Gillian ML Gyte’s research while affiliated with University of Liverpool and other places

Background: Nausea and vomiting are distressing symptoms which are experienced commonly during caesarean section under regional anaesthesia and in the postoperative period. OBJECTIVES: To assess the efficacy of pharmacological and non-pharmacological interventions versus placebo or no intervention given prophylactically to prevent nausea and vomiting in women undergoing regional anaesthesia for caesarean section. Search methods: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (16 April 2020), and reference lists of retrieved studies. Selection criteria: We included randomised controlled trials (RCTs) of studies and conference abstracts, and excluded quasi-RCTs and cross-over studies. Data collection and analysis: Review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Our primary outcomes are intraoperative and postoperative nausea and vomiting. Data entry was checked. Two review authors independently assessed the certainty of the evidence using the GRADE approach. Main results: Eighty-four studies (involving 10,990 women) met our inclusion criteria. Sixty-nine studies, involving 8928 women, contributed data. Most studies involved women undergoing elective caesarean section. Many studies were small with unclear risk of bias and sometimes few events. The overall certainty of the evidence assessed using GRADE was moderate to very low. 5-HT3 antagonists: We found intraoperative nausea may be reduced by 5-HT3 antagonists (average risk ratio (aRR) 0.55, 95% confidence interval (CI) 0.42 to 0.71, 12 studies, 1419 women, low-certainty evidence). There may be a reduction in intraoperative vomiting but the evidence is very uncertain (aRR 0.46, 95% CI 0.29 to 0.73, 11 studies, 1414 women, very low-certainty evidence). There is probably a reduction in postoperative nausea (aRR 0.40, 95% CI 0.30 to 0.54, 10 studies, 1340 women, moderate-certainty evidence), and these drugs may show a reduction in postoperative vomiting (aRR 0.47, 95% CI 0.31 to 0.69, 10 studies, 1450 women, low-certainty evidence). Dopamine antagonists: We found dopamine antagonists may reduce intraoperative nausea but the evidence is very uncertain (aRR 0.38, 95% CI 0.27 to 0.52, 15 studies, 1180 women, very low-certainty evidence). Dopamine antagonists may reduce intraoperative vomiting (aRR 0.41, 95% CI 0.28 to 0.60, 12 studies, 942 women, low-certainty evidence) and postoperative nausea (aRR 0.61, 95% CI 0.48 to 0.79, 7 studies, 601 women, low-certainty evidence). We are uncertain if dopamine antagonists reduce postoperative vomiting (aRR 0.63, 95% CI 0.44 to 0.92, 9 studies, 860 women, very low-certainty evidence). Corticosteroids (steroids): We are uncertain if intraoperative nausea is reduced by corticosteroids (aRR 0.56, 95% CI 0.37 to 0.83, 6 studies, 609 women, very low-certainty evidence) similarly for intraoperative vomiting (aRR 0.52, 95% CI 0.31 to 0.87, 6 studies, 609 women, very low-certainty evidence). Corticosteroids probably reduce postoperative nausea (aRR 0.59, 95% CI 0.49 to 0.73, 6 studies, 733 women, moderate-certainty evidence), and may reduce postoperative vomiting (aRR 0.68, 95% CI 0.49 to 0.95, 7 studies, 793 women, low-certainty evidence). Antihistamines: Antihistamines may have little to no effect on intraoperative nausea (RR 0.99, 95% CI 0.47 to 2.11, 1 study, 149 women, very low-certainty evidence) or intraoperative vomiting (no events in the one study of 149 women). Antihistamines may reduce postoperative nausea (aRR 0.44, 95% CI 0.30 to 0.64, 4 studies, 514 women, low-certainty evidence), however, we are uncertain whether antihistamines reduce postoperative vomiting (average RR 0.48, 95% CI 0.29 to 0.81, 3 studies, 333 women, very low-certainty evidence). Anticholinergics: Anticholinergics may reduce intraoperative nausea (aRR 0.67, 95% CI 0.51 to 0.87, 4 studies, 453 women, low-certainty evidence) but may have little to no effect on intraoperative vomiting (aRR 0.79, 95% CI 0.40 to 1.54, 4 studies; 453 women, very low-certainty evidence). No studies looked at anticholinergics in postoperative nausea, but they may reduce postoperative vomiting (aRR 0.55, 95% CI 0.41 to 0.74, 1 study, 161 women, low-certainty evidence). Sedatives: We found that sedatives probably reduce intraoperative nausea (aRR 0.65, 95% CI 0.51 to 0.82, 8 studies, 593 women, moderate-certainty evidence) and intraoperative vomiting (aRR 0.35, 95% CI 0.24 to 0.52, 8 studies, 593 women, moderate-certainty evidence). However, we are uncertain whether sedatives reduce postoperative nausea (aRR 0.25, 95% CI 0.09 to 0.71, 2 studies, 145 women, very low-certainty evidence) and they may reduce postoperative vomiting (aRR 0.09, 95% CI 0.03 to 0.28, 2 studies, 145 women, low-certainty evidence). Opioid antagonists: There were no studies assessing intraoperative nausea or vomiting. Opioid antagonists may result in little or no difference to the number of women having postoperative nausea (aRR 0.75, 95% CI 0.39 to 1.45, 1 study, 120 women, low-certainty evidence) or postoperative vomiting (aRR 1.25, 95% CI 0.35 to 4.43, 1 study, 120 women, low-certainty evidence). Acupressure: It is uncertain whether acupressure/acupuncture reduces intraoperative nausea (aRR 0.55, 95% CI 0.41 to 0.74, 9 studies, 1221 women, very low-certainty evidence). Acupressure may reduce intraoperative vomiting (aRR 0.52, 95% CI 0.33 to 0.80, 9 studies, 1221 women, low-certainty evidence) but it is uncertain whether it reduces postoperative nausea (aRR 0.46, 95% CI 0.27 to 0.75, 7 studies, 1069 women, very low-certainty evidence) or postoperative vomiting (aRR 0.52, 95% CI 0.34 to 0.79, 7 studies, 1069 women, very low-certainty evidence). Ginger: It is uncertain whether ginger makes any difference to the number of women having intraoperative nausea (aRR 0.66, 95% CI 0.36 to 1.21, 2 studies, 331 women, very low-certainty evidence), intraoperative vomiting (aRR 0.62, 95% CI 0.38 to 1.00, 2 studies, 331 women, very low-certainty evidence), postoperative nausea (aRR 0.63, 95% CI 0.22 to 1.77, 1 study, 92 women, very low-certainty evidence) and postoperative vomiting (aRR 0.20, 95% CI 0.02 to 1.65, 1 study, 92 women, very low-certainty evidence). Few studies assessed our secondary outcomes including adverse effects or women's views. Authors' conclusions: This review indicates that 5-HT3 antagonists, dopamine antagonists, corticosteroids, sedatives and acupressure probably or possibly have efficacy in reducing nausea and vomiting in women undergoing regional anaesthesia for caesarean section. However the certainty of evidence varied widely and was generally low. Future research is needed to assess side effects of treatment, women's views and to compare the efficacy of combinations of different medications.

Background: Caesarean section increases the risk of postpartum infection for women and prophylactic antibiotics have been shown to reduce the incidence; however, there are adverse effects. It is important to identify the most effective class of antibiotics to use and those with the least adverse effects. OBJECTIVES: To determine, from the best available evidence, the balance of benefits and harms between different classes of antibiotic given prophylactically to women undergoing caesarean section, considering their effectiveness in reducing infectious complications for women and adverse effects on both mother and infant. Search methods: For this 2020 update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (2 December 2019), and reference lists of retrieved studies. Selection criteria: We included randomised controlled trials (RCTs) comparing different classes of prophylactic antibiotics given to women undergoing caesarean section. RCTs published in abstract form were also included. We excluded trials that compared drugs with placebo or drugs within a specific class; these are assessed in other Cochrane Reviews. We excluded quasi-RCTs and cross-over trials. Cluster-RCTs 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 and carried out data extraction. We assessed the certainty of the evidence using the GRADE approach. Main results: We included 39 studies, with 33 providing data (8073 women). Thirty-two studies (7690 women) contributing data administered antibiotics systemically, while one study (383 women) used lavage and was analysed separately. We identified three main comparisons that addressed clinically important questions on antibiotics at caesarean section (all systemic administration), but we only found studies for one comparison, 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'. We found no studies for the following comparisons: 'antistaphylococcal cephalosporins (1st and 2nd generation) versus lincosamides' and 'antistaphylococcal cephalosporins (1st and 2nd generation) versus lincosamides plus aminoglycosides'. Twenty-seven studies (22 provided data) included comparisons of cephalosporins (only) versus penicillins (only). However for this update, we only pooled data relating to different sub-classes of penicillins and cephalosporins where they are known to have similar spectra of action against agents likely to cause infection at caesarean section. Eight trials, providing data on 1540 women, reported on our main comparison, 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'. We found data on four other comparisons of cephalosporins (only) versus penicillins (only) using systemic administration: antistaphylococcal cephalosporins (1st and 2nd generation) versus non-antistaphylococcal penicillins (natural and broad spectrum) (9 studies, 3093 women); minimally antistaphylococcal cephalosporins (3rd generation) versus non-antistaphylococcal penicillins (natural and broad spectrum) (4 studies, 854 women); minimally antistaphylococcal cephalosporins (3rd generation) versus broad spectrum penicillins plus betalactamase inhibitors (2 studies, 865 women); and minimally antistaphylococcal cephalosporins (3rd generation) versus broad spectrum and antistaphylococcal penicillins (1 study, 200 women). For other comparisons of different classes of antibiotics, only a small number of trials provided data for each comparison, and in all but one case data were not pooled. For all comparisons, there was a lack of good quality data and important outcomes often included few women. Three of the studies that contributed data were undertaken with drug company funding, one was funded by the hospital, and for all other studies the funding source was not reported. Most of the studies were at unclear risk of selection bias, reporting bias and other biases, partly due to the inclusion of many older trials where trial reports did not provide sufficient methodological information. We undertook GRADE assessment on the only main comparison reported by the included studies, antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors, and the certainty ranged from low to very low, mostly due to concerns about risk of bias, wide confidence intervals (CI), and few events. In terms of the primary outcomes for our main comparison of 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors': only one small study reported sepsis, and there were too few events to identify clear differences between the drugs (risk ratio (RR) 2.37, 95% CI 0.10 to 56.41, 1 study, 75 women, very low-certainty evidence). There may be little or no difference between these antibiotics in preventing endometritis (RR 1.10; 95% CI 0.76 to 1.60, 7 studies, 1161 women; low-certainty evidence). None of the included studies reported on infant sepsis or infant oral thrush. For our secondary outcomes, we found there may be little or no difference between interventions for maternal fever (RR 1.07, 95% CI 0.65 to 1.75, 3 studies, 678 women; low-certainty evidence). We are uncertain of the effects on maternal: wound infection (RR 0.78, 95% CI 0.32 to 1.90, 4 studies, 543 women), urinary tract infection (average RR 0.64, 95% CI 0.11 to 3.73, 4 studies, 496 women), composite adverse effects (RR 0.96, 95% CI 0.09 to 10.50, 2 studies, 468 women), and skin rash (RR 1.08, 95% CI 0.28 to 4.1, 3 studies, 591 women) (all very low certainty evidence). Although maternal allergic reactions were reported by two studies, there were no events. There were no infant outcomes reported in the included studies. For the other comparisons, the results for most outcomes had wide CIs, few studies and few women included. None of the included trials reported on longer-term maternal outcomes, or on any infant outcomes. Authors' conclusions: Based on the best currently available evidence, 'antistaphylococcal cephalosporins' and 'broad spectrum penicillins plus betalactamase inhibitors' may have similar efficacy at caesarean section when considering immediate postoperative infection, although we did not have clear evidence for several important outcomes. Most trials administered antibiotics at or after cord clamping, or post-operatively, so results may have limited applicability to current practice which generally favours administration prior to skin incision. We have no data on any infant outcomes, nor on late infections (up to 30 days) in the mother; these are important gaps in the evidence that warrant further research. Antimicrobial resistance is very important but more appropriately investigated by other trial designs.

Background: The setting in which induction of labour takes place (home or inpatient) is likely to have implications for safety, women's experiences and costs. Home induction may be started at home with the subsequent active phase of labour happening either at home or in a healthcare facility (hospital, birth centre, midwifery-led unit). More commonly, home induction starts in a healthcare facility, then the woman goes home to await the start of labour. Inpatient induction takes place in a healthcare facility where the woman stays while awaiting the start of labour. Objectives: To assess the effects on neonatal and maternal outcomes of third trimester home induction of labour compared with inpatient induction using the same method of induction. Search methods: For this update, we searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (31 January 2020)), and reference lists of retrieved studies. Selection criteria: Published and unpublished randomised controlled trials (RCTs) in which home and inpatient settings for induction have been compared. We included conference abstracts but excluded quasi-randomised trials and cross-over studies. Data collection and analysis: Two review authors independently assessed study reports for inclusion. Two review authors carried out data extraction and assessment of risk of bias independently. GRADE assessments were checked by a third review author. Main results: We included seven RCTs, six of which provided data on 1610 women and their babies. Studies were undertaken between 1998 and 2015, and all were in high- or upper-middle income countries. Most women were induced for post dates. Three studies reported government funding, one reported no funding and three did not report on their funding source. Most GRADE assessments gave very low-certainty evidence, downgrading mostly for high risk of bias and serious imprecision. 