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Journal of Perinatal Medicine

Official Journal of the International Academy of Perinatal Medicine, the New York Perinatal Society, and the Fetus as a Patient Society

Editor-in-Chief: Joachim W. Dudenhausen, MD, FRCOG
Edited by: Thorsten Braun , Frank A. Chervenak , Vincenzo D'Addario , Marty Ellington , Mehmet R. Genc , Anne Greenough , Amos Grunebaum , Wolf Kirschner , Asim Kurjak , Roberto Romero , Daniel W. Skupski , Christel Weiß and Ivica Zalud

Language: English

First published: January 1, 1973

Publication Frequency: 9 issues per year

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Objective
From 2025, the Journal of Perinatal Medicine will be transferred to Diamond Open Access on a year-by-year basis. All articles will then be published immediately under the Creative Commons Attribution (CC-BY-4.0) License. There will be no publication costs for the authors. The open access transformation is based on the Subscribe-to-Open model. You can find detailed information about this model can be found HERE.
Due to the flip to the new publication model, the first three issues of the new volume will not be published in the first three months of the new year, but in February, March and April.

The Journal of Perinatal Medicine (JPM) is an international forum covering the entire field of perinatal medicine. For decades, JPM has focused on publications relevant to perinatal medicine, patient care and patient safety. It is an indispensable news source for all obstetricians, neonatologists, perinatologists and other health professionals who want to keep abreast of advances in perinatal and related research. The journal offers statements on themes of topical interest and different views on controversial topics.
JPM is published in 9 issues per year. All contributions submitted for publication in JPM are subject to double-anonymized peer review by at least two experts in the field, selected and invited by the Editor-in-Chief and a dedicated Editorial Team. JPM publishes only English-language articles in the categories listed below.

Topics
Antenatal Care // Chorioamnionitis // Diabetes // Fetal Anomalia // Fetal Diagnosis // Intapartum Care // Maternal Medicine // Multiples // Neonatal Care // Obstetrics // Prematurity // Preterm Labor and Preterm Birth // Ultrasound

Article formats
Original Article, Review, Mini Review, Opinion Paper, Short Communication, Editorial, Letter to the Editor, Commentary, Guidelines and Recommendations

Your Benefits

Specialized, comprehensive and translational research
High quality peer-review
Rapid publication times
No costs for open access publishing (Subscribe-to-Open model)
Authors retain copyright – articles published under the Creative Commons Attribution (CC-BY-4.0) License
Each article easily discoverable because of Search Engine Optimization (SEO) and comprehensive abstracting and indexing services
Secure archiving by De Gruyter and the independent archiving service Portico

Other publications in the field

Open Access
Evaluation of Doppler parameters and obstetric outcomes in intrahepatic cholestasis of pregnancy

October 6, 2025

Mümine Eda Şık, Miraç Özalp, Murat İbrahim Toplu, Veli Mihmanlı

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Objectives To investigate the association between Doppler ultrasonographic parameters and maternal serum bile acid levels in pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP) and to evaluate their potential role in fetal monitoring. Methods In this prospective observational study, 59 pregnant women diagnosed with ICP and 59 healthy controls were included. The diagnosis of ICP was based on pruritus and serum bile acid levels >10 μmol/L. Doppler assessments – performed by a blinded perinatologist – included the uterine artery pulsatility index (PI), middle cerebral artery (MCA) PI, umbilical artery (UA) PI, and cerebroplacental ratio (CPR). Participants were further stratified by bile acid levels (<10, 10–40, >40 μmol/L), and intergroup comparisons and correlation analyses were performed. Results The ICP cases had significantly higher uterine artery PI and lower MCA PI and CPR values compared to controls (p<0.05). Bile acid levels were positively correlated with uterine artery PI and inversely correlated with MCA PI and CPR. ICP pregnancies also demonstrated increased rates of preterm delivery, low birth weight, and neonatal intensive care unit (NICU) admissions. Conclusions Alterations in uterine and fetal Doppler indices in ICP pregnancies suggest underlying placental dysfunction. These findings support the clinical utility of Doppler ultrasound in the risk stratification and perinatal surveillance of patients with ICP.
Open Access
Low uterine segment thickness in the prediction of cesarean delivery after induction of labor

