being delayed by 48 hours was highest with prostaglandin inhibitors (odds ratio 5.39, 95% credible interval 2.14 to 12.34) followed by magnesium sulfate (2.76, 1.58 to 4.94), calcium channel blockers (2.71, 1.17 to 5.91), beta mimetics (2.41, 1.27 to 4.55), and the oxytocin receptor blocker atosiban (2.02, 1.10 to 3.80). No class of tocolytic was significantly superior to placebo in reducing neonatal respiratory distress syndrome. Compared with placebo, side effects requiring a change of medication were significantly higher for beta mimetics (22.68, 7.51 to 73.67), magnesium sulfate (8.15, 2.47 to 27.70), and calcium channel blockers (3.80, 1.02 to 16.92). Prostaglandin inhibitors and calcium channel blockers were the tocolytics with the best probability of being ranked in the top three medication classes for the outcomes of 48 hour delay in delivery, respiratory distress syndrome, neonatal mortality, and maternal side effects (all cause). Conclusions Prostaglandin inhibitors and calcium channel blockers had the highest probability of delaying delivery and improving neonatal and maternal outcomes.

Background Currently, the techniques for amniocentesis and chorionic villus sampling (CVS) tend to be described in local and national guidelines, but certain aspects, including the choice of instruments, is predominantly based upon the operator's personal preference. A survey of practice in the specialist UK centres revealed a wide variation of practice; therefore, standardising any element of technique could potentially influence the safety of the procedure. Objectives The objective of this review was to compare the safety and effectiveness of all techniques of performing both amniocentesis and CVS for prenatal diagnosis. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (11 April 2012). Selection criteria We included all randomised comparisons of different methods of performing amniocentesis after 15 weeks' gestation, or CVS (transabdominal or transvaginal) with each other or with no testing. We excluded quasi-randomised studies (e.g. alternate allocation). Data collection and analysis Both review authors independently assessed for inclusion all the potential studies identified as a result of the search strategy. Both review authors independently assessed trial quality. Both review authors extracted data. Data were checked for accuracy. Main results We included five randomised studies with total of 1049 women evaluating five different technique modifications during either amniocentesis (three studies) or CVS (two studies). For amniocentesis three interventions were evaluated - intramuscular progesterone, hexoprenaline and selecting high or low puncture sites for late 'blind' procedure - each intervention in a single small study. There was no conclusive evidence of benefit for any of them. The same applies for terbutaline tocolysis and use of continuous vacuum aspiration during CVS. Authors' conclusions Overall, the quality of evidence summarised in this review is not of sufficient quality to change current clinical practice. In the absence of clear evidence, the operators should continue to use methods and technique modifications with which they are most familiar with. Any randomised trials of technique modifications that are performed to high standard with adequate safety outcomes and power to detect important clinical differences would be clearly welcome.

Background Down's syndrome occurs when a person has three copies of chromosome 21 - or the specific area of chromosome 21 implicated in causing Down's syndrome - rather than two. It is the commonest congenital cause of mental retardation. Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Objectives To estimate and compare the accuracy of second trimester serum markers for the detection of Down’s syndrome. Search methods We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to May 2007), EMBASE (1980 to 18 May 2007), BIOSIS via EDINA (1985 to 18 May 2007), CINAHL via OVID (1982 to 18 May 2007), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2007, Issue 1), MEDION (May 2007), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (May 2007), The National Research Register (May 2007), Health Services Research Projects in Progress database (May 2007). We studied reference lists and published review articles. Selection criteria Studies evaluating tests of maternal serum in women at 14-24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. Data collection and analysis Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses. Main results Fifty-nine studies involving 341,261 pregnancies (including 1,994 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Seventeen studies made direct comparisons between tests. Fifty-four test combinations were evaluated formed from combinations of 12 different tests and maternal age; alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free beta human chorionic gonadotrophin (βhCG), free alpha human chorionic gonadotrophin (αhCG), Inhibin A, SP2, CA125, troponin, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PGF) and proform of eosinophil major basic protein (ProMBP). Meta-analysis of 12 best performing or frequently evaluated test combinations showed double and triple tests (involving AFP, uE3, total hCG, free βhCG) significantly outperform individual markers, detecting six to seven out of every 10 Down's syndrome pregnancies at a 5% false positive rate. Tests additionally involving inhibin performed best (eight out of every 10 Down's syndrome pregnancies) but were not shown to be significantly better than standard triple tests in direct comparisons. Significantly lower sensitivity occurred in women over the age of 35 years. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting the accuracy of the sensitivity. Authors' conclusions Tests involving two or more markers in combination with maternal age are significantly more sensitive than those involving one marker. The value of combining four or more tests or including inhibin have not been proven to show statistically significant improvement. Further study is required to investigate reduced test performance in women aged over 35 and the impact of differential pregnancy loss on study findings.