1. Home compared to inpatient induction with vaginal prostaglandin E (PGE) (two RCTs, 1028 women and babies; 1022 providing data). Although women's satisfaction may be slightly better in home settings, the evidence is very uncertain (mean difference (MD) 0.16, 95% confidence interval (CI) -0.02 to 0.34, 1 study, 399 women), very low-certainty evidence. There may be little or no difference between home and inpatient induction for other primary outcomes, with all evidence being very low certainty: - spontaneous vaginal birth (average risk ratio (RR) [aRR] 0.91, 95% CI 0.69 to 1.21, 2 studies, 1022 women, random-effects method); - uterine hyperstimulation (RR 1.19, 95% CI 0.40 to 3.50, 1 study, 821 women); - caesarean birth (RR 1.01, 95% CI 0.81 to 1.28, 2 studies, 1022 women); - neonatal infection (RR 1.29, 95% CI 0.59 to 2.82, 1 study, 821 babies); - admission to neonatal intensive care unit (NICU) (RR 1.20, 95% CI 0.50 to 2.90, 2 studies, 1022 babies). Studies did not report serious neonatal morbidity or mortality. 2. Home compared to inpatient induction with controlled release PGE (one RCT, 299 women and babies providing data). There was no information on whether the questionnaire on women's satisfaction with care used a validated instrument, but the findings presented showed no overall difference in scores. We found little or no difference between the groups for other primary outcomes, all also being very low-certainty evidence: - spontaneous vaginal birth (RR 0.94, 95% CI 0.77 to 1.14, 1 study, 299 women); - uterine hyperstimulation (RR 1.01, 95% CI 0.51 to 1.98, 1 study, 299 women); - caesarean births (RR 0.95, 95% CI 0.64 to 1.42, 1 study, 299 women); - admission to NICU (RR 1.38, 0.57 to 3.34, 1 study, 299 babies). The study did not report on neonatal infection nor serious neonatal morbidity or mortality. 3. Home compared to inpatient induction with balloon or Foley catheter (four RCTs; three studies, 289 women and babies providing data). It was again unclear whether questionnaires reporting women's experiences/satisfaction with care were validated instruments, with one study (48 women, 69% response rate) finding women were similarly satisfied. Home inductions may reduce the number of caesarean births, but the data are also compatible with a slight increase and are of very low-certainty (RR 0.64, 95% CI 0.41 to 1.01, 2 studies, 159 women). There was little or no difference between the groups for other primary outcomes with all being very low-certainty evidence: - spontaneous vaginal birth (RR 1.04, 95% CI 0.54 to 1.98, 1 study, 48 women): - uterine hyperstimulation (RR 0.45, 95% CI 0.03 to 6.79, 1 study, 48 women); - admission to NICU (RR 0.37, 95% CI 0.07 to 1.86, 2 studies, 159 babies). There were no serious neonatal infections nor serious neonatal morbidity or mortality in the one study (involving 48 babies) assessing these outcomes. Authors' conclusions: Data on the effectiveness, safety and women's experiences of home versus inpatient induction of labour are limited and of very low-certainty. Given that serious adverse events are likely to be extremely rare, the safety data are more likely to come from very large observational cohort studies rather than relatively small RCTs.

Background: Induction of labour involves stimulating uterine contractions artificially to promote the onset of labour. There are several pharmacological, surgical and mechanical methods used to induce labour. Membrane sweeping is a mechanical technique whereby a clinician inserts one or two fingers into the cervix and using a continuous circular sweeping motion detaches the inferior pole of the membranes from the lower uterine segment. This produces hormones that encourage effacement and dilatation potentially promoting labour. This review is an update to a review first published in 2005. Objectives: To assess the effects and safety of membrane sweeping for induction of labour in women at or near term (≥ 36 weeks' gestation). Search methods: We searched Cochrane Pregnancy and Childbirth's Trials Register (25 February 2019), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (25 February 2019), and reference lists of retrieved studies. Selection criteria: Randomised and quasi-randomised controlled trials comparing membrane sweeping used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed on a predefined list of labour induction methods. Cluster-randomised trials were eligible, but none were identified. Data collection and analysis: Two review authors independently assessed studies for inclusion, risk of bias and extracted data. Data were checked for accuracy. Disagreements were resolved by discussion, or by including a third review author. The certainty of the evidence was assessed using the GRADE