BJOG mini commentary on study BJOG-21-1829TITLE: Putting patients at the centre of pain managementAlexandra Wojtaszewskaa, Arvind Vashishtb, Martin Hirschc,daWatford General Hospital, Watford, United KingdombInstitute for Women’s Health, University College London, London, United Kingdom.cThe John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom.dOxford Endometriosis CaRe Centre, Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United Kingdom.Conflict of interest : noneFinancial support received : none

Objective To investigate the clinical outcomes and toxicity in patients with locally advanced cervical cancer treated with supplementary applicator guided-intensity modulated radiation therapy (IMRT) based on conventional intracavitary brachytherapy (IC/IMRT). Population Large high risk clinical target volume (HR-CTV) volume (>40cc) at the time of brachytherapy cervical cancer patients were recruited. Methods This study is a retrospective analysis of 76 patients with locally advanced cervical cancer (FIGO IIB-IVA) treated with concurrent chemo-radiotherapy followed by IC/IMRT between June 2010 and October 2016. External radiotherapy (45 Gy in 25 fractions) with cisplatin chemotherapy treated before IC/IMRT. The prescription dose for HR-CTV and IR-CTV were 6 Gy and 5 Gy per fraction for 5 fractions respectively. Results: Mean HR-CTV was 65.8±23.6 cc at the time of brachytherapy. D90 for HR-CTV and IR-CTV were 88.7±3.6 Gy and 78.1±2.5 Gy. D2cc for bladder, rectum, sigmoid and small intestine were 71.8±3.8 Gy, 64.6±4.9 Gy, 63.9±5.3 Gy and 56.7±8.7 Gy respectively. Median follow-up was 85 months (47.9-124.2 months). Five-year local recurrence free survival rate, metastasis recurrence free survival rate, disease free survival rate and cancer special survival rate were 87.6%, 82.4%, 70.9% and 76.3%, respectively. The grade 1+2 gastrointestinal and urinary late toxicities were 15.8% and 21.1%, while grade 3 late toxicities were 3.9% and 5.2%, respectively. Neither acute nor late grade 4 gastrointestinal or urinary toxicities were seen. Conclusions: The combination of ICBT with an applicator-guided supplementary IMRT boost achieved an excellent local control and overall survival with low toxicity for bulky residual cervical tumor

Objective: To test the feasibility of a randomized trial of home blood pressure monitoring paired with a remote lifestyle intervention vs. home blood pressure monitoring alone vs. control in individuals with a hypertensive disorder of pregnancy in the first year postpartum. Design: Single-blinded randomized clinical trial Setting: Two tertiary hospitals and a community organization Population: Overweight and obese individuals with a hypertensive disorder of pregnancy and without pre-pregnancy hypertension or diabetes. Methods: We assessed the feasibility of recruitment and retention of 150 participants to study completion at one-year postpartum with randomization 1:1:1 into each arm. Secondary aims were to test effects of the interventions on weight, blood pressure and self-efficacy. Results: Over 23 months, we enrolled 148 of 400 eligible, screened individuals (37%); 28% Black or Other race, and mean pre-pregnancy BMI of 33.4±6.7 kg/m2. In total, 129 (87%) participants completed the one-year postpartum study visit. Overall, 22% of participants developed stage 2 hypertension [≥140/90 mmHg or on anti-hypertensive medications] by one-year postpartum. Individuals in the lifestyle intervention arm had a greater, non-significant decrease in mean arterial pressure (MAP) compared to individuals in the HBPM alone and control arm [mean change in MAP (95%CI) -3.7(-6.5, -0.9), -0.5(-1.5, 2.6), -1.0(-4.1, 2.2) mmHg], respectively. There were no differences in weight or self-efficacy by study arms. Conclusion: In this pilot, randomized trial, we demonstrate feasibility of HBPM paired with a lifestyle intervention in the first year postpartum. We detected high rates of ongoing hypertension emphasizing the need for effective interventions in this population.

