A document by Sijia Liu. Click on the document to view its contents.

Reply to the Letter to the Editor by Kember et al, Regarding Wilson et al., “A Position Modification Device for the Prevention of Supine Sleep During Pregnancy: A Randomised Crossover Trial” Published in the British Journal of Obstetrics & Gynaecology on 16 September 2024.Danielle L. Wilson, MSc., PhD1,2,3; Carley Whenn1; Maree Barnes, MBBS1,4; Susan P. Walker, MBBS, MD, FRANZCOG, DDU, CMFM2,5; Mark E Howard, MBBS, FRACP, GDEB, PhD1,41Institute for Breathing and Sleep, Austin Health, Heidelberg, Victoria, Australia;2Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia.3School of Electrical Engineering and Computer Science, The University of Queensland, St Lucia, Queensland, Australia.4Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.5Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia.Address correspondence to: Danielle L. Wilson, Institute for Breathing and Sleep, Level 5 Harold Stokes Building, Austin Health, Heidelberg, Victoria, Australia. Tel: 613 9496 3517; Fax: 613 9496 5124; e-mail: danielle.wilson@austin.org.auDear Prof. Aris Papageorghiou,We thank Dr. Kember and his colleagues1 for their interest in our recently published article2. Firstly, we acknowledge the recent publication by Coleman et al3 regarding the benefits of the Prenabelt on foetal growth, as revealed through re-analysis of their data using Bayesian methods. Unfortunately, this paper3 was published after our initial submission. Interestingly, while the frequentist analysis approach just fell short of significance, a Bayesian approach shows promise for supine sleep position interventions, by throwing an interesting light on the likelihood of a benefit depending on prior clinical beliefs. It remains that the mechanisms of action need further exploration however, given that supplemental data from the original publication4 suggests that objectively measured supine sleep in a subset of women did not differ between those using Prenabelt v sham.Secondly, we recognise our study was constrained by the measurement device used. The Night Shift Sleep Positioner (Night Shift) with neck placement was initially chosen, however, during our study a chest belt was introduced by the manufacturer. We performed a sub-study with N=20 of the participants wearing the device at both neck and abdominal placements for one night. An epoch-by-epoch comparison revealed substantial agreement between the two devices for all sleep positions with 88% concordance overall (unweighted κ = .797 [SE .006], p<.001). Regrettably, we neglected to include these data within the original publication.Despite the limitations of our measurement device, we believe that distinguishing between neck and pelvic position would not have substantially impacted our conclusions, given the high concordance between neck and abdominal devices revealed above, and particularly given that the intervention showed a nonsignificant increase in the proportion of supine sleep overnight. As Dr. Kember’s team have demonstrated, sleep positions where the thorax and pelvis are discordant (e.g., supine thorax with left pelvis tilt) are infrequent, occurring in less than 6% of “real-world” sleeping positions during pregnancy.5We agree that the Night Shift lacked sufficient resolution to fully appreciate the complex interplay between maternal positioning and foetal haemodynamics, as mentioned in the limitations section of our paper. Indeed, measurement limitations persist with all position sensing methodologies including infra-red video monitoring, with Dr. Kember’s recent paper5 demonstrating that while the most commonly occurring sleeping positions (left-lateral, right-lateral and supine) were well-recognised by modelling, the twisted/hybrid positions had intermediate performance, with the modelling particularly challenged by left or right tilted positions. To address the limitations of the Night Shift, we have recently completed data collection on a subsequent study using tri-axial accelerometry at abdominal level to characterise maternal sleep position in degrees of roll around the axial plane, with an aim to capture the subtleties of maternal position on uteroplacental haemodynamics and foetal growth.As mentioned, this is an understudied area. Dr. Kember and his team share our drive to gather objective evidence of a causal pathway between supine sleep position and foetal wellbeing, which we believe is particularly important given current guidelines regarding safe sleeping position in late pregnancy are based on retrospective cohort studies of self-reported “going-to-sleep” position. Our team congratulates Dr. Kember and his colleagues for their excellent work in the sleep position during pregnancy space, and we look forward to the outcomes from their upcoming DOSAGE Study.Disclosure of Interests:The authors have no financial disclosures or conflicts of interest.Contributions of Authorship:Dr. Wilson, Prof. Walker and Prof. Howard drafted and revised the manuscript, Ms. Whenn and Dr. Barnes critically revised the manuscript.Details of Ethics Approval:Additional analyses comparing device location were approved under an amendment to the original approval by the Mercy Hospital for Women Human Research Ethics Committee project number 2020-015, on 3rd June 2021.References:https://doi.org/10.1111/1471-0528.179521. Kember A. Placeholder for Letter to the Editor for BJOG.2. Wilson Danielle L, Whenn C, Barnes M, Walker Susan P, Howard Mark E. A position modification device for the prevention of supine sleep during pregnancy: A randomised crossover trial. BJOG: An International Journal of Obstetrics & Gynaecology. 2024; .3. Coleman J, Grewal S, Warland J, Hobson S, Liu K, Kember A. Maternal positional therapy for fetal growth and customised birth weight centile benefit in a Bayesian reanalysis of a double-blind, sham-controlled, randomised clinical trial. BMJ Open. 2024; 14 (4): e078315.4. Coleman J, Okere M, Seffah J, et al. The Ghana PrenaBelt trial: a double-blind, sham-controlled, randomised clinical trial to evaluate the effect of maternal positional therapy during third-trimester sleep on birth weight. BMJ Open. 2019; 9 (4): e022981.5. Kember AJ, Zia H, Elangainesan P, et al. Transitioning sleeping position detection in late pregnancy using computer vision from controlled to real-world settings: an observational study. Sci Rep. 2024; 14 (1): 17380.

