Background: Pharmacological pain management options can relieve women’s pain during labour and birth. Trials of these interventions have used a wide variety of outcomes, complicating meaningful comparisons of their effects. Consensus about key outcomes would facilitate the development of a core outcome set to assess the effectiveness of labour pain management. Objective: To identify all outcomes used in studies of pharmacological pain management interventions during labour and birth. Design: A review of systematic reviews and their included randomised controlled trials was undertaken. Search Strategy: Cochrane CENTRAL was searched to identify all Cochrane systematic reviews describing pharmacological pain management options for labour and birth. Search terms included “pain management”, “labour” and variants, with no limits on year of publication or language. Selection Criteria: Cochrane reviews and randomised controlled trials contained within these reviews were included, provided they compared a pharmacological intervention with other pain management options, placebo or no treatment. Data Collection and Analysis: All outcomes reported by reviews or trials were extracted and tabulated, with frequencies of individual outcomes reported. Main Results: Nine Cochrane reviews and 227 unique trials were included. In total, 148 unique outcomes were identified and categorised into maternal, fetal, neonatal, child, health service, provider’s perspective, or economic outcome domains. Conclusions: Outcomes of pharmacological pain management interventions during labour and birth vary widely between trials. The standardisation of trial outcomes would permit more meaningful comparison between studies. Funding: No external funding was provided. Keywords: Labour and birth; pain management; pharmacological interventions; systematic review

Objective: To assess the incidence of serious complications and reoperations for recurrence after pelvic organ prolapse (POP) surgery and compare the three most common types of repair. Design: Prospective cohort study using a registry. Setting: 19 surgical centres in France. Population: 2309 women participated between 2017 and 2019. Methods: a multivariate analysis including an inverse probability of treatment weighting approach was used to obtain three comparable groups. Main outcome measures: Serious complications and subsequent reoperations for POP recurrence Results: Mean follow-up was 16.6 months. Surgeries included in the analysis were native tissue vaginal repair (N=504), transvaginal mesh placement (692), and laparoscopic sacropexy with mesh (1113). Serious complications occurred among 52 women (2.3%), and reoperation for recurrence was required for 32 (1.4%). At one year, the cumulative weighted incidence of serious complications was 1.8% for native tissue vaginal repair (95% confidence interval 0-3.9), 3.9% for transvaginal mesh (2.0-5.9), and 2.2% for sacropexy (1.1-2.6). Compared with the native tissue vaginal repair group, the risk of serious complications was higher in the transvaginal mesh group (weighted-HR 3.84, 2.43-6.08), and the sacropexy group (2.48, 1.45-4.23), while the risk of reoperation for prolapse recurrence was reduced in both groups (transvaginal mesh [0.22, 0.13-0.39] and sacropexy [0.29, 0.18-0.47]). Conclusions: Laparoscopic sacropexy with mesh appears to have a better risk profile (few serious complications and few reoperations for recurrence) than transvaginal mesh placement (more serious complications) and native tissue vaginal repair (more reoperations for recurrence). These results are useful for informing women and for shared decision making.

Objective: To assess the general population’s knowledge regarding the utility and availability of tools to diagnosis endometriosis, with focus on ultrasound. Design: An international cross-sectional online survey study was performed between August and October 2019. Setting and Population: 5301 respondents, representing 73 countries. Methods: 23 questions survey focused on knowledge of endometriosis diagnosis distributed globally via patient- and community-endometriosis groups using social media. Main outcomes and measures: Descriptive data of the knowledge of diagnostic tools for diagnosing endometriosis, including details about diagnosis using ultrasound. Results: 84.0% of respondents had been previously diagnosed with endometriosis, 71.5% of which were diagnosed at the time of surgery. Ultrasound and MRI were the methods of diagnosis in 6.5% and 1.8%, respectively. 91.8%, 28.8%, and 16.6% of respondents believed surgery, ultrasound and MRI could diagnose endometriosis, respectively (more than one answer allowed). In those diagnosed by surgery, 21.7% knew about ultrasound as a diagnosis method compared to 51.5% knowing in those diagnosed non-surgically (p<0.001). 14.7%, 31.1%, and 18.2% stated superficial, ovarian, and deep endometriosis could be diagnosed with ultrasound (32.9% stated they did not know which phenotypes of endometriosis could be diagnosed). 58.4% of respondents do not believe they could access an advanced ultrasound in their region. Conclusions: There are significant gaps in the understanding of diagnosing endometriosis using non-surgical tools in this study population.

