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: [email protected] 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

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.

Objective To investigate the association between Body Mass Index (BMI) and the odds of reaching the active phase of induced labour. Design Cohort study. Setting Delivery sites in the Central Denmark Region from 2013 to 2022. Population Pregnant women with a singleton foetus in cephalic presentation induced at 37 weeks of gestation or beyond. We excluded women with spontaneous pre-labour rupture of membranes, uterine scar or intrauterine foetal demise. Methods Information was retrieved from the electronic patient record. We used logistic regression analyses adjusting for potential confounders and modelled BMI as categorical and continuous variable using restricted cubic spline analysis. Exposure was defined according to the World Health Organization BMI groups. Main Outcome Measure Reaching active phase of labour. Results Of the 22,114 women in the cohort, the proportion reaching the active phase of labour was 98%, 97%, 96%, 95% and 95%, for each BMI group. Compared to normal weight, the adjusted odds ratios (aOR) and 95% confidence intervals (CI) were aOR 0.6 (95% CI 0.5, 0.8) for overweight, aOR 0.5 (95% CI 0.3, 0.7) for obesity class I, aOR 0.4 (95% CI 0.3, 0.5) for obesity class II and aOR 0.4 (95% CI 0.2, 0.7) for obesity class III. A similar pattern was found when using restricted cubic splines. Conclusion In singleton pregnant women induced at term, higher BMI was associated with lower odds of reaching the active phase of labour. Regardless of BMI, 95% to 98% of all women in the cohort reached the active phase of labour, and 80% to 90% gave birth vaginally.

Objective: To compare the carbon footprint of caesarean and vaginal birth. Design: Life cycle assessment. Setting: Tertiary maternity units and home births in the UK and the Netherlands Methods: A life cycle assessment, including: equipment use, energy, analgesia, hospital stay, waste, sterilisation and laundry, was conducted using primary data combined with data from published sources. Main Outcome Measures: ‘Carbon footprint’ (in kgCO 2e) Results: Excluding analgesia, the carbon footprint of a caesarean birth in the UK was 31.21 kgCO 2e, compared with 12.47 kgCO 2e for vaginal birth in hospital and 7.63 kgCO 2e at home. In the Netherlands the carbon footprint of a caesarean was higher (32.96 kgCO 2e), but lower for vaginal birth in hospital and home (10.74 and 6.27 kgCO 2e respectively). Emissions associated with analgesia for vaginal birth were: 0.08 kgCO 2e (opioid analgesia), 0.75 kgCO 2e (remifentanil), 1.2 kgCO 2e (epidural) and 237.33 kgCO 2e (nitrous oxide with oxygen). Differences in analgesia use resulted in a lower average carbon footprint for vaginal birth in the Netherlands than the UK (11.64 vs. 193.26 kgCO 2e). Conclusion: The carbon footprint of a caesarean is higher than for vaginal birth if analgesia is excluded, but this is very sensitive to the analgesia used; use of nitrous oxide with oxygen multiplies the carbon footprint of vaginal birth 25-fold. Alternative methods of pain relief or nitrous oxide destruction systems would lead to a substantial improvement in carbon footprint. Although clinical need and maternal choice are paramount, protocols should consider the environmental impact of different choices.

Unlike many viral infections such as influenza, and the two previous incarnations of the coronavirus, SARS and MERS, Covid-19 originally appeared to be of similar severity, after adjusting for age, BMI and other co-morbidities, in the pregnant as in the non-pregnant population. Worryingly the paper from the Italian Obstetric Surveillance System COVID-19 Working Group (p …), suggests that, in pregnancy, the virus may be getting more virulent with the advent of newer variants. Specifically the need for ventilation or ICU admission was significantly increased during the second wave (alpha variant predominant) compared to the first (wild-type predominant), albeit with no maternal deaths during the first wave and only one during the second. If real, this is both unexpected and concerning. Unexpected, because viruses tend to mutate in the direction of reduced severity; it is not in the interests of the virus that the host dies. Concerning, because it suggest that the newer variants are behaving more like other viral diseases; causing more severe disease in pregnancy.The evidence from Italy is supported by at least three other sources. In August a preprint from the UK Obstetric Surveillance Service (Vousden et al. MedRxiv 2021.07.22.21261000; doi: https://doi.org/10.1101/2021.07.22.21261000 accessed 30 September) reported disease severity in pregnancy when wild type predominated, when alpha predominated and when delta predominated. In each succeeding phase disease severity in increased. On 24 September the UK Intensive Care National Audit & Research Centre reported (ICNARC 17 September 2021 https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports accessed 30 September) that the absolute numbers of pregnant women admitted to critical care with Covid were significantly higher in the second (alpha) wave than the first (wild type), and looked set to be significantly higher again in the third (delta) wave. Finally a large series from Nair Hospital, the largest hospital caring for Covid in Mumbai (Mahajan et al. Obstet Gynecol: July 7, 2021 doi: 10.1097/AOG.0000000000004529), reported significantly higher maternal mortality during the second (alpha predominant) wave than the first (wild type).The lesson for women is simple, get vaccinated. Vaccines are safe and if the disease is really getting more severe, the balance of risks and benefits will be moving overwhelmingly in favour of vaccination. The lesson for obstetricians is more complicated. Encourage women to get vaccinated and take the disease seriously. Keep women with Covid out of hospital if possible, but monitor them with saturation monitors reliably, so those who deteriorate can be picked up quickly. When they need admission follow evidence-based treatment guidelines, and keep using personal protective equipment. We’re not yet done with Covid.Jim Thornton MD FRCOGEmeritus Professor of Obstetrics & Gynaecology, University of Nottingham.

