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.

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: 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.

A document by Ranee Thakar. Click on the document to view its contents.

The death of a baby during pregnancy, birth or in infancy is an intensely traumatic event for the mother and her family. Many women who suffer such loss go on to conceive another baby during this psychologically fragile time when grief and trauma dominate. Although pregnancy after loss may bring hope, it can come with exceptionally high anxiety and distress. Unfortunately, pregnancy after loss, especially if progressed to beyond gestation of previous loss, is not always recognised by health professionals as an acutely vulnerable time for parents. Whilst many caregivers receive training in how to break bad news and support bereaved parents around the time of loss, few receive guidance on how to optimally care for parents during a subsequent pregnancy. There can also be reluctance on the part of health professionals to talk about the baby who died, which means that many families are left to cope with distress in their own time. However, if the psychosocial aspects of the new pregnancy are negotiated with skill and the right support, this period can restore some psychological balance in preparation for the new baby's arrival. This article, written by parents who have experienced pregnancy after loss and caregivers, offers a list of concrete suggestions for psychosocial care based on how trauma and grief impact women and partners in subsequent pregnancies. We propose a set of communication strategies that involve gently acknowledging the loss and anticipating its effects on how the new pregnancy is experienced, as well as organisational strategies that offer an additional safety net. Together, these suggestions have the potential of creating a pregnancy experience that allows for better communication with health professionals as well as the new baby.

Abstract Objectives: Women experiencing reduced fetal movements (RFM) have an increased risk of adverse pregnancy outcome (APO). Single-population studies may introduce bias and limiting generalisability. This study aimed to identify factors most strongly associated with APO, including stillbirth, fetal growth restriction (FGR), and admission to neonatal intensive care unit in women with RFM. Design and settings: Individual-level data from multiple sites in Manchester and Leicester were synthesised and analysed. Population or Sample: 1,175 women between 28 +0 and 41 +0 weeks’ gestation with singleton pregnancies. Methods: Factors associated with APO were assessed by two-stage individual participant data meta-analysis (IPD-MA). Main Results: 7.7% of RFM pregnancies ended in APO, with the most common complication being FGR (birthweight ≤3 rd centile) in 4.6%. Maternal past medical history (adjusted Odds Ratio, aOR = 2.28, 95% CI 1.08-4.83) and smoking status (aOR = 2.52, 95% CI 1.20-5.29) were most strongly associated with APO. Estimated fetal weight (EFW) percentile (aOR = 0.97, 95% CI 0.96-0.99) and maternal age (aOR = 1.05, 95% CI 1.01-1.09) were also significant risk factors, though high heterogeneity between studies in EFW percentile was observed (I 2 = 76.84%, Tau 2 = 0.0004, Q-statistic p-value = 0.0007). Conclusions: IPD-MA allowed amalgamation of patient-level data across studies, and more accurate and reliable associations were found by accounting for heterogeneity. Further work is required to investigate the model’s generalisability across diverse populations and settings. Funding: This study received no specific funding. Keywords: Individual Participant Data Meta-Analysis; Adverse pregnancy outcome; Stillbirth; Fetal Growth Restriction; Perinatal mortality; Decreased Fetal Movement

Mini commentary on ‘Pre-existing and gestational diabetes and risk of maternal venous thromboembolism: A systematic review and meta-analysis of observational studies’