A document by Lara Lemon. Click on the document to view its contents.

Objective The My Baby’s Movements (MBM) trial aimed to evaluate the impact on stillbirth rates of a multifaceted awareness package (MBM intervention). Design Stepped-wedge cluster-randomised controlled trial. Setting Twenty-seven maternity hospitals in Australia and New Zealand. Population Women with a singleton pregnancy without major fetal anomaly ≥28 weeks’ gestation from August 2016-May 2019. Methods The MBM intervention was implemented at randomly assigned time points with sequential introduction into 8 clusters of 3-5 hospitals at four-monthly intervals. The stillbirth rate was compared in the control and intervention periods. Generalised linear mixed models controlled for calendar time, clustering, and hospital effects. Outcome Measures Stillbirth at ≥28 weeks’ gestation. Results There were 304,853 births with 290,219 meeting inclusion criteria: 150,079 in control and 140,140 in intervention periods. The stillbirth rate during the intervention was lower than the control period (2.2/1000 births versus 2.4, odds ratio [OR] 0.91, 95% Confidence Intervals [CI] 0.78-1.06, p=0.22). The decrease was larger across calendar time with 2.7/1000 in the first 18 months versus 2.0/1000 in the last 18 months (OR 0.74; 95% CI 0.63-0.86; p≤0.01). Following adjustment, stillbirth rates between the control and intervention periods were not significantly different: (aOR 1.18, 95% CI 0.93-1.50; p=0.18). No increase in secondary outcomes, including obstetric intervention or adverse neonatal outcome, was evident. Conclusion The MBM intervention did not reduce stillbirths beyond the downward trend over time, suggesting hospitals may have implemented best practice in DFM management outside their randomisation schedule. The role of interventions for raising awareness of DFM remains unclear

A document by Joan Lalor. Click on the document to view its contents.

Objective To assess if delivery mode and duration of labour in a first labour of spontaneous onset is associated with gestational length, delivery mode 3and neonatal outcome in the subsequent pregnancy. Study Design Retrospective analysis of prospectively collected data. Setting 15 Maternity units in North West London (1988 to 2000). Population 30,840 women with spontaneous onset of labour in pregnancy 1 and a subsequent birth reported in the same database. Methods Assessment of outcomes by mode of delivery in pregnancy 1, restricting the analysis to the difference in the gestational length between pregnancy 1 and 2. Main Outcome Measures Gestational length, mode of delivery and neonatal unit admission in pregnancy 2. Results Caesarean section (CS) in the first or second stage of labour in pregnancy 1 was associated with pregnancy 2 being a median of 5 and 8 days shorter and a preterm birth rate of 6.0% and 10.1% respectively, whereas following a spontaneous or instrumental birth in pregnancy 1 the median duration was similar, with preterm delivery rates of 4.5% and 3.9%. 56.2% of women with a CS in pregnancy 1 had a repeat CS and 12.5% of their babies were admitted to neonatal unit, compared with 5.3% of women with vaginal birth. Longer labours were associated with shorter gestations in pregnancy 2. Conclusions Compared to vaginal birth, an emergency CS in the first term pregnancy is associated with a shorter gestational length, increased rate of repeat CS and increased risk of NNU admission in the next pregnancy.