Re: “Necessity the mother of invention”-wider significance of novel mid-urethral rectus fascial sling. Petros, Peter. Response letter.Author: Abdalla Fayyad.Centre of Urogynaecology and Advanced Laparoscopic Surgery. 12 Khalidi Street, Amman, Jordan 11180.E mail: amfayyad@gmail.comDear Dr Aris Papageorghiou,We thank Professor Petros for the letter to the editor titled “Necessity is the mother of invention”-wider significance of novel mid-urethral rectus fascial sling1 and the interest shown in our novel technique of laparoscopic mid-urethral autologous fascial sling (LMAFS)2. In his letter to the editor, Professor Petros supports our novel approach of using the autologous rectus fascia as mid-urethral sling inserted laparoscopically. We are honored to have our technique endorsed by the discoverer of the integral theory (IT), and the co-developer of the mid-urethral sling (MUS).We agree with Professor Petros that restoring vaginal support does improve pelvic floor symptoms related to prolapse, lower urinary tract symptoms and obstructive daefecation3. We are currently examining the feasibility of using autologous rectus fascia laparoscopically to restore apical support as a non-mesh option. We agree that the potentials of using the rectus fascia laparoscopically can be numerous, but does indeed need further evaluation.It is important, however, to emphasize that surgical interventions for pelvic floor dysfunction should be considered after conservative measures have failed to improve patient’s bothersome symptoms. Regarding the symptoms of overactive bladder (OAB), e.g. urgency and urgency incontinence, we agree with Professor Petros that many patients with OAB do improve following corrective reconstruction of the support of the bladder base and trigone, as the stretch receptors in the bladder are no longer activated at low bladder volumes3. However, it is important to recognise that OAB is a nonspecific, complex and multifactorial symptom syndrome frequent in the general population, and among men as well4,5. There appear to be several distinct subtypes of OAB with different pathophysiology, with overlapping underlying factors including metabolic syndrome, affective disorders, gastrointestinal disorders, hormonal deficiency, and subclinical autonomic nervous dysfunction5. Surgery for prolapse does not necessarily address these potential underlying causes. The mainstay of managing this sub group of patients with OAB, is through conservative measures and medical treatment.In conclusion, we thank Professor Petros for his letter, and agree that understanding the IT provides an important insight into majority of pelvic floor dysfunction symptoms. We used the principles of the IT when we developed the technique of LMAFS1. We are certainly looking for further uses of laparoscopic rectus fascial sling in pelvic floor reconstruction.Word count: 368Conflict of interest: NoneFunding information: None