BACKGROUND: Cervical cerclage is a well‐known surgical procedure carried out during pregnancy. It involves positioning of a suture (stitch) around the neck of the womb (cervix), aiming to give mechanical support to the cervix and thereby reduce risk of preterm birth. The effectiveness and safety of this procedure remains controversial. This is an update of a review last published in 2012. OBJECTIVES: To assess whether the use of cervical stitch in singleton pregnancy at high risk of pregnancy loss based on woman's history and/or ultrasound finding of 'short cervix' and/or physical exam improves subsequent obstetric care and fetal outcome. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (30 June 2016) and reference lists of identified studies. SELECTION CRITERIA: We included all randomised trials of cervical suturing in singleton pregnancies. Cervical stitch was carried out when the pregnancy was considered to be of sufficiently high risk due to a woman's history, a finding of short cervix on ultrasound or other indication determined by physical exam. We included any study that compared cerclage with either no treatment or any alternative intervention. We planned to include cluster‐randomised studies but not cross‐over trials. We excluded quasi‐randomised studies. We included studies reported in abstract form only. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion. Two review authors independently assessed risk of bias and extracted data. We resolved discrepancies by discussion. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: This updated review includes a total of 15 trials (3490 women); three trials were added for this update (152 women). Cerclage versus no cerclage Overall, cerclage probably leads to a reduced risk of perinatal death when compared with no cerclage, although the confidence interval (CI) crosses the line of no effect (RR 0.82, 95% CI 0.65 to 1.04; 10 studies, 2927 women; moderate quality evidence). Considering stillbirths and neonatal deaths separately reduced the numbers of events and sample size. Although the relative effect of cerclage is similar, estimates were less reliable with fewer data and assessed as of low quality (stillbirths RR 0.89, 95% CI 0.45 to 1.75; 5 studies, 1803 women; low quality evidence; neonatal deaths before discharge RR 0.85, 95% CI 0.53 to 1.39; 6 studies, 1714 women; low quality evidence). Serious neonatal morbidity was similar with and without cerclage (RR 0.80, 95% CI 0.55 to 1.18; 6 studies, 883 women; low‐quality evidence). Pregnant women with and without cerclage were equally likely to have a baby discharged home healthy (RR 1.02, 95% CI 0.97 to 1.06; 4 studies, 657 women; moderate quality evidence). Pregnant women with cerclage were less likely to have preterm births compared to controls before 37, 34 (average RR 0.77, 95% CI 0.66 to 0.89; 9 studies, 2415 women; high quality evidence) and 28 completed weeks of gestation. Five subgroups based on clinical indication provided data for analysis (history‐indicated; short cervix based on one‐off ultrasound in high risk women; short cervix found by serial scans in high risk women; physical exam‐indicated; and short cervix found on scan in low risk or mixed populations). There were too few trials in these clinical subgroups to make meaningful conclusions and no evidence of differential effects. Cerclage versus progesterone Two trials (129 women) compared cerclage to prevention with vaginal progesterone in high risk women with short cervix on ultrasound; these trials were too small to detect reliable, clinically important differences for any review outcome. One included trial compared cerclage with intramuscular progesterone (75 women) which lacked power to detect group differences. History indicated cerclage versus ultrasound indicated cerclage Evidence from two trials (344 women) was too limited to establish differences for clinically important outcomes. AUTHORS' CONCLUSIONS: Cervical cerclage reduces the risk of preterm birth in women at high‐risk of preterm birth and probably reduces risk of perinatal deaths. There was no evidence of any differential effect of cerclage based on previous obstetric history or short cervix indications, but data were limited for all clinical groups. The question of whether cerclage is more or less effective than other preventative treatments, particularly vaginal progesterone, remains unanswered.

Background: The pain that women experience during labour is affected by multiple physiological and psychosocial factors and its intensity can vary greatly. Most women in labour require pain relief. Pain management strategies include non-pharmacological interventions (that aim to help women cope with pain in labour) and pharmacological interventions (that aim to relieve the pain of labour). Objectives: To summarise the evidence from Cochrane systematic reviews on the efficacy and safety of non-pharmacological and pharmacological interventions to manage pain in labour. We considered findings from non-Cochrane systematic reviews if there was no relevant Cochrane review. Methods: We searched the Cochrane Database of Systematic Reviews (The Cochrane Library 2011, Issue 5), The Cochrane Database of Abstracts of Reviews of Effects (The Cochrane Library 2011, Issue 2 of 4), MEDLINE (1966 to 31 May 2011) and EMBASE (1974 to 31 May 2011) to identify all relevant systematic reviews of randomised controlled trials of pain management in labour. Each of the contributing Cochrane reviews (nine new, six updated) followed a generic protocol with 13 common primary efficacy and safety outcomes. Each Cochrane review included comparisons with placebo, standard care or with a different intervention according to a predefined hierarchy of interventions. Two review authors extracted data and assessed methodological quality, and data were checked by a third author. This overview is a narrative summary of the results obtained from individual reviews. Main results: We identified 15 Cochrane reviews (255 included trials) and three non-Cochrane reviews (55 included trials) for inclusion within this overview. For all interventions, with available data, results are presented as comparisons of: 1. Intervention versus placebo or standard care; 2. Different forms of the same intervention (e.g. one opioid versus another opioid); 3. One type of intervention versus a different type of intervention (e.g. TENS versus opioid). Not all reviews included results for all comparisons. Most reviews compared the intervention with placebo or standard care, but with the exception of opioids and epidural analgesia, there were few direct comparisons between different forms of the same intervention, and even fewer comparisons between different interventions. Based on these three comparisons, we have categorised interventions into: " What works" ,"What may work", and "Insufficient evidence to make a judgement".WHAT WORKSEvidence suggests that epidural, combined spinal epidural (CSE) and inhaled analgesia effectively manage pain in labour, but may give rise to adverse effects. Epidural, and inhaled analgesia effectively relieve pain when compared with placebo or a different type of intervention (epidural versus opioids). Combined-spinal epidurals relieve pain more quickly than traditional or low dose epidurals. Women receiving inhaled analgesia were more likely to experience vomiting, nausea and dizziness.When compared with placebo or opioids, women receiving epidural analgesia had more instrumental vaginal births and caesarean sections for fetal distress, although there was no difference in the rates of caesarean section overall. Women receiving epidural analgesia were more likely to experience hypotension, motor blockade, fever or urinary retention. Less urinary retention was observed in women receiving CSE than in women receiving traditional epidurals. More women receiving CSE than low-dose epidural experienced pruritus. WHAT MAY WORKThere is some evidence to suggest that immersion in water, relaxation, acupuncture, massage and local anaesthetic nerve blocks or non-opioid drugs may improve management of labour pain, with few adverse effects. Evidence was mainly limited to single trials. These interventions relieved pain and improved satisfaction with pain relief (immersion, relaxation, acupuncture, local anaesthetic nerve blocks, non-opioids) and childbirth experience (immersion, relaxation, non-opioids) when compared with placebo or standard care. Relaxation was associated with fewer assisted vaginal births and acupuncture was associated with fewer assisted vaginal births and caesarean sections.INSUFFICIENT EVIDENCEThere is insufficient evidence to make judgements on whether or not hypnosis, biofeedback, sterile water injection, aromatherapy, TENS, or parenteral opioids are more effective than placebo or other interventions for pain management in labour. In comparison with other opioids more women receiving pethidine experienced adverse effects including drowsiness and nausea. Authors' conclusions: Most methods of non-pharmacological pain management are non-invasive and appear to be safe for mother and baby, however, their efficacy is unclear, due to limited high quality evidence. In many reviews, only one or two trials provided outcome data for analysis and the overall methodological quality of the trials was low. High quality trials are needed.There is more evidence to support the efficacy of pharmacological methods, but these have more adverse effects. Thus, epidural analgesia provides effective pain relief but at the cost of increased instrumental vaginal birth.It remains important to tailor methods used to each woman's wishes, needs and circumstances, such as anticipated duration of labour, the infant's condition, and any augmentation or induction of labour.A major challenge in compiling this overview, and the individual systematic reviews on which it is based, has been the variation in use of different process and outcome measures in different trials, particularly assessment of pain and its relief, and effects on the neonate after birth. This made it difficult to pool results from otherwise similar studies, and to derive conclusions from the totality of evidence. Other important outcomes have simply not been assessed in trials; thus, despite concerns for 30 years or more about the effects of maternal opioid administration during labour on subsequent neonatal behaviour and its influence on breastfeeding, only two out of 57 trials of opioids reported breastfeeding as an outcome. We therefore strongly recommend that the outcome measures, agreed through wide consultation for this project, are used in all future trials of methods of pain management.

BACKGROUND: Recent reports of the risk of morbidity due to uterine rupture are thought to have contributed in some countries to a decrease in the number of women attempting a vaginal birth after caesarean section. The aims of this study were to estimate the incidence of true uterine rupture in the UK and to investigate and quantify the associated risk factors and outcomes, on the basis of intended mode of delivery. METHODS AND FINDINGS: A UK national case-control study was undertaken between April 2009 and April 2010. The participants comprised 159 women with uterine rupture and 448 control women with a previous caesarean delivery. The estimated incidence of uterine rupture was 0.2 per 1,000 maternities overall; 2.1 and 0.3 per 1,000 maternities in women with a previous caesarean delivery planning vaginal or elective caesarean delivery, respectively. Amongst women with a previous caesarean delivery, odds of rupture were also increased in women who had ≥ two previous caesarean deliveries (adjusted odds ratio [aOR] 3.02, 95% CI 1.16-7.85) and