October 6, 2025

Gizem Elif Dizdaroğulları, Aylin Yılmaz, Beyzanur Kurtcephe Kahyaoğlu, İsmail Bağlar, Aslıhan Öztürk, Emine Eda Akalın

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Objectives The aim of our study was to examine the relationship between lower uterine segment (LUS) thickness and cesarean delivery (CD) and compare the capacity two measurement methods of LUS thickness in the prediction of successful induction of labor (IOL). Methods This was a prospective cross-sectional study of consecutive pregnancies undergoing IOL between 2022 and 2023. The inclusion criteria were women with singleton pregnancies with cephalic presentation whose Bishop scores were below six undergoing IOL after 37 weeks of gestation. Patients with a history of CD, fetal anomalies, multiple gestations, and any contraindication to vaginal delivery were excluded from the study group. Results A total of 124 pregnant women were included in the study. LUS (10.13 ± 1.98 mm vs. 7.07 ± 1.66 mm, p<0.001) and myometrial LUS (MLUS) (5.63 ± 1.48 mm vs. 4.10 ± 1.22 mm, p<0.001) in the CD group were significantly higher than in the non-CD group. In the logistic regression analyses, significant independent effects of height (OR:0.88, 95 % CI: 0.79–0.98) and LUS (OR:2.71, 95 % CI: 1.66–4.43) values were observed in the prediction of CD. In the ROC analysis, both LUS (AUC 0.882, p<0.001) and MLUS (AUC 0.756, p<0.001) significantly predicted CD with an optimal cut-off value of 9.8 mm (75.0 % sensitivity, 92.6 % specificity) for LUS, and 5.1 mm (68.8 % sensitivity, 82.4 % specificity) for MLUS. Conclusions Ultrasonographic evaluation of LUS before IOL is a promising ultrasound parameter to predict CD. Although LUS and MLUS thickness measurements can be used to predict CD, LUS thickness has better sensitivity and specificity compared to MLUS thickness.
Open Access
Immunoediting in pregnancy: a new paradigm for understanding fetal tolerance and obstetric disease

October 3, 2025

Muhammad Adrianes Bachnas, Wiku Andonotopo, Julian Dewantiningrum, Mochammad Besari Adi Pramono, Muhammad Ilham Aldika Akbar, Ernawati Darmawan, Dudy Aldiansyah, I Nyoman Hariyasa Sanjaya, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak

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Introduction Pregnancy poses an immunological paradox: the maternal immune system must tolerate a semi-allogeneic fetus while maintaining defense against infections. Rather than being an immunosuppressed state, gestation is now recognized as a dynamic, highly regulated immune condition. Content This review applies the cancer-derived immunoediting framework – elimination, equilibrium, and escape – to maternal–fetal immune tolerance. We examine how immune checkpoints, regulatory T cells, non-classical MHC molecules, and placental exosomes coordinate to create a localized tolerant environment. Integrating knowledge from oncology and reproductive immunology, this perspective provides a unifying concept for pregnancy immune regulation. Summary The immunoediting framework reinterprets obstetric disorders such as preeclampsia, recurrent pregnancy loss, and preterm birth as failures of distinct immune phases rather than isolated pathologies. This conceptual shift allows for a broader understanding of how immune balance influences implantation, placental development, and fetal growth. Outlook Adopting an immunoediting perspective highlights potential clinical advances, including immune checkpoint modulation, regulatory T-cell therapies, and exosome-based biomarkers, paving the way for innovative diagnostic and therapeutic strategies in pregnancy care.
Open Access
Cardiac output-guided maternal positioning may protect the fetal oxygen supply and thereby reduce pregnancy complications

October 1, 2025

Thomas L. Archer

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Chronic and recurrent obstruction of the inferior vena cava by the gravid uterus may be asymptomatic for the mother and yet contribute to preeclampsia, fetal growth restriction, preterm birth, dysfunctional labor and uterine atony. This previously unrecognized possible cause of chronic and recurrent fetal, placental and myometrial hypoxia might be detected and corrected using “cardiac output-guided maternal positioning,” since positional obstruction of the inferior vena cava causes a positional decrease in maternal cardiac output (CO). These positional decreases in CO may therefore constitute an actionable warning signal for a pregnant woman to change her body position and thereby restore optimal uterine perfusion and fetal oxygenation. Continuous, non-invasive and hands-free trending of maternal CO is now feasible in real time in order to detect this warning signal in real time. Further research is required to evaluate this hypothesis, and if it is valid, the approach and therapy proposed might constitute a breakthrough for preventing some complications of pregnancy.
Open Access
Newborn screening for rare diseases: expanding the paradigm in the genomic era