Sir,We welcome Gurol‐Urganci I and Bidwell et al’s evaluation of the impact of the care bundle to reduce obstetric anal sphincter injury (OASI) published in your August edition last year.[1] The article reports much needed evidence on the efficacy of an intervention that has already taken hold in many maternity services across the country.Despite the article’s timely nature, we would like to voice our disappointment in the quality of the evidence of support for the care bundle Meulen and Thakar et al provide, and the recommendations made. The article fails to consider important evidence in this area of maternity care prompting this response. In particular, the authors miss the opportunity to contextualise the relatively low-level evidence they take from five articles – reporting three Scandinavian cohort studies and one educational intervention study on manual assistance during the final part of the second stage of labour (including gripping the baby’s chin through the perineum) - with the compelling findings from the Cochrane review on Perineal techniques during the second stage of labour for reducing perineal trauma. [2] This omission is important because the Cochrane review indicates that warm compresses have a bigger positive effect on OASI than the OASI care bundle reported by Meulen and Thakar et al’s. Furthermore, the Cochrane review provides evidence suggesting that hands off the perineum may protect women from episiotomy; an outcome which Meulen and Thakar et al acknowledge remained unchanged despite the third component in the care bundle aiming to ‘use of episiotomy when clinically indicated’. The selective nature of the evidence quoted, undermines the credibility of inferences that can be made from the findings. We suggest therefore, that caution should be taken when reading the authors conclusions.Our second concern rests upon the authors failure to account for the surprisingly small positive effect of the care bundle compared with the Scandinavian studies they quote. Meulen and Thakar et al report a 0.3% decrease in OASI compared with a 3.6% reduction;[3]3% reduction;[4] a 2.6% reduction for low risk women;[5] and a 2.1% reduction in the various observational studies [6] Such a small effect in an open trial could easily be caused by ascertainment bias. Again, the quality of the previous Scandinavian studies make interpretation difficult but the marked difference in results between Scandinavia and England suggests caution should be taken when reading the authors conclusions.Our final concern pertains to women’s experience of the care bundle. Not only is the acceptability of the intervention not considered in this evaluation – a significant oversight given the conspicuous lack of evidence on this – there are ethical issues within the evaluation that deserve attention. The intervention description in figure 1 claims that women were informed about what could be done to reduce OASI. This does not appear to be entirely true given the lack of consideration of warm compresses and hands off to protect against episiotomy. Even more unsettling is the statement ‘MPP should be used unless the woman objects’, implying little consideration for autonomy and informed consent.For the above reasons, we are not only disappointed with the BJOG article but with the professional stakeholder investment in the intervention which seems to have been widely and uncritically supported, with some support even being somewhat evangelical, despite the limited evidence for support.Signatures,

Objective: To evaluate whether a particular group of women with intrahepatic cholestasis of pregnancy would benefit from treatment with ursodeoxycholic acid. Design: Secondary analysis of the PITCHES trial (ISRCTN91918806). Setting: United Kingdom. Population or Sample: Women with intrahepatic cholestasis of pregnancy. Methods: Subgroup analyses were performed to determine whether baseline bile acid concentrations or baseline itch scores moderated a woman’s response to treatment with ursodeoxycholic acid. Main Outcome Measures: Bile acid concentration and itch score. Results: In women with baseline bile acid concentrations less than 40 μmol/L, treatment with UDCA resulted in increased post-randomisation bile acid concentrations (geometric mean ratio 1.19, 95% CI 1.99 to 1.41, p = 0.048). A test of interaction showed no significance (p = 0.647). A small, clinically insignificant difference was seen in itch response in women with a high baseline itch score (–6.0 mm, 95% CI –11.80 to –0.21, p = 0.042), with a test of interaction not showing significance (p = 0.640). Further subgroup analyses showed no significance. Across all women there was a weak relationship between bile acid concentrations and itch severity. Conclusions: There was no subgroup of women with intrahepatic cholestasis of pregnancy in whom a beneficial effect of treatment with ursodeoxycholic acid on bile acid concentration or itch score could be identified. This confirms that its routine use in women with this condition for improvement of bile acid concentration or itch score should be reconsidered. Funding: NIHR Efficacy and Mechanism Evaluation Programme 12/164/16. Keywords: Cholestasis, Pregnancy, Ursodeoxycholic acid, Perinatal, Stillbirth.