Reply: Free Fetal Hemoglobin in Severe Early-Onset Fetal Growth Restriction

Abstract Objective Assessment of whether maternal anaemia in early pregnancy causes offspring congenital heart disease (CHD) Design Matched case-control study Setting January 1998 - October 2020, England Population Women with a haemoglobin measurement in the first 100 days of pregnancy and a CHD-diagnosed child Methods Data was extracted from the United Kingdom Clinical Practice Research Datalink GOLD database. Cases were 2,776 women with a CHD-diagnosed child. These were compared to 13,880 matched controls, women without a CHD-diagnosed child. Anaemia was classified as <110 g/l haemoglobin following the WHO definition. A conditional logistic regression analysis was conducted, adjusted for potential maternal demographic and health-related confounders. Main Outcome Measures Offspring CHD diagnosed within 5 years of birth Results 123 (4.4 %) cases and 388 (2.8%) controls had anaemia. After adjusting for potential confounders, the odds of giving birth to a CHD-diagnosed child was 47% higher among anaemic mothers (adjusted OR 1.47, 95% CI 1.18,1.83, p<0.001). Conclusions The observed association between maternal anaemia in early pregnancy and increased risk of offspring CHD supports our recent evidence in mice. Approximately two-thirds of anaemia cases globally are due to iron deficiency. A clinical trial of periconceptional iron supplementation might be a minimally invasive and low-cost intervention for prevention of some CHD if iron deficiency anaemia is proven to be a cause. Funding: British Heart Foundation (FS/17/55/33100, FS/SBSRF/22/31022, RE/18/3/34214); the Medical Research Council (MR/W029294/1); the National Institute for Health and Care Research (NIHR00172). Keywords: Congenital Heart Disease; Anaemia; Haemoglobin; Case-control studies; Risk Factor; Clinical Practice Research Datalink

Objective: The primary aim was to assess the feasibility of robotic OSB repair in a preclinical high-fidelity training model, documenting the learning curve and ensuring quality control among surgeons. Design: The learning curve was assessed using the cumulative summation test (LC-CUSUM). Following LC-CUSUM, six additional experiments were performed for competency-cumulative summation (C-CUSUM) analysis to ensure ongoing quality control. Setting: The simulator was created through 3D printing and hand sculpting, simulating a partially exteriorized uterus for laparotomy-assisted laparoscopic OSB surgery. It included a silicone uterus, placenta, and fetal manikin with a simulated OSB lesion, replicating the lesion sac, paraspinal muscles, and neural placode. Population: Four surgeons participated: an expert MFM consultant (TVM), a neurosurgical consultant (AK), an MFM fellow (novice 1, YK), and a neurosurgical resident (novice 2, CK). Methods: The surgical procedure included 8 steps: uterine access, working space creation, lesion exposition, junctional zone dissection, skin mobilization, dural patch application, and closure of myofascial flaps and skin. Success was defined by precise restoration (suture interval <3mm), total operative time ≤180 minutes, and a GEARS score >21/30. Main outcomes: Learning curve and competency were documented via LC-CUSUM and C-CUSUM. Results: Competence was achieved after 15–21 procedures, with novices reaching competency within this range. Participants maintained high performance in subsequent quality-controlled procedures. Conclusion: Robotic-assisted fetal OSB surgery in a high-fidelity simulation is feasible, showing promising outcomes for a large animal model and clinical translation .

Background: Postpartum haemorrhage (PPH) is the leading cause of maternal mortality. Uterotonics are the mainstay of PPH prevention. Objectives: To compare the efficacy of misoprostol and oxytocin for the prevention of PPH, and to evaluate the trustworthiness of trials comparing these uterotonics. Search strategy and selection criteria: Seven databases were searched for peer-reviewed literature, meeting the inclusion criteria of randomized controlled trials (RCTs) comparing misoprostol and oxytocin for the prevention of PPH. Data Collection and Analysis: Data were collected by two independent reviewers. Individual participant data (IPD) was meta-analyzed for outcomes PPH≥500mL and PPH≥1000mL. RCTs that did not share IPD were classified as trustworthy or not and were included in an aggregate data meta-analysis according to trustworthiness. Main results: Of 79 eligible RCTs, ten (12.7%) provided IPD, of which six were included. Analysis of IPD showed PPH≥500mL to be significantly higher in the misoprostol than the oxytocin group (2,022 women, aOR 1.84, 95% CI 1.43- 2.34). For PPH≥1000mL, analysis of IPD showed misoprostol and oxytocin were comparable (2022 women, OR 1.14, 95% CI 0.68- 1.91). Of the 69 studies that did not provide IPD, 23 (33.3%) were assessed as trustworthy. Analysis of trustworthy data (IPD and 23 aggregate data RCTs) showed no difference between misoprostol and oxytocin for PPH≥500mL (24,334 women, OR 1.01, 95% CI 0.69- 1.49), while misoprostol significantly increased the risk for PPH≥1000 (25,249 women, OR 1.36, 95% CI 1.16- 1.59). Conclusions: Of 79 RCTs comparing misoprostol and oxytocin for the prevention of PPH, 36.7% met trustworthiness criteria. Analysis of trustworthy data suggests oxytocin is superior to misoprostol for preventing PPH.

