Pelvic examinations are a routine element of gynaecological and obstetric care but may generate discomfort, pain and anxiety. Objectives To evaluate the effectiveness of interventions to improve women's experience of pelvic examinations. Search Strategy Medline, Cochrane Library, Embase, Web of Science and ScienceDirect were searched to identify randomised interventional trials published between January 1990 and December 2024. Selection Criteria Eligible studies compared an intervention group and control group of > 15-year-old women undergoing pelvic examinations and reported physical and emotional responses, such as pain, anxiety, discomfort and embarrassment. Data Collection and Analysis Two reviewers independently screened, extracted data, and assessed the risk of bias using the Cochrane Risk-of-Bias 2 (RoB2) tool. Data were analysed using pooled standardised mean differences (SMD) with 95% confidence intervals (CI) and random effects models. Heterogeneity was assessed with the I2 statistic. Sixteen RCTs (4641 women) were analysed. Fourteen studies assessed interventions targeting women's perceptions: procedural strategies (n = 10), environmental adaptations (n = 2), and cognitive approaches (n = 2). Two studies evaluated the information provided to the patient about the examination and an online preparatory training (n = 2). The meta-analysis showed a significant reduction in pain (SMD -0.87, 95% CI -1.56 to -0.18; p = 0.001; 8 studies) and in anxiety (SMD -1.13, 95% CI -1.86 to -0.38; p = 0.003; 5 studies). Risk of bias was high (n = 5), some concerns (n = 4), and low (n = 7). Heterogeneity was high (pain: I2 = 96.3%; anxiety: I2 = 94.8%). Simple interventions may reduce pain and anxiety during pelvic examinations and support trauma-informed care, but the heterogeneous evidence requires more high-quality research.
To investigate and contrast the surgical effectiveness and oncological outcomes of total laparoscopic hysterectomy (TLH) versus total abdominal hysterectomy (TAH) in individuals diagnosed with endometrial cancer. Retrospective evaluation. Holy Cross Cancer Centre in Kielce, Poland. 1532 patients who underwent operative management over the period from 2002 to 2020. Survival outcomes were assessed using Kaplan-Meier analysis, and Cox proportional hazards models were applied to evaluate associations with recurrence-free survival (RFS) and overall survival (OS). Multivariable Cox models were adjusted for tumour stage, grade, histological subtype, lymphovascular space invasion, and lymphadenectomy-related variables. No adjustment for key confounders, including body mass index (BMI), comorbidity burden, adjuvant therapy, and year of surgery, was possible, which may introduce residual confounding and confounding by indication. Given the retrospective single-centre design and the extended study period, findings should be interpreted as associations rather than causal effects, as causal inference is inherently limited in this context. Comparative efficacy of TLH versus TAH in terms of surgical outcomes (operative time, blood loss, transfusion requirements, lymph node yield, hospital stay) and oncological outcomes (recurrence-free survival (RFS) and overall survival (OS)). TLH was associated with a significantly shorter mean operative time (121.16 ± 48.79 min vs. 159.26 ± 48.46 min; p < 0.001), lower intraoperative blood loss (median 200 mL in both groups, p = 0.016 indicating differences in distribution), reduced need for blood transfusion (0.6% vs. 5.5%; p = 0.003), more extensive lymphadenectomy (median 10 nodes vs. 6 nodes; p < 0.001) and shorter hospital stay (median 4 days vs. 7 days; p < 0.001). However, five-year overall survival (OS) and recurrence-free survival (RFS) were superior in the TAH group (p = 0.001 and p = 0.010, respectively). No statistically significant survival differences were observed between the two approaches in stage I disease (p > 0.05). These findings may be influenced by unmeasured confounding, selection bias, and temporal changes in clinical practice over the study period. TLH is associated with reduced surgical trauma and faster postoperative recovery, whereas differences in oncological outcomes between TLH and TAH should be interpreted with caution. No causal inference can be drawn due to the retrospective design, single-centre setting, and limited covariate adjustment, as residual confounding cannot be excluded. Surgical approach should be individualised based on patient risk profile, tumour characteristics and comorbidities.