Objective To test the hypothesis that there is seasonal variation in the rates of gestational diabetes (GDM) diagnosed using a 2 hour oral glucose tolerance test. Design Monthly assessment of the percentage of women screened from 1st April 2016 to the 31st December 2020 who were diagnosed as having gestational diabetes Setting London Teaching Hospital Population 28,128 women receiving antenatal care between April 1st 2016 and 31 December 2020. Methods Retrospective study of prospectively collected data. Main Outcome Measures Proportion of women screened diagnosed as having gestational diabetes. Results The mean (SD) percentage of women diagnosed with GDM was 14.78 (2.24) in summer (June, July, August) compared with 11.23 (1.62) in winter (p < 0.001), 12.13 (1.94) in spring (p = 0.002), and 11.88 (2.67) in autumn (p = 0.003). There was a highly significant positive correlation of the percentage testing positive for GDM with the mean maximum monthly temperature (R2 = 0.248, p < 0.001). There was a statistically significant 33.8% increase in the proportion of GDM diagnoses from June 2020 onwards, possibly related to a reduction in exercise secondary to the Covid-19 pandemic. Conclusions There is a 23.3% higher rate of GDM diagnoses in the warmer summer months. There has been a 33.8% rise in GDM diagnoses associated with the Covid-19 pandemic.

BJOG exchange

Background Pregnancy and liver cirrhosis is a rare but increasing combination. Liver cirrhosis can raise the chance of maternal and fetal mortality and morbidity, although the exact risks remain unclear. Objective To provide a systematic literature review and meta-analysis on maternal, fetal and obstetric complications among pregnant women with liver cirrhosis. Search strategy We performed a systematic literature search in the databases PubMed/MEDLINE and EMBASE (Ovid) from inception through 25 January 2021. Selection criteria Studies including pregnancies with liver cirrhosis and controls were eligible. Data collection and analysis Two reviewers independently evaluated study eligibility. We used the random-effects model for meta-analysis. Main results Our search yielded 3118 unique papers. We included 11 studies, including 2912 pregnancies in women with cirrhosis from 1982-2020. Seven studies were eligible for inclusion in the meta-analysis. The overall maternal mortality rate was 0.89%. Maternal mortality and variceal hemorrhage decreased comparing recent and older studies. Most cases of maternal mortality due to variceal hemorrhage (70%) occurred during vaginal delivery. Pregnant women with liver cirrhosis had a higher chance of preterm delivery (OR 6.7 95% CI 5.1- 9.1), cesarean section (OR 2.6, 95% CI 1.7-3.9), preeclampsia (OR 3.8, 95% CI 2.2-6.5) and small for gestational age neonates (OR 2.6, 95% CI 1.6-4.2) compared to the general obstetric population. Subgroup-analyses could not be conducted. Conclusions Liver cirrhosis in pregnant women is associated with serious increases in maternal mortality and obstetric and fetal complications. Large international prospective studies are needed to identify risk factors for unfavorable outcome.

Placenta accreta spectrum: Welcome progress and a call for standardization.Mini-commentary for BJOG on Kayem et al 2021 BJOG-20-1462R3Placenta accreta spectrum (PAS) is among the most feared causes of maternal morbidity worldwide, and yet few prospective data are available to inform best practice. PAS is rare enough that rigorous study in a single center is difficult, but common enough that most obstetric hospitals now encounter PAS. Management and outcomes vary strikingly between hospitals and best practice, regrettably, is guided more by expert consensus than by level I evidence. In fact, most clinical questions regarding management of PAS are informed by essentially no prospective data (Collins et al. Am J Obstet Gynecol. 2019;220:511-526).Into this data void has come the PACCRETA cohort (Kayem et al. Act Obstet Gynecol Scand 2013;92:476-482) and some of its first results, published in this issue of BJOG (Kayem et al. BJOG 2021). PACCRETA is a prospective population-based study from 176 hospitals in France, capturing 30% of all French deliveries, from from 2013 to 2015. The study investigators identified 249, or 4.8 per 10,000, cases of PAS.Of all PAS patients, Kayem and colleagues found that a full half did not have the classic combination of risk factors for PAS (previa with history of cesarean). This group had lower morbidity and milder disease than those with the classic combination. Only 17% of those without classic risk factors were diagnosed antenatally. The message here is mixed: those without classic PAS risk factors are less likely to be diagnosed antenatally (bad) but appear to suffer less morbidity overall (good).But did these patients actually have PAS? Only 21% of those without prior cesarean and previa had a hysterectomy. Although this could be due to a regional preference for conservative treatments, the presence of false positives seems likely. Without a hysterectomy specimen, the diagnosis of PAS is difficult, controversial, and (in our opinion) highly susceptible to overdiagnosis. The authors define “strict” criteria for true cases of PAS, but several criteria depended entirely on the subjective assessment of a clinician faced with a difficult placental removal and the flawed principle of PAS as diagnosis of exclusion . Difficulty in manual placental removal or massive bleeding from an implantation site does not always indicate that microscopic PAS was present. Similarly, areas of prior cesarean section scar dehiscence (windows) where the placenta can be seen through the serosa are often diagnosed as percreta (Figure) without any histological evidence of the villous tissue having invaded through the serosa or beyond (Hecht et al. Modern Pathol 2020;33:2382-2396).We congratulate Kayem and colleagues for the current study and all of their important contributions to our understanding of PAS. However, these data illustrate the need for standardization of the definition of PAS, especially in conservatively managed cases with considerable potential for misdiagnosis. There is a desperate need for controlled studies of patients with antenatally suspected PAS with detailed and objective documentation of imaging, intra-operative findings, and when available, histopathological examination. In absence of such studies, the void of definitive data to guide treatment options will remain wide open.