approach. Main results: We included 44 studies (20 new to this update), reporting data for 6940 women and their infants. We used random-effects throughout. Overall, the risk of bias was assessed as low or unclear risk in most domains across studies. Evidence certainty, assessed using GRADE, was found to be generally low, mainly due to study design, inconsistency and imprecision. Six studies (n = 1284) compared membrane sweeping with more than one intervention and were thus included in more than one comparison. No trials reported on the outcomes uterine hyperstimulation with/without fetal heart rate (FHR) change, uterine rupture or neonatal encephalopathy. Forty studies (6548 participants) compared membrane sweeping with no treatment/sham Women randomised to membrane sweeping may be more likely to experience: · spontaneous onset of labour (average risk ratio (aRR) 1.21, 95% confidence interval (CI) 1.08 to 1.34, 17 studies, 3170 participants, low-certainty evidence). but less likely to experience: · induction (aRR 0.73, 95% CI 0.56 to 0.94, 16 studies, 3224 participants, low-certainty evidence); There may be little to no difference between groups for: · caesareans (aRR 0.94, 95% CI 0.85 to 1.04, 32 studies, 5499 participants, moderate-certainty evidence); · spontaneous vaginal birth (aRR 1.03, 95% CI 0.99 to 1.07, 26 studies, 4538 participants, moderate-certainty evidence); · maternal death or serious morbidity (aRR 0.83, 95% CI 0.57 to 1.20, 17 studies, 2749 participants, low-certainty evidence); · neonatal perinatal death or serious morbidity (aRR 0.83, 95% CI 0.59 to 1.17, 18 studies, 3696 participants, low-certainty evidence). Four studies reported data for 480 women comparing membrane sweeping with vaginal/intracervical prostaglandins There may be little to no difference between groups for the outcomes: · spontaneous onset of labour (aRR, 1.24, 95% CI 0.98 to 1.57, 3 studies, 339 participants, low-certainty evidence); · induction (aRR 0.90, 95% CI 0.56 to 1.45, 2 studies, 157 participants, low-certainty evidence); · caesarean (aRR 0.69, 95% CI 0.44 to 1.09, 3 studies, 339 participants, low-certainty evidence); · spontaneous vaginal birth (aRR 1.12, 95% CI 0.95 to 1.32, 2 studies, 252 participants, low-certainty evidence); · maternal death or serious morbidity (aRR 0.93, 95% CI 0.27 to 3.21, 1 study, 87 participants, low-certainty evidence); · neonatal perinatal death or serious morbidity (aRR 0.40, 95% CI 0.12 to 1.33, 2 studies, 269 participants, low-certainty evidence). One study, reported data for 104 women, comparing membrane sweeping with intravenous oxytocin +/- amniotomy There may be little to no difference between groups for: · spontaneous onset of labour (aRR 1.32, 95% CI 88 to 1.96, 1 study, 69 participants, low-certainty evidence); · induction (aRR 0.51, 95% CI 0.05 to 5.42, 1 study, 69 participants, low-certainty evidence); · caesarean (aRR 0.69, 95% CI 0.12 to 3.85, 1 study, 69 participants, low-certainty evidence); · maternal death or serious morbidity was reported on, but there were no events. Two studies providing data for 160 women compared membrane sweeping with vaginal/oral misoprostol There may be little to no difference between groups for: · caesareans (RR 0.82, 95% CI 0.31 to 2.17, 1 study, 96 participants, low-certainty evidence). One study providing data for 355 women which compared once weekly membrane sweep with twice-weekly membrane sweep and a sham procedure There may be little to no difference between groups for: · induction (RR 1.19, 95% CI 0.76 to 1.85, 1 study, 234 participants, low-certainty); · caesareans (RR 0.93, 95% CI 0.60 to 1.46, 1 study, 234 participants, low-certainty evidence); · spontaneous vaginal birth (RR 1.00, 95% CI 0.86 to 1.17, 1 study, 234 participants, moderate-certainty evidence); · maternal death or serious maternal morbidity (RR 0.78, 95% CI 0.30 to 2.02, 1 study, 234 participants, low-certainty evidence); · neonatal death or serious neonatal perinatal morbidity (RR 2.00, 95% CI 0.18 to 21.76, 1 study, 234 participants, low-certainty evidence); We found no studies that compared membrane sweeping with amniotomy only or mechanical methods. Three studies, providing data for 675 women, reported that women indicated favourably on their experience of membrane sweeping with one study reporting that 88% (n = 312) of women questioned in the postnatal period would choose membrane sweeping in the next pregnancy. Two studies reporting data for 290 women reported that membrane sweeping is more cost-effective than using prostaglandins, although more research should be undertaken in this area. Authors' conclusions: Membrane sweeping may be effective in achieving a spontaneous onset of labour, but the evidence for this was of low certainty. When compared to expectant management, it potentially reduces the incidence of formal induction of labour. Questions remain as to whether there is an optimal number of membrane sweeps and timings and gestation of these to facilitate induction of labour.

