Objective: Increased pelvic floor muscle tone (IPFMt) is associated with somatic symptoms, in different domains, such as sexual dysfunction, lower urinary tract symptoms, defecation problems, pelvic pain and pelvic organ prolapse. This study aims to ascertain the prevalence of symptoms indicating IPFMt in adolescent women. Design: Cross sectional study. Setting: Online spread questionnaire throughout the Netherlands. Population: Women between 18 and 25 years. Methods: This study included Dutch women aged between 18 and 25 years, who had no history of gynecological, urological, gastrointestinal conditions or pregnancy. Participants were recruited through social media and completed the questionnaire ”Amsterdam Hyperactive Pelvic Floor Scale for Women (AHPFS-W)” online. The AHPFS-W distinguishes six different domains of symptoms (max score 30). Main outcome measures: Clinical AHPFS-W cut-off score: no IPFMt (6.00-10.99), mild IPFMt (11.00-12.99), and moderate to severe IPFMt (13.00-30.00). Results: A total of 1,121 eligible women participated in this study, of whom 485 (43.3%) had no indication of IPFMt, and 299 (26.7%) respectively 337 (30.1%) had a mild indication or moderate to severe indication of IPFMt. The highest AHPFS-W score was achieved in the ”Irritable Bowel Symptoms” domain. Conclusions: Among Dutch women aged 18 to 25 years, almost one third reported moderate to severe complaints on the questionnaire, indicating IPFMt. These findings suggest a high prevalence of symptoms that might be associated with IPFMt among adolescent women, thus stressing the need for awareness and further research to IPFMt in this age group.

reprint, amsmath,amssymb, aps, ]revtex4-2 Background: Preterm birth leads to significant neonatal morbidity and mortality. Currently, there are no universal guidance for the ideal method of delivery when managing preterm births. Objective: To determine whether mode of delivery is associated with adverse outcomes in extremely (<28 weeks), very (29–32 weeks) and moderate to late (33-37 weeks) preterm birth. Search strategy and selection criteria: A systematic review and meta-analysis were conducted, including all singleton pregnancies up to 37 weeks. Studies from 2000 to 2025 were included. Data on the most common adverse neonatal outcomes were extracted. Data collection and analysis: 31 studies were included in the meta-analysis, which was conducted using random effects models. The Newcastle-Ottawa Scale was used for qualitative assessment. Results: Mode of delivery was not associated with neonatal mortality at any gestation irrespective of presentation. However, in women with a breech presentation less than 28 weeks, caesarean was associated with a reduction in mortality (OR, 0.30 [95%CI:0.25-0.37]) compared to vaginal delivery. Caesarean delivery below 28 weeks was associated with lower intracranial haemorrhage and higher bronchopulmonary dysplasia rates compared with vaginal delivery (OR, 0.76 [95%CI: 0.59-0.97]) and (OR, 1.56 [95%CI: 1.01-2.39]) respectively. There was an increase in respiratory distress syndrome above 32 weeks in caesarean compared to vaginal delivery (OR, 1.97[95%CI: 1.00-3.88]). Conclusion: There is no indication to undertake caesarean to reduce neonatal mortality in preterm deliveries other than from those with a breech presentation less than 28 weeks. This has important implications for clinical practice.

