Objectives: To explore serum vascular endothelial growth factor (VEGF), β-subunit human chorionic gonadotropin (β-hCG), and soluble Fms-like tyrosine kinasereceptor 1 (sFlt-1) levels in pregnant women with placenta accreta spectrum (PAS) and their prognostic implications.
Methods: Serum levels were measured in PAS patients and non-PAS controls. Depending on the depth of placental penetration into the uterine wall, PAS patients were further classified into placenta accreta, placenta increta and placenta percreta subgroups. Diagnostic efficacy of individual biomarkers and combined indices was evaluated using receiver operating characteristic curves. Correlations between biomarker levels, disease severity, and prognosis were analyzed.
Results: Serum levels of VEGF and β-hCG showed significant positive correlations with the extent of PAS invasion, whereas sFlt-1 levels were inversely associated with disease progression. Combined pregnancy complications, elevated serum VEGF levels and decreased serum sFlt-1 levels were risk factors for poor prognosis in patients with PAS. The AUC values of the indicators combined to predict the diagnosis and prognosis of patients with PAS were greater than serum VEGF, hCG, and sFlt-1 levels alone.
Conclusions: Serum levels of VEGF, β-hCG, and sFlt-1 demonstrate the potential to differentiate between women with and without PAS, and further exhibit a correlation with the depth of myometrial invasion in PAS cases. The combined use of these serum markers enhances both the sensitivity and specificity of prenatal diagnosis and prognostic assessment for PAS compared to individual markers, thereby offering valuable guidance for clinical diagnosis and management of PAS.
{"title":"Analysis of changes in serum VEGF, <i>β</i>-hCG, and sFlt-1 levels in women with placenta accreta spectrum and the impact on prognosis.","authors":"Pan Shang, DongMei Pang, YinLing Zhao","doi":"10.1515/jpm-2025-0291","DOIUrl":"https://doi.org/10.1515/jpm-2025-0291","url":null,"abstract":"<p><strong>Objectives: </strong>To explore serum vascular endothelial growth factor (VEGF), <i>β</i>-subunit human chorionic gonadotropin (<i>β</i>-hCG), and soluble Fms-like tyrosine kinasereceptor 1 (sFlt-1) levels in pregnant women with placenta accreta spectrum (PAS) and their prognostic implications.</p><p><strong>Methods: </strong>Serum levels were measured in PAS patients and non-PAS controls. Depending on the depth of placental penetration into the uterine wall, PAS patients were further classified into placenta accreta, placenta increta and placenta percreta subgroups. Diagnostic efficacy of individual biomarkers and combined indices was evaluated using receiver operating characteristic curves. Correlations between biomarker levels, disease severity, and prognosis were analyzed.</p><p><strong>Results: </strong>Serum levels of VEGF and <i>β</i>-hCG showed significant positive correlations with the extent of PAS invasion, whereas sFlt-1 levels were inversely associated with disease progression. Combined pregnancy complications, elevated serum VEGF levels and decreased serum sFlt-1 levels were risk factors for poor prognosis in patients with PAS. The AUC values of the indicators combined to predict the diagnosis and prognosis of patients with PAS were greater than serum VEGF, hCG, and sFlt-1 levels alone.</p><p><strong>Conclusions: </strong>Serum levels of VEGF, <i>β</i>-hCG, and sFlt-1 demonstrate the potential to differentiate between women with and without PAS, and further exhibit a correlation with the depth of myometrial invasion in PAS cases. The combined use of these serum markers enhances both the sensitivity and specificity of prenatal diagnosis and prognostic assessment for PAS compared to individual markers, thereby offering valuable guidance for clinical diagnosis and management of PAS.</p>","PeriodicalId":16704,"journal":{"name":"Journal of Perinatal Medicine","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: To determine the genetic causes of miscarriage by analyzing products of conception (POC).
Methods: Chromosomal microarray (CMA) using the Affymetrix Cytoscan HD array was performed in 172 POC specimens from women experiencing spontaneous miscarriage before 20 weeks of gestation to detect aneuploidies, copy number variants (CNVs), and loss of heterozygosity (LOH). Whole exome sequencing (WES) with Roche KAPA HyperExome V2 probes was used for cases where CMA results were normal.
Results: Common clinical indications included recurrent pregnancy loss, first-time miscarriage, absence of cardiac activity, intrauterine death, and fetal growth restriction (FGR), making up 72.55 % of cases. CMA identified chromosomal abnormalities in 38.37 % of samples, with numerical anomalies in 16.86 % and structural anomalies in 21.51 %. Turner syndrome (5.8 %) and various trisomies (5.8 %) were frequent numerical anomalies. Mosaicism and LOH were observed in 11.04 and 2.91 % of cases. WES detected pathogenic or likely pathogenic mutations in 21 genes (e.g., KCNQ1, KCNE1, COL1A2, ROBO1) in 18 cases, adding a 10.46 % diagnostic yield. K-means clustering grouped 17 of these genes into three pathways: chondrocyte differentiation, fibrin clot formation, and Ehlers-Danlos syndrome.
Conclusions: Combining CMA and WES provides a diagnostic yield of 48.83 %, offering a powerful approach to uncover genetic causes of pregnancy loss and guide clinical care.