Background: Infants born preterm (before 37 weeks' gestation) have poorer outcomes than infants at term, particularly if born before 32 weeks. Early cord clamping has been standard practice over many years, and enables quick transfer of the infant to neonatal care. Delayed clamping allows blood flow between the placenta, umbilical cord and baby to continue, and may aid transition. Keeping baby at the mother's side enables neonatal care with the cord intact and this, along with delayed clamping, may improve outcomes. Umbilical cord milking (UCM) is proposed for increasing placental transfusion when immediate care for the preterm baby is needed. This Cochrane Review is a further update of a review first published in 2004 and updated in 2012. Objectives: To assess the effects on infants born at less than 37 weeks' gestation, and their mothers of: 1) delayed cord clamping (DCC) compared with early cord clamping (ECC) both with immediate neonatal care after cord clamping; 2) DCC with immediate neonatal care with cord intact compared with ECC with immediate neonatal care after cord clamping; 3) DCC with immediate neonatal care after cord clamping compared with UCM; 4) UCM compared with ECC with immediate neonatal care after cord clamping. Search methods: We searched the Cochrane Pregnancy and Childbirth Group Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 November 2017), and reference lists of retrieved studies. We updated the search in November 2018 and added nine new trial reports to the awaiting classification section to be assessed at the next update. Selection criteria: Randomised controlled trials (RCTs) comparing delayed with early clamping of the umbilical cord (with immediate neonatal care after cord clamping or with cord intact) and UCM for births before 37 weeks' gestation. Quasi-RCTs were excluded. Data collection and analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Random-effects are used in all meta-analyses. Review authors assessed the certainty of the evidence using the GRADE approach. Main results: This update includes forty-eight studies, involving 5721 babies and their mothers, with data available from 40 studies involving 4884 babies and their mothers. Babies were between 24 and 36+6 weeks' gestation at birth and multiple births were included. The data are mostly from high-income countries. Delayed clamping ranged between 30 to 180 seconds, with most studies delaying for 30 to 60 seconds. Early clamping was less than 30 seconds and often immediate. UCM was mostly before cord clamping but some were milked after cord clamping. We undertook subgroup analysis by gestation and type of intervention, and sensitivity analyses by low risk of selection and attrition bias.All studies were high risk for performance bias and many were unclear for other aspects of risk of bias. Certainty of the evidence using GRADE was mostly low, mainly due to imprecision and unclear risk of bias.Delayed cord clamping (DCC) versus early cord clamping (ECC) both with immediate neonatal care after cord clamping (25 studies, 3100 babies and their mothers)DCC probably reduces the number of babies who die before discharge compared with ECC (average risk ratio (aRR) 0.73, 95% confidence interval (CI) 0.54 to 0.98, 20 studies, 2680 babies (moderate certainty)).No studies reported on 'Death or neurodevelopmental impairment' in the early years'.DCC may make little or no difference to the number of babies with severe intraventricular haemorrhage (IVH grades 3 and 4) (aRR 0.94, 95% CI 0.63 to 1.39, 10 studies, 2058 babies, low certainty) but slightly reduces the number of babies with any grade IVH (aRR 0.83, 95% CI 0.70 to 0.99, 15 studies, 2333 babies, high certainty).DCC has little or no effect on chronic lung disease (CLD) (aRR 1.04, 95% CI 0.94 to 1.14, 6 studies, 1644 babies, high certainty).Due to insufficient data, we were unable to form conclusions regarding periventricular leukomalacia (PVL) (aRR 0.58, 95% CI 0.26 to 1.30, 4 studies, 1544 babies, low certainty) or maternal blood loss of 500 mL or greater (aRR 1.14, 95% CI 0.07 to 17.63, 2 studies, 180 women, very low certainty).We identified no important heterogeneity in subgroup or sensitivity analyses.Delayed cord clamping (DCC) with immediate neonatal care with cord intact versus early cord clamping (ECC) (one study, 276 babies and their mothers)There are insufficient data to be confident in our findings, but DCC with immediate neonatal care with cord intact may reduce the number of babies who die before discharge, although the data are also compatible with a slight increase in mortality, compared with ECC (aRR 0.47, 95% CI 0.20 to 1.11, 1 study, 270 babies, low certainty). DCC may also reduce the number of babies who die or have neurodevelopmental impairment in early years (aRR 0.61, 95% CI 0.39 to 0.96, 1 study, 218 babies, low certainty). There may be little or no difference in: severe IVH; all grades IVH; PVL; CLD; maternal blood loss ≥ 500 mL, assessed as low certainty mainly due to serious imprecision.Delayed cord clamping (DCC) with immediate neonatal care after cord clamping versus umbilical cord milking (UCM) (three studies, 322 babies and their mothers) and UCM versus early cord clamping (ECC) (11 studies, 1183 babies and their mothers)There are insufficient data for reliable conclusions about the comparative effects of UCM compared with delayed or early clamping (mostly low or very low certainty). Authors' conclusions: Delayed, rather than early, cord clamping may reduce the risk of death before discharge for babies born preterm. There is insufficient evidence to show what duration of delay is best, one or several minutes, and therefore the optimum time to clamp the umbilical cord remains unclear. Whilst the current evidence supports not clamping the cord before 30 seconds at preterm births, future trials could compare different lengths of delay. Immediate neonatal care with the cord intact requires further study, and there are insufficient data on UCM.The nine new reports awaiting further classification may alter the conclusions of the review once assessed.