We attempted to grade treatment outcomes in female urinary incontinence by the perceived importance of these outcomes for patients, nursing staff and medical staff. One hundred millimeter visual analog scales (VAS) quantifying the relative importance of five clinical outcomes were sent to 100 patients, 50 nursing staff and 135 medical staff involved in continence care and median VAS scores for each outcome were compared between groups. Subjective improvement and improvement in quality of life were rated most highly. Median scores for subjective cure were 93 (76-99) for nurses, 93 (11-100) for patients and 91 (50-100) for ICS (UK) members. Median quality of life improvement scores were 92 (67-100), 93 (3-100) and 93 (74-100), respectively (not significant). There was a striking concordance of opinion regarding the importance of subjective improvement and improvement in quality of life. We suggest that these should become primary outcome measures in all future clinical trials and audits of incontinence treatments.

To determine whether the use of vaginal progesterone in asymptomatic women with a sonographic short cervix (≤ 25 mm) in the midtrimester reduces the risk of preterm birth and improves neonatal morbidity and mortality.Individual patient data metaanalysis of randomized controlled trials.Five trials of high quality were included with a total of 775 women and 827 infants. Treatment with vaginal progesterone was associated with a significant reduction in the rate of preterm birth33 weeks (relative risk [RR], 0.58; 95% confidence interval [CI], 0.42-0.80),35 weeks (RR, 0.69; 95% CI, 0.55-0.88), and28 weeks (RR, 0.50; 95% CI, 0.30-0.81); respiratory distress syndrome (RR, 0.48; 95% CI, 0.30-0.76); composite neonatal morbidity and mortality (RR, 0.57; 95% CI, 0.40-0.81); birthweight1500 g (RR, 0.55; 95% CI, 0.38-0.80); admission to neonatal intensive care unit (RR, 0.75; 95% CI, 0.59-0.94); and requirement for mechanical ventilation (RR, 0.66; 95% CI, 0.44-0.98). There were no significant differences between the vaginal progesterone and placebo groups in the rate of adverse maternal events or congenital anomalies.Vaginal progesterone administration to asymptomatic women with a sonographic short cervix reduces the risk of preterm birth and neonatal morbidity and mortality.

Objective: To evaluate the feasibility of continuous telemetric trans-abdominal fetal electrocardiogram (a-fECG) in women undergoing labour induction at home. Study Design: Low risk women with singleton term pregnancy undergoing labour induction with retrievable, slow-release dinoprostone pessaries (n = 70) were allowed home for up to 24 hours, while a-fECG and uterine activity were monitored in hospital via wireless technology. Semi-structured diaries were analysed using a combined descriptive and interpretive approach. Results: 62/70 women (89%) had successful home monitoring; 8 women (11%) were recalled because of signal loss. Home monitoring lasted between 2-22 hours (median 10 hours). Good quality signal was achieved most of the time (86%, SD 10%). 3 women were recalled back to hospital for suspicious a-fECG. In 2 cases suspicious a-fECG persisted, requiring Caesarean section after recall to hospital. 48/51 women who returned the diary coped well (94%); 46/51 were satisfied with home monitoring (90%). Conclusions: Continuous telemetric trans-abdominal fetal ECG monitoring of ambulatory women undergoing labour induction is feasible and acceptable to women. © 2011 Rauf et al.

Background Besides risks of miscarriage, pregnant women undergoing amniocentesis or chorionic villus sampling (CVS) are also concerned about pain associated with these procedures. Currently, approaches to analgesia can be categorised in two broad categories - non-pharmacological and pharmacological agents. Objectives To evaluate whether different methods of analgesia have any impact on pain reduction during amniocentesis or chorionic villus sampling (CVS). Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2011). Selection criteria All randomised trials comparing different method of analgesia for amniocentesis or CVS. We also include trials with quasi-randomised designs, but analyse and report their results separately. Data collection and analysis Both review authors assessed eligibility and trial quality and performed data extraction. Main results We included a total of five randomised studies (involving 805 women) evaluating different methods of analgesia for amniocentesis; there were no studies in women undergoing CVS.One RCT (N = 203) and one quasi-randomised study (N = 220) compared infiltrative local anaesthesia with no anaesthesia and found no statistical difference in experienced pain on the visual analogue scale (VAS) (mean differences (MD) -2.50 and 1.20; 95% confidence interval (CI) -6.98 to 1.98 and -2.67 to 5.07).One study (N = 200) compared light leg rubbing versus no intervention during amniocentesis and found no change in experienced anxiety (MD 0.2; 95% CI -0.63 to 1.03) or VAS pain score (MD 0.3; 95% CI -0.35 to 0.95) during amniocentesis.Another study with 62 patients did not find any benefit of using subfreezing temperature needle during amniocentesis in terms of decreased VAS pain score (MD -0.8; 95% CI -1.8 to 0.2). In addition, there was no difference between anticipated and actual pain (MD 0.4; 95% CI -0.82 to 1.62) (before/after comparison).There was also no difference in VAS pain scores in the study with 120 participants comparing lidocaine-prilocaine analgesic cream to placebo cream before amniocentesis (MD -0.6; 95% CI -1.44 to 0.24). Authors' conclusions In general, women who undergo amniocentesis could be informed that pain during procedure is minor and that there is currently insufficient evidence to support the use of local anaesthetics, leg rubbing or subfreezing the needle for pain reduction during procedure.