Biopsychosocial approaches to treat female chronic pelvic painJim Thornton, Emeritus professor obstetrics & gynaecology, university of Nottingham, UKNick Brown, Department of Psychology, Linnaeus University, Växjö, SwedenCorresponding author: jim.thornton@nottingham.ac.ukDear Dr. Aris Papageorghiou,We read the recent systematic review of biopsychosocial approaches to treat female chronic pelvic pain (October 2024) [1] with interest. The fact that three included studies had been conducted by the same research group, and differed only in the type and focus of goal setting [2, 3, 4], inspired us to read them carefully.All three studies contain multiple reported mean values, for variables which are normally reported as integers, which appear to be impossible: so-called GRIM inconsistencies [5]. We have posted our concerns on the peer review website PubPeer.com,https://pubpeer.com/publications/A182FA06122C1D2C38E819415EC155\#1, https://pubpeer.com/publications/16A4EA3222C67B2E38AD0790F38E43 and https://pubpeer.com/publications/7B0A50B193748DEF5196E10529FC76\#1 and asked the editors of Maturitas and Archives of Physical Medicine and Rehabilitation to investigate.Although such inconsistencies can be due to typos, or other minor data errors, the occurrence of so many, in three different randomised controlled trials by the same investigator group, raises serious questions about the integrity of the data and, hence, the validity of the results in these articles.We suggest that readers interpret the reliability of these three studies, and hence also the systematic review, which is partly based on them, with caution unless the respective journal investigations indicate no cause for concern. We also think it essential that the authors should provide their data for reanalysis, to determine the origin of these inconsistencies.Jim Thornton, Emeritus professor obstetrics & gynaecology, iniversity of Nottingham, UKNick Brown, Department of Psychology, Linnaeus University, Växjö, SwedenJohnson, S., Bradshaw, A., Bresnahan, R., Evans, E., Herron, K. and Hapangama, D. (2024), Biopsychosocial Approaches for the Management of Female Chronic Pelvic Pain: A Systematic Review. BJOG. https://doi.org/10.1111/1471-0528.17987Ariza-Mateos MJ, Cabrera-Martos I, Ortiz-Rubio A, Torres-Sánchez I, Rodríguez-Torres J, Valenza MC. Effects of a Patient-Centered Graded Exposure Intervention Added to Manual Therapy for Women With Chronic Pelvic Pain: A Randomized Controlled Trial. Arch Phys Med Rehabil. 2019 Jan;100(1):9-16. doi: 10.1016/j.apmr.2018.08.188. Epub 2018 Oct 9. PMID: 30312595.Rodríguez-Torres J, López-López L, Cabrera-Martos I, Prados-Román E, Granados-Santiago M, Valenza MC. Effects of an Individualized Comprehensive Rehabilitation Program on Impaired Postural Control in Women With Chronic Pelvic Pain: A Randomized Controlled Trial. Arch Phys Med Rehabil. 2020 Aug;101(8):1304-1312. doi: 10.1016/j.apmr.2020.02.019. Epub 2020 Apr 20. PMID: 32325162.Ariza-Mateos MJ, Cabrera-Martos I, López-López L, Rodríguez-Torres J, Torres-Sánchez I, Valenza MC. Effects of a patient-centered program including the cumulative-complexity model in women with chronic pelvic pain: a randomized controlled trial. Maturitas. 2020 Jul;137:18-23. doi: 10.1016/j.maturitas.2020.04.005. Epub 2020 Apr 25. PMID: 32498932.Brown, N. J. L., & Heathers, J. A. J. (2017). The GRIM Test: A Simple Technique Detects Numerous Anomalies in the Reporting of Results in Psychology. Social Psychological and Personality Science, 8(4), 363-369. https://doi.org/10.1177/1948550616673876