A document by Isioma Okolo. Click on the document to view its contents.

Objective. To compare the estimates of preterm birth (PTB; 22-36 weeks gestational age, GA) and stillbirth rates during COVID-19 pandemic in Italy with those recorded in the three previous years. Design. A population-based cohort study of liveborn and stillborn infants was conducted using data from Regional Health Systems and comparing the pandemic period (March 1st, 2020-March 31st, 2021, N= 362,129) to an historical period (January 2017- February 2020, N=1,117,172). The cohort covered 84.3% of the births in Italy. Methods. Logistic regressions were run in each Region and meta-analyses were performed centrally. We used an interrupted time series regression analysis to study the trend of preterm births from 2017 to 2021. Main Outcome Measures. The primary outcomes were PTB and stillbirths. Secondary outcomes were late PTB (32-36 weeks’ GA), very PTB (<32 weeks’ GA), and extreme PTB (<28 weeks’ GA), overall and stratified into singleton and multiples. Results. The pandemic period compared with the historical one was associated with a reduced risk for PTB (Odds Ratio: 0.90; 95% Confidence Interval, CI: 0.87, 0.93), late PTB (0.91; 0.87, 0.94), very PTB (0.87; 0.84, 0.91), and extreme PTB (0.88; 0.82, 0.94). In multiples, point estimates were not very different, but had wider CIs. No association was found for stillbirths (1.01; 0.90, 1.13). A linear decreasing trend in PTB rate was present in the historical period, with a further reduction after the lockdown. Conclusions We demonstrated a decrease in PTB rate after the introduction of COVID-19 restriction measures, without an increase in stillbirths.

Exosomes are nano-sized vesicles derived from the endosomal system and involved in multitudinous biological and pathological processes. Emerging evidence has demonstrated that exosomes are closely related to the tumorigenesis and progression of ovarian cancer. Ovarian cancer-related exosomes have cell-specific constituents that could be leveraged for diagnosis. Additionally, exosomes are promising to treat ovarian cancer through functioning as delivery systems or participating in immunotherapy or serving as direct targets. In this review, we discussed the association of exosomes in ovarian cancer progression and look forward to the clinical significance of exosomes relevant to diagnosis and treatment.

Title:Letter to Editor:Re: Impact of analysis technique on our understanding of the natural history of labour