Background and aims: Some studies have observed poorer cognitive development in children born late preterm (34-36 weeks gestation) and early term (37-38 weeks gestation). Few studies have measured school performance in these children. We compared school performance in children born at full term (39-41 weeks gestation) with those born early term, late preterm and moderately/very preterm (< 34 weeks gestation). Methods: We analysed data on 7,655 children from the Millennium Cohort Study who were attending school in England in 2006. School performance was measured using the Foundation Stage Profile (FSP), a statutory assessment by teachers at the end of the child's first school year (age 5). The FSP comprises 13 assessment scales (scored from 0-9). Children who achieve an average of 6 points per scale and at least 6 in certain scales are classified as “reaching a good level of overall achievement”. Results: 51% of full term children had not reached a good level of overall achievement; this proportion increased with prematurity (55% in early term, 59% in late preterm, 64% in moderately/very preterm children). Compared with full term children, there were significantly elevated odds even in late preterm (adjusted OR 1.4, 95% CI: 1.1, 1.7) and early term (adjusted OR 1.2, 95% 1.0, 1.3) children. Early term birth accounted for a similar population attributable fraction (3%) as for all the preterm groups combined (gestation 23-36 weeks) (3%). Conclusions: Late preterm and early term birth are associated with an elevated risk of poorer school performance at age 5.

Objective to explore how severe postpartum haemorrhage (PPH) and its management is experienced by women and their partners, and how they later view events. Design interpretive phenomenological qualitative study with semi-structured interviews. Setting in-depth interviews were conducted in participants' homes and focused on experiences of PPH in hospital and post-discharge. Participants nine women who had experienced severe PPH and six partners. Findings this study demonstrates the stressful and emotional nature of severe PPH and extends the literature by considering partners' perspectives. Women and men had different experiences and information needs, but interviewees often shared a common desire for help to understand past events. A dominant theme of communication difficulties, and two subthemes, disempowerment and information-deprivation arose strongly from the data. Communication difficulties were understandable during the emergency but were frustrating and upsetting in postpartum care and the longer term. Conclusions and implications for practice research is needed to develop better communication and supportive strategies, which might avoid the sense of disempowerment in this potentially vulnerable population. Different information and support needs for women and men should be considered whatever policies are implemented.

Objective to explore women's and their partners' views of recruitment to emergency trials in severe postpartum haemorrhage (PPH). Design interview-based qualitative study. In semi-structured in-depth interviews, five recruitment options for a PPH trial in an emergency context were considered. Setting interviews were carried out in participants' homes. Participants nine women who had experienced a severe PPH and six partners. Findings interviewees rejected three options; decision-making by women prior to delivery, and by partners and legal representatives at the time of the emergency. Preferred options were women making antenatal decisions about trial entry themselves, followed by doctors making decisions at the time of the emergency. Conclusions and implications for practice recruitment options involving women and their partners at the time of an emergency were rejected. Antenatal decision-making raises logistical and ethical considerations for emergency trial teams. Further research is needed to address the possibility of antenatal decisions for emergency trials and to develop and assess supportive post-enrolment recruitment and information strategies which take into account the stressful context of clinical emergencies such as PPH.

BACKGROUND: Peripheral natural killer (pNK) and uterine NK (uNK) cells have been associated with reproductive failure. We systematically reviewed the literature to assess whether numbers or activity of pNK or uNK cells predicted subsequent pregnancy and outcome. METHODS: We searched the electronic MEDLINE database from 1950 to April 2010 for relevant publications by using MeSH terms 'natural killer cells', 'reproduction' and 'pregnancy complications'. We included studies that measured pre-pregnancy pNK and uNK cell numbers or activity in women with recurrent miscarriage (RM) or infertility, and reported subsequent pregnancy outcomes of miscarriage or failure to conceive after assisted reproductive technology (ART). RESULTS: The search identified 783 publications and 12 fulfilled the inclusion criteria. There were too few women entered into the observational studies to assess whether high pNK cell percentages or activity predicted subsequent miscarriage in women with idiopathic RM (numbers: n = 32, OR 17, 95% CI 0.82-350.6, activity: n = 92, OR 2.51, 95% CI 0.16-40.29), or implantation failure (n = 203, OR 1.35, 95% CI 0.28-6.46), or miscarriage in infertile women after ART (n = 79, OR 2.48, 95% CI 0.50-12.32). Similarly, the studies of uNK cells were not large enough to assess whether abnormal uNK cell density predicted subsequent miscarriage in women with idiopathic RM (n = 72, OR 1.33, 95% CI 0.16-11.11). None of the uNK cell studies in women with infertility reported pregnancy outcomes dichotomized for uNK cell numbers. CONCLUSIONS: The prognostic value of measuring pNK or uNK cell parameters remains uncertain. More studies are needed to confirm or refute the role of NK cell assessments as a predictive test for screening women who may benefit from immunotherapy.