{"title":"Clinical utility of chromosomal microarray and whole exome sequencing in evaluating genetic causes for pregnancy loss using products of conception specimens.","authors":"Kanaka Durga Devi Yadam Reddy, Suresh Kumaraswamy, Palanichamy Palanikumar, Tajamul Hussain, Shaik Mohammad Naushad","doi":"10.1515/jpm-2025-0240","DOIUrl":"https://doi.org/10.1515/jpm-2025-0240","url":null,"abstract":"<p><strong>Objectives: </strong>To determine the genetic causes of miscarriage by analyzing products of conception (POC).</p><p><strong>Methods: </strong>Chromosomal microarray (CMA) using the Affymetrix Cytoscan HD array was performed in 172 POC specimens from women experiencing spontaneous miscarriage before 20 weeks of gestation to detect aneuploidies, copy number variants (CNVs), and loss of heterozygosity (LOH). Whole exome sequencing (WES) with Roche KAPA HyperExome V2 probes was used for cases where CMA results were normal.</p><p><strong>Results: </strong>Common clinical indications included recurrent pregnancy loss, first-time miscarriage, absence of cardiac activity, intrauterine death, and fetal growth restriction (FGR), making up 72.55 % of cases. CMA identified chromosomal abnormalities in 38.37 % of samples, with numerical anomalies in 16.86 % and structural anomalies in 21.51 %. Turner syndrome (5.8 %) and various trisomies (5.8 %) were frequent numerical anomalies. Mosaicism and LOH were observed in 11.04 and 2.91 % of cases. WES detected pathogenic or likely pathogenic mutations in 21 genes (e.g., KCNQ1, KCNE1, COL1A2, ROBO1) in 18 cases, adding a 10.46 % diagnostic yield. K-means clustering grouped 17 of these genes into three pathways: chondrocyte differentiation, fibrin clot formation, and Ehlers-Danlos syndrome.</p><p><strong>Conclusions: </strong>Combining CMA and WES provides a diagnostic yield of 48.83 %, offering a powerful approach to uncover genetic causes of pregnancy loss and guide clinical care.</p>","PeriodicalId":16704,"journal":{"name":"Journal of Perinatal Medicine","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: The use of technological methods in childbirth is becoming increasingly common. This study aimed to evaluate the effects of virtual reality (VR) glasses on fear of childbirth, duration of labor, and fetal well-being in women undergoing term vaginal delivery.
Methods: This single-blind randomized controlled trial included 144 pregnant women, equally divided into VR and control groups, stratified by parity. The intervention group watched nature videos via VR glasses in two sessions during the active phase of labor. Data were collected using clinical record forms, a nonstress test (NST) monitoring form, and the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ-A/B).
Results: The use of VR significantly reduced fear of childbirth and shortened the active phase of labor among both primiparous and multiparous women (p<0.05). No significant differences were found in the total duration of labor or other phases. While significant differences were observed in fetal movements and accelerations between groups, no clinically adverse effects on fetal well-being were reported. No side effects or complications related to the VR intervention were observed.
Conclusions: VR appears to be a safe and effective non-pharmacological method to reduce childbirth fear and shorten the active phase of labor. Further studies are recommended to confirm its effects on labor physiology and neonatal outcomes.
{"title":"Effects of virtual reality on fear of birth, length of labor, and fetal well-being: a randomized controlled trial.","authors":"Mine Oruç, Kamile Kabukcuoglu","doi":"10.1515/jpm-2025-0462","DOIUrl":"https://doi.org/10.1515/jpm-2025-0462","url":null,"abstract":"<p><strong>Objectives: </strong>The use of technological methods in childbirth is becoming increasingly common. This study aimed to evaluate the effects of virtual reality (VR) glasses on fear of childbirth, duration of labor, and fetal well-being in women undergoing term vaginal delivery.</p><p><strong>Methods: </strong>This single-blind randomized controlled trial included 144 pregnant women, equally divided into VR and control groups, stratified by parity. The intervention group watched nature videos via VR glasses in two sessions during the active phase of labor. Data were collected using clinical record forms, a nonstress test (NST) monitoring form, and the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ-A/B).</p><p><strong>Results: </strong>The use of VR significantly reduced fear of childbirth and shortened the active phase of labor among both primiparous and multiparous women (p<0.05). No significant differences were found in the total duration of labor or other phases. While significant differences were observed in fetal movements and accelerations between groups, no clinically adverse effects on fetal well-being were reported. No side effects or complications related to the VR intervention were observed.</p><p><strong>Conclusions: </strong>VR appears to be a safe and effective non-pharmacological method to reduce childbirth fear and shorten the active phase of labor. Further studies are recommended to confirm its effects on labor physiology and neonatal outcomes.</p>","PeriodicalId":16704,"journal":{"name":"Journal of Perinatal Medicine","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: We aim to clarify the association and strength of association between antiphospholipid syndrome (APS) and adverse pregnancy outcomes.
Methods: Our study included an analysis of 191 hospitalized singleton pregnant women with APS and 984 healthy singleton pregnant women at Obstetrics and Gynecology Hospital Affiliated to Fudan University from July 2017 to September 2023. The exposure factor was diagnosed as antiphospholipid syndrome, and the main outcomes were adverse pregnancy outcomes, including miscarriage, preterm birth, low birth weight, gestational hypertension, and eclampsia.