September 29, 2025

Urh Grošelj

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Background Newborn screening (NBS) has long been a cornerstone of public health, initially designed to detect a few congenital disorders such as phenylketonuria and congenital hypothyroidism. This early intervention prevents irreversible health consequences. With the advent of genomic technologies, NBS programs are expanding to include a broader range of rare diseases (RDs), offering new opportunities and challenges in clinical implementation, ethics, and health system readiness. Content This mini-review traces the evolution of NBS from biochemical assays to next-generation sequencing (NGS) and whole-exome sequencing (WES). It highlights complexities in integrating RDs into NBS panels, including condition selection, test validation, confirmatory pipelines, and the need for robust follow-up. Ethical tensions between public health goals – focused on population benefit – and the personalized medicine paradigm are discussed, along with the importance of international harmonization to ensure equitable access. Summary Expanding NBS to include RDs can transform early diagnosis, reduce diagnostic delays, and enable timely interventions that improve outcomes. Successful genomic NBS (gNBS) integration requires clear, evidence-based inclusion criteria, validated diagnostics, and sustainable follow-up systems. Outlook Rapidly evolving genomic tools will reshape NBS, demanding agile policies, secure data infrastructures, and careful attention to consent, privacy, and equity. International collaboration and stakeholder engagement will be essential to ensure these technologies are implemented ethically and effectively, balancing public health priorities with individualized care.
Open Access
Preeclampsia is associated with increased NT-proBNP and altered lipid profiles in umbilical cord blood: a propensity score-matched analysis

September 26, 2025

Ji Eun Park, Juseok Yang, Hyen Chul Jo, Jong Chul Baek, Jeong Kyu Shin

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Objectives Preeclampsia (PE) is a hypertensive disorder of pregnancy related to adverse maternal and neonatal outcomes. While its effects on maternal health are well established, its impact on neonatal cardiovascular health remains incompletely understood. The aim of this study was to analyze metabolic and cardiovascular biomarkers in umbilical cord blood from pregnancies affected by PE. Methods A single-center retrospective observational study was conducted at Gyeongsang National University Changwon Hospital from September 2023 to December 2024. Umbilical cord blood samples from neonates of mothers with PE (n=72) and normotensive pregnancies (n=456) were analyzed to identify the lipid profiles and measure the levels of cardiovascular biomarkers. Propensity score matching (PSM) was applied to control for confounding variables such as maternal BMI and gestational age. Results After PSM, neonates born to mothers with PE had significantly higher total umbilical cord blood cholesterol levels (80.12 ± 32.45 vs. 67.27 ± 20.00 mg/dL, p<0.001), lower HDL cholesterol levels (29.12 ± 7.36 vs. 31.24 ± 6.75 mg/dL, p=0.042), and elevated NT-proBNP levels (3,805.43 ± 8,412.21 vs. 1,516.50 ± 2,439.78 pg/mL, p=0.004). Troponin-T levels were not significantly different between the groups after matching (p=0.320). Conclusions PE significantly alters umbilical cord blood lipid profiles and cardiovascular biomarkers, suggesting negative implications for the cardiovascular health of the fetus and early metabolic programming. Elevated NT-proBNP levels may serve as an early marker of neonatal cardiac stress, whereas abnormal lipid profiles may necessitate long-term cardiovascular monitoring.
Open Access
Plant-based antioxidant strategies with potential for preeclampsia prevention: clinical and mechanistic insights

September 24, 2025

Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, Theresia Monica Rahardjo, Aloysius Suryawan, Bambang Rahardjo, I Nyoman Hariyasa Sanjaya, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak

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Background Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, driven by oxidative stress, endothelial dysfunction, and systemic inflammation. Current preventive strategies, such as low-dose aspirin, offer modest benefit, highlighting the need for alternative approaches. Medicinal plants with antioxidant and anti-inflammatory properties, long used in maternal health traditions, may provide biological pathways relevant to preeclampsia prevention. Summary This review synthesizes human clinical and mechanistic evidence on four medicinal plants with documented antioxidant activity – Curcuma longa , Moringa oleifera , Orthosiphon aristatus , and Centella asiatica . These botanicals demonstrate potential mechanisms of action including redox modulation, preservation of endothelial function, and suppression of pro-inflammatory pathways, all of which are implicated in preeclampsia pathophysiology. Content A PRISMA-guided systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library (2000–2025) identified human studies evaluating these plants’ effects on oxidative stress and vascular health. Evidence was synthesized narratively due to heterogeneous study designs and outcomes. Most studies were small, often not pregnancy-specific, and used non-standardized botanical formulations. Outlook These medicinal plants offer biologically plausible pathways to reduce preeclampsia risk. However, pregnancy-focused randomized trials, dose optimization, pharmacokinetic profiling, and safety evaluations are essential before clinical integration into maternal care.
Open Access
FetalDenseNet: multi-scale deep learning for enhanced early detection of fetal anatomical planes in prenatal ultrasound

September 24, 2025

Samrat Kumar Dey, Arpita Howlader, Md. Shabukta Haider, Tonmoy Saha, Deblina Mazumder Setu, Tania Islam, Umme Raihan Siddiqi, Md. Mahbubur Rahman

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Objectives The study aims to improve the classification of fetal anatomical planes using Deep Learning (DL) methods to enhance the accuracy of fetal ultrasound interpretation. Methods Five Convolutional Neural Network (CNN) architectures, such as VGG16, ResNet50, InceptionV3, DenseNet169, and MobileNetV2, are evaluated on a large-scale, clinically validated dataset of 12,400 ultrasound images from 1,792 patients. Preprocessing methods, including scaling, normalization, label encoding, and augmentation, are applied to the dataset, and the dataset is split into 80 % for training and 20 % for testing. Each model was fine-tuned and evaluated based on its classification accuracy for comparison. Results DenseNet169 achieved the highest classification accuracy of 92 % among all the tested models. Conclusions The study shows that CNN-based models, particularly DenseNet169, significantly improve diagnostic accuracy in fetal ultrasound interpretation. This advancement reduces error rates and provides support for clinical decision-making in prenatal care.
Open Access
Endocrine disrupting chemicals: translating mechanisms into perinatal risk assessment

September 23, 2025

Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, Muhammad Ilham Aldika Akbar, Ernawati Darmawan, I. Nyoman Hariyasa Sanjaya, Dudy Aldiansyah, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak

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Objectives To evaluate the evidence linking prenatal exposure to environmental endocrine-disrupting chemicals (EDCs) – including bisphenol A (BPA), phthalates, and per- and polyfluoroalkyl substances (PFAS) – with adverse pregnancy and fetal developmental outcomes, and to assess the potential translation of this evidence into clinical perinatal risk assessment. Methods A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published between January 2000 and May 2025. Eligible studies included epidemiological and experimental research addressing prenatal EDC exposure and fetal-placental outcomes. After duplicate removal and screening, 52 studies met inclusion criteria and were categorized by study type (epidemiological, mechanistic, translational). Data extraction included exposure metrics, critical developmental windows, and reported effect sizes (odds ratios, risk ratios, hazard ratios). Results Evidence suggests that EDC exposure during early pregnancy is associated with placental dysfunction, altered fetal growth trajectories, endocrine and epigenetic modifications, and increased risk of selected neonatal outcomes. Effect sizes were variable, often modest (many<2.0), but consistently indicated biological plausibility supported by mechanistic data. Biomonitoring studies demonstrate widespread EDC exposure across populations, including higher body burdens in lower-income and racially diverse groups. Despite robust basic science evidence, clinical screening for EDC exposure remains limited, and routine risk assessment frameworks rarely incorporate environmental chemical exposures. Conclusions Prenatal EDC exposure is biologically linked to disrupted fetal-placental development, yet translation into clinical practice remains incomplete. Integrating environmental exposure assessment and preventive counseling into perinatal care may improve maternal-fetal health and reduce disparities.
Open Access
Evaluation of safety and performance of CentaFlow™ in the assessment of fetal growth restriction – a randomized trial and prospective cohort study