Background: Social deprivation is associated with higher rates of preterm birth and subsequent infant mortality. Our objective was to identify risk factors for preterm birth in the UK's largest maternity unit, with a particular focus on social deprivation, and related factors. Methodology/Principal Findings: Retrospective cohort study of 39,873 women in Liverpool, UK, from 2002-2008. Singleton pregnancies were stratified into uncomplicated low risk pregnancies and a high risk group complicated by medical problems. Multiple logistic regression, and generalized additive models were used to explore the effect of covariates including area deprivation, smoking status, BMI, parity and ethnicity on the risk of preterm birth (34(+0) weeks). In the low risk group, preterm birth rates increased with deprivation, reaching 1.6% (CI95 1.4 to 1.8) in the most deprived quintile; the unadjusted odds ratio comparing an individual in the most deprived quintile, to one in the least deprived quintile was 1.5 (CI95 1.2 to 1.9). Being underweight and smoking were both independently associated with preterm birth in the low risk group, and adjusting for these factors explained the association between deprivation and preterm birth. Preterm birth was five times more likely in the high risk group (RR 4.8 CI95 4.3 to 5.4), and there was no significant relationship with deprivation. Conclusions: Deprivation has significant impact on preterm birth rates in low risk women. The relationship between low socio-economic status and preterm births appears to be related to low maternal weight and smoking in more deprived groups.

Background Peripartum cardiomyopathy (PPCM or PCMO) is a rare disease of unknown etiology, characterised by an acute onset of heart failure in women in the late stage of pregnancy or in the early months postpartum. Objectives To assess the effectiveness and safety of any intervention for the care of women and/or their babies with a diagnosis of peripartum cardiomyopathy. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 July 2010) and the reference lists of identified studies. Selection criteria Randomised and quasi-randomised controlled trials of any intervention for treating peripartum cardiomyopathy. Such interventions include: drugs; cardiac monitoring and treatment; haemodynamic monitoring and treatments; supportive therapies and heart transplant. 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 identified and included one pilot study, involving 20 women, undertaken in South Africa. Women were diagnosed postnatally and included in the study within 24 hours of diagnosis. Authors' conclusions There are insufficient data to draw any firm conclusions. Treatment with bromocriptine appears promising, although women would be unable to breastfeed due to suppression of lactation.