Results: Our analysis indicated that the odds ratio (OR) for miscarriage in APS patients was 2.50 (95 % CI, 1.025 ± 15.794; p=0.046), for preterm birth was 2.8 (95 % CI, 1.025 ± 15.794; p=0.046), for low birth weight was 2.28 (95 % CI, 1.025 ± 15.794; p=0.046), and for fetal growth restriction was OR=2.48 (1.45, 4.23) p<0.05. The OR for preeclampsia was 1.00, and for gestational hypertension was 0.96, p>0.05. After adjustment for confounders of age and BMI confounders, the odds ratio (OR) for miscarriage was 2.50 (95 % CI: 1.52-4.11) p<0.05. Preterm birth was 2.89 (95 % CI: 1.79-4.65) p<0.05, low birth weight was 2.28 (95 % CI: 1.52-3.55) p<0.05, intrauterine growth restriction was 2.48 (95 % CI: 1.45-4.23) p<0.05. The OR of preeclampsia was 1.00 (95 % CI: 0.59-1.71) p>0.05, and that of pregnancy-induced hypertension was 0.96 (95 % CI: 0.53-1.75) p>0.05. After adjustment for confounders of age, BMI, eclampsia and diabetes, the OR for preterm infants were 3.06 (95 % CI: 1.87-5.00) p<0.05, and those of low birth weight infants were 2.55 (95 % CI: 1.49-4.37) p<0.05. After adjustment for confounders of age, BMI, diabetes, eclampsia, and gestational week, the OR for low birth weight infants was 2.02 (95 % CI: 1.26-3.26) p<0.05.
Conclusions: Antiphospholipid syndrome was significantly associated with the risk of miscarriage, preterm birth, low birth weight, and intrauterine growth restriction as adverse pregnancy outcomes.
{"title":"The association of antiphospholipid syndrome under medical treatment with adverse pregnancy outcomes.","authors":"Huilin Tang, Mingjie Xiang","doi":"10.1515/jpm-2025-0156","DOIUrl":"https://doi.org/10.1515/jpm-2025-0156","url":null,"abstract":"<p><strong>Objectives: </strong>We aim to clarify the association and strength of association between antiphospholipid syndrome (APS) and adverse pregnancy outcomes.</p><p><strong>Methods: </strong>Our study included an analysis of 191 hospitalized singleton pregnant women with APS and 984 healthy singleton pregnant women at Obstetrics and Gynecology Hospital Affiliated to Fudan University from July 2017 to September 2023. The exposure factor was diagnosed as antiphospholipid syndrome, and the main outcomes were adverse pregnancy outcomes, including miscarriage, preterm birth, low birth weight, gestational hypertension, and eclampsia.</p><p><strong>Results: </strong>Our analysis indicated that the odds ratio (OR) for miscarriage in APS patients was 2.50 (95 % CI, 1.025 ± 15.794; p=0.046), for preterm birth was 2.8 (95 % CI, 1.025 ± 15.794; p=0.046), for low birth weight was 2.28 (95 % CI, 1.025 ± 15.794; p=0.046), and for fetal growth restriction was OR=2.48 (1.45, 4.23) p<0.05. The OR for preeclampsia was 1.00, and for gestational hypertension was 0.96, p>0.05. After adjustment for confounders of age and BMI confounders, the odds ratio (OR) for miscarriage was 2.50 (95 % CI: 1.52-4.11) p<0.05. Preterm birth was 2.89 (95 % CI: 1.79-4.65) p<0.05, low birth weight was 2.28 (95 % CI: 1.52-3.55) p<0.05, intrauterine growth restriction was 2.48 (95 % CI: 1.45-4.23) p<0.05. The OR of preeclampsia was 1.00 (95 % CI: 0.59-1.71) p>0.05, and that of pregnancy-induced hypertension was 0.96 (95 % CI: 0.53-1.75) p>0.05. After adjustment for confounders of age, BMI, eclampsia and diabetes, the OR for preterm infants were 3.06 (95 % CI: 1.87-5.00) p<0.05, and those of low birth weight infants were 2.55 (95 % CI: 1.49-4.37) p<0.05. After adjustment for confounders of age, BMI, diabetes, eclampsia, and gestational week, the OR for low birth weight infants was 2.02 (95 % CI: 1.26-3.26) p<0.05.</p><p><strong>Conclusions: </strong>Antiphospholipid syndrome was significantly associated with the risk of miscarriage, preterm birth, low birth weight, and intrauterine growth restriction as adverse pregnancy outcomes.</p>","PeriodicalId":16704,"journal":{"name":"Journal of Perinatal Medicine","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, I Nyoman Hariyasa Sanjaya, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, Dudy Aldiansyah, Cut Meurah Yeni, Nuswil Bernolian, Sri Sulistyowati, Waskita Ekamaheswara Kasumba Andanaputra, Milan Stanojevic, Asim Kurjak
Objectives: To introduce the KANET-connectome matrix (KANET-Con) as a conceptual framework linking fetal behaviors observed on four-dimensional (4D) ultrasound to underlying neural network maturation, and to evaluate optimal gestational timing for functional neurodevelopmental screening.
Methods: A narrative review was conducted using a PRISMA-guided literature identification and screening process. PubMed, Scopus, and Web of Science were searched (January 2000-March 2025) for studies addressing fetal connectomics, fetal neurobehavior, KANET scoring, and developmental neuroimaging. Forty-two peer-reviewed studies met inclusion criteria. Observed fetal behaviors-including facial mimicry, eye blinking, limb movement, and overall gestalt coordination-were aligned with their most plausible neural substrates using evidence from developmental neuroscience and imaging.