Title PageArticle Type: Letter to the Editor

Objective – To evaluate parents’ psychological distress and emotional suppression in the antenatal and postnatal periods of a pregnancy following a perinatal death. Design – Questionnaire. Setting – Tertiary Maternity Unit in the UK. Sample – Parents who were pregnant and attending a specialist antenatal clinic for pregnancy after loss. Methods – Partners and mothers completed questionnaire measures which evaluated their levels of depression, anxiety, post-traumatic stress (PTS) and emotional suppression at 23 and 32 weeks’ gestation, and 6 weeks postnatally. Levels were plotted over time and examined to determine if there were significant changes between time points. The proportion of partners and mothers scoring above threshold for each measure was identified, and differences in scores between mothers and partners were examined. Main outcome measures – Psychological distress and emotional suppression Results – Parents’ depression levels significantly decreased after the birth of a live baby and anxiety levels significantly decreased for mothers but not partners. PTS did not change across the course of a pregnancy, and symptoms continued into the postnatal period for mothers. Partners are more likely to hide their emotions during pregnancy than mothers. Conclusion – Both parents who have experienced a prior perinatal death are likely to experience high levels of psychological distress in a subsequent pregnancy which may continue into the postnatal period. Specialist mental health support offered within a dedicated pregnancy after loss service is one way to support parents. Further research is needed to determine whether psychological distress impacts on parent-child bonding.

Objective: To evaluate the predictive value of maternal neutrophil-to-lymphocyte ratio (NLR) for spontaneous delivery within 24 hours in women with preterm premature rupture of membranes (PPROM). Study Design and setting: Retrospective cohort study in a single, university-affiliated tertiary medical center. Population: Women with PPROM at <33+6 weeks’ gestation planning vaginal delivery. Exclusions included cases of labor induction or cesarean delivery. Main outcome measure: Women who delivered spontaneously within 24 hours from rupture of membrane Methods: Maternal demographic and clinical data, including age, gestational age, body mass index, parity, and mode of conception, were collected. Women who delivered spontaneously within 24 hours of membrane rupture were compared to those who did not via univariate and multivariate Cox analyses.   Results:  Among 145,833 deliveries during the study period, 1,442 women (0.9%) presented with PPROM. After exclusions, 249 women were included, with 115 (46.2%) delivering spontaneously within 24 hours. Cox regression analysis identified NLR >10 (HR = 2.86, 95% CI 1.42–5.7, p = 0.003) and multiple gestation (HR = 5.87, 95% CI 2.57–13.45, p < 0.001) as independent risk factors for spontaneous delivery within 24 hours. Conclusion: An elevated maternal NLR is a promising predictor of spontaneous delivery within 24 hours in PPROM cases. These findings support the potential of NLR as a practical clinical tool for anticipating imminent preterm delivery, aiding in management decisions for this population. Funding: None.