Triaging a patient to colposcopy v. watchful waiting using current and prior HPV type and cytology result will help focus care on those at highest risk, and avoid overtreatment of women at low risk of cancerSarah Feldman MD MPHDivision of Gynecologic Oncology, Department of Obstetrics and GynecologyHarvard Medical SchoolBrigham and Women’s Hospital75 Francis StreetBoston, Ma 02115617-732-8840sfeldman@bwh.harvard.eduI have no conflicts of interest to disclose.The findings by Gustafson, et al, that the rate of CIN2+ (high grade cervical precancers) was significantly higher in LLETZ specimens (32.4%) than in biopsies (14.7%) in Danish women age 45+ with type 3 transformations zone (ie part of the upper limit of the transformation zone is not visible) is based on a thoughtful analysis. Patients were screened and managed by Danish guidelines which included predominantly cytology based screening during the period of study, for all but women aged 60-64 (and some up to 69), with HPV testing only being offered to some women ages 30-59. Although the HPV test used in the study (Cobas) automatically provides HPV16 and 18 genotyping, this information was not used for triage. In this study all women underwent colposcopy and diagnostic LLETZ at the same visit. Although the Denmark guidelines recommend blind 4 quadrant biopsies for those without a visible lesion, endocervical curettage, which is a part of many other guidelines (Perkins RB, et al 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2020;24:102–31), is not offered in Denmark. Although the diagnostic LLETZ picked up more CIN2+ than biopsy alone, as the authors state, the majority of women would not have needed the LLETZ if their risk could have been better predicted.Can we use currently available technology and information to more effectively and safely triage patients to detect and treat high grade lesions but avoid aggressive and costly treatment for the majority? Many studies have suggested that knowledge of a patients past screening history in addition to current results, in particular knowledge of the HPV status over time, whether HPV16 or 18 are present, as well as the severity of the cytology smear can help clarify who is at highest risk and who can be followed. (Egemen D, et al. Risk estimates supporting the 2019 ASCCP risk-based management consensus guidelines. J Low Genit Tract Dis 2020 Apr;24:132–43, Smith MA, et al. National experience in the first two years of primary human papillomavirus (HPV) cervical screening in an HPV vaccinated population in Australia: observational study. BMJ. 2022 Mar 30;376)The underlying risk of the population studied affects the results and any downstream conclusions. In this case, the population studied had been predominantly screened by cytology, until the final screen, which was predominantly by HPV. Multiple studies have shown that HPV based screening has a better sensitivity than cytology alone and a reassuring result has as a more reliable negative predictive value than cytology, especially when lesions are in the endocervical canal or not fully visible. A prior negative or positive screen with an HPV based test might have aided in risk assessment and triage in this cohort. Adding p16ki67 staining to the initial cytology would also help to predict long term risk of high grade dysplasia, determining who could be followed and who treated. (Clarke MA, et al Five-Year Risk of Cervical Precancer Following p16/Ki-67 Dual-Stain Triage of HPV-Positive Women. JAMA Oncol. 2019 Feb 1;5(2):181-186.) Finally, an endocervical curettage, even with a brush, might have better sampled the endocervical canal and is less painful and costly than four blind biopsies.Despite some of the limitations of the study, which the authors outline well, there is an important message-the CIN2+ rate in this older cohort of women is high- and if we are to prevent cervical cancer among older women, screening with HPV before exiting screening, and appropriately evaluating and treating women at risk of high grade dyspasia or cancer is essential.

A document by Markus Gonser. Click on the document to view its contents.

DEATH AND SEVERE MORBIDITY IN ISOLATED PERIVIABLE SMALL-FOR-GESTATIONAL-AGE FETUSESBy Meler et alDescriptive title:Middle cerebral artery Doppler improves risk stratification of SGA babies at a peri-viable gestationMini-commentary by Lawrence ImpeySmall for gestational age (SGA) babies identified before 26 weeks are a heterogenous group but the largest contributor is ‘isolated’ SGA’. Most are ‘constitutionally’ small, but placental issues are common. Traditionally, the ultrasound Doppler parameters used to identify the most at risk are the umbilical artery (UA) and uterine artery (UtA). This paper (Meler et al, BJOG, 2022) challenges the dogma that MCA Doppler in early onset-SGA babies is of limited use, reporting an 87% detection rate for a 14% false positive rate for UA and MCA together in predicting a severe composite adverse outcome (CAO).The analysis uses Doppler findings at referral, thereby reducing but not eliminating the ‘intervention paradox’, common to many analyses, whereby an ‘abnormal’ finding’s association with an outcome is altered because it leads to intervention.The group is defined by local centiles and only comprises those referred but, by including both apparently FGR and SGA babies, is less subject to selection bias. Because of the high risk nature and size of this cohort, the frequency of adverse outcomes is adequate for analysis of a severe CAO (20.4%), of death (15.4%) or long term morbidity that is sufficiently serious and includes postnatal follow up (minimum 9 months).The role of MCA Doppler with placental failure is poorly understood. Near term, as part of the cerebroplacental ratio (CPR), it helps identify the at-risk SGA baby (Veglia et al, UOG, 2018), and even some at-risk normally grown babies. Earlier, however, the role of UA Doppler is clear (Alfirevic et al, Cochrane, 2017). That MCA Doppler adds predictive value at diagnosis is important because it will allow enable more appropriate counselling, follow up and potentially better timing of iatrogenic birth.What does the analysis make of UtA Doppler and the ductus venosus (DV)? It is surprising (Allen et al, UOG 2016) that the former was not predictive, but as its role is well established, this could be the subject of intervention bias. Mild abnormalities (PI>95th c) of the DV were not useful, but severe ones, occurring late in the deterioration in FGR, will still be useful to time iatrogenic birth (Lees et al, Lancet, 2015).MCA Doppler in referred small peri-viable babies improves risk stratification, a process central to maternity care. The ‘checklist’ approach to risk must be replaced by models using continuous variables (as opposed to cut offs of ‘abnormal’) of multiple independent risk factors: as with aneuploidy screening. Only then can we better identify high risk (sensitivity) whilst not over-medicalising pregnancy (specificity). Developing this is complex, not least because of the rarity and gestation-dependence of serious perinatal events and because of the presence of the intervention paradox in large datasets. Nevertheless, the Tommy’s app (https://www.tommys.org/) is a welcome start. Such screening is likely to need to be staged, and this analysis demonstrates one risk factor potentially worth including following a 20 week scan.