September 23, 2025

Cathrine Vedel, Ane Rom, Dave Wright, Richard Farlie, Lise Hald Nielsen, Anne Hammer Lauridsen, Simone Hansen, Hanne Hegaard, Frederikke Huitfeldt Sander, Mie de Wolff, Olav Bjørn Petersen

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Objectives The aim was to evaluate the sensitivity and specificity of centaflow (CF) in a prospective multicenter study, and secondary to evaluate the safety of the CF device in a randomized multicenter study. Methods A sponsor-initiated multicenter randomized controlled clinical trial with termination of the randomization after enough women had been included to evaluate safety. The study proceeded as a prospective multicenter study including high-risk women (estimated fetal weight <−15 %, FGR). The first part randomized women to either standard care (SC) or SC+CF. Participants underwent CF evaluation with subsequent analysis for sensitivity and specificity for FGR at birth. Secondarily, adverse events were evaluated. Clinical assessments of fetal size conducted by midwives served as a reference. The performance of CF and SC was compared by McNemar’s Test. The performance analysis of CF was done per-protocol sample. Results A total of 1,601 pregnant women were enrolled, with 886 undergoing CF evaluation. A total of 123 were FGR (<3rd percentile) at birth, of which 88 were evaluated by CF, and 117 had a clinical assessment of the estimated fetal weight. CF demonstrated no evidence of benefit for detecting FGR with a sensitivity of 50 % and specificity of 43 %. Adverse events associated with CF use were limited to minor skin irritation. McNemar’s test showed SC was superior to CF regarding specificity as a screening tool (p=0.014). Conclusions While CF was safe to use, we found no evidence that CF can be used as a predictor of FGR. Further refinement of signal analysis is necessary to enhance CFs diagnostic utility.
Open Access
Postpartum maternal complications: a retrospective single-center study

September 23, 2025

Nuša Stopar, Andreja Trojner Bregar

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Objectives To evaluate the incidence and underlying causes of postpartum complications, with a focus on infections, among women who delivered at a tertiary maternity hospital over a 17-year period. Methods This retrospective observational study was conducted at the University Medical Center Ljubljana, the largest maternity hospital in Slovenia. The study included all women who delivered vaginally or via cesarean section between 2008 and 2024 and subsequently required medical assessment or hospitalization within six weeks postpartum. We analyzed the frequency and types of complications, paying special attention to infection rates by delivery method and microbiological findings from wound swabs. Results Postpartum complications were observed in 7.6 % of women following vaginal birth and 10.6 % after cesarean delivery. Infections and breastfeeding-related problems were the most common causes for medical reevaluation. After vaginal delivery, breast complications such as mastitis or milk stasis represented 36.4 % of all cases, followed by minor perineal issues. Following cesarean section, surgical site complications were most frequent (42.1 %), with a wound infection rate of 7.7 %. Between 2020 and 2024, readmissions to intensive care occurred in 0.92 % of vaginal deliveries and 2.76 % of cesarean deliveries. Endometritis was the most common infection after vaginal birth, while wound infections predominated post-cesarean. Wound swab cultures often revealed polymicrobial flora. Conclusions Postpartum infections remain a leading complication, particularly after cesarean delivery. Strengthening preventive measures including antibiotic prophylaxis, timely postpartum follow-up, and continuous microbial surveillance is critical to reducing maternal morbidity and supporting more effective, targeted interventions.
Open Access
Integrating generative AI in perinatology: applications for literature review