BACKGROUND: Induction of labour is carried out for a variety of indications and using a range of methods. For women at low risk of pregnancy complications, some methods of induction of labour or cervical ripening may be suitable for use in outpatient settings. OBJECTIVES: To examine pharmacological and mechanical interventions to induce labour or ripen the cervix in outpatient settings in terms of effectiveness, maternal satisfaction, healthcare costs and, where information is available, safety. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (30 November 2016) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials examining outpatient cervical ripening or induction of labour with pharmacological agents or mechanical methods. Cluster trials were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed evidence using the GRADE approach. MAIN RESULTS: This updated review included 34 studies of 11 different methods for labour induction with 5003 randomised women, where women received treatment at home or were sent home after initial treatment and monitoring in hospital. Studies examined vaginal and intracervical prostaglandin E₂ (PGE₂), vaginal and oral misoprostol, isosorbide mononitrate, mifepristone, oestrogens, amniotomy and acupuncture, compared with placebo, no treatment, or routine care. Trials generally recruited healthy women with a term pregnancy. The risk of bias was mostly low or unclear, however, in 16 trials blinding was unclear or not attempted. In general, limited data were available on the review's main and additional outcomes. Evidence was graded low to moderate quality. 1. Vaginal PGE₂ versus expectant management or placebo (5 studies) Fewer women in the vaginal PGE₂ group needed additional induction agents to induce labour, however, confidence intervals were wide (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.27 to 0.99; 150 women; 2 trials). There were no clear differences between groups in uterine hyperstimulation (with or without fetal heart rate (FHR) changes) (RR 3.76, 95% CI 0.64 to 22.24; 244 women; 4 studies; low‐quality evidence), caesarean section (RR 0.80, 95% CI 0.49 to 1.31; 288 women; 4 studies; low‐quality evidence), or admission to a neonatal intensive care unit (NICU) (RR 0.32, 95% CI 0.10 to 1.03; 230 infants; 3 studies; low‐quality evidence). There was no information on vaginal birth within 24, 48 or 72 hours, length of hospital stay, use of emergency services or maternal or caregiver satisfaction. Serious maternal and neonatal morbidity or deaths were not reported. 2. Intracervical PGE₂ versus expectant management or placebo (7 studies) There was no clear difference between women receiving intracervical PGE₂ and no treatment or placebo in terms of need for additional induction agents (RR 0.98, 95% CI 0.74 to 1.32; 445 women; 3 studies), vaginal birth not achieved within 48 to 72 hours (RR 0.83, 95% CI 0.68 to 1.02; 43 women; 1 study; low‐quality evidence), uterine hyperstimulation (with FHR changes) (RR 2.66, 95% CI 0.63 to 11.25; 488 women; 4 studies; low‐quality evidence), caesarean section (RR 0.90, 95% CI 0.72 to 1.12; 674 women; 7 studies; moderate‐quality evidence), or babies admitted to NICU (RR 1.61, 95% CI 0.43 to 6.05; 215 infants; 3 studies; low‐quality evidence). There were no uterine ruptures in either the PGE₂ group or placebo group. There was no information on vaginal birth not achieved within 24 hours, length of hospital stay, use of emergency services, mother or caregiver satisfaction, or serious morbidity or neonatal morbidity or perinatal death. 3. Vaginal misoprostol versus placebo (4 studies) One small study reported on the rate of perinatal death with no clear differences between groups; there were no deaths in the treatment group compared with one stillbirth (reason not reported) in the control group (RR 0.34, 95% CI 0.01 to 8.14; 77 infants; 1 study; low‐quality evidence). There was no clear difference between groups in rates of uterine hyperstimulation with FHR changes (RR 1.97, 95% CI 0.43 to 9.00; 265 women; 3 studies; low‐quality evidence), caesarean section (RR 0.94, 95% CI 0.61 to 1.46; 325 women; 4 studies; low‐quality evidence), and babies admitted to NICU (RR 0.89, 95% CI 0.54 to 1.47; 325 infants; 4 studies; low‐quality evidence). There was no information on vaginal birth not achieved within 24, 48 or 72 hours, additional induction agents required, length of hospital stay, use of emergency services, mother or caregiver satisfaction, serious maternal, and other neonatal, morbidity or death. No substantive differences were found for other comparisons. One small study found that women who received oral misoprostol were more likely to give birth within 24 hours (RR 0.65, 95% CI 0.48 to 0.86; 87 women; 1 study) and were less likely to require additional induction agents (RR 0.60, 95% CI 0.37 to 0.97; 127 women; 2 studies). Women who received mifepristone were also less likely to require additional induction agents (average RR 0.59, 95% CI 0.37 to 0.95; 311 women; 4 studies; I² = 74%); however, this result should be interpreted with caution due to high heterogeneity. One trial each of acupuncture and outpatient amniotomy were included, but few review outcomes were reported. AUTHORS' CONCLUSIONS: Induction of labour in outpatient settings appears feasible and important adverse events seem rare, however, in general there is insufficient evidence to detect differences. There was no strong evidence that agents used to induce labour in outpatient settings had an impact (positive or negative) on maternal or neonatal health. There was some evidence that compared to placebo or no treatment, induction agents administered on an outpatient basis reduced the need for further interventions to induce labour, and shortened the interval from intervention to birth. We do not have sufficient evidence to know which induction methods are preferred by women, the interventions that are most effective and safe to use in outpatient settings, or their cost effectiveness. Further studies where various women‐friendly outpatient protocols are compared head‐to‐head are required. As part of such work, women should be consulted on what sort of management they would prefer.

A pregnancy reaching 42 completed weeks (294 days) is defined as postterm (PT). The use of ultrasound in early pregnancy for precise dating significantly reduces the number of PT pregnancies compared to dating based on the last menstrual period. Although the fetal, maternal and neonatal risks increase beyond 41 weeks, there is no conclusive evidence that prolongation of pregnancy, per se, is the major risk factor. Other specific risk factors for adverse outcomes have been identified, the most important of which are restricted fetal growth and fetal malformations. In order to prevent PT and associated complications routine induction before 42 weeks has been proposed. There is no conclusive evidence that this policy improves fetal, maternal and neonatal outcomes as compared to expectant management. It is also unclear if the rate of cesarean sections is different between the two management strategies. After careful identification and exclusion of specific risks, it would seem appropriate to let women make an informed decision about which management they wish to undertake. There is consensus that the number of inductions necessary to possibly avoid one stillbirth is very high. If induction is preferred, procedures for cervical ripening should be used, especially in nulliparous women. Close intrapartum fetal surveillance should be offered, irrespective of whether labor was induced or not.