Objective: To analyse prescribing trends for oral and transdermal hormone replacement therapy (HRT) in Wales from 1996 to 2023, including predictors of discontinuation within one year of initiation. Design: Observational study using the Secure Anonymised Information Linkage (SAIL) databank. Setting: Primary and secondary care data from Wales, encompassing 86% of the population. Population: Annual HRT prescription rates from 1996 to 2023 were assessed for all women in Wales. Predictors of HRT discontinuation within one year were assessed in women aged 40–65 (n = 103,114), excluding those with oophorectomy, hysterectomy, or premature menopause. Methods: HRT prescription rates were normalised per 1000 people and categorised by HRT type, age groups, and deprivation quintiles. Predictors of discontinuation were assessed using zero-inflated negative binomial regression. Main Outcome Measures: Annual HRT prescription rates and predictors of discontinuation, including age, deprivation, time period, and HRT type. Results: From 1996 to 2023, 189,593 women were prescribed oral or transdermal HRT in Wales. Transdermal prescriptions rose exponentially post-2021, while oral prescriptions declined post-2002. Discontinuation rates followed a curvilinear trend: increasing at ages 40–43 and mid-50s onwards and decreasing in mid-40s to early 50s. Oral formats were linked to decreased discontinuation, while transdermals showed increased discontinuation. Deprivation reduced HRT prescriptions overall. Prescriptions post-2000 predicted increased discontinuation, with highest rates seen post-2021. Conclusions: Disparities in HRT prescribing patterns reflect GP and patient perceptions of safety. Women in mid-40s to early 50s, often at a natural menopause stage, adhered better, particularly to oral tablets, suggesting administration route and symptom relief influence adherence. Socioeconomic deprivation remains a barrier to HRT access. Time trends highlight the influence of widely publicised studies and media on uptake, albeit adherence has continually declined since 2001. Additional research is needed to tackle socioeconomic inequalities and assess strategies for achieving cost-effective and efficient HRT prescribing practices.

Pregnancy-related venous thromboembolism risk perception and prevention in risk-averse times – significant change required; a commentaryMagee LA1 , Arya R2, Boag C3, Buxton L4, Coleman MA5, Jivraj F6, Scott R7, Sheen K8, Silverio SA1,9, von Dadelszen P1

††slugcomment: To be submitted to the Astrophysical Journal Letter”Endometriosis and contemporary pain science: five ’simple rules’ for managing symptoms with different neurobiological mechanisms”Marcelo de França Moreira1, Marco Aurelio Pinho Oliveira2Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, BrazilDepartment of Gynecology, State University of Rio de Janeiro,Rio de Janeiro, RJ, Brazilmfmmindfulness@gmail.comDear Dr. Aris Papageorghiou,We appreciate the thoughtful engagement of Vercellini et al.1 with our article and their contribution to the ongoing discussion on endometriosis-related pain. Our intention was to highlight fundamental concepts from contemporary pain science that, in our view, are still underrepresented in gynecologic practice. The authors’ five “simple rules” offer a pragmatic set of clinical considerations that represent a starting point for helping gynecologists broaden their understanding of hormonal influences on pain mechanisms. We particularly value the fifth rule, which highlights the crucial role of clinician behavior and therapeutic relationships in promoting effective care.Nonetheless, we believe it is important to caution against an oversimplification of the complex processes involved in the condition and of the strategies best suited to infer them. We agree with the authors that timely pain management is crucial—preventing prolonged nociceptive stimulation may reduce the risk of central sensitization and the development of nociplastic pain, but this may not occur in many scenarios2,3. The first four rules, however, seem to primarily reinforce the lesion at the top as the primary driver of pain, central sensitization, and the development of a nociplastic profile, by suggesting that other pain processes should only be assessed after initially targeting the lesion.One of the core messages of our article is to encourage clinicians to move beyond a purely peripheral-first framework4. Pain in endometriosis likely results from a mosaic of processes that can precede, amplify, or outweigh the role of lesions in the development and severity of chronic pain; consequently, the proposed rules may contribute to mechanistic clinical reasoning regarding prior hormonal exposure, rather than offering a linear pathway to prospective insight. Nociplastic pain—a pattern not justified by a peripheral nociceptive and neuropathic components—can emerge in the presence of endometriotic foci. The clinical trap lies in allowing the lesion to capture all of the clinician’s attention, even when it may function more as an “innocent bystander” than a primary driver of pain, with central top-down processes already predominant3. Keeping classification criteria and other contributing factors in mind during assessment—whether in first episodes or chronic scenarios—can support this inference without delaying broader clinical reasoning in favor of pharmacological testing, particularly because such testing cannot substitute for direct assessment against formal criteria.Effective pain management requires recognizing and addressing broader contributors beyond endometriotic lesions early, shifting from a condition- to a person-centered approach. Achieving meaningful, lasting improvement may be better supported by integrating therapeutic strategies targeting relevant inferred processes, without necessarily relying on time-consuming or resource-intensive individual therapies. Exploring group-based interventions targeting interacting transdiagnostic processes may offer a more feasible, holistic alternative—an approach we are currently investigating5.Finally, we reaffirm the need to expand clinical reasoning: to remain attentive to the evolving pain classification frameworks, to recognize the full spectrum of pain contributors, and to cultivate the skills needed to identify them in clinical practice. This also calls for acknowledging the limits of our own disciplinary training and embracing horizontal, transdisciplinary collaboration across all members of the care team.References1. Vercellini P, Cetera GE, Salmeri N, Viganò P, Somigliana E. Endometriosis and contemporary pain science: Five “simple rules” for managing symptoms with different neurobiological mechanisms. BJOG. 2025 Apr 28 [cited 2025 Apr 29]; Available from: http://dx.doi.org/10.1111/1471-0528.182012. As-Sanie S, Till SR, Schrepf AD, Griffith KC, Tsodikov A, Missmer SA, et al. Incidence and predictors of persistent pelvic pain following hysterectomy in women with chronic pelvic pain. Am J Obstet Gynecol. 2021 Nov;225(5):568.e1–568.e11. Available from: http://dx.doi.org/10.1016/j.ajog.2021.08.0383. Kaplan CM, Kelleher E, Irani A, Schrepf A, Clauw DJ, Harte SE. Deciphering nociplastic pain: clinical features, risk factors and potential mechanisms. Nat Rev Neurol. 2024 May 16; Available from: http://dx.doi.org/10.1038/s41582-024-00966-84. Moreira M de F, Oliveira MAP. Bringing endometriosis to the road of contemporary pain science. BJOG. 2025 Feb 5; Available from: https://pubmed.ncbi.nlm.nih.gov/39905907/5. Moreira M de F, Oliveira MAP. Exploring the Immediate Effects of an Online Self-Regulation Intervention on Pain, Affect, and Arousal in Women with Endometriosis: An Observational Study Protocol. 2025. Available from: https://www.researchsquare.com/article/rs-5969427/v1