Objective Determination of lactate in fetal scalp blood (FBS) during labor has been studied since the 1970s. The internationally accepted cut-off of >4.8mmol/L indicating fetal acidaemia is exclusive for the point-of-care device (POC) LactateProTM, which is no longer in production. The aim of this study was to present a new cut-off for scalp lactate based on neonatal outcomes with the use of StatstripLactate®/StatstripXpress® Lactate system, the only POC lactate meter designed for hospital use. Design Observational Study Setting January 2016 to March 2020 labouring women with an indication for FBS were prospectively included from seven Swedish and one Australian delivery unit. Population Inclusion criteria: singleton pregnancy, vertex presentation, ≥35+0 gestational weeks. Method Based on the optimal correlation between FBS lactate and cord pH/lactate, only cases with ≤25 minutes from FBS to delivery were included in the final calculations. Main outcome measures Metabolic acidosis in cord blood was defined as pH <7.05 plus BDecf >10 mmol/L and/or lactate >10 mmol/L. Results 3334 women were enrolled of which 799 were delivered within 25 minutes. The areas under the ROC curves (AUC) and corresponding optimal lactate cut-off values were as follows; metabolic acidosis AUC 0.87(95% CI:0.77-0.97), cut-off 5.7mmol/L; pH <7.0 AUC 0.83(95% CI:0.68-0.97), cut-off 4.6mmol/L; pH <7.05 plus BD ≥12mmol/L AUC 0.97(95% CI:0.92-1), cut-off 5.8mmol/L; Apgar score <7 at 5 minutes AUC 0.74(95% CI:0.63-0.86), cut-off 5.2mmol/L; and pH <7.10 plus composite neonatal outcome AUC 0.76(95% CI:0.67-0.85), cut-off 4.8mmol/L. Conclusions Suggested intervention threshold for fetal acidemia is scalp lactate of 5.2mmol/L using the StatstripLactate®/StatstripXpress®.

Objective: To estimate the association between chronic hypertension and perinatal mortality and evaluate the extent to which this risk is impacted by preterm delivery. Design: Cross-sectional analysis. Setting: US, 2015-2018. Population: Singleton births from 20-44 weeks’ gestation. Main outcomes and measures: We derived the risk of perinatal mortality in relation to chronic hypertension from fitting log-linear Poisson models with robust variance. Risk ratios (RR) and 95% confidence intervals (CI) were estimated after adjusting for confounders. The impact of misclassifications and unmeasured confounding biases were assessed. Causal mediation analysis was performed to quantify the impact of preterm delivery on the association. Results: Of the 15,090,678 singleton births, perinatal mortality was 22.5 per 1000 births in chronic hypertensive pregnancies compared to 8.2 per 1000 births in normotensive pregnancies (adjusted RR 2.05, 95% CI 2.00, 2.10). Corrections for exposure misclassification and unmeasured confounding biases substantially increased the risk estimate. Although, causal mediation analysis revealed that most of the effect of chronic hypertension on perinatal mortality was mediated through preterm delivery, the perinatal mortality rates were highest at early term, term, and late term gestations, suggesting that a planned early term delivery at 37-386/7 weeks may optimally balance risk in these pregnancies. Additionally, 87% (95% CI 84, 90) of perinatal deaths could be eliminated if preterm deliveries, as a result of chronic hypertension were prevented. Conclusions: Chronic hypertensive pregnancies are associated with increased risk for perinatal mortality. Planned early term delivery and targeting modifiable risk factors for chronic hypertension may reduce perinatal mortality rates.

