Language：English   Publisher：Scientific Reports  

The growing recognition of the importance of interpregnancy care to reduce gestational diabetes mellitus (GDM) risk underscores the importance of effective preventive strategies. However, developing effective systems is still challenging. We aimed to bridge this gap by developing a weight management specific prediction model. This study retrospectively analyzed the data of women who underwent two childbirths across 15 medical facilities, including both primary and tertiary facilities. A derivation cohort was constructed using data from 2009 to 2019 (n = 1,640). Data between 2020 and 2024 was used to construct a separate temporal-validation cohort (n = 293). Using the data from another tertiary center between 2017 and 2023, the geographical-validation cohort was constructed (n = 339). A prediction model for GDM development in the second pregnancy was developed by applying logistic regression analysis using 5 key clinical information. GDM in the second pregnancy occurred in 9.5% (156 of 1,640, derivation), 16.7% (49 of 293, temporal-validation), and 7.7% (26 of 339, geographical-validation). The prediction model demonstrated consistent discrimination across cohorts, with c-statistics of 0.75, 0.80, and 0.79, respectively. Precision–recall analyses, accounting for the low prevalence of GDM, further confirmed performance well above the baseline (0.095 in the derivation cohort), with AUC-PRs of 0.43, 0.47, and 0.41 for the three cohorts. Calibration showed alignment with slopes of 1.04, 0.87, and 0.59 for each cohort. This simple and accurate model supports personalized weight management goals, offering a practical tool to reduce GDM risk in future pregnancies through inter-pregnancy weight management.

DOI： 10.1038/s41598-025-30028-y

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Language：English   Publisher：Pediatric Research  

Background: Fetal cardiac output is typically assessed using gestational age (GA) or estimated fetal weight (EFW), but the optimal reference remains unclear due to limited validation. Methods: We retrospectively analyzed prospectively collected data from singleton fetuses at 27 + 2 to 29 + 6 weeks of gestation. Subjects included those with small for gestational age (SGA; EFW <10th percentile), large for gestational age (LGA; EFW > 90th percentile), and appropriate for gestational age (AGA), all without structural abnormalities. Associations between fetal cardiac output and both GA and EFW were evaluated using generalized additive models. Results: Among 443 fetuses with EFWs ranging from 873 to 1631 g, GA showed no significant association with any cardiac parameter (p ≥ 0.282). In contrast, EFW demonstrated significant and largely linear associations with all parameters (p < 0.001, F ≥ 16.7), consistent across GA and EFW ranges. Cardiac parameter distributions by EFW were similar across AGA, SGA, and LGA groups. Conclusion: EFW showed stronger and more consistent correlations with fetal cardiac parameters than GA, supporting its use as a more reliable reference for fetal cardiac evaluation across different growth statuses. Impact: Fetal cardiac output is typically assessed using reference ranges based on either gestational age (GA) or estimated fetal weight (EFW), both derived from appropriate for gestational age (AGA) fetuses. We showed that EFW is superior to GA for fetal cardiac evaluation. Including non-AGA fetuses confirmed they can be assessed similarly to AGA fetuses. The new EFW-based reference ranges offer a uniform standard, enabling more definitive assessments across varied fetal growth.

DOI： 10.1038/s41390-025-04584-y

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Language：English  

DOI： 10.7759/cureus.97996

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PubMed

Language：English   Publisher：Journal of Medical Ultrasonics Singapore  

DOI： 10.1007/s10396-025-01552-1

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Language：English   Publisher：Journal of Obstetrics and Gynaecology Research  