Lung cancer during pregnancy is exceptionally rare, with only 93 reported cases from 1953 to 2024. Our study identified 40 cases of lung cancer during pregnancy from a 9 million patient database, contributing to a total to 133 documented instances in the literature, and the only powered case series. Using the HCUP-NIS database (2004-2014), we conducted a retrospective analysis comparing maternal and fetal outcomes in women with and without lung cancer. Results showed that pregnant women with lung cancer were older and had higher rates of smoking, chronic hypertension, and pregestational diabetes (P<0.01, all). Significant risks included placenta previa (OR: 5.67, 95% CI:1.36-23.65, p=0.017), abruptio placenta (OR: 4.99, 95% CI: 1.49-16.74, p=0.009), operative vaginal delivery (OR: 4.88, 95% CI: 2.14-11.11, p<0.001), and transfusion (OR: 8.92, 95% CI: 3.28-24.28, p<0.001). They also have markedly higher odds of venous thromboembolism (OR:21.83, 95% CI: 2.92-163.47, p<0.001), disseminated intravascular coagulation (OR:  8.45, 95% CI: 1.14-62.42, p=0.04), and maternal death (OR: 195.02, 95% CI: 40.61-936.55, p<0.001), highlighting the necessity for specialized care and further research into this rare and complex condition.

A document by Bethany Atkins. Click on the document to view its contents.

Mini Commentary on BJOG-23-1596.R1: Pregnancy and Birth Complications and Maternal Mental Health – The case is clearNicole Votruba - nicole.votruba@wrh.ox.ac.ukUniversity of OxfordNuffield Department of Women’s & Reproductive HealthWomen’s Centre (Level 3)John Radcliffe HospitalOX3 9DU Oxford15 October 2024 Pregnancy and birth complications and long-term maternal mental health outcomes are clearly interlinked. Although commonly known, little research has been conducted to investigate these associations. Bodunde and colleagues have recently provided robust evidence that complications during pregnancy and birth increase the risks for long-term depression, anxiety and post-traumatic stress disorder (PTSD)(1).Birth complications are frequent, affecting up to 40% of pregnant women, and can continue to be burdensome for mothers and children beyond birth. Whilst there is a well-established body of evidence about the effect of these complications on mental health in the immediate postpartum period, particularly the first six months, much less is known about the impact these complications have longer term, during the first year after birth and beyond.(1)The authors have carried out the first, comprehensive meta-analysis estimating rates of long-term maternal mental health outcomes for women following pregnancy and birth complications. They performed a rigorous, substantial systematic review and meta-analysis, consolidating 33 studies with almost 4 million participants. The authors found significant associations between pregnancy terminations, miscarriage and preterm birth, with maternal depression and anxiety, and preterm birth (but not caesarean section) being significantly associated with PTSD.What do their findings tell us beyond the clear link of pregnancy complications and adverse maternal mental health outcomes? Firstly, that in spite of a relatively large number of studies and participants, there is an evident lack of high-quality studies on the associations of pregnancy complications and long-term mental health outcomes. Depression and anxiety were the most reported associations across all studies, and the authors note the absence of studies on other mental disorders than anxiety, depression and PTSD, which made further meta-analyses impossible.Secondly, with the total of 33 studies being from 15 countries, the findings confirm the striking lack of research from low- and middle-income countries (LMICs): Only four of the identified studies are from Asia, one from South America, and none from Africa. Whilst the extent of maternal morbidity is hard to estimate, looking at the burden of maternal mortality points at an excessive gap: nearly 95% of maternal deaths occurred in LMICs in 2020,(2), with the mental health related impact being largely hidden due to a lack of data.Thirdly, and perhaps most strikingly, we are missing the extent of maternal suicide as an adverse mental health outcome. The authors’ primary review outcomes were common and severe maternal mental disorders, and regrettably suicidality has been omitted as a primary mental health outcome. Maternal suicide is the leading cause of direct death in the postnatal period.(3) In high income countries 5-20% of maternal deaths are from suicide,(4) however stigma and challenges in unified approaches to reporting and measurement obscure the picture, with a lack of evidence beyond the immediate post-partum period, and particularly from LMICs.(5). Given the high burden, there is an urgent need to understand these links as substantial long-term adverse maternal mental health outcomes of adverse pregnancy outcomes.Beyond the post-partum impact, evidence on the long-term mental health outcomes in relation to adverse pregnancy outcomes is limited. What Bodunde and colleagues have added is clear and highly needed evidence for the direct associations of adverse pregnancy outcomes and long-term mental health conditions. What is now required is more robust evidence on prevalence and associations of these conditions and their long-term effects, particularly studies from LMICs, and including maternal suicide. Research examining more effective intervention is critical: studies should explore and test what interventions are acceptable, effective and scalable in different settings and communities, to support women who experience adverse pregnancy outcomes in their mental health, and prevent long term mental ill health particularly in populations with the greatest burden of disease.Disclosure of Interests: n.a.Funding: NV is funded by the Medical Research Council (Grant MR/Y503319/1), the Oxford MSD Improving Equitable Access to Healthcare grant, and partially supported by the UK Medical Research Council (UKRI) for the Indigo Partnership (MR/R023697/1) award1. Bodunde EO, Buckley D, O’Neill E, Al Khalaf S, Maher GM, O’Connor K, et al. Pregnancy and birth complications and long-term maternal mental health outcomes: A systematic review and meta-analysis.n/a(n/a).2. World Health Organization. Trends in maternal mortality 2000 to 2020: estimates by WHO, UNICEF, UNFPA, World Bank Group and UNDESA/Population Division: World Health Organization; 2023.3. Knight M, Bunch K, Tuffnell D, R P, Shakespeare J, Kotnis R, et al. Saving Lives, Improving Mothers’ Care-Lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2017-19. Oxford: National Perinatal Epidemiology Unit, University of Oxford 2021.4. Howard LM, Khalifeh H. Perinatal mental health: a review of progress and challenges. World Psychiatry. 2020;19(3):313-27.5. Simmons E, Gong J, Daskalopoulou Z, Quigley MA, Alderdice F, Harrison S, et al. Global contribution of suicide to maternal mortality: a systematic review protocol. 2024;14(9):e087669.