Uterus transplantation (UTx) is fast evolving from an experimental to a clinical procedure, combining solid organ transplantation with assisted reproductive technology. The commencement of the first human uterus transplant trial in the UK leads us to examine and reflect upon the legal and regulatory aspects closely intertwined with UTx from the process of donation to potential implications on fertility treatment and the birth of the resultant child. As the world’s first ephemeral transplant, the possibility of organ restitution requires consideration and is discussed herein. Public funding of fertility treatments pertaining to UTx remains variable and warrants review.

A document by Alexandra Emms. Click on the document to view its contents.

Letter to the Editor, BJOG Title: ESMiE confidential enquiry: Broader view besides focus on errors by birth-attendants.Re: Rowe R, Draper ES, Kenyon S, Bevan C, Dickens J, Forrester M, Scanlan R, Tuffnell D, Kurinczuk JJ. Intrapartum-related perinatal deaths in births planned in midwifery-led settings in Great Britain: findings and recommendations from the ESMiE confidential enquiry. BJOG 2020;127:1665–1675.Author: Mr. Shashikant L SHOLAPURKARMD, DNB, MRCOGDept of Obstetrics & Gynaecology,Royal United Hospital, Bath, BA1 3NG, UKShort running title: ESMiE enquiry: broader viewEmail: s.sholapurkar@nhs.net Tel: 07906620662Word count: 500Corresponding Author: Mr. Shashikant L SHOLAPURKARMD, DNB, MRCOGDept of Obstetrics & Gynaecology,Royal United Hospital, Bath, BA1 3NG, UKStatement of interest: The author has no conflict of interest or funding to declare.