BJOG mini-commentary on BJOG-22-0097This manuscript by McCall et al reports that UK and France have very different approaches to managing women with PAS. More women in France received a uterus conserving approach. Major haemorrhage was more common in the UK series. The authors speculate that this may be related to treatment modality. The ACOG/SMFM committee opinion (Obstet Gynecol 2018;132:e259–75) recommends caesarean hysterectomy as the most generally accepted approach. Does this report imply that we should stop offering hysterectomies and recommend conservative treatment?Before we make up our mind, it is important to consider what else was different in the two cohorts. The case definitions used by UK OSS and PACCRETA investigators were different. However, the authors of the current report have included only those cases that satisfied a harmonised definition. UK prevalence (1.7/10 000) was significantly lower as compared to that from France (4.2/10 000). This raises the question: Is UK under-reporting or is France over-reporting? Screening studies may give some idea about the ‘true’ prevalence. A prevalence of 5.8/10 000 (Panaiotova et al, Ultrasound Obstet Gynecol 2019; 53: 101–106) was reported with screening for Caesarean scar pregnancies. Coutinho et al (Ultrasound Obstet Gynecol 2021; 57: 91–96) reported a prevalence of 3.8/10 000 with screening for PAS in late pregnancy. In both these reports all women had either placenta previa or a low-lying placenta. In contrast, placenta previa was present in 64% and 63% of women from UK and France, respectively. In this light, one would expect a higher, rather than lower prevalence of PAS as compared to the two screening studies. One explanation could be increasing Caesarean section rate and better awareness with time.A systematic review reported high (>90%) sensitivity for the detection of PAS using ultrasound in women at high risk of PAS (D’Antonio et al, Ultrasound Obstet Gynecol 2013; 42: 509–517). The prenatal detection was disappointingly low at < 50% in both UK and France. Before we begin to berate ourselves, it is noteworthy that these are 7-12 year-old data. The current study took place between May 2010 - April 2011(UK) and November 2013 - October 2015(France).What about the differences in median blood loss? Manual removal of the placenta was attempted in fewer women in France. Even then, unplanned hysterectomy was more common in the French group. The blood loss may be lower with conservative management, but this advantage should be weighed against the uncertainty about the possibility and timing of developing major haemorrhage in the post-operative period. Moreover, it is possible that the UK series had particularly severe cases as compared to the French cohort given the significantly lower prevalence. A head-to-head comparison of the two treatment modalities has never been reported. This will necessitate a unified definition and accurate prenatal detection. Such a study would be extremely challenging given the strong views of women regarding fertility preservation and of physicians regarding ongoing uncertainty with complications and personal experience. The jury is still out on this one.