Background: As pregnancy is a physiological prothrombotic state, pregnant women may be at increased risk of developing coagulopathic and/or thromboembolic complications associated with COVID-19. Objectives: To investigate the occurrence of haemostatic and thrombo-embolic complications in pregnant women with COVID-19. Search Strategy: Two biomedical databases were searched between September 2019 and June 2020 for case reports and series of pregnant women with COVID-19. Additional registry cases known to the authors were included. Steps were taken to minimise duplicate patients. Selection criteria: Pregnant women with COVID-19 based either on a positive swab or high clinical suspicion e.g. symptoms and radiographic evidence. Data Collection and Analysis: Information on coagulopathy based on abnormal coagulation test results or clinical evidence of disseminated intravascular coagulation (DIC), and on arterial or venous thrombosis, were extracted using a standard form. If available, detailed laboratory results and information on maternal outcomes were analysed. Main Results: 1063 women met the inclusion criteria, of which three (0.28%) had arterial and/or venous thrombosis, seven (0.66%) had DIC, and a further three (0.28%) had coagulopathy without meeting the definition of DIC. Five hundred and thirty-seven women (56%) had been reported as having given birth and 426 (40%) as having an ongoing pregnancy. There were 17 (1.6%) maternal deaths in which DIC was reported as a factor in two. Conclusions: Our data suggests that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Detection of the former may be useful in the identification of women at risk of deterioration.

Authors’ reply re: ’Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such transmission: A systematic review and critical analysis (Response to BJOG-20-1416)Kate F Walker1, Keelin O’Donoghue2, Nicky Grace3, Jon Dorling4, Jeannette L Comeau4, Wentao Li5 Jim G Thornton11Division of Child Health, Obstetrics and Gynaecology, School of Medicine, University of Nottingham2The Irish Centre for Maternal and Child Health, University College Cork, Cork University Maternity Hospital, Cork, Ireland3 School of English, University of Nottingham4Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada5Department of Obstetrics and Gynaecology, Monash University, Clayton, AustraliaThank you for the opportunity to comment on the letter by Dr Xue from Shanghai Jiao Tong University. We agree there are many weaknesses in the data we reviewed. Dr Xue has identified one. Others are the incomplete reporting of infant feeding and mother-child interactions, and the frequent lack of infant testing to confirm or refute the possibility of vertical transmission of COVID-19. Finally, although we simply provided summary totals, it would be statistically preferable to combine series using the Mantel-Haenszel method and calculate a relative risk. We judged that doing this in light of the uncertainties around the data which Dr Xue has identified, might give a spurious precision to our results. As he says, more work is needed. For now we think it remains reasonable to not regard COVID-19 in itself, as an indication for Caesarean, artificial feeding or separation, in the mother and baby’s interest.

Two papers in this issue, on births to Covid-19 infected mothers, are important additions to this rapidly evolving literature. They are both broadly reassuring.The paper from Lombardy, the epicentre of the pandemic in Italy, is the first detailed report of pregnancies from this large region (Ferrazzi et al. BJOG 2020 xxxx). Among 42 affected women, 19 developed pneumonia, of whom seven required oxygen and four critical care. Eighteen babies were delivered by Caesarean, although in eight the indication was unrelated to Covid-19. Three babies tested positive for SARS-COV-2. Two to women who had developed Covid-19 postnatally and had breast-fed without a mask; the presumed source was the mother. One baby who delivered vaginally and did not breast-feed, developed respiratory symptoms requiring one day’s ventilation and tested positive. No mothers or babies died.The paper from China reports SARS-COV-2 viral tests in a range of body fluids from mothers and babies with COVID-19, cared for at Renmin Hospital of Wuhan University (RHWU) (Yanting Wu et al. BJOG 2020 xxxx). This hospital appears on the Global Research Identifier Database (GRID) here https://grid.ac/institutes/grid.412632.0. Readers should know that the GRID database reports that RHWU has the following English aliases “People’s Hospital of Wuhan University”, “Hubei Provincial People’s Hospital”, “First Affiliated Hospital of Wuhan University”, “Wuhan University Renmin Hospital” and “Hubei General Hospital”. This raises the possibility that some or all of the cases may have been reported previously.With this proviso, the detailed information that 1/9 stool samples, 0/13 vaginal samples, and 1/3 breast milk samples were positive is important. Of the five babies who have delivered, none tested positive for Covid-19, although two, both preterm, had pneumonia diagnosed on chest x ray. Apart from one biochemical pregnancy in the first trimester in which a serum human chorionic gonadotrophin of 25.9 IU/L reverted to negative, no mothers or babies died.Taken together with other accumulating data, it is already clear that Covid-19 is less severe in pregnancy than the two previous coronavirus infections, Severe Acute Respiratory Syndrome-related coronavirus (SARS) and Middle East Respiratory Syndrome-related coronavirus (MERS). Nevertheless, four of the mothers from Lombardy required critical care, and there have been other reports of both mother and baby deaths in association with Covid-19. It remains an important disease in pregnancy, which should be taken seriously.No disclosures. A completed disclosure of interest form is available to view online as supporting information.