Aims: Preterm delivery (PTD) is a leading cause of neonatal morbidity and mortality. Accurate prediction is crucial for optimizing clinical outcomes, particularly in women with a short cervix. Although fetal fibronectin (FFN) is widely used to predict PTD, placental alpha-microglobulin-1 (PAMG-1) has gained attention for its potential to improve predictive accuracy. This study aimed to evaluate the utility of quantitative PAMG-1 assessment for predicting impending PTD in asymptomatic women with a short cervix (≤25 mm) between 24 and 34 weeks of gestation. Methods: This observational cohort study analyzed 212 cervicovaginal fluid samples from 77 patients (132 from 49 singleton and 80 from 28 twin pregnancies). PAMG-1 and FFN levels were measured, and multivariate logistic regression was performed to evaluate their association with PTD risk. Results: In singleton pregnancies, positive PAMG-1 was independently associated with impending PTD, with odds ratios of 7.84 (95% confidence interval [CI], 2.02–30.50; p = 0.003) and 7.34 (95% CI, 2.75–19.60; p < 0.001) for PTD within 1 and 2 weeks, respectively. Quantitative PAMG-1 showed a dose-dependent relationship, with PTD risks increasing from 4.3% (<1000 pg/mL) to 50.0% (≥3000 pg/mL) within 1 week and from 10.0% to 90.0% for PTD within 2 weeks. In twin pregnancies, both PAMG-1 and FFN showed limited predictive utility. Conclusions: This study highlights the potential of PAMG-1 quantification as a valuable tool for refining PTD risk stratification, particularly in singleton pregnancies. While further prospective multicenter validation is needed, these findings provide new clinical insights for improving PTD management.

DOI： 10.1111/jog.70071

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Language：English   Publisher：Communications Biology  

Platinum-resistant ovarian cancer (PROC) is a clinically severe unresolved issue, and it remains unclearly defined by molecular biology. Extracellular vesicles (EVs) play an essential role in cell-to-cell communication in the tumor microenvironment. This study aimed to investigate the molecular mechanisms of PROC, focusing on the unique ascites environment of ovarian cancer. Multi-transcriptome analyses using clinical samples revealed that PROC exhibited an activated Janus kinase (JAK)/signal transducer and activator of transcription pathway with high JAK1 expression in cancer cells. Immunohistochemistry for patient tissues confirmed the negative association between JAK1 expression and platinum response. JAK inhibitors were effective in PROC cell lines and cell- and patient-derived xenograft models, as well as synergistic with platinum. Furthermore, small RNA sequencing indicated that activated peritoneal mesothelial cell-derived EVs enriched in miR135a-5p increased JAK expression and platinum resistance in cancer cells. Collectively, EVs in ascites regulated platinum sensitivity in ovarian cancer cells, and JAK targeting therapeutic strategy overcomes PROC.

DOI： 10.1038/s42003-025-08771-9

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Language：English   Publisher：Journal of Obstetrics and Gynaecology Research  

Aim: This study aimed to evaluate the current antenatal corticosteroid (ACS) treatment practices for hypertensive disorders of pregnancy (HDP) in Japan, by evaluating annual trends and identifying clinical disparities and factors influencing non-administration of ACS. Methods: This retrospective population-based study was conducted using the Japanese Perinatal Research Network Database from 2013 to 2022. We analyzed ACS administration rates over time, across facility types, and the timing of delivery. Factors influencing non-administration were identified using univariate and multivariate logistic regression analyses. Results: ACS administration rates among patients with HDP nearly doubled over the past decade, reaching 64.0% in 2022. Approximately 70% of patients with HDP who received ACS delivered before 34 weeks of gestation; however, only 30% achieved the optimal administration-to-birth interval of 48 h to 7 days. ACS administration rates in patients with HDP differed by facility type: 67.8% (1641/2419) in general perinatal medical centers, 60.5% (1107/1830) in regional perinatal medical centers, and 39.7% (23/58) in non-perinatal medical centers. Factors contributing to non-administration included smoking during pregnancy, eclampsia, placental abruption, HELLP syndrome, regional perinatal medical centers, non-perinatal medical centers, and gestational hypertension. Conversely, conditions such as fetal growth restriction, threatened preterm labor, and preterm premature rupture of membranes were associated with higher rates of ACS administration. Conclusions: Although ACS administration rates in patients with HDP have improved over time, challenges remain in achieving optimal administration timing and addressing facility-based disparities. To improve administration rates, clinicians should increase awareness of ACS treatment and proactively manage HDP-related emergencies.