Objective: To study the impact of shoulder dystocia (SD) simulation training on the SD management and the incidence of permanent brachial plexus birth injury (BPBI). Design: Retrospective observational study Setting: Helsinki University Women’s Hospital, Finland Sample: Deliveries with SD Methods: Multi-professional, regular and systematic simulation training for obstetric emergencies began in 2015 and SD was one of the main themes. A study was conducted to assess changes in SD management and the incidence of permanent BPBI. The study period was from 2010 to 2019; years 2010–2014 were considered the pre-training period and 2015–2019 the post-training period. Main outcome measures: The primary outcome measure was the incidence of permanent BPBI after the implementation of systematic simulation training. Also changes in the SD management were analysed. Results: During the study period, 113,085 vertex deliveries were recorded. The incidence of major SD risk factors (gestational diabetes, induction of labour, vacuum extraction) increased and was significantly higher for each of these (p <0.001) during the post-training period. The incidence of SD also increased significantly (0.01 vs 0.3%, p <0.001) during the study period, but the number of children with permanent BPBI decreased dramatically after the implementation of systematic simulation training (0.04 vs 0.02%, p <0.001). The most significant change in the management of SD was increased incidence of a successful delivery of the posterior arm. Conclusions: Systematic simulation-based training of midwives and doctors can translate into an improved individual and team performance and significantly reduce the incidence of permanent BPBI.

A document by Awol Yemane. Click on the document to view its contents.

Original Manuscript ID: BJOG-21-1723.R1 Descriptive: The Impact of Respectful and Compassionate Bereavement Care Following Stillbirth Running Title: Respectful Bereavement Care After Stillbirth Author information: Mehali Patel, Senior Research Officer, Saving Babies’ Lives Team, Sands Contact Details: 07709602633 Mehali.patel@sands.org.uk Sands Office, CAN Mezzanine, 49-51 East Road, London, N1 6AH