Results: Findings demonstrated clear temporal associations between specific fetal behaviors and neural circuit development. Eye blinking and facial expressions (24-26 weeks) correlated with brainstem-cortical integration; hand-to-face gestures (26-30 weeks) reflected emerging interhemispheric pathways; and complex limb coordination (28-32 weeks) was linked to corticospinal and basal ganglia maturation. Collectively, these data indicate that 24-32 weeks of gestation represents an optimal window for KANET-based neurobehavioral screening. Additionally, emerging artificial intelligence applications show potential to enhance scoring objectivity by detecting subtle movement features such as behavioral entropy, asymmetry, and latency.
Conclusions: KANET, interpreted through a fetal connectomic lens, provides a functional window into early neural integration. The KANET-Con offers a clinically relevant, globally accessible conceptual model to support early detection of neurodevelopmental deviations and inform risk stratification, particularly in resource-limited settings.
目的:介绍kanet -连接组矩阵(KANET-Con)作为一个概念框架,将胎儿四维(4D)超声观察到的行为与潜在的神经网络成熟联系起来,并评估功能神经发育筛查的最佳妊娠时间。方法:采用prism引导的文献识别和筛选过程进行叙述性回顾。检索了PubMed, Scopus和Web of Science(2000年1月- 2025年3月)关于胎儿连接组学,胎儿神经行为,KANET评分和发育神经影像学的研究。42项同行评审的研究符合纳入标准。观察到的胎儿行为——包括面部模仿、眨眼、肢体运动和整体完形协调——利用发育神经科学和成像的证据与他们最可信的神经基质相一致。结果:研究结果表明胎儿特定行为与神经回路发育之间存在明确的时间关联。眨眼和面部表情(24-26 周)与脑干-皮层整合相关;手对脸的手势(26-30 周)反映了新出现的半球间通路;复杂肢体协调(28-32 周)与皮质脊髓和基底神经节成熟有关。总的来说,这些数据表明妊娠24-32 周是基于kanet的神经行为筛查的最佳窗口。此外,新兴的人工智能应用显示出通过检测细微的运动特征(如行为熵、不对称和延迟)来提高评分客观性的潜力。结论:通过胎儿连接晶体解读KANET,为早期神经整合提供了一个功能窗口。KANET-Con提供了一个临床相关的、全球可访问的概念模型,以支持早期发现神经发育偏差,并为风险分层提供信息,特别是在资源有限的环境中。
{"title":"Revisiting KANET in the context of fetal connectomics: defining optimal gestational windows for neurodevelopmental screening.","authors":"Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, I Nyoman Hariyasa Sanjaya, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, Dudy Aldiansyah, Cut Meurah Yeni, Nuswil Bernolian, Sri Sulistyowati, Waskita Ekamaheswara Kasumba Andanaputra, Milan Stanojevic, Asim Kurjak","doi":"10.1515/jpm-2025-0234","DOIUrl":"https://doi.org/10.1515/jpm-2025-0234","url":null,"abstract":"<p><strong>Objectives: </strong>To introduce the KANET-connectome matrix (KANET-Con) as a conceptual framework linking fetal behaviors observed on four-dimensional (4D) ultrasound to underlying neural network maturation, and to evaluate optimal gestational timing for functional neurodevelopmental screening.</p><p><strong>Methods: </strong>A narrative review was conducted using a PRISMA-guided literature identification and screening process. PubMed, Scopus, and Web of Science were searched (January 2000-March 2025) for studies addressing fetal connectomics, fetal neurobehavior, KANET scoring, and developmental neuroimaging. Forty-two peer-reviewed studies met inclusion criteria. Observed fetal behaviors-including facial mimicry, eye blinking, limb movement, and overall gestalt coordination-were aligned with their most plausible neural substrates using evidence from developmental neuroscience and imaging.</p><p><strong>Results: </strong>Findings demonstrated clear temporal associations between specific fetal behaviors and neural circuit development. Eye blinking and facial expressions (24-26 weeks) correlated with brainstem-cortical integration; hand-to-face gestures (26-30 weeks) reflected emerging interhemispheric pathways; and complex limb coordination (28-32 weeks) was linked to corticospinal and basal ganglia maturation. Collectively, these data indicate that 24-32 weeks of gestation represents an optimal window for KANET-based neurobehavioral screening. Additionally, emerging artificial intelligence applications show potential to enhance scoring objectivity by detecting subtle movement features such as behavioral entropy, asymmetry, and latency.</p><p><strong>Conclusions: </strong>KANET, interpreted through a fetal connectomic lens, provides a functional window into early neural integration. The KANET-Con offers a clinically relevant, globally accessible conceptual model to support early detection of neurodevelopmental deviations and inform risk stratification, particularly in resource-limited settings.</p>","PeriodicalId":16704,"journal":{"name":"Journal of Perinatal Medicine","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, I Nyoman Hariyasa Sanjaya, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, Dudy Aldiansyah, Cut Meurah Yeni, Nuswil Bernolian, Waskita Ekamaheswara Kasumba Andanaputra, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak
Introduction: The traditional view of a sterile intrauterine environment has been challenged by sequencing studies detecting low-biomass microbial DNA in placenta, amniotic fluid, and fetal tissues. These findings suggest that maternal microbiota-derived signals may contribute to fetal brain development and influence long-term neuropsychiatric outcomes.