DOI： 10.1111/jog.16364

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Language：English   Publisher：Japan Society for the Study of Hypertension in Pregnancy  

<p><b>Aim:</b> Growing evidence exists on the association between hypertensive disorders of pregnancy (HDP) and long-term cardiovascular and metabolic disease risks. Here we evaluated obstetric care providers’ knowledge of future HDP-related risks and their engagement in counseling women with HDP in Japan.</p><p><b>Methods:</b> A questionnaire-based survey regarding knowledge of HDP and counseling practices of obstetric care providers in Aichi Prefecture was conducted via a web-based platform from March to June 2024.</p><p><b>Results:</b> A total of 169, 402, and 135 valid responses were obtained from obstetrician-gynecologists, midwives, and nurses, respectively. While more than 80% of the obstetrician-gynecologists were aware of HDP-related risks, only 29.6% regularly provided counseling, while 24.2% rarely or never engaged in such practices. The primary reason for not providing counseling was a lack of knowledge about counseling methods and necessary content, followed by unavailability of appointment slots and time constraints. Among midwives and nurses, approximately 40% rarely or never provided counseling, while many lacked knowledge of the preventive use of low-dose aspirin (67.2%).</p><p><b>Conclusions:</b> This survey demonstrated that, despite a high level of knowledge among healthcare providers, there is a substantial gap between knowledge and the implementation of counseling practices. These findings highlight the need for targeted education and training programs for obstetric care providers.</p>

DOI： 10.14390/jsshp.hrp2024-015

Open Access

CiNii Research

Language：English   Publisher：Scientific Reports  

To evaluate the role of high glucose variability (High-GV) in early pregnancy as a potential mediating factor between pre-pregnancy overweight/obesity and late-onset HDP (LoHDP), where effective preventive strategies remain limited. This multicenter retrospective study analyzed data from 802 pregnancies across 14 facilities. Pregnancies with a 75 g-OGTT performed by 20 weeks of gestation were included. Structural equation modeling (SEM) was used to evaluate direct and indirect effects of body mass index (BMI), High-GV, and covariates (e.g., age, ART, primiparity) on LoHDP. Overweight/obese women had significantly higher rates of High-GV (26.1 vs. 16.4%, p = 0.001) and LoHDP (17.6 vs. 7.9%, p < 0.001) compared to non-overweight/obese women. SEM revealed that BMI influenced LoHDP through both direct and indirect pathways. BMI had a direct effect on LoHDP (β = 0.20, p < 0.01), and an indirect effect mediated by High-GV, with BMI significantly associated with High-GV (β = 0.15, p < 0.01), and High-GV positively associated with LoHDP (β = 0.12, p < 0.01). In Non-GDM pregnancies, High-GV showed an even stronger association with LoHDP (β = 0.25, p < 0.001). This study identifies High-GV as a key mediator linking pre-pregnancy overweight/obesity to LoHDP. These findings suggest that targeting glucose variability in early pregnancy could mitigate LoHDP risk, particularly in overweight/obese women, regardless of GDM status. Future preventive strategies should integrate multifaceted approaches addressing maternal BMI and glucose regulation to improve maternal and neonatal outcomes.

DOI： 10.1038/s41598-025-02965-1

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Language：English   Publisher：Journal of Translational Medicine  