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.

Background Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can reduce blood loss and are routinely recommended. There are several uterotonic drugs for preventing PPH, but it is still debatable which drug or combination of drugs is the most effective. Objectives To identify the most effective and cost-effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile. Methods The Cochrane Pregnancy and Childbirth’s Trials Register (1 June 2015), ClinicalTrials.gov and the World Health Organization (WHO)’s International Clinical Trials Registry Platform (ICTRP) were searched for unpublished trial reports (30 June 2015). In addition, reference lists of retrieved studies (updated October 2017) were searched for randomised trials evaluating uterotonic drugs for preventing PPH. The study estimated relative effects and rankings for preventing PPH, defined as blood loss of ≥ 500 ml and ≥ 1000 ml. Pairwise meta-analyses and network meta-analysis were performed to determine the relative effects and rankings of all available drugs and combinations thereof [ergometrine, misoprostol (Cytotec ® ; Pfizer Inc., New York, NY, USA), misoprostol plus oxytocin (Syntocinon ® ; Novartis International AG, Basel, Switzerland), carbetocin (Pabal ® ; Ferring Pharmaceuticals, Saint-Prex, Switzerland), ergometrine plus oxytocin (Syntometrine ® ; Alliance Pharma plc, Chippenham, UK), oxytocin, and a placebo or no treatment]. Primary outcomes were stratified according to the mode of birth, prior risk of PPH, health-care setting, drug dosage, regimen and route of drug administration. Sensitivity analyses were performed according to study quality and funding source, among others. A model-based economic evaluation compared the relative cost-effectiveness separately for vaginal births and caesareans with or without including side effects. Results From 137 randomised trials and 87,466 women, ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin were found to reduce the risk of PPH blood loss of ≥ 500 ml compared with the standard drug, oxytocin [ergometrine plus oxytocin: risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83; carbetocin: RR 0.72, 95% CI 0.52 to 1.00; misoprostol plus oxytocin: RR 0.73, 95% CI 0.6 to 0.9]. Each of these three strategies had 100% cumulative probability of being ranked first, second or third most effective. Oxytocin was ranked fourth, with an almost 0% cumulative probability of being ranked in the top three. Similar rankings were noted for the reduction of PPH blood loss of ≥ 1000 ml (ergometrine plus oxytocin: RR 0.77, 95% CI 0.61 to 0.95; carbetocin: RR 0.70, 95% CI 0.38 to 1.28; misoprostol plus oxytocin: RR 0.90, 95% CI 0.72 to 1.14), and most secondary outcomes. Ergometrine plus oxytocin and misoprostol plus oxytocin had the poorest ranking for side effects. Carbetocin had a favourable side-effect profile, which was similar to oxytocin. However, the analysis was restricted to high-quality studies, carbetocin lost its ranking and was comparable to oxytocin. The relative cost-effectiveness of the alternative strategies is inconclusive, and the results are affected by both the uncertainty and inconsistency in the data reported on adverse events. For vaginal delivery, when assuming no adverse events, ergometrine plus oxytocin is less costly and more effective than all strategies except carbetocin. The strategy of carbetocin is both more effective and more costly than all other strategies. When taking adverse events into consideration, all prevention strategies, except oxytocin, are more costly and less effective than carbetocin. For delivery by caesarean section, with and without adverse events, the relative cost-effectiveness is different, again because of the uncertainty in the available data. Limitations There was considerable uncertainty in findings within the planned subgroup analyses, and subgroup effects cannot be ruled out. Conclusions Ergometrine plus oxytocin, carbetocin and misoprostol plus oxytocin are more effective uterotonic drug strategies for preventing PPH than the current standard, oxytocin. Ergometrine plus oxytocin and misoprostol plus oxytocin cause significant side effects. Carbetocin has a favourable side-effect profile, which was similar to oxytocin. However, most carbetocin trials are small and of poor quality. There is a need for a large high-quality trial comparing carbetocin with oxytocin; such a trial is currently being conducted by the WHO. The relative cost-effectiveness is inconclusive, and results are affected by uncertainty and inconsistency in adverse events data. Study registration This study is registered as PROSPERO CRD42015020005; Cochrane Pregnancy and Childbirth Group (substudy) reference number 0871; PROSPERO–Cochrane (substudy) reference number CRD42015026568; and sponsor reference number ERN_13–1414 (University of Birmingham, Birmingham, UK). Funding Funding for this study was provided by the National Institute for Health Research Health Technology Assessment programme in a research award to the University of Birmingham and supported by the UK charity Ammalife (UK-registered charity 1120236). The funders of the study had no role in study design, data collection, data synthesis, interpretation or writing of the report.

Objective: To develop core outcome sets (COS) for studies evaluating interventions for (1) prevention and (2) treatment of PPH, and recommendations on how to report the COS. Design: A two-round Delphi survey and face-to-face meeting. Population: Health care professionals and women's representatives. Methods: Outcomes were identified from systematic reviews of PPH studies and stakeholder consultation. Participants scored each outcome in the Delphi on a Likert scale between 1 (not important) and 9 (critically important). Results were discussed at the face-to-face meeting to agree the final COS. Consensus at the meeting was defined as ≥ 70% of participants scoring the outcome as critically important (7-9). Lectures, discussion and voting were used to agree how to report COS outcomes. Main outcome measures: outcomes from systematic reviews and consultations. Results: Both Delphi rounds were completed by 152/205 (74%) participants for prevention and 143/197 (73%) for treatment. For prevention of PPH, nine core outcomes were selected: blood loss, shock, maternal death, use of additional uterotonics, blood transfusion, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding and adverse effects. For treatment of PPH, 12 core outcomes were selected: blood loss, shock, coagulopathy, hysterectomy, organ dysfunction, maternal death, blood transfusion, use of additional haemostatic intervention, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding and adverse effects. Recommendations were developed on how to report these outcomes where possible. Conclusions: These COS will help standardise outcome reporting in PPH trials. This article is protected by copyright. All rights reserved.

To assess the scores of postpartum women using the WHO Disability Assessment Schedule 2.0 36-item tool (WHODAS-36), considering different morbidities. Secondary analysis of a retrospective cohort of women who delivered at a referral maternity in Brazil and were classified with and without severe maternal morbidity (SMM). WHODAS-36 was used to assess functioning in postpartum women. Percentile distribution of total WHODAS score was compared across three groups: Percentile (P)<10, 10<P<90, and P>90. Cases of SMM were categorized and WHODAS-36 score was assessed according to hypertension, hemorrhage, or other conditions. A total of 638 women were enrolled: 64 had mean scores below P<10 (1.09) and 66 were above P>90 (41.3). Of women scoring above P>90, those with morbidity had a higher mean score than those without (44.6% vs 36.8%, P=0.879). Women with higher WHODAS-36 scores presented more complications during pregnancy, especially hypertension (47.0% vs 37.5%, P=0.09). Mean scores among women with any complication were higher than those with no morbidity (19.0 vs 14.2, P=0.01). WHODAS-36 scores were higher among women with hypertensive complications (19.9 vs 16.0, P=0.004), but lower among those with hemorrhagic complications (13.8 vs 17.7, P=0.09). Complications during pregnancy, childbirth, and the puerperium increase long-term WHODAS-36 scores, demonstrating a persistent impact on functioning among women, up to 5 years postpartum.

The maternal health agenda is undergoing a paradigm shift from preventing maternal deaths to promoting women's health and wellness. A critical focus of this trajectory includes addressing maternal morbidity and the increasing burden of chronic and noncommunicable diseases (NCD) among pregnant women. The WHO convened the Maternal Morbidity Working Group (MMWG) to improve the scientific basis for defining, measuring, and monitoring maternal morbidity. Based on the MMWG's work, we propose paradigms for conceptualizing maternal health and related interventions, and call for greater integration between maternal health and NCD programs. This integration can be synergistic, given the links between chronic conditions, morbidity in pregnancy, and long-term health. Pregnancy should be viewed as a window of opportunity into the current and future health of women, and offers critical entry points for women who may otherwise not seek or have access to care for chronic conditions. Maternal health services should move beyond the focus on emergency obstetric care, to a broader approach that encompasses preventive and early interventions, and integration with existing services. Health systems need to respond by prioritizing funding for developing integrated health programs, and workforce strengthening. The MMWG's efforts have highlighted the changing landscape of maternal health, and the need to expand the narrow focus of maternal health, moving beyond surviving to thriving.