Women with polycystic ovary syndrome (PCOS) exhibit a substantially increased risk of miscarriage, yet the underlying mechanisms remain inadequately understood. This study aimed to investigate whether specific gut microbial dysbiosis and metabolic disturbance are associated with and may potentially contribute to endometrial dysfunction and adverse pregnancy outcomes in women with PCOS. Prospective cohort study integrated with mechanistic experiments. Women's Hospital, School of Medicine, Zhejiang University, China (2022-2024). A total of 110 women with PCOS and 110 age- and body mass index-matched controls were enrolled. We performed 16S rRNA and metagenomic sequencing of gut microbiota, with untargeted and targeted serum metabolomics. Functional validation was conducted using primary human endometrial stromal cells and a PCOS rat model intervened with Parabacteroides merdae (P. merdae) supplementation or faecal microbiota transplantation. Gut microbiota composition, serum metabolites, endometrial senescence markers, and pregnancy outcomes. Women with PCOS exhibited significantly higher miscarriage rates than controls, accompanied by a marked depletion of P. merdae abundance and elevated serum levels of branched-chain amino acids, particularly isoleucine. Exogenous isoleucine induced cellular senescence in human endometrial stromal cells in a dose-dependent manner. Restoration of P. merdae levels in the PCOS rat model resulted in decreased serum isoleucine levels, amelioration of the senescent endometrial phenotype, and reduction in the fetal resorption rate. These findings suggest that P. merdae depletion and the concurrent accumulation of isoleucine may be associated with endometrial senescence and elevated risk of miscarriage, suggesting the possible involvement of a gut microbiota-metabolite pathway in PCOS-related reproductive dysfunction. These results also provide a mechanistic basis for future translational investigations.
To assess the measurement properties of the International Consultation on Incontinence-Perinatal Pelvic Health Self-Assessment Questionnaire (ICIQ-PPHSAQ) and to identify symptom subscales for scoring. Two cohorts of perinatal women (antenatal and postnatal) at nine NHS trusts in England completed ICIQ-PPHSAQ at baseline (16-19 weeks' gestation for the antenatal cohort and 6-9 weeks postnatal for the postnatal cohort) and at up to three further timepoints, with follow-up extending to 9 months postnatal. Descriptive analyses and exploratory factor analyses (EFAs) identified symptom subscales from which subscale scores were calculated. Internal consistency was evaluated using Cronbach's alpha (α). Test-retest reliability was assessed using an interval of 1 week after baseline, using weighted Kappa (κ) for individual ordinal items and the intraclass correlation coefficient (ICC) for subscale scores. Construct validity and known-groups validity were assessed by comparison with the Patient Global Impression of Severity (PGI-S). Responsiveness was assessed by examining the mean differences between baseline and each timepoint. A total of 162 antenatal women who were 16-19 weeks gestation, and 173 women 6-9 weeks postnatal were recruited. Almost all the items performed acceptably in the test-retest analyses and completion rates were high in all the scored items (< 5% missing data). EFAs derived nine symptom subscales; seven of which had acceptable overall reliability indicators, except the vaginal symptom and vaginal changes subscales. Known-groups validity was demonstrated for all nine subscales, and six out of nine showed responsiveness to change (p < 0.05) over the study time-period. The study provides evidence supporting the validity and reliability of ICIQ-PPHSAQ, with responsiveness demonstrated across several domains. The instrument can be used to assess perinatal pelvic floor dysfunction risk factors and symptoms in English perinatal pelvic health services.
To estimate the incidence of eclampsia, characterise maternal and perinatal profiles, and document outcomes across seven countries within the International Obstetric Survey System and identify inter-country differences that may improve maternal and perinatal care. Multi-country analysis of population-based cohort data. Six high-income countries (Belgium, France, Italy, the Netherlands, Norway, Slovakia) and one upper-middle-income country (Suriname). All women admitted with eclampsia in participating countries between 2012 and 2019. Individual participant data meta-analysis. Incidence of eclampsia, maternal demographics, pregnancy characteristics, clinical management, mode of delivery and maternal and perinatal outcomes. 615 cases of eclampsia were notified resulting in a pooled incidence of eclampsia of 2.2 per 10,000 deliveries in high-income countries and 36.6 per 10,000 deliveries in Suriname. About 42% of women were diagnosed with preeclampsia before seizure onset and one-third experienced their first seizure postpartum. Hypertension was the most reported clinical sign (91.1%). Most women were treated with magnesium sulphate (91.1%) and antihypertensive medications (89.8%). Caesarean section was performed in 72.7% of cases. About 53% of births was preterm with most of them linked to antepartum cases. Maternal and neonatal deaths were rare but more frequent in Suriname. The declining incidence of eclampsia in Europe may be attributed to enhanced management, supported by ongoing audits and confidential enquiries; however, potential ascertainment bias limits causal interpretation. Global efforts remain crucial to promote awareness, timely prevention and implement standardised management guidelines for eclampsia across all settings.
Adverse maternal and perinatal outcomes such as preeclampsia, small-for-gestational age (SGA) and preterm birth remain major global health concerns. Beyond known high-risk placental features, emerging evidence suggests lateral placenta to be associated with impaired uteroplacental blood flow resulting in placenta dysfunction and adverse outcomes. A better understanding of these associations requires synthesizing both crude and adjusted effect estimates from available evidence. To comprehensively review and synthesize available evidence on the association between lateral placenta and adverse maternal and perinatal outcomes. MEDLINE (PubMed), EMBASE, Scopus and Cochrane CENTRAL were searched on 25th August, 2025. Studies that assessed the association between lateral placentation and adverse maternal and perinatal outcomes in singleton pregnancies. Data were independently extracted by two reviewers. The random-effects model was used to pool estimates of both crude and adjusted odds ratios (ORs) with corresponding 95% confidence interval (CI). Statistical heterogeneity was assessed by the I2 statistic and Cochran's Q test. Twenty one eligible studies with a total of 162 727 singleton pregnancies were included in the meta-analyses. Lateral placenta was associated with preeclampsia (OR = 1.65, 95% CI: 1.25, 2.19, I2 = 41.0%), SGA (OR = 1.40, 95% CI: 1.17, 1.68, I2 = 69.0%), preterm birth < 34 weeks (OR = 2.10, 95% CI: 1.62, 2.72, I2 = 0.0%), preterm birth < 37 weeks (OR = 1.50, 95% CI: 1.26, 1.80, I2 = 60.5%), retained placenta (OR = 2.52, 95% CI: 1.60, 3.95, I2 = 87.7%), and non-vertex foetal presentation at birth (OR = 1.50, 95% CI: 1.19, 1.89, I2 = 28.6%). Two individual studies reported independent association between lateral placenta and preeclampsia; with adjusted odds ratio (aOR) of 2.04 (95% CI: 1.28, 3.25) and 1.32 (95% CI: 1.04, 1.67). Pooled adjusted OR (95% CI) demonstrated increased odds of SGA (aOR = 1.84, 95% CI: 1.33, 2.53, I2 = 0.0%), and retained placenta (aOR = 4.43, 95% CI: 1.70, 11.53, I2 = 76.1%). Marginal increase in odds was noted for preterm birth < 34 weeks (aOR = 2.14, 95% CI: 1.34, 3.41, I2 = 0.00%) and preterm birth < 37 weeks (aOR = 1.54, 95% CI: 1.11, 2.13, I2 = 38.8%). Lateral placenta is associated with increased odds of preeclampsia, SGA, preterm birth, non-vertex foetal presentation, and retained placenta. After controlling for confounders, lateral placenta remained independently associated with increased odds of SGA, preterm birth, and retained placenta. More studies that adjust for confounders are, however, needed to further clarify and strengthen the evidence base of this independent association.
To compare Vaginal Hysterectomy (VH) with Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery (NOTES) hysterectomy (VANH) as a day-care procedure. Single-blind, multicentre randomised controlled trial. Two Dutch non-academic teaching hospitals. Women aged ≥ 18 years undergoing hysterectomy for benign indications. Women were randomised 1:2 (VH or VANH). Primary outcome was SDD. Secondary outcomes included operative time, rate of elective salpingectomies, intraoperative blood loss, complications (Clavien-Dindo), pain scores (NRS) and analgesic use, post-operative recovery (RI-10), and quality of life (EQ-5D-5L). Analyses were performed on an intention-to-treat basis. A total of 113 patients were included in the analyses (n = 42 VH, and n = 71 VANH). SDD occurred significantly more frequently in the VANH group (87.3%) than VH group (71.4%; OR 2.76, 95% CI 1.04-7.25; p = 0.04). VANH was associated with a significantly shorter operative time (median 55 min versus 65 min; p = 0.005), less blood loss (median 50 mL vs. 150 mL; p < 0.001) and more often elective opportunistic salpingectomy compared to VH (100% vs. 77.4%; p = 0.008). NRS were significantly lower in the VANH group the first hour post-operative (3 vs. 1, p < 0.001). Post-operative complications (VH 9.5% vs. VANH 15.5%; p = 0.34), readmission (VH 4.8% vs. VANH 8.5%; p = 0.47), analgesic use, recovery, and quality of life were not statistically significant. VANH is a safe and effective alternative to VH, offering a higher likelihood of SDD, shorter operative time, reduced blood loss, and more often an elective salpingectomy, without increased complications or differences in pain, recovery, or quality of life.
To quantify the discrepancy between anatomical and motor levels in foetuses with open spinal dysraphism and identify prenatal factors associated with this difference. We also examined associations between anatomical level and ultrasound findings. Retrospective observational study. Single tertiary referral centre. A total of 187 foetuses diagnosed with open spinal dysraphism between 2011 and 2022. Anatomical level was defined as the highest non-closed vertebra on ultrasound. Motor level was determined through dynamic assessment of the most caudal active muscle group. The anatomical-motor level difference was calculated, and linear regression analyses were used to evaluate associated clinical and ultrasound variables, adjusting for anatomical level. Difference between anatomical and motor levels; association of ultrasound features with anatomical level. In 85.0% of foetuses, the motor level was more caudal than the anatomical level, with a median difference of two vertebral segments (range -3 to +15). Greater discrepancies were associated with myeloschisis compared to myelomeningocele (adjusted coefficient: 0.78, p < 0.001). Bilateral talipes and kyphosis were linked to smaller discrepancies. Higher anatomical levels were significantly associated with ventriculomegaly and vertebral anomalies. In foetuses with open spinal dysraphism, the motor level assessed by prenatal ultrasound is frequently more caudal than the anatomical level, with a discrepancy in over 80% of cases. The magnitude is influenced by lesion type and anatomical height, with myeloschisis and higher lesions showing greater differences. Additionally, anatomical level correlates with several ultrasound findings, including ventriculomegaly and vertebral anomalies.
Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality, with risk factors reported across a vast literature base fragmented between social and clinical factors. To develop a comprehensive conceptual framework of the strongest risk factors and their relationships contributing to pre-eclampsia incidence. Medline, Embase, Health Technology Assessments and Database of Abstracts of Reviews of Effects, Cochrane Library were searched. Reviews, randomized controlled trials and cohort studies (> 1000 participants), reporting social and clinical factors associated with pre-eclampsia were included. The strongest factors, defined as those with at least moderate strength of association and quality of evidence using GRADE, were compiled from our previously published individual frameworks to create a combined conceptual framework. Indirect associations were searched and the strongest indirect factors were added. The conceptual framework integrated 35 social and clinical determinants of pre-eclampsia. Key modifiable factors included BMI, interlinked with chronic hypertension/elevated blood pressure in early pregnancy, type 2 diabetes mellitus, and obstructive sleep apnoea, as well as antenatal care attendance, interconnected with maternal/work stress and prenatal micronutrient supplementation. Other modifiable factors included smoking, antiphospholipid syndrome, infection, exposure to occupational hazards, distance to health facility, maternal heat exposure in early gestation, and UV-B exposure. There are strong social factors alongside clinical factors associated with pre-eclampsia incidence. Interwoven relationships between factors highlight the multifactorial aetiology of pre-eclampsia. Many determinants were potentially modifiable, which provides actionable intervention points for clinical care and public health strategies.
Royal College of Obstetricians and Gynaecologists (RCOG) Green-top Guidelines (GTGs) provide evidence-based recommendations in women's health. Even where evidence is considered high quality, it is uncertain whether factors known to influence maternity outcomes are reflected in study design. To determine distribution of recommendation grades across obstetric GTGs. For Grade A recommendations, to evaluate if supporting studies reported equity-relevant design features and methodological robustness. Review of RCOG obstetric GTGs. United Kingdom. All RCOG non-archived obstetrics GTGs published up to 20 April 2025. Frequencies of Grade A-D recommendations and Good Practice Points were recorded. For Grade A recommendations, underpinning studies were assessed for health equity and generalisability. All primary studies underpinning every Grade A recommendation were included; where a single study supported multiple recommendations, it was included every time and mapped to each relevant recommendation. The median health equity and generalisability score for each recommendation (if > 1 supporting studies) and a median score of all Grade A recommendations per guideline was calculated. Distribution of recommendation grades: health equity and methodological robustness scores for studies underpinning Grade A recommendations. Variable frequencies of Grade A, B, C, D recommendations and GPP from 37 eligible guidelines were noted. Only 28 GTGs had Grade A recommendations, with median health equity and generalisability scores of 1 of 13 and 6 of 10 respectively across those recommendations. Twenty-four percent of obstetric GTGs have no Grade A recommendations. Of those that do, consideration of health equity and generalisability in associated studies is limited. These design and reporting features should be considered in future research to improve applicability of clinical guidance to all patient groups.
Menopause, marked by hormonal decline and menstrual cessation, is associated with various symptoms. Socio-demographic and behavioural factors may influence symptom type and severity. Understanding these associations can inform better symptom management. To identify factors associated with the presence and severity of menopausal symptoms through systematic review and meta-analysis. We searched Medline, Embase, CINAHL and Cochrane for studies on demographic, behavioural, or health factors linked to vasomotor, vaginal dryness and joint symptoms in women aged 40-60. Studies reporting odds ratios or raw numbers for symptom presence or severity were included. Studies were combined for meta-analysis, reporting odds ratios and 95% confidence intervals. Quality assessment was performed to quantify the risk of bias. Of 9228 screened articles, 61 were meta-analysed. Compared with White women, Black women had higher odds of vasomotor symptom presence (OR 1.65, 1.41-1.94) and severity (OR 1.91, 1.10-3.29), and vaginal dryness presence (OR 1.27, 1.10-1.47), while Asian had lower vasomotor symptom presence and severity (OR 0.40, 0.22-0.72; OR 0.55, 0.53-0.56). Higher education (OR 1.31, 1.09-1.56), high income (OR 1.41, 1.01-1.97) and depression (OR 2.36, 1.51-3.70) were associated with increased presence of vasomotor symptoms. Smoking and obesity were associated with both presence (OR 1.63, 1.30-2.04 and 1.35, 1.02-1.78) and severity (OR 1.56, 1.07-2.27 and 1.42, 1.11-1.83) of vasomotor symptoms. Socio-demographic and behavioural factors, including ethnicity, education, income, smoking, obesity and depression, influence menopausal symptoms, highlighting the need for personalised care. PROSPERO number: CRD42023459154.
To develop antenatal prediction models for shoulder dystocia and birth trauma using routinely collected maternal and sonographic variables. Retrospective cohort study. Single tertiary referral centre in the UK. All singleton term liveborn pregnancies delivered between January 2016 and November 2024 with a third-trimester ultrasound performed at or beyond 36 weeks' gestation. Multivariable logistic regression was used to develop antenatal prediction models for shoulder dystocia and birth trauma, incorporating maternal characteristics and fetal biometry including abdominal circumference (AC; centile or mm) and estimated fetal weight (EFW; grams or centile). Model performance was assessed using tests for multicollinearity, discrimination (area under the ROC curve, AUC) and calibration. Shoulder dystocia and birth trauma, the latter defined as a composite of shoulder dystocia, postpartum haemorrhage requiring blood transfusion, caesarean delivery at full dilatation, or hypoxic-ischaemic encephalopathy (HIE ≥ 1). A total of 24 334 singleton term pregnancies were included; 432 (1.8%) were complicated by shoulder dystocia and 1210 (5.0%) by birth trauma. The model including maternal characteristics and AC centile demonstrated the best discrimination. For shoulder dystocia, the apparent AUC was 0.706 (95% CI 0.682-0.730); the optimism-corrected AUC after bootstrap validation was 0.699. For birth trauma, the apparent AUC was 0.669 (95% CI 0.654-0.685); the optimism-corrected AUC was 0.665. At a 10% false-positive rate, sensitivity was 31.5% for shoulder dystocia and 22.8% for birth trauma, compared with 20.4% and 14.0%, respectively, using EFW ≥ 90th centile. Antenatal models combining fetal AC centile with maternal risk factors outperform EFW-based thresholds currently used in clinical practice. Although discrimination was modest, the model may be useful for antenatal risk stratification and counselling, rather than as a stand-alone clinical test. Such models may help identify pregnancies at increased risk of delivery-related complications associated with fetal overgrowth and inform future studies evaluating targeted interventions.
To investigate whether angiogenic biomarkers at term in low-risk pregnancies are associated with the timing of spontaneous and induced labour, and to assess changes from term to post-term gestation. Prospective, non-interventional, observational cohort study. Single tertiary care centre, Switzerland. Low-risk term and post-term pregnancies. Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured and time intervals from sampling to delivery were analysed in spontaneous (n = 136) and induced labour (n = 48). Time to spontaneous labour onset and delivery; induction-to-delivery intervals; biomarker changes from term to post-term. In spontaneous labour, higher sFlt-1 levels and sFlt-1/PlGF ratios were inversely correlated with time to delivery (both p = 0.03). The sFlt-1/PlGF ratio remained independently associated with shorter time to delivery after adjustment for gestational age, maternal body mass index, and parity. In induced labour, higher PlGF levels were associated with longer induction-to-delivery intervals (p = 0.02). From term to post-term, PlGF declined (median 208 vs. 148 pg/mL, p < 0.0001), whereas sFlt-1 (median 3128 vs. 3631 pg/mL) and the sFlt-1/PlGF ratio (14 vs. 24) increased (both p < 0.0001). In low-risk term pregnancies, an anti-angiogenic profile is associated with shorter time to spontaneous delivery and increases from term to post-term consistent with physiological placental maturation. In induced labour, biomarkers reflect placental state but do not independently predict induction dynamics. Their potential role in late-term risk assessment warrants further investigation.
Development and validation of two prediction models for obstetric anal sphincter injury (OASI). Population-based cohort study. Nationwide (the Netherlands). Data from the Netherlands Perinatal Registry, describing nulliparous women who delivered a singleton live born infant in cephalic presentation at term from 2016 to 2020, with spontaneous (SVD) or operative vaginal delivery (OVD). Based on literature and clinical expertise, a set of potential predictors was defined and derived from the national perinatal registry. A predictive model was constructed, and accessible nomograms provided. Internal and temporal external validation was performed. OASI rate. The risk of OASI in 171 046 women with SVD was 4.1%. After logistic regression with step-wise backward selection using Akaike Information Criterion (AIC), ten predictors were retained. These were: mediolateral episiotomy (MLE), expected fetal birth weight, duration of the 2nd stage, occipitoposterior presentation, induction of labour, epidural analgesia, Asian ethnicity, maternal age, gestational age and fetal sex. The final model had a moderate discriminative ability (AUC 0.67, 95% CI 0.67-0.68) and excellent calibration (Brier score 0.039). The average risk of OASI in 37 547 women with OVD was 3.5%. Seven predictors were retained in the model: MLE, expected fetal birth weight, duration 2nd stage of labour, occipitoposterior fetal presentation, epidural analgesia, Asian ethnicity and gestational age. The final model had moderate discrimination (AUC 0.68, 95% CI 0.67-0.70) and excellent calibration (Brier score 0.032). A prediction model for OASI was developed and validated for both nulliparous women with spontaneous vaginal delivery and with operative vaginal delivery. These models can form a basis to identify women with a high risk of OASI.
To evaluate whether the IOTA ADNEX model and the Two-Step Strategy improve triage and referral of adnexal masses in routine gynaecologic care compared with the RMI and to identify an appropriate malignancy-risk threshold. Prospective multicenter cohort study. Thirteen non-tertiary hospitals and clinics and one tertiary referral hospital in Denmark. A complete-case cohort of 966 patients with adnexal masses. Malignancy risk was estimated using prospectively collected clinical data, ultrasound findings, and CA125 levels. Reference standard was histopathology or ≥ 12 months of clinical follow-up. Performance was evaluated across predefined thresholds (1%-30% for ADNEX/Two-Step Strategy (modified benign descriptors + ADNEX); ≥ 200 for RMI), stratified by centre type. Negative and positive predictive values (NPV, PPV), sensitivity, referral rates to assess correct and incorrect referrals. In non-tertiary centres, NPVs were ≥ 96% for IOTA models versus 95% for RMI; corresponding values in the tertiary centre were 82%-100% versus 78%. PPVs increased with higher thresholds and approached RMI at 20% threshold. In non-tertiary centres, where referral decisions are made, a 15% threshold provided the most favourable balance between sensitivity (~63%) and referral rate (~14%). At thresholds ≥ 25%, referral rates were similar to RMI (~8%), with only marginal gains in sensitivity (~50% vs. 39%). Most additionally detected tumours were stage I ovarian cancers or borderline tumours. For masses classified as benign by modified benign descriptors, ADNEX showed high NPVs but low PPVs and negligible net benefit, providing limited additional diagnostic value over the Two-Step Strategy. IOTA-based models improve early detection but increase referral rates. A 15% risk threshold appears to offer a clinically reasonable balance between early detection of malignancy and referral burden, based on observed trade-offs between detection and referral rates. ClinicalTrials.gov identifier: NCT04188652.
To describe pregnant individuals with blood lead levels (BLLs) ≥ 45 mcg/dL and their pregnancy outcomes to inform clinical practice and public health policy. Inclusion criteria required New York City (NYC) residence and a venous BLL ≥ 45 mcg/dL during pregnancy. BLL data were linked to case events notes, risk assessment findings, and newborn data. NYC, 2004 to 2023. Pregnant individuals with BLLs ≥ 45 mcg/dL. Characteristics of pregnant individuals and pregnancy outcomes were summarised using descriptive statistics. Birth outcomes were compared with WHO standards and across trimesters of referral. Fisher's exact and Z tests were used to assess the significance of differences. Demographic characteristics, pregnancy outcome data, chelation of mother, and chelation of newborn. There were 44 pregnant individuals identified with BLLs ≥ 45 mcg/dL during pregnancy. The majority of cases were foreign-born, with 52% from Mexico and 25% from South Asia. The miscarriage rate (9%) was more than twice the citywide rate. Potential lead sources varied by region, with 50% from Mexico and the Caribbean reporting pica, and 71% from India using traditional remedies. Cases identified earlier were more likely to have newborns with BLLs ≤ 10 mcg/dL and less likely to require chelation. Those treated with CaNa2EDTA alone had newborns with significant BLL declines. For the newborns, the prevalence of birth lengths and head circumferences below 5% was higher than expected, and if chelated, the BLL took about 27 months to decline < 5 mcg/dL. Cultural practices, pica, and using traditional remedies were frequently identified in pregnant individuals with BLLs ≥ 45 mcg/dL.
To examine the association between urinary protein excretion (UPE) level in preeclampsia and long-term risk of maternal hypertension, chronic kidney disease (CKD), and cardiovascular disease (CVD). Nationwide, population-based cohort study utilising routinely collected individual-level data from medical databases. Denmark, 1998-2018, with follow-up through 2021. All pregnancies ≥ 20 weeks among women aged ≥ 15 years. We calculated cumulative incidences (risks) of hypertension, CKD, and CVD by preeclampsia status, including UPE level (no/mild versus moderate/severe, based on established urine protein/albumin cutoffs). Adjusted risk differences and risk ratios were computed for women with preeclampsia compared with those without, adjusting for age, smoking, obesity, residential region, and year. 10-year risk, adjusted risk difference, and risk ratio of hypertension, CKD and CVD by preeclampsia status and UPE level. Among 286 078 pregnant women, 9538 (3.3%) developed preeclampsia, which was associated with higher risks of later hypertension, CKD or CVD. Among women with preeclampsia with no/mild UPE, 10-year risks were 11.9% (95% CI: 10.9-13.0) for hypertension, 1.2% (95% CI: 0.9-1.6) for CKD and 1.1% (95% CI: 0.8-1.5) for CVD. With moderate/severe UPE, 10-year risks were 16.0% (95% CI: 14.6-17.5) for hypertension, 5.1% (95% CI: 4.3-5.9) for CKD and 1.2% (95% CI: 0.8-1.7) for CVD. For hypertension and CVD, adjusted risk differences and risk ratios were similar across UPE levels, whereas CKD risk increased with higher UPE. Preeclampsia is associated with increased long-term maternal risk of hypertension, CKD, and CVD. Higher UPE levels correlate with higher risk of later hypertension and CKD.
Long-term child outcomes after intra-uterine exposure to 17-alpha-hydroxyprogesterone caproate (17-OHPC) versus placebo. Follow-up of the AMPHIA randomised controlled trial assessing neonatal outcomes after weekly 17-OHPC injections compared to placebo in multiple pregnancies. Multicentre. Children born in the AMPHIA study. Children were assessed at 11-14 years of age by record linkage and through self-reported, parental and teacher questionnaires. Mean differences or odds ratios (OR) with 95% confidence intervals (95% CI) were calculated with cluster robust standard errors for twins and adjustment for confounders using inverse probability weighting (IPW). Child mortality, educational attainment, cognition, behaviour, gender identity, general health, and a composite of abnormal development. Up to 14 years, 60/1356 children had died (n = 24 17-OHPC and n = 36 placebo (OR 0.75 95% CI 0.36-1.53)). Record linkage was completed for 1027/1296 (79%) surviving children (n = 517 17-OHPC and n = 510 placebo). No significant difference was found regarding educational attainment. Detailed developmental outcomes through questionnaires were collected for 303/1296 (23%) surviving children (n = 159 17-OHPC and n = 144 placebo). No differences in cognition, behaviour, gender identity, and general health up to 14 years of age were found between both groups. The composite of abnormal development did not differ between 17-OHPC (23.3%) and placebo (20.1%) groups (OR 1.31 95% CI 0.66-2.56). In offspring of women with a multiple pregnancy, the use of 17-OHPC in pregnancy is unlikely to provide positive or negative effects on child outcome related to mortality, educational attainment, cognition and behaviour.
To compare the efficacy, safety and tolerability of elagolix with dienogest in women with moderate-to-severe endometriosis-associated pain. A multicentre, double-blind, double-dummy, randomised, parallel-group, active-controlled, non-inferiority phase III study. Nineteen clinical centres across India. Women (18-49 years) diagnosed with endometriosis and experiencing moderate-to-severe pain. Participants were randomised (1:1) to receive oral elagolix (150 mg once daily) or dienogest (2 mg once daily) for 24 weeks. The primary outcome was change in endometriosis-related pain (Numeric Rating Scale [NRS]) from baseline to Day 85. Secondary outcomes included changes in NRS (Day 169), dysmenorrhoea, non-menstrual pelvic pain (NMPP) scores (Days 85 and 169), rescue medication use, patient global impression of change (PGIC), adverse events and bone mineral density. Of 340 patients screened, 230 were randomised (115 per group). At Day 85, both arms showed similar reductions in NRS pain scores with a treatment difference of 0.04 (95% CI: -0.3, 0.37) [p = 0.9747] demonstrating non-inferiority as upper 95% CI was below pre-specified margin of 1.5. At Day 169, both arms showed comparable improvements in overall pain, dysmenorrhoea and NMPP from baseline (p = 0.9372, p = 0.8884, and p = 0.9616, respectively). Rescue medication use and PGIC were comparable between treatment arms. Adverse event incidence was similar (elagolix: 14.8%; dienogest: 19.1%), with no serious TEAEs or discontinuations. No significant bone mineral density changes were observed. Elagolix demonstrated non-inferiority to dienogest with an acceptable safety and tolerability profile, supporting its use in managing endometriosis-associated pain. ClinicalTrials.gov identifier: CTRI/2023/01/049292.
To quantify and compare the gestational age (GA)-specific risks of stillbirth across pre-pregnancy body mass index (BMI) categories, stratified by pre-pregnancy diabetes status: DESIGN: Retrospective population-based cohort study. United States from 2022 to 2023. Singleton live and stillbirths between 20 and 43 weeks' gestation. Data were obtained from the live birth and fetal death certificates available from the National Center for Health Statistics. We used Piecewise Additive Mixed Models to assess the GA-specific relationship between pre-pregnancy BMI and stillbirth in women with and without pre-pregnancy diabetes mellitus adjusted for confounders. Results were expressed as gestational age-specific adjusted hazard ratios (aHR), and weekly risk estimates from 37 to 40 weeks' gestation. Stillbirth. A total of 6 923 146 women were included of which 187 734 (2.7%) were underweight, 2 631 390 (38.0%) had normal BMI, 1 915 636 (27.7%) were overweight, and 1 169 109 (16.9%), 591 078 (8.5%), and 428 199 (6.1%) had obesity class I, II and III, respectively. Overall, stillbirth rates increased with increasing BMI and were higher in women with pre-pregnancy diabetes (16.6 per 1 000 total births) than those without these conditions (4.4 per 1 000 total births). The gestational age-specific associations between elevated BMI and stillbirth differed depending on the presence of pre-pregnancy diabetes across all gestational weeks. For example, at 31 weeks' gestation, the aHR for women with a BMI of 40 kg/m2 vs. 20 kg/m2 and diabetes was 0.68 (95% CI = 0.54 to 0.85), while the same aHR for a non-diabetic pregnancy was 1.22 (95% CI = 1.13, 1.33). Absolute risks were highest in diabetic women with class III obesity. Among obese women, the optimal gestational age for delivery depends on the presence of other risk factors such as pre-pregnancy diabetes.