Title: BJOG -24-0687.R1 Postpartum haemorrhage care in Ghana and Uganda: grounds for hope and concern.

TITLE Letter to the editor BJOG “Necessity the mother of invention”- wider significance of novel mid-urethral rectus fascial sling.1 Professor PEP Petros DSc DS (UWA) PhD (Uppsala) MB BS MD (Syd) FRCOG (Lond) FRANZCOG CU.31/93 Elizabeth Bay Rd Elizabeth Bay NSW 2011 AUSTRALIAPelvic Floor Surgeon (retired)1Single and corresponding author.1Affiliation None. Retired pelvic surgeonEmail pp@kvinno.comTel+61 411 181 731

A document by Hala Eldamanhoury. Click on the document to view its contents.

Response to: “Advocating for Change: Lifting Mesh Suspension in SUI Surgery Based on Established Literature and Long-Term TVT Study Results”Corresponding author: Berit Rein Solhaug (Gynecologist, PhD student) Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim, Norway Department of Clinical and Molecular Medicine, Norwegian University of Technology and Science, Trondheim, Norway berit.r.solhaug@ntnu.noRune Svenningsen (Gynecologist, Professor II) Department of Obstetrics and Gynecology, Oslo University Hospital,Oslo, NorwayInstitute of Clinical Medicine, University of Oslorune.svenningsen@medisin.uio.no   Maria Oyasaeter Nyhus (Gynecologist, PhD) Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim, Norway Department of Clinical and Molecular Medicine, Norwegian University of Technology and Science, Trondheim, Norway maria.o.nyhus@ntnu.no   Ingrid Volloyhaug (Gynecologist, Professor II) Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim, Norway Department of Clinical and Molecular Medicine, Norwegian University of Technology and Science, Trondheim, Norway ingrid.volloyhaug@ntnu.no

ERAS in gynecologic surgery: insights and future directionsAuthors: Jiayu Yan, Bilan Li, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, Chinalibilan@51mch.comThis study was supported by grants from the National Natural Science Foundation of China (No.82372925 to LBL,No.82172714 to LBL, No. 81602281 to LBL), Natural Science Foundation of Shanghai (No.22Y11906300 and No.20ZR1443900 to LBL), Clinical Research Plan of SHDC (No. SHDC2020CR4086).