Re: Training in the use of intrapartum electronic fetal monitoring with cardiotocography: systematic review and meta‐analysis. Cardiotocography training is a complex intervention and requires complex evaluations: a letter to editor.Lightly K, Weeks AD, Scott HCorrespondence to Dr Kate Lightly – klightly@liverpool.ac.uk07875642837Clinical Research Fellow, Sanyu Research Unit, University of Liverpool and Liverpool Women’s NHS Foundation Trust, members of Liverpool Health Partners, Crown Street, Liverpool, L8 7SS.Professor Andrew D WeeksProfessor of International Maternal Health, Sanyu Research Unit, University of Liverpool and Liverpool Women’s NHS Foundation Trust, members of Liverpool Health Partners, Crown Street, Liverpool, L8 7SS.Professor Hazel ScottDean of School of Medicine, School of Medicine, University of Liverpool, Cedar House, Liverpool, L69 3GE.Running title - CTG training requires complex evaluationsWe congratulate Kelly et al on their review on the effects of training in cardiotocography (CTG).i It is a critical step towards understanding how to correctly implement CTG training. However, we query the relevance of some of the included studies and whether using Kirkpatrick’s model adequately captures all of the relevant complexities. We believe that further work is needed to understand how such training will impact on practice.Some of the CTG research projects reviewed were poorly representative of the needs of clinicians tasked with improving fetal monitoring in their hospitals. For clinicians, their population of interest is practising clinicians who work on labour wards (sometimes infrequently); studies involving undergraduates alone may not be generalisable. Training in intermittent auscultation is also relevant. Considerable detail on the training intervention is required, including not only the format of teaching, but the duration, curriculum and proportion of relevant staff trained. Detail is also required of supporting interventions and context, as training alone is unlikely to impact change. Many would consider ‘no training’ unethical and therefore not a relevant comparator . In the UK, CTG training and competency is now required for all maternity staff.ii The ultimate aim of CTG (and therefore CTG training) is to detect the hypoxic fetus, so that timely intervention can be undertaken to avoid perinatal harm, without unnecessary intervention. Therefore, the outcomes of interest have to include intrapartum stillbirths, hypoxic ischaemic encephalopathy and mode of delivery.Kirkpatrick’s model was used in this review to evaluate training at four levels (reaction, knowledge, behaviour change and organisational performance). However, it does not attempt to understand why interventions work, or the context, or the causal pathways between training and change in practice.iii Whether participants like training (‘reaction’) is of little relevance, and knowledge acquisition (‘knowledge’) is a proxy which does not equate with improved on the job performance and outcomes. Maternal and perinatal outcomes (‘performance’) were only collected in a small number of studies.CTG training is a complex intervention which aims to create change, not simply knowledge acquisition. We therefore believe that a formal Realist Evaluation is needed. This emerging methodology has been used successfully to understand healthcare change processes and supplement traditional Cochrane style reviews. It aims to understand why complex interventions work, how, for whom, in what context and to what extentiv. Collaboration with the relevant authors to gain detailed intervention descriptions, with a realist approach, may add some much needed explanatory power to this critical subject.Training alone is unlikely to impact change. Even the best educational package will fail without the necessary support - it needs an educational and working culture which supports learning and change, aligned and clear policies, and motivated, well supported drivers and leaders.How doctors learn and what supports them to put new knowledge into practice are key research questions. High quality, methodologically appropriate, properly funded studies are needed to address these questions. Not answering them means many research findings are redundant, as they simply will not be implemented.ReferencesI Kelly S, Redmond P, King S, Oliver‐Williams C, Lamé G, Liberati E et al. Training in the use of intrapartum electronic fetal monitoring with cardiotocography: systematic review and meta‐analysis. BJOG. 2021; 00: 1–12. https://doi.org/10.1111/1471-0528.16619ii NHS England. Saving Babies’ Lives Version Two. A care bundle for reducing perinatal mortality. London: NHS England 2019. [cited 2021 Feb 3]. Available from: www.england.nhs.ukiii Moreau KA. Has the new Kirkpatrick generation built a better hammer for our evaluation toolbox? Med Teach. 2017 Sep; 39(9): 999-1001. https://doi.org/10.1080/0142159X.2017.1337874iv Wong G, Westhorp G, Greenhalgh J, Manzano A, Jagosh J, Greenhalgh T. Quality and reporting standards, resources, training materials and information for realist evaluation: the RAMESES II project. Health Services and Delivery Research. 2017 5 (28): 1–108. https://doi.org/10.3310/hsdr05280.Acknowledgements – NilDisclosure of interests - NilContribution to authorshipKL wrote the first draft of this letter and then it was revised by AW and HS.Details of ethics approval – N/AFunding – Dr Lightly’s PhD entitled “Improving intrapartum fetal monitoring in India: A mixed methods approach” is funded by MRC/DfID/Wellcome Trust Joint Global Health Trials Fund. MR/R006/1801

Objective: To determine the incidence of and risk factors for perioperative blood transfusions after urogenital fistula repairs in Uganda. Design: A retrospective cohort study. Setting: A community hospital in Masaka, Uganda. Population: Women who underwent fistula repair at the Kitovu Hospital between 2013 and 2019. Methods: Retrospective review of demographics, and clinical perioperative characteristics of patients surgically treated for urogenital fistula. Patient characteristics were compared between those who did and did not require a blood transfusion. Main Outcome Measures: need for perioperative blood transfusion, risk factors Results: 546 patients treated for urogenital fistulas were included in this study. The median age was 31.1 ± 13.2. A vaginal surgical approach was used in the majority of patients (84.6%). Complications occurred in 3.5% of surgical repairs, and the incidence of blood transfusions was 6.2%. In multivariable analyses, women with fistula repairs approached abdominally were 4.3 (95% CI: 1.85–10.00) times more likely to require transfusions than vaginal operations. A borderline association was observed between timing of repair and perioperative transfusions such that patients who underwent repair after three months from the time of developing the fistula were at lower risk of perioperative transfusions (aOR: 0.48, 95% CI: 0.22–1.04). Conclusions: The incidence of blood transfusions among urogenital fistula repairs in our population is twice that of developed nations. An abdominal surgical approach to urogenital fistula is a significant risk factor for perioperative blood transfusions. Timing of repair may warrant further study.