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.

Abstract Objective: Pregnant women may develop disseminated intravascular coagulation (DIC), possibly resulting in massive maternal haemorrhage and perinatal death. The Japan guideline recommends use of antithrombin Ⅲ (ATⅢ) for DIC in obstetrics; however, its effect remains uncertain. The present study therefore aimed to investigate the effect of ATⅢ for DIC patients in obstetrics, using a national inpatient database in Japan. Design: Nationwide observational study Setting: Japan Population: We used the Diagnosis Procedure Combination inpatient database to identify patients who delivered at hospital and were diagnosed with DIC from July 2010 to March 2018. Methods: Propensity score matching analyses were performed to compare in-hospital maternal mortality and hysterectomy during hospitalization between users and non-users of ATⅢ on the day of delivery. Main Outcome Measures: In-hospital mortality, hysterectomy Results: A total of 9,920 patients were enrolled, including 4,329 patients (44%) who used ATⅢ and 5,511 patients (56%) who did not use ATⅢ. One-to-one propensity score matching created 3290 pairs. In-hospital maternal mortality did not differ significantly between the propensity-matched groups (0.3% in the ATⅢ group vs. 0.5% in the control group; odds ratio, 0.73; 95% confidence interval, 0.35–1.54). Patients in the ATⅢ group, compared with those in the control group, had a significantly lower proportion of receiving hysterectomy during hospitalization (5.3% vs. 8.7%; difference, -2.9%; 95% confidence interval, -4.2 to -1.6%). Conclusions: The present study did not show mortality-reducing effect of ATIII for patients with DIC in obstetrics. ATⅢ may have clinical benefit in terms of reduction in receiving hysterectomy.

OBJECTIVE: The objective of this study was to evaluate C-section rates, before and after the implementation of the Project Appropriate Birth based on the Robson 10-group classification system. DESIGN: An observational, cross-sectional study. SETTING: Maternity hospital in South Brazil. POPULATION: All pregnant women attending, April 2016 through April 2017 (phase 1, pre-implementation of the Project Appropriate Birth) and June 2017 through June 2018 (phase 2, post-implementation of the Project Appropriate Birth). METHODS: Maternal and obstetric characteristics were evaluated, including Robson’s classification, based on the characteristics of pregnancy and childbirth. Chi-square test and crude and adjusted prevalence ratios were used to analyze study variables. The significance level was set at 5%. MAIN OUTCOME MEASURES: C-section rate for each group, their contribution to the overall c-section rate and the differences in these contributions before and after PPA implementation. RESULTS: C-section rates decreased from 62.4% to 55.6%, which represented a 10.9% reduction after the implementation of the Project Appropriate Birth. Pregnant women in Robson classification groups 1 through 4 had the greatest decrease in C-section rates, ranging from 49.1% to 38.6%, which represents a 21.5% reduction. The greatest contributors to the overall C-section rates were group 5 and group 2, accounting for more than 60% of the C-section deliveries. CONCLUSION: The Project Appropriate Birth had an important impact on the reduction of C-section rates, especially in Robson classification groups 1 through 4, which indicates that providing mothers with evidence-based interventions for labor and childbirth assistance will contribute to reduce C-section rates.

Objective: Long-term cost-effectiveness of app-based treatment for female stress, urgency, or mixed urinary incontinence (UI) compared to care-as-usual in primary care. Design: A pragmatic, randomised controlled, superiority trial. Setting: Primary care in the Netherlands from 2015 to 2018, follow-up at 12 months. Population: Women with ≥2 UI-episodes per week, access to mobile apps, wanting treatment. 262 women randomised equally to app or care-as-usual; 89 (68%) and 83 (63%) attended follow-up. Methods: The standalone app included conservative management for UI with motivation aids (e.g., reminders). Care-as-usual delivered according to the Dutch GP guideline for UI. Main outcome measures: Effectiveness assessed by the change in symptom severity score (ICIQ-UI-SF) and the change in quality of life (ICIQ-LUTS-QoL, EQ-5D-5L) on superiority with linear regression on an intention-to-treat basis. Cost-effectiveness and -utility from a societal perspective, based on Incontinence Impact Adjusted Life Years (IIALYs) and Quality Adjusted Life years (QALYs). Results: Clinically relevant improvement of UI severity for both app (-2.17 ± 2.81) and care-as-usual (-3.43 ± 3.6), with a non-significant mean difference of 0.903 (-0.66 to 1.871). Costs were lower for app-based treatment with \euro-161 (95%CI: -180 to -151) per year. Cost-effectiveness showed small mean differences in effect for IIALY (0.04) and QALY (-0.03) and thus larger ICER (-3,696) and ICUR (\euro6,379). Conclusion: App-based treatment is a viable alternative to care-as-usual for UI in primary care in terms of long-term cost-effectiveness. Funding: Dutch Organisation for Health Research and Development (ZonMw: 837001508), sub-funding P.W. Boer Foundation Dutch Trial Register identifier: Trial NL4948 (www.trialregister.nl/trial/4948).