Objective To evaluate Virtual Reality (VR) as a distraction technique to diminish pain perception and improve satisfaction in patients who underwent an outpatient hysteroscopy (OH). Design A prospective, parallel group, 1:1 randomized controlled trial. Setting Spanish University Hospital. Sample A total of 120 patients between 18 and 70 years old undergoing an outpatient hysteroscopy. Method A total of 120 patients were randomly allocated to undergo an outpatient hysteroscopy either with standard treatment with vocal-local support (n=60) or with the use of a VR device (n=60) between January and June 2022. Main Outcome Measures The primary outcome was worst and average patient reported pain score (0 to 10) during the procedure. The secondary outcome was patient satisfaction (1 to 5) with the OH and with the use of VR. Results Mean duration of the procedure (4.57 vs 5.63 min p=0.11) and procedure performed did not differ among groups. There were no statistically significant differences on worst pain perception (VAS score 4.83 vs 4.84 p=0.95) or average pain perception (VAS score 2.91 vs 3.21 p=0.41) between the standard care and the VR group. There were no statistically significant differences on patient satisfaction between both groups. Conclusions The use of VR was as effective as the standard care with vocal-local support to improve pain perception and patient satisfaction in patients undergoing OH. Funding This research was supported by the own funds of the Hysteroscopy and Minimally Invasive Surgery Unit. Keywords Virtual reality, pain, outpatient hysteroscopy, distraction technique, vocal-local, patient satisfaction, randomized controlled trial. Clinical Trial Registration ClinicalTrials.gov ID NCT06463210 URL:[https://clinicaltrials.gov/study/NCT06463210?cond=hysteroscopy%20virtual%20reality&rank=9](https://clinicaltrials.gov/study/NCT06463210?cond=hysteroscopy%20virtual%20reality&rank=9)