Background: Preterm birth (PTB) is a major contributor to neonatal morbidity, mortality, and long-term health complications. Despite advances in perinatal care, PTB rates remain high, and its multifactorial etiology is not fully understood. Increasing evidence suggests that maternal gut microbiota plays a critical role in pregnancy maintenance, potentially through modulation of immune responses. However, the underlying causal mechanisms remain unclear. We hypothesized that dysbiosis disrupts immune tolerance and promotes PTB, and that butyrate (short-chain fatty acid produced by specific gut bacteria) may counteract this effect by enhancing regulatory T cell (Treg)-mediated immune regulation. Methods: We established a dysbiosis-induced PTB mouse model using vancomycin treatment combined with subclinical immune activation via anti-CD3ε antibody. Pregnant mice were fed either a standard or butyrate-enriched diet. Outcomes included gestational length, PTB incidence, live pup rates, and Treg cell levels assessed by flow cytometry. Parallelly, 16S rRNA gene sequencing was performed on fecal samples from 32 pregnant women to compare gut microbial composition between spontaneous PTB and term birth groups. Multivariate logistic regression and correlation analyses were conducted to assess associations with gestational outcomes. Results: Vancomycin-induced dysbiosis in mice significantly reduced Treg cell populations and increased PTB rates (43.3% in dysbiosis vs. 0% in controls; p < 0.05), while butyrate supplementation reduced PTB incidence (p = 0.03), prolonged gestation (p = 0.01), and restored Treg counts (p < 0.001). In human samples, significant reductions in Lachnospiraceae and Ruminococcaceae, representative butyrate-producing bacteria, were seen in PTB cases. Their combined abundance was independently associated with sPTB risk (p = 0.019) and positively correlated with gestational age (r = 0.59, p < 0.001). Conclusions: Our findings demonstrate that maternal dysbiosis increases PTB risk via impaired immune tolerance, and that butyrate supplementation effectively reverses this effect in vivo. Human data support the translational relevance of butyrate-producing microbiota in pregnancy maintenance. These results highlight butyrate as a promising target for dietary interventions aimed at reducing PTB incidence by restoring immune homeostasis. Trial registration Not applicable.

DOI： 10.1186/s12967-025-06534-y

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Language：English   Publisher：Hypertension Research  

The growing recognition of the importance of interpregnancy weight management in reducing hypertensive disorders of pregnancy (HDP) underscores the importance of effective preventive strategies. However, developing effective systems remains a challenge. We aimed to bridge this gap by constructing a prediction model. This study retrospectively analyzed the data of 1746 women who underwent two childbirths across 14 medical facilities, including both tertiary and primary facilities. Data from 2009 to 2019 were used to create a derivation cohort (n = 1746). A separate temporal-validation cohort was constructed by adding data between 2020 and 2024 (n = 365). Furthermore, the external-validation cohort was constructed using the data from another tertiary center between 2017 and 2023 (n = 340). We constructed a prediction model for HDP development in the second pregnancy by applying logistic regression analysis using 5 primary clinical information: maternal age, pre-pregnancy body mass index, and HDP history; and pregnancy interval and weight change velocity between pregnancies. Model performance was assessed across all three cohorts. HDP in the second pregnancy occurred 7.3% in the derivation, 10.1% in the temporal-validation, and 7.9% in the external-validation cohorts. This model demonstrated strong discrimination, with c-statistics of 0.86, 0.88, and 0.86 for the respective cohorts. Precision-recall area under the curve values were 0.90, 0.85, and 0.91, respectively. Calibration showed favorable intercepts (−0.02 to −0.00) and slopes (0.96–1.02) for all cohorts. In conclusion, this externally validated model offers a robust basis for personalized interpregnancy weight management goals for women planning future pregnancies. (Figure presented.)

DOI： 10.1038/s41440-024-02024-8

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Language：English   Publisher：Hypertension Research  

Preeclampsia (PE) is a common pregnancy complication characterized by hypertension, proteinuria, and end-organ dysfunction. However, to date, no effective treatment has been established other than iatrogenic delivery, and the importance of prevention as an alternative approach to addressing PE has been emphasized. There is growing evidence on the effectiveness of pharmacological and non-pharmacological prophylaxis in preventing PE. In this review, we focused on dietary supplements as non-pharmacological prophylaxis for PE. Calcium is a well-documented supplement for the prevention of PE. Daily 500 mg calcium supplementation can roughly halve the risk of PE in settings where calcium intake is low, including in Japan. According to recent systematic reviews and network meta-analyses, current evidence on the efficacy of vitamin D supplementation is inconsistent. Although vitamin D is a candidate for the prevention of PE, future large-scale randomized control trials are necessary to draw definitive conclusions. We also reviewed other dietary supplements, including vitamins (vitamins A, B6, C, and E, folic acid, and multivitamins), minerals (magnesium, zinc, and iron), amino acids (l-arginine and l-carnitine), anti-oxidants (lycopene, resveratrol, and astaxanthin), and other agents (omega-3 fatty acids, coenzyme Q10, melatonin, and s-equol). In this study, we provide a comprehensive approach to help develop better preventive strategies and ultimately reduce the burden of PE. (Figure presented.)