BACKGROUND: Abnormal waveforms from Doppler ultrasound may indicate poor fetal prognosis. It is also possible that Doppler ultrasound could encourage inappropriate early delivery. OBJECTIVES: The objective of this review was to assess the effects of Doppler ultrasound in high risk pregnancies on obstetric care and fetal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group trials register. Date of last search: June 2001. SELECTION CRITERIA: Randomised trials of Doppler ultrasound for the investigation of umbilical artery waveforms in high risk pregnancies compared to no Doppler ultrasound. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted by both reviewers. Study authors were contacted for additional information. MAIN RESULTS: Eleven studies involving nearly 7000 women were included. The trials were generally of good quality. Compared to no Doppler ultrasound, Doppler ultrasound in high risk pregnancy (especially those complicated by hypertension or presumed impaired fetal growth) was associated with a trend to a reduction in perinatal deaths (odds ratio 0.71, 95% confidence interval 0.50 to 1.01). The use of Doppler ultrasound was also associated with fewer inductions of labour (odds ratio 0.83, 95% confidence interval 0.74 to 0.93) and fewer admissions to hospital (odds ratio 0.56, 95% 0.43 to 0.72), without reports of adverse effects. No difference was found for fetal distress in labour (odds ratio 0.81, 95% confidence interval 0.59 to 1.13) or caesarean delivery (odds ratio 0.94, 95% 0.82 to 1.06). AUTHORS' CONCLUSIONS: The use of Doppler ultrasound in high risk pregnancies appears to improve a number of obstetric care outcomes and appears promising in helping to reducing perinatal deaths.

Background Each year, worldwide about 530,000 women die from causes related to pregnancy and childbirth. Of the deaths 99% are in low and middle income countries. Obstetric haemorrhage is the leading cause of maternal mortality, most occurring in the postpartum period. Systemic antifibrinolytic agents are widely used in surgery to prevent clot breakdown (fibrinolysis) in order to reduce surgical blood loss. At present there is little reliable evidence from randomised trials on the effectiveness of tranexamic acid in the treatment of postpartum haemorrhage. Methods The Trial aims to determine the effect of early administration of tranexamic acid on mortality, hysterectomy and other morbidities (surgical interventions, blood transfusion, risk of non-fatal vascular events) in women with clinically diagnosed postpartum haemorrhage. The use of health services and safety, especially thromboembolic effect, on breastfed babies will also be assessed. The trial will be a large, pragmatic, randomised, double blind, placebo controlled trial among 15,000 women with a clinical diagnosis of postpartum haemorrhage. All legally adult women with clinically diagnosed postpartum haemorrhage following vaginal delivery of a baby or caesarean section will potentially be eligible. The fundamental eligibility criterion is the responsible clinician's 'uncertainty' as to whether or not to use an antifibrinolytic agent in a particular woman with postpartum haemorrhage. Treatment will entail a dose of tranexamic acid (1 gram by intravenous injection) or placebo (sodium chloride 0.9%) will be given as soon as possible after randomisation. A second dose may be given if after 30 minutes bleeding continues, or if it stops and restarts within 24 hours after the first dose. The main analyses will be on an 'intention to treat' basis, irrespective of whether the allocated treatment was received or not. Subgroup analyses for the primary outcome will be based on type of delivery; administration or not of prophylactic uterotonics; and on whether the clinical decision to consider trial entry was based primarily on estimated blood loss alone or on haemodynamic instability. A study with 15,000 women will have over 90% power to detect a 25% reduction from 4% to 3% in the primary endpoint of mortality or hysterectomy. Trial registration Current Controlled Trials: ISRCTN76912190 and Clinicaltrials.gov ID: NCT00872469

Introduction: As a consequence of the introduction of effective screening methods, the number of invasive prenatal diagnostic procedures is steadily declining. The aim of this review is to summarize the risks related to these procedures. Material and Methods: Review of the literature. Results: Data from randomised controlled trials as well as from systematic reviews and a large national registry study are consistent with a procedure-related miscarriage rate of 0.5–1.0% for amniocentesis as well as for chorionic villus sampling (CVS). In single-center studies performance may be remarkably good due to very skilled operators, but these figures cannot be used for general counselling. Amniocentesis performed prior to 15 weeks had a significantly higher miscarriage rate than CVS and mid-trimester amniocentesis, and also increased the risk of talipes equinovarus. Amniocentesis should therefore not be performed before 15 + 0 weeks’ gestation. CVS on the other hand should not be performed before 10 weeks’ gestation due to a possible increase in risk of limb reduction defects. Discussion: Experienced operators have a higher success rate and a lower complication rate. The decreasing number of prenatal invasive procedures calls for quality assurance and monitoring of operators’ performance.