Content: This narrative review synthesizes evidence from over 90 preclinical and clinical studies examining maternal microbiota-fetal brain interactions. Maternal immune activation - characterized by elevated cytokines such as interleukin (IL)-6 and IL-17A - has been shown in mouse models to disrupt cortical layering and synaptic organization, while human cohort studies involving more than 250,000 pregnancies link maternal inflammatory markers to increased autism spectrum disorder (ASD) risk. Microbial metabolites, including short-chain fatty acids (butyrate, acetate, propionate), bile acids, and tryptophan derivatives, regulate microglial maturation, blood-brain barrier integrity, and hippocampal neurogenesis. Epigenetic mechanisms - DNA methylation, histone acetylation, and chromatin remodeling - have been observed in placenta and cord blood from pregnancies affected by obesity or dysbiosis. Large-scale epidemiological studies also associate prenatal infection and antibiotic exposure with higher rates of ASD and attention-deficit/hyperactivity disorder (ADHD).
Summary: Collectively, the evidence indicates that maternal microbiota influence fetal brain development through converging immune, metabolic, epigenetic, and hormonal pathways. Strong mechanistic insights come from animal models, whereas human data remain largely observational, limiting causal interpretation.
Outlook: Recognizing the maternal microbiome as a modifiable prenatal factor highlights opportunities for prevention. Early translational approaches - including maternal microbiota profiling, dietary optimization, and probiotic supplementation - are under investigation, but require rigorous clinical validation before integration into prenatal care.
{"title":"The intrauterine microbiome-neurodevelopment axis: decoding the prenatal microbial imprint on lifelong mental health.","authors":"Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, I Nyoman Hariyasa Sanjaya, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, Dudy Aldiansyah, Cut Meurah Yeni, Nuswil Bernolian, Waskita Ekamaheswara Kasumba Andanaputra, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak","doi":"10.1515/jpm-2025-0242","DOIUrl":"https://doi.org/10.1515/jpm-2025-0242","url":null,"abstract":"<p><strong>Introduction: </strong>The traditional view of a sterile intrauterine environment has been challenged by sequencing studies detecting low-biomass microbial DNA in placenta, amniotic fluid, and fetal tissues. These findings suggest that maternal microbiota-derived signals may contribute to fetal brain development and influence long-term neuropsychiatric outcomes.</p><p><strong>Content: </strong>This narrative review synthesizes evidence from over 90 preclinical and clinical studies examining maternal microbiota-fetal brain interactions. Maternal immune activation - characterized by elevated cytokines such as interleukin (IL)-6 and IL-17A - has been shown in mouse models to disrupt cortical layering and synaptic organization, while human cohort studies involving more than 250,000 pregnancies link maternal inflammatory markers to increased autism spectrum disorder (ASD) risk. Microbial metabolites, including short-chain fatty acids (butyrate, acetate, propionate), bile acids, and tryptophan derivatives, regulate microglial maturation, blood-brain barrier integrity, and hippocampal neurogenesis. Epigenetic mechanisms - DNA methylation, histone acetylation, and chromatin remodeling - have been observed in placenta and cord blood from pregnancies affected by obesity or dysbiosis. Large-scale epidemiological studies also associate prenatal infection and antibiotic exposure with higher rates of ASD and attention-deficit/hyperactivity disorder (ADHD).</p><p><strong>Summary: </strong>Collectively, the evidence indicates that maternal microbiota influence fetal brain development through converging immune, metabolic, epigenetic, and hormonal pathways. Strong mechanistic insights come from animal models, whereas human data remain largely observational, limiting causal interpretation.</p><p><strong>Outlook: </strong>Recognizing the maternal microbiome as a modifiable prenatal factor highlights opportunities for prevention. Early translational approaches - including maternal microbiota profiling, dietary optimization, and probiotic supplementation - are under investigation, but require rigorous clinical validation before integration into prenatal care.</p>","PeriodicalId":16704,"journal":{"name":"Journal of Perinatal Medicine","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: This study aims to investigate the role of fetal thymus and adrenal medulla dimensions in the pathogenesis of preterm prelabor rupture of membranes (PPROM).
Methods: A prospective, case-control study was conducted involving 45 pregnant women with PPROM between 28 and 37 weeks of gestation and 45 matched healthy controls. Ultrasonographic measurements of fetal thymus (width, length, TTR) and adrenal glands (length, width, depth, volume), including the adrenal medulla, were performed. Biochemical markers (WBC, CRP) and neonatal outcomes were recorded. Statistical analyses included comparisons between groups, correlation assessments, and ROC curve analysis to evaluate predictive parameters.
Results: The fetal thymus dimensions and TTR ratio were significantly smaller in the PPROM group. The adrenal medulla volume, length, and depth were notably reduced, while total adrenal gland size showed no significant difference. Moderate negative correlations were observed between inflammatory markers and TTR. ROC analysis indicated that TTR and adrenal medulla volume could predict NICU admission with moderate sensitivity and specificity.
Conclusions: The findings suggest that alterations in fetal thymus and adrenal medulla sizes are associated with PPROM and may serve as potential biomarkers for its diagnosis and prognosis. Further large-scale studies are warranted to validate these parameters and explore their clinical applications.