BJOG Commentary  Title: Fetal movement trials: where is the evidence in settings with high burden of stillbirths?Authors: Natasha Housseine1,2, natasha.housseine@aku.edu, natasha.housseine@outlook.comJoyce Browne2, J.L.Browne@umcutrecht.nlNanna Maaløe3 nannam@sund.ku.dkBrenda Sequeira Dmello1,4 bseqdmello@gmail.comSam Ali2,5, alisambecker@gmail.comMuzdalifat Abeid1, muzdalifat.abeid@aku.eduTarek Meguid6, tarekmeguid@gmail.comMarcus J Rijken2,7,8, mrijken2@umcutrecht.nlHussein Kidanto1, hussein.kidanto@aku.edu Affiliations 1.      Aga Khan University, Medical College East Africa, Dar es Salaam campus2.      Julius Global Health, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, The Netherlands3.      Global Health Section, Department of Public Health, University of Copenhagen, Denmark4.      Comprehensive Community Based Rehabilitation in Tanzania, Dar es salaam, Tanzania5.      Research Department, Ernest Cook Ultrasound Research and Education Institute (ECUREI), P.O. Box 7161, Kampala, Uganda6.      Child Health Unit, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa7.      Vrouw en Baby department, University Medical Centre Utrecht, Utrecht University, The Netherlands8.      Obstetric department, Amsterdam University Medical Center, Amsterdam, The Netherlands Corresponding author:Natasha HousseineThe Aga Khan University Medical CollegeUfukoni Road, P. O. Box 38129, Dar es salaam, Tanzania Telephone: +255 745 338 950  Fetal movement (FM) is a sign of fetal life and wellbeing that is felt by the pregnant woman, and reduced FM is known to precede stillbirths (1,2). Therefore, healthcare providers may advise women to monitor and report if their babies’ movements are fewer than usual. In high-income countries (HIC), there has been a renewed interest in FM with a recent wave of large-scale randomised controlled clinical trials investigating its potential to reduce stillbirths. The My Baby’s Movement trial in Australia/New Zealand, and the Mindfetalness trial in Sweden investigated the effects of intervention aimed at increasing women’s awareness of FM (3,4). The British AFFIRM trial investigated the effects of an FM awareness package coupled with a standardised management protocol (5). The ongoing CEPRA study in the Netherlands, UK and Australia and aims to evaluate Cerebro Placental Ratio as an indicator for delivery in women with reduced FM (6). None of the completed trials, however, found significant reductions in stillbirths. Moreover, they showed conflicting results on some potential harmful consequences, such as increased rates of obstetric interventions. In this commentary, we reflect on these trials through a global lens, and we urgently call for more trials – but this time in settings suffering the majority (98%) of the world’s two million annual stillbirths. Importantly, the global applicability of these HIC trials is questionable. They were conducted in settings where women are aware of the importance of reduced FM and are empowered to access highest standards of care. The contextual realities of pregnancy care are vastly different in low- and middle-income countries (LMICs) where antenatal care and health education are substandard. Women lack health information to self-monitor and report reduced FM. Furthermore, antenatal clinics are often overcrowded and understaffed, with lack of supplies, clinical guidelines, and adequate training of health workers. Recent estimates show stillbirth rates as high as 22 per 1000 per total births in Sub-Saharan Africa, compared to less than 3 per 1000 in HICs (7). Given the downward trend of stillbirths reported in all the HIC trials, it is possible that the completed trials may be demonstrating a lack of evidence rather than a lack of effectiveness. We hypothesise that involving women in their care, through training on how to monitor their baby’s movement and when and how to respond coupled with strengthening healthcare workers’ respect and response to women’s concerns on reduced FM, is a low-cost intervention with potential to significantly reduce stillbirths in high-burden LMICs. Surprisingly, high-quality studies from LMICs that have assessed the effect of FM interventions on perinatal deaths are lacking (2). Of note, the authors of the above-mentioned trials did not consider the well-known major differences in clinical context globally as a limitation while discussing the generalisability of their findings. In fact, the latest My Baby’s Movement trial was not even published open access, limiting access to less privileged clinicians, researchers and policymakers (4). This lack of a global perspective on the international health crisis of preventable stillbirths is an epistemic injustice and a missed opportunity (8). We are concerned that the results of the above trials could prematurely prompt policies discouraging the use of FM awareness among pregnant women (9). It is thus crucial that the lack of generic applicability of these trials’ findings are stressed, and that their high-resource contexts are considered when developing global clinical guidelines and future research priorities. Notably, it has been seen too often how the unbalanced evidence production from HICs has had unintended harmful influences on clinical practice in LMICs (10). For instance, it appears that the breech trials from HICs have led to policy change also in LMICs with increased use of caesarean section in case of breech presentation. However, the risk ratios of vaginal breech births versus caesarean sections differ dramatically between high-resource and low-resource settings with lower surgical safety in LMICs (11,12).The prevailing constraints in LMICs should stimulate innovation and creativity to design low-cost solutions that strengthen three areas 1) FM awareness and monitoring; 2) diagnosis to identify babies truly at risk, and 3) care provision protocols of pregnant women with reduced FM to improve perinatal outcomes. While such strategies or their evidence base are often lacking in LMICs, there is some evidence about possible low-cost diagnostic approaches to assess fetal risk following reduced FM: for example, measuring maternal blood pressure, fetal heart rate, and fundal height (13), or antenatal (hand-held) ultrasound to detect and monitor high-risk pregnancies. Measuring fetal blood flow in Doppler ultrasound studies has also been useful particularly in detecting growth restriction (6,14).  