DOI： 10.1038/s41440-025-02144-9

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Language：English   Publisher：Journal of Obstetrics and Gynaecology Research  

Aim: Given the increasing recognition of the importance of postpartum follow-up care for women with a history of hypertensive disorders of pregnancy (HDP) to mitigate their future risk of cardiovascular and metabolic diseases, here we aimed to evaluate the current status of postpartum follow-up care in Japan and explore the challenges to its implementation. Methods: A web-based survey was conducted using a smartphone application among postpartum women between March and May 2024 to assess their knowledge of HDP-related future risk and postpartum follow-up care. Results: A total of 880 valid responses were obtained, 73 (8.3%) of which were from women with a history of HDP. Of them, 56.2% were aware of the heightened risk of cardiovascular disease and even fewer knew about the risks of metabolic syndrome (37.0%) and the preventive use of low-dose aspirin (12.3%); in fact, 31.5% reported receiving no information about their risk or preventive measures from healthcare providers. Furthermore, 43.8% did not consult specialists or attend regular checkups after their 1-month checkup. Among women with a history of HDP, those who received information and guidance were more likely to implement behavioral changes than those who did not. Conclusions: Patient awareness level of HDP-related risk was low and the information provided by their healthcare professionals was insufficient, indicating that postpartum follow-up care in Japan is not satisfactory. This study highlights the need for improved educational strategies and systematic follow-up protocols to ensure that women are adequately informed and supported in managing their long-term health risks.

DOI： 10.1111/jog.16183

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Language：English   Publisher：Reproductive BioMedicine Online  

Research question: What are the risk factors for a prolonged third stage of labour, closely related to postpartum haemorrhage, and what is the effect of assisted reproductive technology (ART) on the third stage of labour? Design: Clinical data of women who delivered vaginally at term at 12 primary maternity hospitals in Japan (2010–2018) (n = 25,336) were obtained; 1148 (4.5%) conceived through ART and 2246 (8.9%) through non-ART treatments. The risk of a prolonged third stage of labour (defined as ≥20 min) was evaluated by univariable and multivariable regression analyses. Adjusted odds ratios (aOR) of a prolonged third stage of labour were evaluated, stratified by the type of ART, with natural conception as a reference. Results: Multivariable analysis showed that pregnancy achieved through ART (aOR 4.38, 95% CI 3.12 to 6.15), history of spontaneous miscarriage (OR 1.40, 95% CI 1.06 to 1.84) and prolonged labour (OR 1.52, 95% CI 1.09 to 2.12) were identified as independent risk factors. Frozen embryo transfer (FET), FET in a hormone replacement cycle (HRC–FET) and blastocyst-stage embryo transfer were significantly associated with a prolonged third stage of labour (aOR 4.07, 95% CI 2.75 to 6.04, aOR 4.11, 95% CI 2.58 to 6.57 and aOR 2.13, 95% CI 1.15 to 3.95, respectively). No significant difference was observed in the duration of third stage of labour between natural conception and non-ART treatment (P = 0.61). Conclusion: Pregnancy achieved through ART, particularly FET, HRC–FET and blastocyst-stage embryo transfer, was a significant risk factor for a prolonged third stage of labour.