{"title":"Assessment of fetal adrenal gland and thymothoracic ratio in preterm premature membrane rupture: a prospective case-control study.","authors":"Burcu Bozkurt Ozdal, Atakan Tanacan, Betul Akgun Aktas, Huseyin Kayaalp, Gulnihal Reyhan Toptas, Esra Karatas, Ozgur Kara, Dilek Sahin","doi":"10.1515/jpm-2025-0261","DOIUrl":"https://doi.org/10.1515/jpm-2025-0261","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to investigate the role of fetal thymus and adrenal medulla dimensions in the pathogenesis of preterm prelabor rupture of membranes (PPROM).</p><p><strong>Methods: </strong>A prospective, case-control study was conducted involving 45 pregnant women with PPROM between 28 and 37 weeks of gestation and 45 matched healthy controls. Ultrasonographic measurements of fetal thymus (width, length, TTR) and adrenal glands (length, width, depth, volume), including the adrenal medulla, were performed. Biochemical markers (WBC, CRP) and neonatal outcomes were recorded. Statistical analyses included comparisons between groups, correlation assessments, and ROC curve analysis to evaluate predictive parameters.</p><p><strong>Results: </strong>The fetal thymus dimensions and TTR ratio were significantly smaller in the PPROM group. The adrenal medulla volume, length, and depth were notably reduced, while total adrenal gland size showed no significant difference. Moderate negative correlations were observed between inflammatory markers and TTR. ROC analysis indicated that TTR and adrenal medulla volume could predict NICU admission with moderate sensitivity and specificity.</p><p><strong>Conclusions: </strong>The findings suggest that alterations in fetal thymus and adrenal medulla sizes are associated with PPROM and may serve as potential biomarkers for its diagnosis and prognosis. Further large-scale studies are warranted to validate these parameters and explore their clinical applications.</p>","PeriodicalId":16704,"journal":{"name":"Journal of Perinatal Medicine","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145588047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julian Dewantiningrum, Wiku Andonotopo, Efendi Lukas, Mochammad Besari Adi Pramono, Wisnu Prabowo, Muhammad Adrianes Bachnas, I Nyoman Hariyasa Sanjaya, Anak Agung Gede Putra Wiradnyana, Anak Agung Ngurah Jaya Kusuma, Khanisyah Erza Gumilar, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, Dudy Aldiansyah, Aloysius Suryawan, Ridwan Abdullah Putra, Anita Deborah Anwar, Laksmana Adi Krista Nugraha, Waskita Ekamaheswara Kasumba Andanaputra, Wibisana Andika Krista Dharma, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak
Objective: Perinatal anxiety is one of the most common yet least systematically addressed complications of preg- nancy and childbirth. Despite abundant evidence that collaborative and integrated care models improve maternal outcomes, obstetric practice still lacks a defined operational standard for addressing anxiety alongside routine obstetric care. Fragmented screening, insufficient referral systems, and financing barriers continue to delay intervention, widening inequities across populations and settings.
Methods: This opinion article synthesizes recent evidence (2010-2025) from PubMed, Google Scholar, and professional guidelines to propose a practical framework for embedding mental health care within obstetric workflows. Drawing upon studies from high- and low-resource contexts, we outline a ten-point minimum standard for perinatal-anxiety management and a three-tier maturity model that describes the progressive integration of collaborative care-from basic screening to digitally supported, team-based systems. The model identifies measurable implementation metrics and policy levers that enable sustainability and equity.
Results: Rather than advocating new research, this article translates two decades of findings into a clinically actionable standard. It emphasizes the central role of ob- stetric teams in early detection, stepped care, and follow-up through coordination with mental-health professionals.
Conclusions: Integrating mental health into obstetric practice is both a moral and operational imperative. By adopting the proposed minimum standard and maturity model, health systems can transform perinatal anxiety care from discre- tionary innovation to routine expectation-achieving faster response, broader access, and better maternal-infant out- comes worldwide.
{"title":"Integrating mental health into obstetric practice: a review of collaborative care models for perinatal anxiety.","authors":"Julian Dewantiningrum, Wiku Andonotopo, Efendi Lukas, Mochammad Besari Adi Pramono, Wisnu Prabowo, Muhammad Adrianes Bachnas, I Nyoman Hariyasa Sanjaya, Anak Agung Gede Putra Wiradnyana, Anak Agung Ngurah Jaya Kusuma, Khanisyah Erza Gumilar, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, Dudy Aldiansyah, Aloysius Suryawan, Ridwan Abdullah Putra, Anita Deborah Anwar, Laksmana Adi Krista Nugraha, Waskita Ekamaheswara Kasumba Andanaputra, Wibisana Andika Krista Dharma, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak","doi":"10.1515/jpm-2025-0300","DOIUrl":"https://doi.org/10.1515/jpm-2025-0300","url":null,"abstract":"<p><strong>Objective: </strong>Perinatal anxiety is one of the most common yet least systematically addressed complications of preg- nancy and childbirth. Despite abundant evidence that collaborative and integrated care models improve maternal outcomes, obstetric practice still lacks a defined operational standard for addressing anxiety alongside routine obstetric care. Fragmented screening, insufficient referral systems, and financing barriers continue to delay intervention, widening inequities across populations and settings.</p><p><strong>Methods: </strong>This opinion article synthesizes recent evidence (2010-2025) from PubMed, Google Scholar, and professional guidelines to propose a practical framework for embedding mental health care within obstetric workflows. Drawing upon studies from high- and low-resource contexts, we outline a ten-point minimum standard for perinatal-anxiety management and a three-tier maturity model that describes the progressive integration of collaborative care-from basic screening to digitally supported, team-based systems. The model identifies measurable implementation metrics and policy levers that enable sustainability and equity.</p><p><strong>Results: </strong>Rather than advocating new research, this article translates two decades of findings into a clinically actionable standard. It emphasizes the central role of ob- stetric teams in early detection, stepped care, and follow-up through coordination with mental-health professionals.</p><p><strong>Conclusions: </strong>Integrating mental health into obstetric practice is both a moral and operational imperative. By adopting the proposed minimum standard and maturity model, health systems can transform perinatal anxiety care from discre- tionary innovation to routine expectation-achieving faster response, broader access, and better maternal-infant out- comes worldwide.</p>","PeriodicalId":16704,"journal":{"name":"Journal of Perinatal Medicine","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: Existing studies yielded conflicting evidence regarding the associations between genital tract microbial and funisitis, chorioamnionitis and adverse pregnancy outcomes. This study aims to provide additional evidence for their association through systematic investigation.