Involving women and health workers in studies will ensure consideration of health-system constraints and allow these to be embedded in the design, implementation, and evaluation of any new intervention. If proven effective, this will increase the chance of seamless integration of the intervention into existing care, positive perceptions by providers and pregnant women- and not increase the burden on already overwhelmed healthcare workers.  Unfortunately, maternal perception of FM is still too often the only signal of complications in the absence of regular high-quality antenatal checks (15)– and there are possibly many babies’ lives lost by ignoring this danger sign. Given the burden of need and the context-specific realities that determine interventions’ effectiveness, we hope these recent waves of FM trials will continue into LMICs to investigate if and how FM awareness coupled with context-tailored management protocol can reduce stillbirths.    Contribution to AuthorshipNH conceived and wrote the first draft. JB, NM, BSD and MJR contributed to subsequent drafting of the manuscript. All authors revised the commentary for important intellectual content and approved the final version to be published and agree to be accountable for all aspects of the work. Details of ethics approvalNo ethics approval applicable for this commentary FundingThere was no financial support for this commentary Disclosure of interests  Reference1.        Bekiou A, Gourounti K. Reduced Fetal Movements and Perinatal Mortality. Mater Sociomed. 2020;32(3). 2.        Hayes DJL, Smyth R, Heazell AEP. Investigating the significance and current state of knowledge and practice of absent or reduced fetal movements in low and lower middle-income countries : a scoping review. 2019;3:1–12. 3.        Akselsson A, Lindgren H, Georgsson S, Pettersson K, Steineck G, Skokic V, et al. Mindfetalness to increase women’s awareness of fetal movements and pregnancy outcomes: a cluster-randomised controlled trial including 39 865 women. BJOG An Int J Obstet Gynaecol. 2020 Jun 1;127(7):829–37. 4.        Flenady V, Gardener G, Ellwood D, Coory M, Weller M, Warrilow KA, et al. My Baby’s Movements: a stepped-wedge cluster-randomised controlled trial of a fetal movement awareness intervention to reduce stillbirths. BJOG An Int J Obstet Gynaecol. 2022 Jan 1;129(1):29–41. 5.        Norman JE, Heazell AEP, Rodriguez A, Weir CJ, Stock SJE, Calderwood CJ, et al. Awareness of fetal movements and care package to reduce fetal mortality (AFFIRM): a stepped wedge, cluster-randomised trial. www.thelancet.com. 2018;392. 6.        Damhuis SE, Ganzevoort W, Duijnhoven RG, Groen H, Kumar S, Heazell AEP, et al. The CErebro Placental RAtio as indicator for delivery following perception of reduced fetal movements, protocol for an international cluster randomised clinical trial; the CEPRA study. BMC Pregnancy Childbirth. 2021 Dec 1;21(1). 7.        Hug L, You D, Blencowe H, Mishra A, Wang Z, Fix MJ, et al. Global, regional, and national estimates and trends in stillbirths from 2000 to 2019: a systematic assessment. Lancet. 2021 Aug 28;398(10302):772–85. 8.        Bhakuni H, Abimbola S. Epistemic injustice in academic global health. Lancet Glob Heal. 2021;9:e1465–70. 9.        Walker KF, Thornton JG. Encouraging awareness of fetal movements is harmful. Lancet. 2018 Nov 3;392(10158):1601–2. 10.      Maaløe N, Ørtved AMR, Sørensen JB, Sequeira Dmello B, van den Akker T, Kujabi ML, et al. The injustice of unfit clinical practice guidelines in low-resource realities. Lancet Glob Heal. 2021;9(6):e875–9. 11.      van Roosmalen J, Meguid T. The dilemma of vaginal breech delivery worldwide. Lancet. 2014;338(9932): 12.      Sobhy S, Arroyo-Manzano D, Murugesu N, Karthikeyan G, Kumar V, Kaur I, et al. Maternal and perinatal mortality and complications associated with caesarean section in low-income and middle-income countries: a systematic review and meta-analysis. Lancet. 2019 May 11;393(10184):1973–82. 13.      Housseine N, Rijken MJ, Weller K, Nassor NH, Gbenga K, Dodd C, et al. Development of a clinical prediction model for perinatal deaths in low resource settings. eClinicalMedicine. 2022 Feb;44:101288. 14.      Ali S, Kawooya MG, Byamugisha J, Kakibogo IM, Biira EA, Kagimu AN, et al. Middle cerebral arterial flow redistribution is an indicator for intrauterine fetal compromise in late pregnancy in low-resource settings: a prospective cohort study. BJOG An Int J Obstet Gynaecol. 2022 Feb 4; 15.      World Health Organization. WHO recommendations on antenatal care for a positive pregnancy experience [Internet]. 2016 [cited 2020 Jul 30]. Available from: https://www.who.int/reproductivehealth/publications/maternal_perinatal_health/anc-positive-pregnancy-experience/en/ ‘This article has a Video Abstract presented by Natasha Housseine.’