Objective: There are increasing concerns about the trustworthiness of the medical literature. When identified after publication, such concerns about published papers can be addressed through a post-publication review (PPR) system. We evaluated the effectiveness and efficiency of this system while addressing studies in women’s health. Design: Cohort study Setting: The project was conducted at the Department of Obstetrics and Gynaecology, Monash University, Australia. Sample: Papers Published in Women’s Health Journals Methods: We wrote to the editors and publishers about potentially untrustworthy papers in women’s health and requested an investigation according to the procedure established by the Committee of Publication Ethics (COPE). Main outcome measure: For each paper, we tabulated the trial characteristics, investigation outcome [retraction, expression of concern (EoC), correction or no wrongdoing found] and time to decision. We also report the case completion rate per journal and publisher. Results: Between 7 th November 2017 and 30 th April 2024, we wrote to editors and publishers of 891 potentially untrustworthy papers published in 206 different journals. At present, 263 (30%) of 891 papers received an outcome, with 227 (86%) labelled as problematic (152 (58%) papers retracted; 75 (29%) EoC). It took a median time of 16 months for editors and publishers to decide, with 13% of the flagged cases reaching a decision within 12 months. Conclusions: The current PPR process is inefficient and ineffective in assessing and removing untrustworthy data from the medical literature. Funding: No funding was sought for this project.

Objectives: To assess fetal circulating free fetal haemoglobin (fHbF) levels and heme defences, correlated to fetal circulatory biometry and fetal sex in severe early-onset fetal growth restriction. Design, Setting & Population: A prospective study severe early-onset fetal growth restriction pregnancies with close clinical management (EFW<3 rd centile and <600g at 20-26+6 weeks; N=20). Method & Main Outcome Measures: Temporal fetal vascular obstetric biometry was recorded. Cord blood fHbF and key heme-scavenger defences were measured and compared with normal term births (N=26) and births with late-onset FGR (N=12). Results: fHbF was elevated in early-onset FGR compared with normal pregnancy: 0.437(0.337/0.753) mg/mL; P<0.0001; 0.098(0.045/0.264) mg/mL; P<0.0001), respectively; whilst hemopexin was downregulated in early- and late-onset FGR compared to normal pregnancy: 36(14/81) μg/mL, P<0.001; 25(19/40) μg/mL, P<0.0001; 155(132/219) μg/mL, respectively; median(interquartile ranges). Early-onset FGR male fetuses had higher fetal haemoglobin compared with the normal males: 0.710(0.433/0.857) mg/mL; P<0.001; 0.099(0.043/0.246) mg/mL, respectively; median(interquartile ranges). In early-onset FGR, ratios of mid-cerebral artery and umbilical artery pulsatility indices correlated positively with heme-scavenger levels (hemopexin and a heme-handling composite measure: P<0.05 and P<0.01, respectively), indicating lower levels are associated with cerebral vascular redistribution. These heme handling measures also positively correlated with gestational age at delivery (P<0.01, both) and birthweight (P<0.001 and P<0.05, respectively). Conclusion: Free fetal haemoglobin overproduction may be one route to placental vascular compromise in early-onset FGR, implicated in reduced placental and fetal blood flow.

Objective. The purpose of this study was to explore individuals’ beliefs, values, and experiences surrounding stillbirth evaluation decisions. Design. Qualitative research Setting. University of Utah Health Population. Parents who experienced a stillbirth in the past 5 years (n=19) were interviewed about their experiences and decision to consent or decline postmortem evaluations Methods. Qualitative content analysis Main outcome measures. Barriers and facilitators to parents’stillbirth postmortem decision-making. Results. Participants communicated several facilitators and barriers that contributed to their stillbirth evaluation decision. Reasons for consenting to evaluations were belief in science, background in medicine, altruism, to inform future pregnancies, thinking about preventing another stillbirth, and how patients viewed the care of their stillborn by the medical team. Reasons for declining evaluations were receiving a diagnosis prior to being offered a postmortem evaluation, intent to avoid causing further harm to the baby, interest to spend more time with their baby, and cost of the evaluation. Conclusion. Participants identified stillbirth as one of their most difficult experiences as a parent. Diagnostic and emotional barriers create further challenges to decision-making for stillbirth postmortem evaluations. Parents often rely on inadequate information and personal values and beliefs during this time-sensitive decision process. Decision support for stillbirth evaluations and training for medical providers could benefit parents, may increase stillbirth evaluation uptake, and potentially prevent decisional regret.