Objective: To test the association between preterm-birth and time to occurrence of a subsequent pregnancy, compared with term-birth. Design: Prospective cohort study using health and demographic surveillance system data. Setting: Matlab area, Bangladesh (1990-2020). Population or Sample: 52,502 pregnancies from 24,559 women, excluding pregnancies with multiple fetuses and women whose first pregnancy occurred after 45 years of age. Methods: Main exposure was preterm-birth. Previous miscarriages and stillbirths served as secondary exposures. Associations were assessed using recurrent survival analysis.. Impact of infant mortality was assessed by including death of the previous child under one year of age as time-dependent variable. Hazard ratio (HR) of a subsequent pregnancy was calculated with 95% confidence intervals (CIs). Main Outcome Measures: time to occurrence of a subsequent pregnancy counted as the date of the previous event until the date of the next last menstrual period. Results: Women with a previous extremely-very and moderately preterm-birth had an increased likelihood for subsequent pregnancy, compared to women with a term-birth (Adj.HR: 1.22 (95% CI 1.08-1.39; 1.13 (1.04-1.23), respectively). After adjusting for death of the previous child HRs reduced to 0.97 (0.85-1.09) and 1.03 (0.95-1.12), suggesting that the increased HRs observed was explained by infant death. Previous stillbirth and miscarriage were associated with approximately three-fold likelihood of a subsequent pregnancy. Conclusions: In Matlab, women with a previous preterm-birth were more likely to get pregnant than women with a previous term-birth. However, after adjusting for infant mortality there was no difference in pregnancy rates between previous preterm or term-birth.

Objective: To clarify the specific causes of inconsistencies between prenatal fetal genetic results and preimplantation genetic testing (PGT) outcomes via ECIT. Design: A retrospective clinical study focusing on embryo origin tracing and PGT result discrepancy analysis. Setting: Institute of the Women, Children, and Reproductive Health, Shandong University. Sample: 16 patients with successful pregnancies after PGT-selected embryo transfer (April 2021–June 2024); clinical samples with discordant fetal genetic and PGT results were analyzed. Methods: PGT results were first rechecked to confirm accurate embryo transfer. ECIT was then used for pregnancy embryo origin tracing and discrepancy clarification. Main Outcome Measures: Identification of PGT-prenatal diagnosis inconsistency causes (natural conception, embryonic mosaicism); confirmation of embryo origin in sequential transfers and optimal implantation window. Results: Among 15 discordant cases, 2 gestational embryos were not PGT-selected or cycle-matched, but genetically related to the mother, confirming natural conception. The remaining 13 cases involved consistent embryo origin between gestation and PGT transfer, verifying accurate targeted embryo transfer with discrepancies likely attributed to embryonic mosaicism. In one sequential PGT transfer case, miscarriage tissue was confirmed as the day-5 transferred embryo. Conclusions: This study introduces a novel pregnancy embryo tracing technology applicable to a variety of clinical scenarios. It can be used to analyze the causes of fetal abnormalities and pregnancy loss, define the optimal implantation window in sequential transfer, and further refine and optimize the clinical PGT quality control system. Funding: This study was supported by Key R&D Program of Shandong Province, China（2023ZLGX02）; Key R&D Program of Shandong Province, China （2023CXPT010）. Key words: Embryo Traceability | Kinship Identification | Window of Implantation | PGT Quality

Objective: To evaluate the impact of the Manchester Maternity Assessment Triaging Tool (MMATT) on the number and risk profile of women assigned to the higher-risk (orange) triage category. Design: Quality improvement study. Setting: Three maternity hospitals, UK. Population: All attendances maternity triage February-2024 to August-2025. Methods: Comparative analysis of triage attendances using Birmingham Symptom-specific Obstetric Triage system (BSOTS) and MMATT. Main Outcome Measures: Proportion, profile, patient journey and triage occupancy for each triage category. Results: Data from maternity triage attendances (n=42,019 BSOTS, n=23,066 MMATT) were included. The number of women with an orange triage category was reduced from 25% to 22% (p<0.0001) using MMATT, and the proportions presenting with reduced fetal movements were 42% vs 14%, and with suspected labour 23% vs 63% (p<0.001) for BSOTS and MMATT, respectively. Triage occupancy differed significantly between BSOTS and MMATT, with women categorised as orange making up a smaller proportion of triage occupancy using MMATT (p < 0.0001). The likelihood of achieving ongoing care within 15 minutes increased by 19% (OR 1.19[1.07-1.33]; p=0.002). For women in the lower-risk yellow/green categories, there was a significant reduction in the number of births (within four hours) in theatre following implementation of MMATT (p=0.012) and the number of women transferred for high dependency care (within six hours) appeared comparable between the two time periods. Conclusions: Implementation of MMATT positively influenced both the characteristics and care pathways of women categorised as higher risk (orange); further evaluation of this revised triage tool in other hospitals is justified.