Methods: A total of 98 FFPE umbilical cord specimens confirmed as funisitis and chorioamnionitis through histopathological examination were tested for seven genital tract microorganisms using quantitative polymerase chain reaction (qPCR). Electronic medical records of mothers and neonates were retrieved to analyze the risk associations between microorganism-positive cases and chorioamnionitis as well as adverse pregnancy outcomes. The umbilical cord samples with Ureaplasma parvum positive had been sequenced for serovars analysis.
Results: Ureaplasma parvum (UP), Ureaplasma urealyticum (UU), Group B Streptococcus (GBS) and Mycoplasma homini s (MH) were all detected in the study with prevalence of 36.5 %, 7.9 %, 18.6 %, and 5.8 %, respectively, while Mycoplasma genitalium (MG), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) were not detected. Ureaplasma spp. were identified as the predominant microorganisms detected in 98 umbilical cord cases by using qPCR, demonstrating concordance with clinical vaginal swab findings from pregnant women. Genital microorganisms infection was associated with high stage chorioamnionitis (p = 0.0254) and adverse pregnant outcomes (p = 0.0053). In addition, the prevalence of U. parvum demonstrated a strong significant association with neonatal pneumonia (p = 0.0037).
Conclusions: Umbilical cord specimens tested positive for U. parvum demonstrated a significant association with adverse perinatal outcomes and neonatal pneumonia. Additional studies are warranted to investigate the determinants enabling commensal U. parvum in the genital tract to ascend and induce intrauterine infection, thereby leading to adverse clinical outcomes.
{"title":"Ureaplasma parvum detected in umbilical cord tissues diagnosed with funisitis associated with adverse pregnancy outcomes and neonatal pneumonia.","authors":"Wen Lei, Leijun Huo, Qiuping Chen, Yanxia Liao, Mi Li, Xiangcheng Zhou, Jiali Zhang, Shuai Zhou, Liang Zhang, Hongyi Gao, Hua Deng","doi":"10.1515/jpm-2025-0321","DOIUrl":"https://doi.org/10.1515/jpm-2025-0321","url":null,"abstract":"<p><strong>Objectives: </strong>Existing studies yielded conflicting evidence regarding the associations between genital tract microbial and funisitis, chorioamnionitis and adverse pregnancy outcomes. This study aims to provide additional evidence for their association through systematic investigation.</p><p><strong>Methods: </strong>A total of 98 FFPE umbilical cord specimens confirmed as funisitis and chorioamnionitis through histopathological examination were tested for seven genital tract microorganisms using quantitative polymerase chain reaction (qPCR). Electronic medical records of mothers and neonates were retrieved to analyze the risk associations between microorganism-positive cases and chorioamnionitis as well as adverse pregnancy outcomes. The umbilical cord samples with <i>Ureaplasma parvum</i> positive had been sequenced for serovars analysis.</p><p><strong>Results: </strong><i>Ureaplasma parvum</i> (UP), <i>Ureaplasma urealyticum</i> (UU), Group B <i>Streptococcus</i> (GBS) and <i>Mycoplasma homini s</i> (MH) were all detected in the study with prevalence of 36.5 %, 7.9 %, 18.6 %, and 5.8 %, respectively, while <i>Mycoplasma genitalium</i> (MG), <i>Chlamydia trachomatis</i> (CT) and <i>Neisseria gonorrhoeae</i> (NG) were not detected. <i>Ureaplasma</i> spp. were identified as the predominant microorganisms detected in 98 umbilical cord cases by using qPCR, demonstrating concordance with clinical vaginal swab findings from pregnant women. Genital microorganisms infection was associated with high stage chorioamnionitis (p = 0.0254) and adverse pregnant outcomes (p = 0.0053). In addition, the prevalence of <i>U. parvum</i> demonstrated a strong significant association with neonatal pneumonia (p = 0.0037).</p><p><strong>Conclusions: </strong>Umbilical cord specimens tested positive for <i>U. parvum</i> demonstrated a significant association with adverse perinatal outcomes and neonatal pneumonia. Additional studies are warranted to investigate the determinants enabling commensal <i>U. parvum</i> in the genital tract to ascend and induce intrauterine infection, thereby leading to adverse clinical outcomes.</p>","PeriodicalId":16704,"journal":{"name":"Journal of Perinatal Medicine","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Young Eun Chung, You-Ri Lee, Sooji Ham, Boram Park, Kyunga Kim, Ji-Hee Sung, Yun Dan Kang, Suk-Joo Choi, Soo-Young Oh, Jung-Sun Kim, Cheong-Rae Roh
Objectives: We aimed to identify the associations between specific pathologic placental findings and abnormal Doppler results as well as perinatal outcomes in preterm fetal growth restriction (FGR).