DOI： 10.1016/j.rbmo.2024.104382

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Language：English   Publisher：Journal of Obstetrics and Gynaecology Research  

Aim: Prenatal maternal depression is known to affect the neurodevelopment of offspring. This study aimed to investigate the profile of umbilical cord serum in mothers with major depressive disorder (MDD). Methods: Liquid chromatography–tandem mass spectrometry (LC–MS) was conducted using umbilical cord serum from mothers with MDD (n = 5) and controls (control, n = 5). The levels of several differentially expressed proteins in umbilical cord serum were compared between the MDD (n = 10) and control groups (n = 10) by enzyme-linked immunosorbent assay. Results: The proteomic profiles in the umbilical cord serum were different between the MDD and control groups, including the pathways of regulation of plasma lipoprotein particle levels, and synapse organization. Only apolipoprotein A4 (APOA4) was significantly higher in the cord blood of MDD group. APOA4 levels in maternal serum were also significantly higher in the MDD group than those in the control group. The APOA4 levels in the umbilical cord serum were higher than that in the maternal serum. Conclusions: The levels of APOA4, a biomarker of depression, in the umbilical cord serum at birth were elevated in the neonates of MDD mothers. It is, therefore, likely that fetuses of MDD mothers were exposed to higher APOA4 levels in utero and this could have developmental and mental health implications for the offspring.

DOI： 10.1111/jog.16096

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Language：English   Publisher：Japan Medical Association / The Japanese Associaiton of Medical Sciences  

<p><b>Introduction:</b> Few studies have explored the preventive efficacy of vaginal progesterone (VD) treatment for preterm delivery (PTD) in Japanese clinical practice. In this study, the efficacy of the VD treatment in pregnant women with a short cervix (sCX) diagnosed after 24 weeks is evaluated, focusing on perinatal outcomes.</p><p><b>Methods:</b> A retrospective historical cohort study. Clinical data of 273 singleton women hospitalized for preventing PTD were extracted. Inclusion criteria are diagnosed sCX at 24-33 weeks. We excluded women with factors including treatment start before 24 weeks, medically induced PTD, PTD on admission day, and fetal demise. Consequently, logistic regression analyses were conducted on data from 79 women during Period 1 (November 2015 to March 2018, using prolonged intravenous ritodrine hydrochloride) and 82 women during Period 2 (August 2018 to August 2022, implementing VD treatment), adjusting maternal age, parity, body mass index, gestational age, cervical length, and histological chorioamnionitis. The primary outcomes involved PTD <37 and <34 weeks and neonatal intensive care unit admission. Secondary outcomes included the interval from the diagnosis of sCX to delivery <14 and <28 days, infant intubation, and surfactant administration. Since VD use is off-label in Japan, we obtained written informed consent prior to treatment.</p><p><b>Results:</b> VD treatment (Period 2) significantly decreased the incidence of PTD (birth < 37 weeks) (adjusted odds ratios [ORs] 0.43, 95% confidence intervals [CIs] 0.19-0.96), impending delivery within 14 and 28 days after confirming sCX (adjusted OR 0.12, 95% CI 0.06-0.72; adjusted OR 0.25, 95% CI 0.09-0.74, respectively), and neonatal intubation rate (adjusted OR 0.17, 95% CI 0.04-0.75).</p><p><b>Conclusions:</b> The VD treatment can prevent PTD in asymptomatic women with sCX diagnosed after 24 weeks of gestation. Although further validation is warranted, these findings may contribute to expanding the use of VD treatment in Japanese clinical practice.</p>

DOI： 10.31662/jmaj.2024-0036

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CiNii Research

Language：English   Publisher：Archives of Gynecology and Obstetrics  

Purpose: There is growing evidence that preterm infants born to mothers with chorioamnionitis (CAM) have increased risk of various neonatal morbidities and long-term neurological disorders; however, the effect of CAM on postnatal growth remains insufficiently investigated. This study evaluated the effect of histological CAM on postnatal growth trajectories in very preterm infants using a nationwide neonatal database in Japan. Method: A multicenter retrospective study was conducted using clinical data of 4220 preterm neonates who weighed ≤ 1500 g and were born at < 32 weeks of gestation between 2003–2017 (CAM group: n = 2110; non-CAM group: n = 2110). Z-scores for height and weight were evaluated at birth and 3 years of age. Univariable and multivariable analyses were conducted to evaluate the effect of histological CAM on ΔZ-scores of height and weight during the first three years with a stratification by infant sex and the stage of histological CAM. Results: Multivariable analyses showed that histological CAM was associated with accelerated postnatal increase (ΔZ-score) in weight (β coefficient [95% confidence interval]; 0.10 [0.00 to 0.20]), but not in height among females (0.06 [− 0.04 to 0.15]) and not in height and weight among males (0.04 [− 0.04 to 0.12] and 0.02 [− 0.07 to 0.11], respectively). An interaction analysis demonstrated no significant difference in the effect of histological CAM on the ΔZ-scores of height and weight during the first three years between male and female infants (height, p = 0.81; weight p = 0.25). Conclusions: Intrauterine exposure to maternal CAM contributes to accelerated postnatal weight gain in female preterm infants during the first three years.

DOI： 10.1007/s00404-024-07757-y

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Language：English   Publisher：Molecular and Cellular Endocrinology  

Adequate extravillous trophoblast (EVT) invasion into the maternal decidua is important for human placental development. We identified that E2F transcription factor 8 (E2F8) suppresses EVT invasion, and that tight junction protein-1 (TJP1) is a potential downstream target gene of E2F8. We investigated the role of TJP1 in the human placenta and regulation of TJP1 expression by E2F8. TJP1 expression decreased in E2F8 knockdown HTR-8/SVneo cells. TJP1 and E2F8 were co-expressed in villi in the first-trimester placenta and in EVTs and villi in the third-trimester placenta. TJP1 was significantly increased in the pre-eclamptic compared with control placenta. TJP1 knockdown increased the invasion of HTR-8/SVneo cells, while TJP1 overexpression inhibited cell invasion. Halo-E2F8 overexpression significantly increased TJP1 expression and TJP1 transcription compared with control placenta. Our findings suggest that E2F8 promotes TJP1 transcription, and that TJP1 expression by E2F8 inhibits EVT invasion. TJP1 and E2F8 may be related to pre-eclampsia pathogenesis.

DOI： 10.1016/j.mce.2024.112277

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Language：English   Publisher：Preventive Medicine Reports  

Background: Cardiovascular-disease (CVD) is the leading cause of death, and the association between obesity and CVD is particularly significant among women. Given the evidence highlighting the significance of weight-gain velosity, we aimed to elucidate its influence on cardio-ankle vascular index (CAVI), a reliable surrogate marker of CVD, and identify the high-benefit population where this influence is most pronounced. Methods: This multicenter retrospective study used electronic data from annual health checkups for workers in Japan. Individuals who voluntarily measured CAVI in 2019 were included, and weight-gain velosity was defined as the mean BMI gain from 2015 to 2019. Our primary outcome was the relationship between weight-gain velosity and CAVI. Results: Among 459 individuals, 53 had CAVI ≥ 9. Random forest analysis revealed that age was the most important factor, followed by lipid metabolism, weight-gain velosity, and glucose metabolism, with sex being the least important. Non-linear regression analysis of the effect of age on CAVI ≥ 9 showed the effect was pronounced after age 60, and the trend was greater in women. Among individuals aged 60 or younger, the aOR of weight-gain velosity for CAVI ≥ 9 was significantly positive (aOR 11.95, 95 %CI 1.13–126.27), while it was not significant for those older than 60. The relationship between weight-gain velosity and CAVI provides a new perspective on CVD risk factors. The effects of age, especially after 60, and weight-gain velosity in early- to middle-adulthood on arterial stiffness are emphasized. Conclusions: These findings underscore the importance of weight management under age 60, especially in women.

DOI： 10.1016/j.pmedr.2024.102782

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Language：English   Publisher：Journal of Extracellular Biology  

Congenital diaphragmatic hernia (CDH) is a life-threatening condition with high morbidity and mortality rates. The survival rate of neonates with severe CDH is reportedly only 10%–15%. However, prenatal prediction of severe cases is difficult, and the discovery of new predictive markers is an urgent issue. In this study, we focused on microRNAs (miRNAs) in amniotic fluid-derived small EVs (AF-sEVs). We identified four miRNAs (hsa-miR-127-3p, hsa-miR-363-3p, hsa-miR-493-5p, and hsa-miR-615-3p) with AUC > 0.8 to classify good prognosis group and poor prognosis group in human study. The AUC for hsa-miR-127-3p and hsa-miR-615-3p, for predicting the poor prognosis, were 0.93 and 0.91, respectively. In addition, in the in vivo study, the miRNA profiles of the lung tissues of CDH rats were different from those of control rats. Additionally, two elevated miRNAs (rno-miR-215-5p and rno-miR-148a-3p) in the lung tissues of CDH rats were increased in the AF-sEVs of CDH rats. Our results suggest that severe CDH neonates can be predicted prenatally with high accuracy using miRNAs contained in AF-sEVs. Furthermore, miRNA profile changes in AF-sEVs reflected the lung status in CDH. Our findings may contribute to the development of advanced perinatal care for patients with CDH.

DOI： 10.1002/jex2.160

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Language：English   Publisher：Hypertension Research  

Hypertensive disorders of pregnancy (HDP) are common complications associated with maternal and neonatal morbidity and mortality worldwide. Insights gained from long-term cohort studies have revealed that women with a history of HDP are predisposed to recurrent HDP in subsequent pregnancies and face heightened risks for cardiovascular and metabolic diseases later in life. Pregnancy is a unique condition that overloads maternal cardiac and metabolic functions, and is recognized as a “maternal stress test” for future cardiovascular and metabolic diseases. Pregnancy and postpartum period provide a valuable opportunity for identifying women with underlying and unrecognized cardiovascular and metabolic risk factors. Establishing an effective postpartum healthcare program for women who have experienced HDP is crucial in reducing the future risk of health complications. Postpartum care consists of supportive care for both mothers and children, including not only the assessment of physical and psychological well-being but also long-term postpartum preventive health management. Interpregnancy care is a continuum from postpartum care and includes supportive care to prepare for future pregnancies. Various initiatives across nations have been initiated to establish follow-up programs for women with a history of HDP; however, sufficient evidence of the impact of such programs is not available. Substantial challenges persist in establishing an efficient postpartum follow-up program, including educational strategies, selection of effective lifestyle interventions, and collaboration among various healthcare providers. This review outlines the postpartum and interpregnancy care of women who have experienced HDP as well as the current status and challenges of related healthcare initiatives in Japan. (Figure presented.)

DOI： 10.1038/s41440-024-01641-7

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Language：English   Publisher：Reproductive Medicine and Biology  

Purpose: Non-previa placenta accreta spectrum (PAS) is associated with assisted reproductive technology (ART), particularly frozen embryo transfer during hormone replacement therapy (HRC-FET). We especially aimed to evaluate the prevalence and risk factors for non-previa PAS in HRC-FET pregnancies. Methods: Overall, 279 women who conceived through ART at three ART facilities and delivered at a single center were included in this retrospective study. Data regarding endometrial thickness at embryo transfer, previous histories, and type of embryo transfer—HRC-FET, frozen embryo transfer during a natural ovulatory cycle (NC-FET), and fresh embryo transfer (Fresh-ET)—were collected. Univariable logistic regression analyses were conducted. Results: The prevalence of non-previa PAS was 27/192 (14.1%) in the HRC-FET group and 0 (0.0%) in both the NC-FET and Fresh-ET groups. Significantly high odds ratio [95% confidence interval] of non-previa PAS was associated with a history of artificial abortion (6.45 [1.98–21.02]), endometrial thickness <8.0 mm (6.11 [1.06–35.12]), resolved low-lying placenta (5.73 [2.13–15.41]), multiparity (2.90 [1.26–6.69]), polycystic ovarian syndrome (2.62 [1.02–6.71]), and subchorionic hematoma (2.49 [1.03–6.04]). Conclusions: A history of artificial abortion, endometrial thickness <8.0 mm, and resolved low-lying placenta may help in antenatal detection of a high-risk population of non-previa PAS in HRC-FET pregnancies.

DOI： 10.1002/rmb2.12592

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