Objective To evaluate whether preovulatory intrauterine saline flushing, compared with a sham procedure, improves live birth in patients with unexplained infertility. Design A two-centre, triple-blind, parallel-group, superiority randomised controlled trial. Setting Two Canadian fertility clinics Population A total of 192 patients aged 18–37 years with unexplained infertility for at least 12 months. Methods Participants were randomised on the day of the luteinising hormone surge to receive either preovulatory intrauterine flushing with 20 mL of physiological saline (intervention) or a sham procedure consisting of 10 mL intravaginal saline (sham). Main Outcome Measures Live births (primary outcome) and pregnancies (secondary outcome) over one cycle of treatment. Results Ninety-six participants were assigned to each group, with no loss to follow up. Groups were comparable at baseline, including a mean age of 31.8 ±3.0 and 31.5 ± 3.3 years with 51 and 54% of primary infertility in the intervention and sham groups, respectively. Three live births occurred in each arm (relative risk [RR] 1.0; 95% confidence interval [CI] 0.2–4.8). One spontaneous abortion occurred in the sham group, with no difference between groups in pregnancy rates (RR 0.8; 95% CI 0.2–3.3). Pain during the procedure was more common in the intervention group (55% vs. 13%; p<0.001), although usually mild. No pelvic infections occurred, and severe pain was reported by only 1% (1/96) of participants in the intervention group. Conclusions Despite prior data suggesting uterine flushing as an effective treatment for unexplained infertility, this trial does not support its efficacy when performed with physiological saline.

Commentary

Background: Unexpected news in Fetal Medicine (FM) includes suspected fetal anomalies, uncertain ultrasound findings, or risks that may alter pregnancy management or outcomes. How such news is communicated can have lasting emotional and decisional consequences, particularly for women with pre-existing mental health conditions (MHCs). Objective: To explore communication practices used by FM healthcare professionals (HCPs) when delivering unexpected news to pregnant women with MHCs. Design: Qualitative co-production study Setting: Three FM services in East London, UK Population: Pregnant women with pre-existing MHC attending FM consultations, their accompanying significant others, and FM HCP. Methods: Twenty-one real-life FM consultations were audio- and/or video-recorded. Recordings were analysed collaboratively by academic researchers and public contributors with lived experience using applied conversation analysis. Main outcome measures: Observable communication practices and their interactional consequences within consultations. Results: Communication practices that supported understanding and emotional containment included clear and inclusive opening practices, explanation of ongoing activities, use of accessible language, acknowledgement of emotional cues, allowing time for processing, and involvement of significant others. Practices associated with noticeable uncertainty or distress included rushed encounters, unexplained silences or questions, technical language without clarification, vague reassurance, missed emotional cues, and exclusion of companions. Conclusions: This co-produced analysis identifies communication practices that shape how unexpected news is experienced in FM consultations. The findings can inform training and service development to support clearer, more empathetic, and more inclusive communication, particularly for women with MHCs.

Objectives: This study aimed to evaluate whether IL-6, TNF-α, free fatty acids (FFAs), branched-chain amino acids (BCAAs), and acylcarnitines (C2, C4, C5, and C8) were associated with glycaemia in early and late stages of pregnancy Design: Multicentre Cross-sectional study Population: African women divided into two cohorts: early pregnancy (≤20 weeks) and late pregnancy (24-32 weeks). Methods: Potential biomarkers selected from the literature were analysed in both groups. Biomarker levels were compared between women with and without GDM in late pregnancy, and their discriminatory power was assessed by receiver-operator characteristic (ROC) curve analysis and their correlation with glycaemia levels was measured in both cohorts. Main outcome measures: Gestational diabetes mellitus (GDM) Results: A total of 477 and 170 women in late and early pregnancy, respectively, were included in the analysis. Among the 477 women, 78 (16.4%) had GDM. Women with GDM showed significantly higher levels of FFAs, and isoleucine, alongside lower levels of C2, C4, and C5 acylcarnitines, when compared to the non-GDM group (all p-values < 0.05), but ROC curves demonstrated sensitivities from 7.7% to 44.9% and specificities from 79.3% to 87.7% for GDM diagnosis. In early pregnancy, only valine correlated with blood glucose, independent of BMI and age (p=0.029). Conclusion: The selected biomarkers are not suitable for the diagnosis of GDM in a black African Population. Furthermore, they are not related to glycaemia in early pregnancy (except for valine) but are in late pregnancy, where they demonstrate altered FFA and BCAA metabolism in those with GDM.

Objective: Evidence on the stress–fecundability relationship is mixed, and both the population heterogeneity and the effects of moderate stress remain understudied. We aimed to investigate the association of stress with fecundability in women planning pregnancy, and to explore whether this association varied by gravidity, health status, or lifestyle factors. Design: Perspective cohort study. Setting: National Free Pre-conception Check-up Project (NFPCP), China Population: 512,735 reproductive-aged women who participated in the NFPCP between 2012 and 2018. Methods: Perceived psychological stress was assessed at enrollment using a two-item questionnaire rated on a 5-point Likert scale. Associations between perceived stress levels and fecundability were estimated using Cox proportional hazards regression models, adjusting for potential confounders. Main outcome measures: Participants were followed every three months for one year or until pregnancy was confirmed by gynecologic ultrasonography, whichever came first. The primary outcome was time to pregnancy. Results: Compared with the no-stress group, fecundability was 2% higher in the moderate-stress group (HR, 1.02; 95% CI, 1.01, 1.03) and 15% lower in the high-stress group (HR, 0.85; 95% CI, 0.81, 0.90). The beneficial effect was specific to moderate stress arising from life and work, whereas financial strain showed no such reproductive advantage. Subgroup analyses revealed that the positive association was more pronounced among women without tobacco exposure or with hyperglycemia (impaired glucose tolerance or diabetes), and the adverse impact of high stress was significantly exacerbated in women with obesity or a history of prior pregnancies. Conclusions: In this large-scale cohort, we identified an inverse U-shaped association where moderate stress from life or work enhanced fecundability. These findings challenge the view that all stress is harmful, offering reassurance that moderate life or work stress is compatible with conception. Nevertheless, high stress levels warrant careful attention, particularly among women with obesity or those with a history of prior pregnancies.

Objective: To evaluate the association between the mode of delivery and gastrointestinal outcomes in patients with endometriosis. Design: Retrospective Cohort Study Setting: TriNetX Research Network encompassing data from 107 healthcare organizations. Population: Patients with endometriosis who underwent either cesarean or vaginal delivery. Methods: Each cohort included 16,652 patients. Propensity score matching was applied to balance age, race, BMI, and tobacco use. Primary outcomes included postoperative adhesions, fistulas, and bowel obstruction. Analyses included risk estimation, Kaplan-Meier survival curves, and recurrence assessments. Main Outcomes Measures: Postoperative adhesions, fistulas, and bowel obstruction. Results: Cesarean delivery was associated with a significantly higher risk of adhesions (9.3% vs. 4.9%; RR 1.89; HR 2.00, 95% CI 1.84–2.18, p < 0.001) and bowel obstruction (1.5% vs. 1.3%; RR 1.21; HR 1.26, 95% CI 1.05–1.51, p = 0.04). No significant difference was observed in fistula formation (0.084% vs. 0.108%, p = 0.48). Survival analysis confirmed a higher cumulative incidence of adhesions and bowel obstruction in the cesarean group. Frequency of repeated events did not differ significantly between cohorts. Conclusion: In patients with endometriosis, cesarean delivery is associated with a higher baseline risk of adhesions and bowel obstruction, especially at first birth, compared with vaginal delivery. These findings highlight the long-term surgical implications of selecting the delivery method in this population and may inform counseling and obstetric decision-making.

Background: Left uterine displacement (LUD) during caesarean delivery (CD) is widely recommended to prevent aortocaval compression and improve maternal haemodynamic and neonatal outcomes. However, prior Cochrane review conducted a decade ago found limited evidence supporting LUD’s efficacy. Objective: To evaluate the impact of LUD on maternal haemodynamic state, vasopressor requirements, and neonatal outcomes during CD Search Strategy: MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled trials (CENTRAL) from January 1966 to August 2025. Selection Criteria: Randomized controlled trials comparing LUD + supine versus supine position during CD. No language restrictions. Data Collection and Analysis: Using PRISMA guidelines two reviewers independently screened studies, extracted data and assessed risk of bias. A random effects model was used for meta-analysis to estimate pooled odds ratios with 95 % confidence intervals. The protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023408564). Main Results: Seven studies (666 patients) met inclusion criteria. Pooled data showed no significant differences between LUD + supine versus supine groups for the primary outcome of the incidence of hypotension (OR 0.51, 95% CI: 0.24 to 1.06) or umbilical artery pH (MD (95%CI): 0.01 (-0.01 to 0.02). Maternal systolic or mean blood pressure, incidence of nausea/vomiting or vasopressor requirements did not show significant differences nor did any other neonatal outcomes, including APGAR scores. Conclusion: Left uterine displacement does not significantly impact maternal haemodynamic state, vasopressor use, or neonatal outcomes in the current obstetric anaesthesia practice. Routine LUD application during CD should be reconsidered.

Background: In 2023-24, 33% of labours were induced in England. The prostaglandin dinoprostone is commonly used, but evidence is increasing that misoprostol may be a better alternative. Objectives: Compare the efficacy and safety of vaginal dinoprostone with vaginal misoprostol for labour induction. Search Strategy: Electronic databases (Medline, Scopus, CINAHL, Cochrane Central Register) were searched in 2025. Selection Criteria: Randomised controlled trials comparing singleton, term inductions with vaginal dinoprostone or misoprostol published after 2000. Primary outcome was vaginal births within 24 hours. Secondary outcomes included birth mode, induction to birth interval, oxytocin augmentation, uterine hyperstimulation and adverse maternal or neonatal outcomes. Data Collection and Analysis: Data extraction used a standardised proforma including the Cochrane Risk of Bias. A random effects meta-analysis was performed using R. Main Results: From 8,529 records, 44 papers reported 7,040 participants induced with vaginal misoprostol and 6,604 with dinoprostone. Risk of bias was moderate. Participants given misoprostol were 48% (OR 1.48 95% CI 1.20, 1.84) more likely to achieve vaginal birth within 24 hours compared with those given dinoprostone, although heterogeneity was high. The rates of the above-mentioned secondary outcomes were comparable. In the misoprostol group, fewer patients required augmentation with oxytocin (OR 0.51 95% CI 0.40, 0.65). Conclusion: Induction of labour with vaginal misoprostol seems to improve the rate of vaginal birth within 24 hours when compared to dinoprostone without increasing the incidence of adverse events with fewer patients requiring oxytocin augmentation. We encourage consideration of vaginal misoprostol as a first-line agent for labour induction.

Objective: To evaluate the cost-effectiveness of the Fetal Medicine Foundation (FMF) strategy, compared with the National Institute for Health and Care Excellence (NICE) strategy, for first-trimester screening for preterm preeclampsia (PE) in the United Kingdom (UK). Design: Cost-effectiveness analysis. Setting: UK National Health Service and personal social services perspective. Population: A total of 10,000 simulated patients with singleton pregnancies at 11-13 weeks’ gestation, across a one-year horizon. Methods: A decision-tree model was developed to perform a cost-effectiveness analysis. In the base-case analysis, NICE-recommended screening was compared with FMF screening, using maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF). The model assumed that patients identified as high-risk for PE were prescribed 150mg aspirin daily until 36 weeks’ gestation. Scenario analyses varied PE incidence, aspirin adherence, and biomarker combinations of FMF strategy components. Main outcome measure: Incremental cost-effectiveness ratios (ICERs) were calculated using incremental costs and quality-adjusted life years (QALYs). Dominant ICERs demonstrated lower costs and higher QALYs. Results: Compared with NICE-recommended screening, the FMF strategy demonstrated a cost-saving of £5,419 and QALY gain of 0.92 per 10,000 patients (dominant ICER), with a cost-saving of £339 per preterm PE case avoided. In scenario analyses, the FMF strategy was cost-effective across 3%, 5%, and 7% PE incidence, and 75% and 100% aspirin adherence. The base-case FMF strategy (maternal factors+MAP+UtA-PI+PlGF) was the most clinically effective option. Conclusions: The FMF strategy was more cost-effective versus the NICE strategy for first-trimester preterm PE screening in the UK.

Abstract Background: Polycystic ovary syndrome (PCOS) features metabolic and hyperandrogenic abnormalities. Myo-inositol and metformin are insulin-sensitizers with unclear comparative effectiveness. Objectives: To compare the anthropometric, endocrine, metabolic, and reproductive effects of myo-inositol and metformin in women with PCOS. Search Strategy: PubMed, Google Scholar, and Cochrane Library were searched from inception through August 26, 2025, in accordance with (PRISMA 2020) guidelines. Selection Criteria: Thirty-Two randomized controlled trials and observational studies comparing myo-inositol with metformin in women with PCOS were included. Data Collection and Analysis: Anthropometric, endocrine, metabolic, reproductive outcomes, and adverse effects assessed at three and six months of treatment. Forest plots were generated using Review Manager 5.4. Sensitivity and subgroup analyses were conducted with R 4.5.2. Meta-regression was performed to explore sources of heterogeneity. Certainty of evidence was assessed using the GRADE approach. Main Results: Anthropometric outcomes included BMI at six months (SMD 0.20, 95% CI −0.09 to 0.93; p = 0.11) was comparable. Metabolic outcome fasting insulin at six months (SMD −0.16, 95% CI −0.70 to 0.38; p = 0.57) was similar. Endocrine outcomes favored myo-inositol for testosterone at three months (SMD −0.32; p = 0.04) and the LH/FSH ratio at six months (SMD −1.26; p = 0.04). Myo-inositol was associated with fewer adverse effects (RR 0.23; p < 0.00001). Conclusion: Myo-inositol and metformin demonstrate largely comparable efficacy across key outcomes in PCOS, and superior tolerability favoring myo-inositol. Funding: There is no role of funding for this project. Key Words: Polycystic ovary syndrome; myo-inositol; metformin; insulin resistance; hyperandrogenism

Background Systemic testosterone therapy is increasingly prescribed to peri- and postmenopausal women, often for symptoms beyond its established indication. While testosterone is evidence-based for hypoactive sexual desire disorder (HSDD), its role in vasomotor symptoms (VMS) and other menopausal domains remains unclear, contributing to a gap between evidence and clinical practice. Objective To evaluate the efficacy and safety of systemic testosterone therapy for vasomotor symptoms and other menopausal outcomes in peri- and postmenopausal women using randomised controlled trial (RCT) evidence. Search Strategy MEDLINE, Embase, and Cochrane CENTRAL were searched from January 1995 to November 2025, supplemented by trial registries and citation tracking. Selection Criteria Double-blind RCTs of ≥12 weeks duration evaluating systemic testosterone (oral, transdermal, injectable, or implant) in peri- or postmenopausal women, compared with placebo or active hormonal comparators, were included. Data Collection and Analysis Two reviewers independently screened studies, extracted data, and assessed risk of bias. Random-effects meta-analyses were performed where appropriate. Certainty of evidence was assessed using GRADE. This review was conducted in accordance with PRISMA 2020 and prospectively registered with PROSPERO (CRD420251170997). Main Results Forty studies (36 RCTs; 8,480 women) were included. Testosterone showed no benefit for vasomotor symptoms (pooled MD 0.01, 95% CI −0.08 to 0.10), regardless of formulation, menopausal type, or estrogen use. In contrast, testosterone significantly improved sexual function in postmenopausal women with HSDD, increasing satisfying sexual events (MD +0.85 per 28 days, 95% CI 0.52–1.18) and reducing sexual distress. Effects on mood, cognition, bone, and physical function were neutral or inconsistent at physiological doses. Non-oral formulations demonstrated a favorable cardiometabolic safety profile, with mild, reversible androgenic effects. Conclusions Systemic testosterone should not be used to treat vasomotor symptoms but is an effective, evidence-based therapy for postmenopausal HSDD. Guideline-aligned, indication-specific prescribing is essential, and off-label use for unproven menopausal symptoms should be discouraged.

Objective: To determine associations between number of prenatal care visits and smoking cessation during pregnancy and postpartum. Design: Cross-sectional analysis utilizing national data from Phase 8 of the Pregnancy Risk Assessment Monitoring System (PRAMS). Setting: Phase 8 of the PRAMS dataset (2016-2021); United States of America. Sample: Women who reported smoking in the three months prior to pregnancy (n = 9,450). Survey weights were applied to ensure the results were representative of the target population. Methods: Multivariable logistic regression assessed associations between prenatal visit frequency and smoking cessation, adjusting for maternal age, education, and socioeconomic status. Main Outcome Measures: Smoking cessation status during the last three months of pregnancy and postpartum. Smoking cessation status was evaluated in relation to demographic, behavioral, spatial, and prenatal care factors. Results: Among respondents who reported smoking prior to pregnancy, 49% continued smoking throughout pregnancy (Sustained Smoking), 20% stopped and then restarted (Restarted), 4% quit after birth (Postpartum Cessation), and 27% quit and did not restart (Sustained Cessation). Higher numeric categories of prenatal care visits were significantly associated with increased odds of smoking cessation during and after pregnancy compared to those with 0-3 prenatal care visits. The odds of cessation more than doubled for those with 9-12 visits in the “Sustained Cessation” group (AOR 2.18, CI 1.34-3.53), and with 13-16 visits in the “Postpartum Cessation” group (AOR 2.09, CI 1.40-3.10). Conclusions: Prenatal care has positive and protective effects against smoking during and after pregnancy, with the impact increasing with the number of visits. Funding: No external funding

Objectives: To investigate the relationship between the first trimester microbiome, inflammation, and small vulnerable newborns (SVN). Setting: Rural low, middle-income country: Bangladesh Population: 213 pregnant women were enrolled during the first trimester of pregnancy as part of the NICHD Global Network for Women’s and Children’s Health registry, Bangladesh. Methods: Blood and stool samples were collected at enrollment and birth outcomes within 72 hours of delivery. Using random forest machine learning models, whether the first-trimester maternal microbiome predicted SVN was evaluated. Main outcome measures: Small vulnerable newborns (born preterm, low birth weight, or small for gestational age). Results: The birth outcome SVN could be discriminated from non-SVN using a microbiome-trained random forest model (AUC = 0.653, 95% CI 0.518-0.789) supporting that the microbiome can influence gestation and fetal development. The microbiome also predicted the inflammatory markers plasma alpha-1-acid glycoprotein and fecal calprotectin (AUC = 0.742, 95% CI: 0.616-0.868 and AUC = 0.793, 95% CI: 0.680-0.905, respectively), while micronutrient concentrations, anemia, C-reactive protein, and the presence of atypical Enteropathogenic E. coli were not reliably predicted. Connecting inflammation to SVN, it was found that higher α-1-acid glycoprotein was significantly associated with SVN (logistic regression: aOR = 1.98; 95% CI: 1.04-3.85) whereas no significant association between calprotectin and SVN was observed. Conclusions: Together, these findings support that the first-trimester maternal gut microbiome contributes to SVN via induction of chronic systemic inflammation but not micronutrient absorption and demonstrates that the pathogenesis of SVN starts as early as the first trimester.