Background Pregnancy and childbirth increase the risk for pelvic floor dysfunction, including sexual dysfunction. So far, the mechanisms and the extent to which certain risk factors play a role, remain unclear. Objectives In this systematic review of literature, we aimed to determine the risk factors for sexual dysfunction in the first year after delivery. Search Strategy We searched MEDLINE, Embase and CENTRAL using the search strategy: Sexual dysfunction AND Obstetric events. Selection Criteria We included original English, comparative studies that used validated questionnaires and the ICS/IUGA terminology for sexual dysfunction, dyspareunia and vaginal dryness. Data Collection and Analysis We assessed the quality and the risk of bias of the included studies with the Newcastle Ottawa Scale. We extracted the reported data and we performed random-effects meta-analysis to obtain the summary Odds Ratios (OR) with 95% Confidence Intervals. Heterogeneity across studies was assessed using the I2 statistic. Main Results We found no significant difference in the odds for both sexual dysfunction and dyspareunia between cesarean section and spontaneous delivery (OR:1.17[0.88-1.57] and OR:0.75[0.53-1.07]) and between operative delivery and spontaneous delivery (OR:1.56[0.87-2.79] and OR:1.35[0.75-2.42]). Anal sphincter injury was associated with increased odds for both sexual dysfunction (OR:3.00[1.28-7.03]) and dyspareunia (OR:1.71[1.09-2.67]). Episiotomy was associated with dyspareunia (OR:1.65[1.20-2.29]) but not with sexual dysfunction (OR:1.90[0.94-3.84]). We retrieved one study of low quality which reported on vaginal dryness and found no significant association with obstetric events.

Risk stratification of HPV positive women in routine cervical screeningHigh risk HPV primary screening is replacing organised cytology-based screening based on increased sensitivity to detect high grade intra-epithelial neoplasia and the very high negative predictive value which will allow extended screening intervals. The benefit of increased CIN detection and cancer prevention needs to balance against the disbenefits to screen positive women in over investigation not east the psychological impact. For colposcopy services, the English cervical screening programme reported a 80% increase in colposcopy referrals in the first round of screening, creating huge pressures on service capacity (Rebolj M et al BMJ 2019;364:l240). The lower positive predictive value also impacts on colposcopy performance with a different referral population wit proportionately less high grade CIN present. In this issue of BJOG, Gori M et al provide observational data from a large longitudinal study of routine primary HPV screening in an organised quality assured cervical screening programme in 3 regions of Italy. Whilst routinely collected data from real-world programmes will have limitations, they do provide an insight into disease detection and importantly impact on colposcopy provision. In a comparison of triage strategies, combined HPV genotyping for HPV16 and high-grade cytology offered an acceptable balance of risk of CIN3+ with number of colposcopies needed to detect one lesion. These results differ from the English pilot (Rebolj M et al 2019 BJC;121(6):455-463) where HPV16/18 genotyping detected only 1.2% more cases of CIN2+ with 5.9% additional colposcopies. Gori M et al did not combine HPV16/18 but they did report that HPV18 on genotyping was not as clinically useful at baseline or 12-month follow-up. Furthermore, 90% of women screened were aged over 35 years when HPV screening is more clinically effective whereas the English pilot started screening at age 25 years when HPV infection is more prevalent and less likely to be clinically significant. Longer follow-up, importantly at the next screening round, is not yet available when the relevance of non-HPV 16 types may be more apparent.The impact of the Covid 19 pandemic on health services and in particular screening, has sharpened the argument of risk stratification following primary screen positive testing both for service providers and those in the target population. Ciavattini A et al (2020 Int J Cancer 30(8):1097-1100) reported on suspension or postponement of cervical screening programmes across Europe relevant to both routine screening and onward referral to colposcopy. As services have needed to adapt to Covid infection rates and health service capacity, the ability to triage effectively and avoid unnecessary hospital visits is critical. Clinicians and women need information on their risk to inform clinical practice and provide reassurance. In the current second wave, the suspension of screening implemented in the first wave is no longer acceptable. Whilst data, such as these from Gori et al, continue to emerge from national and regional screening programmes, Covid has highlighted the need to be responsive and adaptive to allow cancer prevention to continue.

A document by Jianghui Cai. Click on the document to view its contents.

Mini-commentary on BJOG-20-1156.R2: Post-mortem confirmation of fetal brain abnormalities: challenges highlighted by the MERIDIAN cohort study

A document by Nathan Gold. Click on the document to view its contents.

Mini-commentary on BJOG-20-1640.R2: Aetiologic testing compared with syndromic management for sexually transmitted infections in Human Immunodeficiency Virus-infected pregnant women in South Africa: a non-randomised prospective cohort study

Mini Commentary: BJOG-20-1978.R1Title: Complement Receptors in Preeclampsia: Cleaning up Placental DebrisAuthor: Richard M. Burwick, MD, MPHAffiliation: Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA