Utforsk forskningen

To describe the uptake of respiratory syncytial virus (RSV) prevention products during the first 2 seasons after availability in the US in a large health system. Using multisource immunization data from a single health system, we identified a retrospective cohort of infants born from October 2023 to April 2024 (season 1) and from September 2024 to April 2025 (season 2) and their birth parents. We described the uptake of RSV prefusion F protein (RSVpreF) vaccination and nirsevimab and evaluated factors associated with receipt using multivariable logistic regression. Among 10 196 infants, 5868/10 196 (57.6%) were exposed to an RSV-preventive product. Overall, in our maternal-infant dyads, 3850/10 196 (37.8% of total) received RSVpreF, 1837/10 196 infants (18.0% of total) received nirsevimab, and in 181/10 196 (1.8%), both were received. Uptake increased from 2100/4555 (46.1%) in season 1 to 3768/5641 (66.8%) in season 2 ( P < .001). Maternal RSVpreF vaccination increased from 1280/4555 (28.1%) to 2570/5641 (45.6%), and nirsevimab uptake increased from 749/4555 (16.4%) to 1088/5641 (19.3% both P < .001). Nirsevimab receipt at <6 days of life increased from 242/749 (32.2%) to 502/1088 (46.1%, P < .001). RSVpreF uptake was higher among older, privately insured pregnant individuals and those engaged in other preventative care and lower among those with higher area deprivation, more complex obstetric histories, or other children. Nirsevimab uptake was higher among infants with prematurity or from multifetal births and lower among those with siblings, later-season birth, or no early outpatient care. Social and structural disparities in nirsevimab uptake improved in the second season, whereas disparities in RSVpreF uptake persisted. The uptake of RSV preventive strategies increased across 2 seasons, with a higher uptake of maternal RSVpreF vaccination than nirsevimab.

Physiological changes during pregnancy can impact the pharmacokinetics of medications. Due to a variety of practical and ethical factors, clinical pharmacokinetic studies are challenging to perform during pregnancy. In addition, information on fetal toxicity of drugs requires years of study. As a result, evidence-based guidance for optimizing drug dosing in pregnancy, including therapeutic drug monitoring (TDM), is currently sparse. The most complete practice guidelines are related to antiseizure medications, with data also accumulating for antipsychotic and antidepressant medications. There are many avenues for future research and clinical practice improvement for TDM in pregnancy.

This diagnostic test accuracy meta-analysis evaluated the accuracy of the Appendicitis Inflammatory Response (AIR) score for acute appendicitis (AA) in pregnant women. Following PRISMA guidance, PubMed, Embase, Scopus, and Web of Science were searched from inception through March 2026 for studies providing data to construct 2 × 2 contingency tables. Pooled sensitivity, specificity, and area under the curve (AUC) were estimated using a bivariate random-effects Reitsma model. Methodological quality was assessed using QUADAS-2. Meta-regression explored AIR cutoff, disease prevalence, and reference-standard category as potential sources of heterogeneity. Five studies met the eligibility criteria. The pooled sensitivity was 66.7% (95% CI: 44.2-83.5%) and specificity was 75.5% (95% CI: 40.0-93.5%), with a false-positive rate of 24.5% (95% CI: 6.5-60.0%). Overall diagnostic accuracy was moderate (AUC = 0.752; normalized pAUC = 0.669). Substantial heterogeneity was observed (Zhou-Dendukuri I² = 75.6%). AIR cutoff significantly moderated specificity (P < 0.001), but not sensitivity (P = 0.911). In a within-study analysis, increasing the cutoff from ≥4 to ≥9 reduced sensitivity from 99.1% to 36.8% and increased specificity from 42.4% to 97.0%. The AIR score provides moderate accuracy for AA in pregnancy and should be used as an adjunct to clinical assessment rather than as a stand-alone diagnostic tool. Threshold selection contributes to variability in diagnostic performance. Prospective multicenter studies are needed to establish pregnancy-specific cutoffs.

Congenital Chagas disease remains an underdiagnosed cause of neonatal morbidity and mortality in endemic regions. Although most infected neonates are asymptomatic or present with nonspecific findings, severe and atypical manifestations involving the central nervous system or coexistence with genetic disorders are rarely reported. The full spectrum of neurologic injury and potential interactions between Trypanosoma cruzi infection and fetal developmental conditions remain poorly characterized. We report two unusual clinical presentations of T. cruzi infection during early infancy and pregnancy from El Salvador and Colombia. The first case involved a 2-month-old female infant who presented with septic shock, acute kidney injury, coagulopathy, and respiratory failure. Direct parasitological examination revealed circulating T. cruzi trypomastigotes, confirming acute Chagas disease; however, the route of transmission could not be definitively established. Despite a favorable parasitological response to nifurtimox, brain magnetic resonance imaging subsequently demonstrated bilateral cystic leukoencephalomalacia and widespread ischemic sequelae, which were interpreted as secondary hypoxic-ischemic injury after the severe systemic illness. The second case involved a pregnant woman with confirmed T. cruzi infection whose fetus was prenatally diagnosed with achondroplasia. The neonate developed severe respiratory failure and died 10 days after birth. No alternative infectious or metabolic causes that explained the skeletal dysplasia or fatal outcome were identified. These cases highlight unusual presentations of T. cruzi infection during early infancy and pregnancy, including severe systemic disease followed by hypoxic-ischemic neurologic sequelae and coexistence with fetal achondroplasia. They underscore the importance of maternal screening and systematic evaluation of exposed neonates.

Anemia in pregnancy is a severe public health problem in low- and middle-income countries, yet the uptake of recommended iron supplementation remains critically low. In a post-conflict and resource-constrained setting like Somaliland, there is a significant evidence gap regarding the factors that determine whether pregnant women use these essential supplements. This study aimed to identify the individual and community-level factors associated with the uptake of iron supplements during pregnancy in Somaliland. We conducted a cross-sectional analysis of data from the 2020 Somaliland Demographic and Health Survey (SLDHS), including a nationally representative weighted sample of 2577 women aged 15-49 years who had a live birth in the 5 years preceding the survey. A multilevel binary logistic regression model was used to identify determinants of iron supplement uptake while accounting for the hierarchical data structure. The uptake of iron supplements was alarmingly low, with only 37.08% of women reporting use during their most recent pregnancy. The strongest predictor was attending four or more antenatal care (ANC) visits (adjusted odds ratio [AOR] = 6.20; 95% confidence interval [CI]: 4.70-8.19). Other significant positive determinants included belonging to a rich household (AOR = 1.93; 95% CI: 1.43-2.60), having a husband in paid employment (AOR = 2.13; 95% CI: 1.71-2.66), and exposure to television. Conversely, women whose husbands had no formal education had significantly lower odds of uptake (AOR = 0.68; 95% CI: 0.51-0.91). Significant regional disparities were observed, with markedly lower uptake in the Sool and Sanaag regions. Iron supplement uptake in Somaliland is critically deficient and driven by profound inequities in healthcare access and socioeconomic status. A multipronged strategy is urgently needed, focusing on strengthening ANC services, leveraging mass media and mHealth for targeted health promotion, addressing socioeconomic barriers, and engaging male partners to improve maternal and child health outcomes.

Unintended pregnancy remains a significant public health issue with lasting consequences. Adverse childhood experiences are linked to risky behaviors and poor reproductive outcomes; however, limited research has examined optimal approaches to measuring adverse childhood experience exposure in rural populations. This study examines the relationship between adverse childhood experiences and pregnancy intendedness in North Dakota from 2017 to 2020. This cross-sectional study used North Dakota Pregnancy Risk Assessment Monitoring System data (N=2,973). A cumulative adverse childhood experience score was calculated. Exploratory factor analysis identified 2 adverse childhood experience groupings (abuse/neglect and household dynamics). Pregnancy intendedness was dichotomized as intended or unintended; a sensitivity analysis supported this categorization. Multivariable logistic regression assessed the associations between adverse childhood experiences and unintended pregnancy, controlling for sociodemographic and behavioral factors. The models compared the cumulative adverse childhood experience score, factor-based groupings, and individual adverse childhood experience items. Unintended pregnancy was more common among women with ≥4 adverse childhood experiences (51%) than among women with no adverse childhood experiences (32%). A dose-response relationship was observed, with increasing adverse childhood experience exposure associated with increased odds of unintended pregnancy. In adjusted models, younger age, being unmarried, higher parity, marijuana use before pregnancy, and higher adverse childhood experience exposure were independently associated with unintended pregnancy, whereas no significant differences were observed by residence or maternal race. The cumulative adverse childhood experience score showed greater predictive value than factor-based or item-only models. Sensitivity analyses revealed consistent adverse childhood experience gradients across subcategories of unintended pregnancy. Higher cumulative adverse childhood experience exposure is associated with a greater risk of unintended pregnancy. Findings support the use of cumulative adverse childhood experience measures in reproductive health research and highlight the importance of trauma-informed care and upstream strategies that address childhood adversity.

Rupture of an ovarian artery aneurysm is a rare but potentially life-threatening cause of retroperitoneal haemorrhage during pregnancy. Most reported cases have occurred postpartum in multiparous women. This report describes an unusual case in a 26-year-old primigravid woman with symptom onset in the second trimester. She presented with recurrent left-sided abdominal pain from 21 + 6 weeks of gestation. Following repeated normal initial assessments, CT angiography at 31 + 6 weeks revealed a ruptured left ovarian artery aneurysm with retroperitoneal haemorrhage. She underwent a successful transarterial embolization, later developed pre-eclampsia, and delivered a healthy infant by planned caesarean section at 37 + 3 weeks of gestation. The case demonstrates that pregnancy-associated ovarian artery aneurysm may rupture in nulliparous women and present as early as the second trimester with recurrent, non-specific abdominal pain. Early vascular imaging and timely intervention may improve maternal and fetal outcomes.

Maternal immune activation (MIA) during pregnancy has been implicated in offspring neurodevelopment, but evidence linking maternal gestational immune mediators with autism spectrum disorder (ASD) remains heterogeneous. This systematic review and meta-analysis evaluated whether maternal circulating cytokine and chemokine levels during pregnancy are associated with autism in offspring. Five databases were searched for human observational studies measuring maternal blood cytokines or chemokines during pregnancy and reporting autism outcomes in offspring. Eligible studies included autism versus control comparisons using maternal serum or plasma samples. Random-effects meta-analyses were conducted using odds ratios (ORs) as the primary effect measure. Standardised mean differences (SMDs) were also analysed where group-level concentration data were available. Heterogeneity was assessed using I² statistics, and small-study effects were explored using Egger's test where estimable. Seven studies met the eligibility criteria. In OR-based analyses, nominal associations with autism were observed for IL-10 (OR 1.34, 95% CI 1.06-1.69), CXCL10 (OR 1.62, 95% CI 1.24-2.11), IL-1α (OR 1.42, 95% CI 1.23-1.65), IL-5 (OR 1.49, 95% CI 1.18-1.89), and IL-17A (OR 0.81, 95% CI 0.70-0.94). CCL4 showed a borderline association. Supportive SMD analyses indicated higher IL-6 and lower IL-1β concentrations in autism-associated pregnancies. Heterogeneity varied across analytes and was substantial for IL-10 and CCL4. Maternal gestational immune profiles may differ in pregnancies later associated with autism, but current evidence does not support a single robust cytokine biomarker. Progress requires larger prospective cohorts with repeated sampling, harmonised assays, pathway-level analyses, and integrated placental-foetal neurodevelopmental phenotyping.

Frozen-thawed embryo transfer (FET) failure rates still account for a considerable percentage in assisted reproductive technology (ART) treatment, which seriously hinders the reproductive needs of infertile families. This study investigates the potential role of miR-146b level in repeated failures of FET. 175 patients with repeated implantation failure (RIF) after FET (the RIF population [RIFP]) and 155 patients with successful pregnancy after FET (SP) (the SP population [SPP]) were enrolled. The plasma miR-146b level was measured by RT-qPCR. The ROC curve was utilised to evaluate the predictive value of miR-146b for RIF after FET. The chi-square test was employed to explore the correlation between clinical items and miR-146b expression. Logistic regression analysis was used to identify the risk factors for RIF after FET. The miR-146b expression was higher in the RIFP group than in the SPP group, and miR-146b exerts a higher predictive value for RIF after FET. Endometrial thickness, serum E 2 /P, AMH, and 25-hydroxy vitamin-D 3 levels were correlated with miR-146b expression. The endometrial thickness and miR-146b expression were risk factors for RIF after FET. Collectively, these findings indicate that miR-146b may be a potential target for predicting the repeated failures of FET.

This study evaluated pregnancy outcomes after history- and ultrasound-indicated cerclage and predictors of gestational age at delivery and pregnancy prolongation. 11-year retrospective cohort study in a tertiary center in the Netherlands. Women were included with singleton pregnancies receiving history- or ultrasound-indicated cerclage for suspected cervical insufficiency and/or short cervix < 24 + 0 weeks. Analyses were stratified by cerclage indication. Ultrasound-indicated group was subdivided by obstetric history (with suspected prior cervical insufficiency [UIC-A] or without [UIC-B]). Kaplan-Meier analysis and univariable linear regression were used to assess associations between pre-/post-cerclage factors and gestational outcomes. A total of 272 women received history-indicated and 79 ultrasound-indicated cerclage (UIC-A: 36, UIC-B: 43). Median gestational age at delivery was comparable (37.9-38.4 weeks). Among women with suspected prior cervical insufficiency, spontaneous preterm birth < 34 weeks was significantly less frequent after history-indicated than ultrasound-indicated cerclage (12% vs 25%), with comparable perinatal survival. Among ultrasound-indicated cases, UIC-A showed higher rates of spontaneous preterm birth < 34 weeks (25% vs 7%) and preterm premature rupture of membranes (31% vs 9%). Greater post-cerclage distance between external os and cerclage was associated with higher gestational age at delivery and pregnancy prolongation, whereas pre-cerclage measures showed little association. Pregnancy outcomes after cerclage differ according to clinical context and cerclage indication. In women with suspected prior cervical insufficiency, ultrasound-indicated cerclage after cervical shortening identified a subgroup at higher risk of spontaneous preterm birth and pregnancy complications. Post-cerclage cervical parameters were the strongest predictors. Optimizing cerclage placement height may be associated with improved outcomes.

Asthma is a chronic respiratory disease prevalent among women of reproductive age and has important implications for fertility, pregnancy, and offspring health. This review summarizes current evidence on the bidirectional interactions between asthma and female reproductive physiology, with particular emphasis on fertility and pregnancy. Perimenstrual asthma represents a distinct phenotype associated with greater disease severity and increased healthcare utilization. Asthma impairs fertility and is associated with longer time to conception, higher rates of infertility, and greater use of fertility treatment, although appropriately controlled asthma does not appear to adversely affect fertility rates or assisted reproductive technique outcomes. During pregnancy, poor asthma control and exacerbations are the principal drivers of adverse maternal and fetal outcomes, including hypertensive disorders, preterm birth, fetal growth restriction, and neonatal morbidity. Contemporary evidence supports continuation of guideline-directed asthma therapy, including inhaled corticosteroids and selected biologics when indicated. Prenatal vitamin D supplementation has shown a reduction in early childhood asthma or recurrent wheeze in pooled analyses, while omega-3 fatty acid supplementation has demonstrated variable benefit and is being evaluated in an ongoing confirmatory trial. Asthma influences multiple aspects of female reproductive health. Optimizing disease control before conception and throughout pregnancy remains the most effective strategy for improving maternal and offspring outcomes. Although asthma has been associated with delayed conception and greater use of fertility treatment, appropriate disease control does not reduce overall fertility.

To assess whether the changing direction of serum β-subunit of human chorionic gonadotropin (β-hCG) after high-intensity focused ultrasound (HIFU) and before ultrasound-guided dilation and curettage (USg-D&C) influences procedural safety and outcome in caesarean scar pregnancy (CSP). This retrospective study was conducted at Deyang People's Hospital, Deyang, China. A total of 210 patients with cesarean scar pregnancy (CSP) were enrolled and divided into two groups based on the direction of serum β-hCG change after HIFU: the hCG declining group ( n = 75) and the hCG rising group ( n = 135). Baseline features, sonication parameters, blood loss, use of adjuvant haemostasis, re-intervention rate and time to β-hCG normalisation were compared. No significant differences were found in baseline data or HIFU parameters between groups. β-hCG on post-curettage day 1 remained higher in the rising group ( p < 0.05), yet the percentage drop from post-HIFU value was similar in two groups ( p > 0.05). Median intra-curettage blood loss (10 vs 20 mL), adjuvant haemostatic procedures (4.0% vs 6.7%) and re-intervention (6.7% vs 7.4%) also showed no differences (all p > 0.05). In this cohort, a post-HIFU rise or fall in β-hCG was not associated with differences in USg-D&C procedure, blood loss or re-intervention. These findings do not establish equivalence, but suggest that short-term β-hCG direction alone may not be a reliable predictor of procedural outcomes.

This study aimed to evaluate whether pregnancy loss during early, mid, or late gestation periods is associated with parity, uterine health, or season of breeding in a Mexican intensive, temperate semi-arid production system. In a retrospective cohort observational study (n = 772), primiparous and multiparous cows with a retained placenta and/or metritis were categorized as having uterine disease (UTD), whereas cows without these conditions were categorized as healthy (HLT). Two seasons of breeding were considered: dry (November-April) and rainy (May-October). Pregnancy loss was classified into three gestation periods: early (33 to 42 days, n = 772), mid (43 to 110 days, n = 706), and late (111 to 202 days, n = 599). Data were analyzed using multivariate logistic regression and Cox proportional hazard regression models. Overall, cows that experienced uterine disease had a higher risk of losing their pregnancy during the early (P = 0.0280), mid (P = 0.0441), and late (P = 0.0340) evaluation periods compared to healthy cows. Concurrently, multiparous cows exhibited a higher risk of pregnancy loss during the mid (P = 0.0048) period compared to primiparous cows. The Cox proportional hazard model indicated that the probability of remaining pregnant over time was consistently lower for UTD cows (P = 0.0010) and multiparous cows (P = 0.0006) compared to their healthy and primiparous counterparts, respectively. In conclusion, postpartum uterine diseases and multiparity are critical risk factors that compromise long-term pregnancy maintenance in dairy cattle managed under intensive, temperate semi-arid production systems in México.

Cardiac disease complicating pregnancy is a major contributor to maternal morbidity and mortality worldwide, particularly in low- and middle-income countries where access to specialized care remains limited. Data from Eastern Indonesia are scarce, limiting effective risk stratification and health system planning. This study aimed to establish a prospective regional registry describing the burden, clinical spectrum, and outcomes of cardiac disease in pregnancy in a tertiary referral center. A prospective descriptive registry was conducted at Regional General Hospital (RSUD) Provinsi Nusa Tenggara Barat, Indonesia, from September 2023 to August 2024. All pregnant women diagnosed with cardiac disease during pregnancy were consecutively enrolled. Maternal demographic characteristics, obstetric history, cardiac diagnoses, comorbidities, and maternal-fetal outcomes were collected and analyzed descriptively. Among 1023 pregnant women managed during the study period, 39 (3.8%) were diagnosed with cardiac disease. Most patients were multigravida, with third pregnancies being the most common (30.8%). Valvular heart disease was present in 18.0% of cases, predominantly involving the mitral valve. Cardiac arrhythmias occurred in 23.1%, including atrial fibrillation and supraventricular tachycardia. Hypertension was the most frequent cardiovascular comorbidity (30.8%). Heart failure developed in 25.6% of patients. Maternal in-hospital mortality was 10.3%, while 17.9% of pregnancies resulted in preterm birth. Cardiac disease in pregnancy in Eastern Indonesia is associated with a high burden of maternal and neonatal complications, including heart failure, preterm birth, and substantial maternal mortality. These findings highlight the urgent need for structured cardio-obstetric services, early risk stratification, and preconception counseling. Regional prospective registries play a crucial role in informing context-specific strategies to reduce preventable adverse outcomes in resource-limited settings.

Background: Post-traumatic stress disorder (PTSD) is associated with functional impairment and primarily affects women, with potential impacts on reproductive health. However, evidence regarding pregnancy and neonatal outcomes among women with PTSD prior to delivery remains limited. Objective: To examine whether PTSD is associated with adverse pregnancy and neonatal outcomes in a nationwide population-based cohort of women in Taiwan. Method: This population-based matched cohort study used Taiwan's Birth Reporting and National Health Insurance Research Database. Pregnant women with PTSD within 1 year before delivery were identified and matched 1:1 with comparison subjects using propensity scores. Primary outcomes included adverse pregnancy outcomes (cesarean delivery, stillbirth) and neonatal outcomes (low birth weight, preterm birth, small for gestational age, abnormal 5-minute Apgar score, and congenital defects). Logistic regression was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: The matched cohorts included 4,353 women with PTSD and 4,353 without PTSD. Relevant findings show that PTSD was associated with increased risks of cesarean delivery (aOR 1.18; 95% CI 1.08-1.28), low birth weight (aOR 1.19; 95% CI 1.04-1.37), and preterm birth (aOR 1.21; 95% CI 1.06-1.38). These associations were more obvious among women aged ≤ 35 years and those with gestational diabetes or anemia. Nevertheless, no significant associations were observed for stillbirth, small for gestational age, abnormal Apgar scores, or congenital anomalies. Conclusions: Pre-delivery PTSD slightly increased risks of cesarean delivery, low birth weight, and preterm birth. However, the lack of association with severe neonatal outcomes, such as congenital anomalies and stillbirth, provides essential reassurance. These findings underscore the importance of integrating mental health monitoring into routine prenatal care to optimise maternal and infant well-being without causing undue alarm. Pre-delivery PTSD was associated with cesarean delivery, LBW, and preterm birth.Findings were more pronounced in mothers aged ≤ 35 years.No associations with stillbirth, SGA, low Apgar, or congenital defects. Antecedentes: El trastorno de estrés postraumático (TEPT) está asociado con el deterioro funcional y afecta principalmente a las mujeres, con posibles impactos en la salud reproductiva. Sin embargo, la evidencia sobre el embarazo y las consecuencias neonatales en mujeres con TEPT antes del parto sigue siendo limitada. Objetivo: Examinar si el TEPT está asociado con consecuencias adversas en el embarazo y periodo neonatal en una cohorte poblacional nacional de mujeres en Taiwán. Método: Este estudio poblacional realizó un diseño transversal utilizando las bases de datos de Informes de Nacimientos y Seguro Nacional de Salud de Taiwán. Mujeres embarazadas con TEPT dentro del año antes del parto fueron identificadas y emparejadas 1:1 con sujetos de comparación utilizando puntuaciones de propensión. Los resultados primarios incluyeron consecuencias adversas del embarazo (cesárea, muerte al nacer) y consecuencias neonatales (bajo peso al nacer, parto prematuro, pequeño para la edad gestacional, puntuación Apgar anormal a los 5 minutos y defectos congénitos). Se utilizó regresión logística para calcular las razones de probabilidades ajustadas (aOR en su sigla en inglés) e intervalos de confianza (IC) del 95%. Resultados: Las cohortes emparejadas incluyeron a 4.353 mujeres con TEPT y 4.353 sin TEPT. Los hallazgos relevantes muestran que el TEPT se asoció con un aumento del riesgo de parto por cesárea (aOR 1,18; IC 95% 1,08–1,28), bajo peso al nacer (aOR 1,19; IC 95% 1,04–1,37) y parto prematuro (aOR 1,21; IC 95% 1,06–1,38). Estas asociaciones eran más evidentes entre mujeres de ≤35 años y aquellas con diabetes gestacional o anemia. No obstante, no se observaron asociaciones significativas con la muerte fetal, pequeño la edad gestacional, puntuaciones Apgar anormales o anomalías congénitas. Conclusiones: El TEPT previo al parto aumentó ligeramente el riesgo de cesárea, bajo peso al nacer y parto prematuro. Sin embargo, la falta de asociación con consecuencias neonatales graves, como anomalías congénitas y muerte fetal, proporciona una tranquilidad esencial. Estos hallazgos subrayan la importancia de integrar la monitorización de la salud mental en la atención prenatal rutinaria para optimizar el bienestar materno e infantil sin causar alarmas innecesarias.

The modified World Health Organization (mWHO) risk classification provides a practical framework to stratify maternal cardiovascular risk in pregnancy. For general obstetric providers, particularly those practicing outside tertiary centers, this tool can guide management decisions across different health care settings, both urban and rural. The result is the opportunity for early identification of patients who will benefit from multidisciplinary input and require transfer of care. It also provides reassurance when routine obstetric care is appropriate. A structured yet flexible approach that combines mWHO classification, clinical judgment, and multidisciplinary collaboration is recommended to optimizing outcomes in this population.

The pregnant population undergoes significant changes during pregnancy that ultimately leads to gait alterations, pain, and increased risk of falls. The goal of this literature review was to identify gait changes in pregnancy with specific interest in the lower extremities. We included 39 research articles in this review in which we analyzed their methods as well as results, finding reports of significant changes to spatiotemporal parameters, kinematics, kinetic, foot biomechanics, and dynamic balance and stability during pregnancy.

Maternal passive smoking (PS) during pregnancy remains a common environmental exposure associated with adverse perinatal outcomes. However, its effects on fetal lipid mediator profiles have not been fully characterized. To investigate whether maternal PS during pregnancy is associated with alterations in umbilical cord blood lipid mediator profiles in term neonates. We retrospectively analyzed umbilical cord blood samples from 56 term neonates, comprising 17 born to mothers with documented PS exposure and 39 born to mothers without PS exposure. Targeted lipid mediator profiling was performed using liquid chromatography-tandem mass spectrometry. Orthogonal partial least squares discriminant analysis, univariate analyses with Benjamini-Hochberg false discovery rate correction, receiver operating characteristic curve analysis, and exploratory multivariable linear regression were performed. Four lipid mediators showed nominal differences between the groups, with higher levels of 14,15-LTE₄, platelet-activating factor, and 13-HpODE and lower levels of oleoylethanolamide (OEA) in the PS-exposed group. However, none remained statistically significant after correction for multiple comparisons. OEA was subsequently evaluated in post-hoc exploratory multivariable analysis and remained associated with maternal PS exposure after adjustment for maternal pre-pregnancy BMI and diabetes mellitus. This exploratory study identified several candidate cord blood lipid mediator signals related to maternal PS exposure, although none remained statistically significant after correction for multiple comparisons. These findings are hypothesis-generating but suggest that lipid mediator pathways involved in inflammatory and metabolic signaling may warrant further investigation in relation to prenatal tobacco smoke exposure.

Childhood pneumonia remains a leading cause of morbidity and mortality worldwide. Prenatal Zika virus (ZIKV) infection has been associated with severe outcomes such as Congenital Zika Syndrome (CZS), linked to excess hospitalisations. However, the long-term respiratory consequences of prenatal ZIKV exposure across the full clinical spectrum, including children without CZS, remain poorly understood. We aimed to examine the association between prenatal ZIKV exposure and community-acquired pneumonia-related hospitalisation or death during childhood. We conducted a population-based cohort study of live-born singletons in Brazil (January 2015-November 2018). We applied three complementary approaches under a triangulation framework, to strengthen confidence in the observed associations: IPTW-weighted Cox regression, a within-sibling stratified Cox model, and a negative control outcome analysis. Separate analyses compared ZIKV-exposed children with and without CZS to unexposed children. We included 4,108,409 unexposed children, 3900 ZIKV-exposed without CZS, and 1786 with CZS. Female sex accounted for 48.8%, 46.7%, and 53.1% across the three groups; the majority in each were of Brown/ Pardo maternal race/ethnicity (64.6%, 67.8%, and 72.4%). By 42 months, cumulative incidence of pneumonia-related hospitalisation or death was 15.6% (95% CI 13.7-17.5) among children with CZS, versus 3.9% (95% CI 3.2-4.7) among ZIKV-exposed children without CZS and 4.6% (95% CI 4.6-4.7) among unexposed children. In IPTW-weighted models, CZS was associated with a fourfold increased risk (aHR 4.12, 95% CI 3.64-4.66), consistent with the sibling comparison (aHR 4.15, 95% CI 1.62-10.64). Prenatal ZIKV exposure without CZS was not associated with the outcome across any approach. Negative control analyses suggested limited residual confounding. Children exposed to ZIKV in utero without CZS had a risk of pneumonia-related morbidity and mortality comparable to unexposed children, a reassuring finding for most exposed children. An increased risk was associated with prenatal ZIKV exposure only among children with CZS. These findings underscore the need for long-term follow-up and targeted respiratory prevention strategies for children with CZS. Wellcome Trust, Royal Society, and CNPq. A pneumonia adquirida na comunidade permanece como uma das principais causas de morbidade e mortalidade em crianças no mundo. A infecção pré-natal pelo vírus Zika (ZIKV) tem sido associada a desfechos graves, como a Síndrome Congênita do Zika (SCZ), que está associado ao aumento hospitalizações entre crianças com esta síndrome. Contudo, as consequências respiratórias tardias decorrentes da exposição pré-natal ao ZIKV, incluindo em crianças nascidas sem SCZ, permanecem pouco compreendidas. Foi realizado um estudo de coorte de base populacional com nascidos vivos de gestações únicas no Brasil (janeiro de 2015 a novembro de 2018) para estimar o efeito total da exposição pré-natal ao ZIKV sobre a hospitalização e/ou óbito por pneumonia adquirida na comunidade durante a infância. Três abordagens complementares foram utilizadas na perspectiva da triangulação de evidências para fortalecer a inferência causal: regressão de Cox ponderada por IPTW, modelo de Cox estratificado com comparação entre irmãos e análise de desfecho de controle negativo. Análises separadas compararam crianças expostas ao ZIKV, com e sem SCZ, a crianças não expostas. Um total de 4.108.409 crianças não expostas, 3.900 crianças expostas ao ZIKV sem SCZ e 1.786 com SCZ foram analisadas. Aos 42 meses, a incidência acumulada de hospitalização e/ou óbito por pneumonia foi de 15·6% (IC 95% 13·7–17·5) entre as crianças com SCZ, enquanto entre as crianças expostas ao ZIKV sem SCZ e as não expostas, os riscos acumulados foram 3·9% (IC 95% 3·2–4·7) e 4·6% (IC 95% 4·6–4·7), respectivamente. Nos modelos ponderados por IPTW, a SCZ associou-se a um risco quatro vezes maior (aHR 4·12, IC 95% 3·64–4·66), consistente com a comparação entre irmãos (aHR 4·15, IC 95% 1·62–10·64). A exposição pré-natal ao ZIKV sem SCZ não se associou a aumento de risco em nenhuma das abordagens analíticas. As análises de controle negativo sugeriram confundimento residual limitado. Neste estudo, a exposição pré-natal ao ZIKV aumentou a morbidade e a mortalidade por pneumonia apenas entre as crianças com SCZ; as crianças expostas sem SCZ apresentaram riscos comparáveis aos das não expostas. Esses achados reforçam a necessidade de seguimento de longo prazo e de estratégias direcionadas de prevenção respiratória para crianças com SCZ. Wellcome Trust, Royal Society, CNPq.

Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by ectopic endometrial-like glands and stroma, persistent pelvic inflammation, pain, infertility, and frequent recurrence. The limited availability of nonhormonal and lesion-directed therapies supports the investigation of alternative pharmacological mechanisms and regional drug-delivery strategies. Arimoclomol is a co-inducer of the endogenous heat-shock response with the capacity to amplify stress-dependent proteostasis, whereas Pluronic F127 is an amphiphilic PEO-PPO-PEO copolymer that forms drug-associated micellar assemblies in aqueous media. This exploratory study evaluated the physicochemical properties, in vitro release profile, and early biological response to arimoclomol-loaded Pluronic F127 nanomicelles in an autologous-transplantation rat model of endometriosis. The formulation was prepared by dispersing 30 mg of arimoclomol in 2 mL of Pluronic F127 at 20% (w/v), followed by stirring and ultrasonication under cooling. Because no centrifugation, filtration, dialysis, lyophilization, or other drug-removal step was applied after incorporation, the nominal process loading efficiency was 100%, based on formulation mass balance. The corresponding theoretical drug content was 6.98% w/w of total formulation solids and 7.5% w/w relative to the polymer mass. Drug-polymer association was supported by scanning electron microscopy coupled to energy-dispersive X-ray spectroscopy, Raman spectroscopy, and UV-Vis spectroscopy. In vitro dialysis at 37 °C showed a rapid increase in acceptor-medium arimoclomol concentration, reaching 14.33 ± 0.18 µg/mL at 2 h, followed by a progressive decline, with arimoclomol remaining detectable at 72 h (2.76 ± 0.04 µg/mL). Endometriosis was induced in ten female Wistar rats. On day 16, animals received a single intraperitoneal administration of arimoclomol-loaded nanomicelles (n = 4), empty nanomicelles (n = 3), or free arimoclomol (n = 3). The arimoclomol dose was 3 mg/animal, equivalent to approximately 14.7-16.8 mg/kg according to the recorded body-weight range. Twenty-four hours after treatment, representative lesions from the loaded-nanomicelle group appeared smaller macroscopically and showed mildly atrophic glands, stromal disorganization, and less prominent inflammatory infiltration than representative lesions from the empty-carrier and free-drug groups. All clinical welfare scores remained zero, and no overt short-term intolerance was observed. These findings demonstrate nominal quantitative drug retention based on process mass balance, a biphasic in vitro release pattern, and an early treatment-associated morphological and histological response. These preliminary findings require confirmation in larger, blinded, power-calculated studies with quantitative lesion endpoints, mechanistic biomarkers, lesion-specific pharmacokinetics, and longitudinal safety assessment.

Endometriosis is a chronic, estrogen-dependent inflammatory disorder characterized by ectopic endometrial-like lesions, fibrosis, and persistent pelvic pain. Although ectopic lesions are important contributors to pain, symptom severity often correlates poorly with lesion burden, suggesting lesion-independent mechanisms. Here, we investigated the contribution of ectopic lesion-derived cells to persistent pelvic adhesions, fibrotic remodeling, and endometriosis-associated behavioral alterations using a mouse model. A syngeneic model combined with inducible diphtheria toxin receptor (iDTR)-mediated cell ablation was used to selectively eliminate donor-derived progesterone receptor-expressing ectopic cells. Endometriosis was induced by transplantation of uterine tissue from Pgr cre/+ Rosa26 iDTR/mTmG donor mice into recipients, followed by diphtheria toxin-mediated lesion ablation. Lesion burden, pelvic adhesions, and fibrotic remodeling were assessed by imaging, histology, and molecular analyses, while behavioral outcomes were evaluated using non-evoked assays. Selective ablation eliminated detectable GFP-positive ectopic lesions. Histological and molecular analyses demonstrated significantly reduced collagen deposition and α-SMA-positive fibrotic remodeling within adhesion-associated tissues relative to established ectopic lesions, although these measures remained elevated above sham controls. However, despite lesion ablation, no statistically significant differences were detected between DT- and vehicle-treated mice in nesting or marble-burying performance, although the modest cohort size may have limited detection of partial behavioral effects. These findings indicate that, although fibrosis in adhesion-associated tissues was reduced relative to established ectopic lesions, residual fibrotic remodeling persisted above sham levels, whereas behavioral outcomes showed variable responses without a significant, uniform reversal, highlighting the potential importance of targeting fibrotic and adhesive remodeling in addition to ectopic lesions.