Objective To identify phenotypes of pain in patients with endometriosis and to investigate their associations with predictors and quality of life (QoL). Design Population-based study. Setting A referral university center in Quebec City, Canada. Population or Sample A total of 352 patients aged 18‒50 years and diagnosed with endometriosis. Methods Latent class analysis (LCA) was used to identify pain phenotypes. To assess the associations, the three-step approach of LCA was applied. Main Outcome Measures Pain phenotypes, predictors of pain phenotypes, QoL. Results A total of 352 patients were included in the analyses. The diagnosis of endometriosis was either based on histology (N=135), imaging (N=106) or clinical presentation (N=111). The optimal model identified two distinct and homogeneous phenotypes of patients with endometriosis. The two groups had distinct clinical presentations, one with more severe and frequent pain symptoms and poorer quality of life (54%); the other with mild and less frequent pain symptoms (46%). Predictors of a high pain phenotype were a previous treatment failure, use of pain killers, a family history of endometriosis, a low annual family income, and pain comorbidities such as painful bladder, fibromyalgia, migraines, low back pain, irritable bowel syndrome, anxiety, and depression or mood disorders. The presence of endometrioma was predictive of the low pain phenotype. Phenotype membership was associated with distinct quality of life profiles (p<0.001). Conclusion Patients with endometriosis and pelvic pain can be grouped into two distinct and homogeneous phenotypes. Phenotypes membership correlates with quality of life and can be predicted with the patients’ characteristics. These findings will need to be validated in other populations and may inform the development of more specialized or personalized interventions based on the pain phenotypes.

Objective: Child marriage forces a girl into adult roles before physical and psychological maturity, which can take a toll on women’s health over the life course. This paper aims to assess whether child marriage and adolescent childbearing are associated with elevated risk of gynecologic disorders leading to hysterectomy. Design: Cross-sectional and survival analysis. Setting: India, nationally representative survey. Population: 528,816 ever married women, aged 20-49 years. Methods: Women were grouped in four mutually exclusive categories – i) married adult – not an adolescent mother (reference category), ii) married adult – adolescent mother, iii) married child – not an adolescent mother, and iv) married child – adolescent mother. Multivariable logistic regressions were fitted to assess the odds of hysterectomy for these groups. Non-parametric Kaplan-Meier survivor functions were estimated to evaluate survival rates across the groups. Main outcome measures: Whether had a hysterectomy and age when hysterectomy was performed. Results: Compared to women married as adult – not an adolescent mother, women married in childhood and who gave birth in adolescence were 1.87 (95% CI: 1.78–1.96) times more likely to have a hysterectomy and had the lowest survival rate for hysterectomy. Women married as children but not an adolescent mother also had higher odds of hysterectomy (AOR = 1.40, 95% CI: 1.31–1.50). These results were robust across sub-groups including geographic regions, urban/rural residence, education, and income. Conclusions: Our results, showing a strong relationship between child marriage and hysterectomy, contribute to the literature on later-life health consequences of child marriage and call for strengthening efforts to eradicate child marriage.

Objective To evaluate costs and cost-effectiveness to the healthcare system, and costs to families, of a national prenatal exome sequencing (pES) service additional to standard testing, compared to standard testing alone. Design A cost-effectiveness analysis combining costs, outcomes, parent and professional interview and professional survey data. Setting The English National Health Service (NHS) Genomic Medicine Service. Sample 413 cases referred for pES testing from 01/10/2021 to 30/06/2022. Methods We costed the incremental resource required to deliver the pES clinical pathway, synthesising this with unit costs and outcomes data on additional cases diagnosed to analyse cost-effectiveness. We estimated the annual NHS budget requirement based on case numbers. We determined parental costs from interviews. Main Outcome Measures Incremental costs of pES to the NHS and families, incremental cost per additional diagnosis, NHS budget impact. Results Of 413 referred cases, 241 were tested, at a cost of £2,331 (95% credibility interval £1,894-£2,856) per referred case, or £3,592 (£2,959-£4,250) per case that proceeded with testing. The incremental cost per diagnosis (yield 35.3%) was £11,326 (£8,582-£15,361). At current demand levels pES costs the NHS approximately £1.7m annually. Family costs could not be separated from other pregnancy related appointments but were not considered burdensome as most appointments were concurrent or remote. Conclusions pES is more expensive than predecessor prenatal genetic testing technologies, has a higher diagnostic yield and informs pregnancy management and decision making. Further research into potential savings from the foregone diagnostic odyssey resulting from pES may be informative.