Methods: This retrospective study included 465 consecutive singleton pregnancies with FGR delivered between 22+0 and 36+6 weeks of gestation. Abnormal Doppler was defined as absent or reversed end-diastolic flow in the umbilical artery (UA) and a pulsatility index less than the 10th percentile in the middle cerebral artery (MCA). Placental pathology was evaluated focusing on villous or vascular findings of maternal (MVM) and fetal vascular malperfusion (FVM) based on Amsterdam criteria.
Results: The average gestational age at delivery and neonatal birth weight were 32 weeks (±4 weeks) and 1,299 g (±575 g), respectively. Placental MVM lesions were observed in the majority of cases (90.3 %) and were significantly related to abnormal UA and MCA Doppler. Meanwhile, FVM lesions was observed in about half of the cases (44.8 %) and were significantly related to abnormal MCA Doppler, but not abnormal UA Doppler. Both villous and vascular lesions of MVM and FVM were associated with lower neonatal birth weight. Among specific key findings of MVM and FVM, distal villous hypoplasia was highly associated with abnormal UA Doppler (crude OR 5.01, 95 % CI 1.27-19.68), while intramural fibrin deposition in large fetal vessels was significantly associated with abnormal MCA Doppler (crude OR 2.49, 95 % CI 1.01-6.13). Of note, intramural fibrin deposition of large fetal vessels was associated with neonatal mortality (crude OR 3.25, 95 % CI 1.52-6.92).
Conclusions: We identified key findings among placental MVM and FVM associated with abnormal UA and MCA Doppler as well as neonatal mortality in preterm FGR.
目的:我们旨在确定早产胎儿生长受限(FGR)的特定病理胎盘表现与异常多普勒结果以及围产期结局之间的关系。方法:本回顾性研究纳入465例妊娠22+0 ~ 36+6周连续单胎妊娠FGR患者。多普勒异常定义为脐动脉(UA)舒张末期血流缺失或逆转,大脑中动脉(MCA)脉搏指数小于10百分位。根据阿姆斯特丹标准,对胎盘病理进行评估,重点关注母胎(MVM)和胎儿血管灌注不良(FVM)的绒毛或血管表现。结果:平均胎龄32周(±4周),新生儿出生体重1299 g(±575 g)。胎盘MVM病变占绝大多数(90.3 %),与UA和MCA多普勒异常有显著关系。同时,FVM病变约占一半(44.8% %),与MCA多普勒异常有显著关系,而与UA多普勒异常无显著关系。MVM和FVM的绒毛和血管病变都与新生儿出生体重低有关。在MVM和FVM的具体关键表现中,远端绒毛发育不全与UA多普勒异常高度相关(粗比值5.01,95 % CI 1.27-19.68),而大胎儿血管内纤维蛋白沉积与MCA多普勒异常显著相关(粗比值2.49,95 % CI 1.01-6.13)。值得注意的是,胎内大血管纤维蛋白沉积与新生儿死亡率相关(粗比值比3.25,95 % CI 1.52-6.92)。结论:我们确定了胎盘MVM和FVM与早产儿FGR中UA和MCA多普勒异常以及新生儿死亡率相关的关键发现。
{"title":"Abnormal Doppler and perinatal outcomes according to the placental lesions of maternal and fetal vascular malperfusion in preterm fetal growth restriction.","authors":"Young Eun Chung, You-Ri Lee, Sooji Ham, Boram Park, Kyunga Kim, Ji-Hee Sung, Yun Dan Kang, Suk-Joo Choi, Soo-Young Oh, Jung-Sun Kim, Cheong-Rae Roh","doi":"10.1515/jpm-2025-0140","DOIUrl":"https://doi.org/10.1515/jpm-2025-0140","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to identify the associations between specific pathologic placental findings and abnormal Doppler results as well as perinatal outcomes in preterm fetal growth restriction (FGR).</p><p><strong>Methods: </strong>This retrospective study included 465 consecutive singleton pregnancies with FGR delivered between 22+0 and 36+6 weeks of gestation. Abnormal Doppler was defined as absent or reversed end-diastolic flow in the umbilical artery (UA) and a pulsatility index less than the 10th percentile in the middle cerebral artery (MCA). Placental pathology was evaluated focusing on villous or vascular findings of maternal (MVM) and fetal vascular malperfusion (FVM) based on Amsterdam criteria.</p><p><strong>Results: </strong>The average gestational age at delivery and neonatal birth weight were 32 weeks (±4 weeks) and 1,299 g (±575 g), respectively. Placental MVM lesions were observed in the majority of cases (90.3 %) and were significantly related to abnormal UA and MCA Doppler. Meanwhile, FVM lesions was observed in about half of the cases (44.8 %) and were significantly related to abnormal MCA Doppler, but not abnormal UA Doppler. Both villous and vascular lesions of MVM and FVM were associated with lower neonatal birth weight. Among specific key findings of MVM and FVM, distal villous hypoplasia was highly associated with abnormal UA Doppler (crude OR 5.01, 95 % CI 1.27-19.68), while intramural fibrin deposition in large fetal vessels was significantly associated with abnormal MCA Doppler (crude OR 2.49, 95 % CI 1.01-6.13). Of note, intramural fibrin deposition of large fetal vessels was associated with neonatal mortality (crude OR 3.25, 95 % CI 1.52-6.92).</p><p><strong>Conclusions: </strong>We identified key findings among placental MVM and FVM associated with abnormal UA and MCA Doppler as well as neonatal mortality in preterm FGR.</p>","PeriodicalId":16704,"journal":{"name":"Journal of Perinatal Medicine","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145540963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}