Endometriosis is a chronic, estrogen-dependent inflammatory disease that, despite its benign histology, displays several cancer-relevant features, including clonal expansion, somatic alteration-associated lesion evolution, tissue invasion, apoptosis resistance, immune evasion, angiogenesis, fibrosis, and metabolic adaptation. These features are particularly important in ovarian endometriosis, where recurrent hemorrhage, iron-driven oxidative stress, and chronic inflammatory remodeling may promote malignant transformation. This review examines endometriosis through an oncologic framework by integrating current evidence on disease initiation, clonal lesion evolution, and the peritoneal, ovarian, and deep-infiltrating microenvironments. We discuss how epithelial, stromal, immune, endothelial, mesothelial, and neural components cooperate to support lesion survival, dissemination, vascularization, fibrosis, neuroinflammation, and treatment resistance. Particular attention is given to cancer-associated molecular programs, including PI3K-AKT-mTOR, RAS-MAPK, WNT/β-catenin, hypoxia, oxidative-stress, inflammatory, and epigenetic signaling, and their relationship to endometriosis-associated ovarian cancer. We also critically evaluate animal models, organoids, three-dimensional scaffolds, and microfluidic systems for their ability to reproduce lesion heterogeneity, microenvironmental interactions, therapeutic responses, and malignant progression. Finally, we assess current and emerging therapeutic strategies, emphasizing non-hormonal interventions directed against inflammatory, immune, fibrotic, angiogenic, metabolic, and oncogenic vulnerabilities, together with biomarker-guided and fertility-sparing approaches. Viewing endometriosis as a cancer-relevant inflammatory and clonal disease may reveal actionable mechanisms for precision treatment and interception of endometriosis-associated malignancy.

Endometriosis exhibits tissue- and cell-compartment heterogeneity in inflammatory and metabolic activity. We evaluated compartment-specific remodeling in primary endometriosis tissues and used TCGA-UCEC as an independent cancer comparison. We reanalyzed GSE179640 single-cell RNA-sequencing data (14 donors, 24 libraries; 21,600 cells) and bulk RNA-sequencing data (24 biopsies). Analyses included Harmony integration, library-level program scoring, DESeq2, matched TCGA-UCEC tumor-normal comparisons, survival analysis, and CD45/CD24 flow cytometry. Inflammatory and metabolic programs varied by tissue and cellular compartment. In myeloid summaries, inflammation correlated with glycolysis (rho = 0.52, P = 0.009), whereas the bulk-wide association was weak (rho = 0.21, P = 0.320); the myeloid M2-like/iron-redox association was not significant (rho = 0.40, P = 0.054). Bulk analysis identified 31, 4480, and 4632 significant genes in eutopic endometrium, ectopic peritoneal lesions, and ectopic ovarian lesions versus controls, respectively. In TCGA-UCEC, paired tumor-normal glycolysis and oxidative-phosphorylation effects were significant, but the survival composite was null (HR = 1.00, 95% CI 0.82-1.22; P = 0.968), and five-program effects were not correlated across endometriosis and TCGA contrasts (rho = -0.30, P = 0.624). Flow cytometry detected 4.73% CD24-positive cells in endometriotic tissue versus 1.92% in control endometrium (P < 0.01). Endometriosis shows compartment- and tissue-specific inflammatory and metabolic remodeling. The myeloid inflammation-glycolysis relationship was not reproduced in bulk biopsies. TCGA-UCEC provides an independent cancer comparison but does not support an endometriosis-to-cancer progression mechanism.

Does pyruvate carboxylase drive the progression of endometriosis, and, if so, what is the underlying mechanism? The expression of pyruvate carboxylase in clinical endometrial specimens was examined via immunohistochemistry. After knockdown or overexpression of pyruvate carboxylase in immortalized human endometriotic stromal cells (ihESC), cell proliferation and migration were assessed using 5-ethynyl-2'-deoxyuridine (EdU), colony formation and Transwell assays. Quasi-targeted metabolomics, RNA sequencing and western blotting were adopted to explore downstream molecular changes, and an allogeneic mouse endometriotic model was applied for in-vivo functional verification. Expression of pyruvate carboxylase was up-regulated significantly in eutopic and ectopic endometrial tissues of patients with endometriosis compared with controls (P = 0.022 and P < 0.001, respectively). In-vitro and in-vivo experiments showed that pyruvate carboxylase promoted the progression of endometriosis. In addition, quasi-targeted metabolomics showed that knockdown of pyruvate carboxylase decreased the abundance of glycolytic metabolites in ihESC. Furthermore, RNA sequencing and western blotting identified that pyruvate carboxylase enhanced activity of the phosphoinositide-3-kinase-AKT pathway. Using AKT agonist (SC79) and inhibitor (AZD5363), pyruvate carboxylase was shown to modulate the expression of glycolytic enzymes and the progression of endometriosis through the AKT pathway. Finally, pyruvate carboxylase inhibitors ZY-444 and octyl gallate attenuated the progression of endometriosis. Pyruvate carboxylase is up-regulated significantly in eutopic and ectopic endometrial tissues from patients with endometriosis, and modulates the expression of glycolytic enzymes as well as the progression of endometriosis via activation of the AKT pathway. These findings provide mechanistic insight into the metabolic reprogramming underlying the pathogenesis of endometriosis.

Endometriosis is a chronic condition in reproductive-age women, and diagnosis can be delayed for 4-11 years due to nonspecific symptoms and limited imaging. This underscores the need for new methods to overcome these diagnostic challenges. Fibroblast activation protein, strongly expressed in the perilesional stroma of endometriotic lesions, is a promising PET target. We included 8 women who underwent 68 Ga-FAPI-04 PET/CT for cyclic pelvic or extrapelvic pain and solid nodular lesions, later histopathologically confirmed as endometriosis. In these patients, we showed the targeting diagnostic potential of FAPI PET/CT and endometriotic foci with high accuracy compared with other imaging methods.