TYPE OF ARTICLE: LETTER TO EDITOR

Objectives: We evaluated radiotherapy planning CT-based radiomics for predicting clinical endpoints [tumor complete response (CR), 5-year overall survival (OS), hypohemoglobin, and leucopenia] after intensity-modulated radiation therapy (IMRT) in locally advanced cervical cancer (LACC). Methods: This study retrospectively collected 257 LACC patients treated with IMRT from 2014 to 2017. Patients were allocated into the training/validation sets (3:1 ratio) using proportional random sampling, resulting in the same proportion of groups in the two sets. We extracted 254 radiomic features from each of the gross target volume (GTV), pelvis, and sacral vertebrae in planning CT images. The sequentially backward elimination support vector machine algorithm was used for feature selection and endpoint prediction. Model performance was evaluated using area under the curve (AUC). Results: A combination of 10 clinicopathological parameters and 34 radiomic features achieved the best performance for predicting CR [validation balanced accuracy: 80.79%]. For OS, 54 radiomic features showed good prediction accuracy [validation balanced accuracy: 85.75%], and the threshold value of their scores can stratify patients into the low-risk and high-risk groups (P<0.001). The clinical and radiomic models were also predictive of hypohemoglobin and severe leucopenia [validation balanced accuracies: 70.96% and 69.93%]. Conclusion: This study demonstrated that combining clinicopathological parameters with CT-based radiomics had good predictive value for treatment outcomes and hematologic toxicities to radiotherapy in LACC. The prediction of clinical endpoints prior to radiotherapy may assist the radiation therapists to select the optimal therapeutic strategy with the minimal toxicity and best curative effect.

Objective: To compare the incidences of early and late onset neonatal sepsis, including group B streptococcus (GBS) and Escherichia coli (E.coli) before and after implementation of universal screening. Design: Retrospective cohort study Setting: Eight public hospitals with obstetrics services under the Hospital Authority and 31 Maternal and Child Health Centres (MCHC) under the Department of Health in Hong Kong Population: 460552 women attending routine antenatal service from 2009 to 2020. Methods: Universal culture-based GBS screening was offered to eligible women since 2012. Total maternity, births, GBS screening tests, GBS isolated in maternal genital tract, neonatal sepsis with positive blood or cerebrospinal fluid were retrieved from clinical and laboratory database of the Hospital Authority using clinical data analysis and reporting system (CDARS) and clinical system of MCHCs. Main outcome measures: Maternal GBS colonisation rate, early onset GBS disease, early onset E. coli infection, late onset GBS disease, and late onset E. coli infection Results: Of 318740 women with universal culture-based screening, 63767 women (20.0%) were screened positive. After implementation of GBS screening, the incidences of both early and late onset neonatal sepsis reduced significantly, including those caused by GBS. There was no change in the incidence of early onset E.coli sepsis, while the incidence of late onset E.coli sepsis reduced. Conclusions: Universal culture-based GBS screening in Hong Kong has been successful in prevention of early and late onset neonatal sepsis, including those caused by GBS. E.coli has become more common than GBS in early neonatal sepsis, although the incidence remained similar.