September 23, 2025

Rodrigo Ayala-Yáñez, Amos Grünebaum, Frank A. Chervenak

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Perinatology relies on continuous engagement with an expanding body of clinical literature, yet the volume and velocity of publications increasingly exceed the capacity of clinicians to keep pace. Generative artificial intelligence (GAI) tools – such as ChatGPT4, Claude AI, Gemini, and Perplexity AI – offer a novel approach to assist with literature retrieval, comparison of clinical guidelines, and manuscript drafting. This study evaluates the strengths and limitations of these tools in maternal-fetal medicine, using structured clinical prompts to simulate real-world applications. Perplexity AI demonstrated the best citation accuracy, while ChatGPT4 and Claude excelled in content summarization but required manual verification of citations. In simulated trials, GAI tools reduced the time to generate clinically relevant summaries by up to 70 % compared to traditional PubMed searches. However, risks such as hallucinated references and overreliance on machine-generated text persist. Use cases include summarizing aspirin use guidelines for preeclampsia and comparing ACOG vs. NICE protocols. GAI should be viewed as a supportive assistant, not a substitute, for expert review. To ensure responsible integration, clinicians must develop AI literacy, apply rigorous oversight, and adhere to ethical standards. When used judiciously, GAI can enhance efficiency, insight, and evidence-based decision-making in perinatal care.
Open Access
Liver fibrosis markers as predictors of adverse outcomes in pregnancy-related hypertensive disorders

September 18, 2025

Murad Gezer, Ümit Taşdemir, Mucize Eriç Özdemir, Sevdenur Yiğit, Büşra Cambaztepe, Oya Demirci

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Objectives This study aimed to compare noninvasive liver fibrosis markers, including the Aspartate Aminotransferase Platelet Ratio Index (APRI) and FIB-4, between patients with hypertensive disorders of pregnancy (HDP) and healthy controls and to investigate the association between these markers and adverse maternal and perinatal outcomes. Methods In this retrospective case-control study, 205 patients with HDP and 192 normotensive controls were included for evaluation. Demographic data, laboratory findings, and maternal and perinatal outcomes were compared. FIB-4 and APRI scores were calculated using second-trimester AST, ALT, and platelet levels. ROC curve analysis was used to assess the predictive accuracy of these indices for HELLP syndrome and other complications. Linear regression analysis was applied to evaluate the parameters associated with the FIB-4 score. Results FIB-4 and APRI scores were significantly higher in patients with HDP compared to controls (p<0.05). Among patients with severe preeclampsia and HELLP syndrome, fibrosis scores were markedly elevated. FIB-4 and APRI showed excellent diagnostic performance for HELLP syndrome (AUC: 0.976 and 0.992, respectively), with optimal cutoffs of 1.52 and 0.7. However, their predictive role for general adverse maternal and perinatal outcomes was limited. In multivariate regression, systolic blood pressure, maternal age, and adverse maternal outcomes were independent predictors of increased FIB-4 scores (p<0.05). Conclusions FIB-4 and APRI may be considered simple, noninvasive indices that could contribute to early risk stratification for HELLP syndrome among patients with HDP. Although their predictive capacity remains to be validated in larger prospective studies, they may offer preliminary insights into hepatic dysfunction during pregnancy.
Open Access
Incidence and mortality trends in congenital diaphragmatic hernia in the United States

September 18, 2025

Nihaal D. Shah, Fredrick Dapaah-Siakwan

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Objectives The average incidence of congenital diaphragmatic hernia (CDH) in the United States (US) is 2.6 per 10,000 live births but it varies based on the population studied, the database used, and the study period. Further, previous studies suggest that pre-discharge mortality in CDH is declining but this may not capture the ‘hidden mortality’ and post-discharge mortality. We examined a population-based database to evaluate the trends in the incidence (2016–2023) and CDH-related infant mortality rate (CDH-IMR) [2007–2022] in the US. Methods We conducted a retrospective cross-sectional analysis of the CDC WONDER database. First, we queried the 2016–2023 natality dataset derived from birth certificates for live births with CDH (ICD-10 code Q79.0). We expressed CDH incidence as per 10,000 live births. Next, we queried the linked birth/infant death dataset from 2007 to 2022 for CDH-IMR through 1 year of age. CDH-IMR was expressed per 100,000 live births. Trends were evaluated with Joinpoint regression and reported using average annual percentage change (AAPC) with 95 % confidence intervals (CI). Results Among 29, 880, 509 live births between 2016 and 2023, 3,797 had CDH (1.3 per 10,000). Of these, 33.4 % were transferred within 24 h after birth. There was no significant change in the CDH incidence during the study period (AAPC 0.93 %; CI: −0.1, 2.0). The overall CDH-IMR (per 100,000) was 5.7, and it declined significantly from 6.3 in 2007 to 4.7 in 2022 (AAPC: −1.5 %; CI: −2.2, −0.8). Conclusions The CDH incidence, which was lower than previously reported and did not change from 2016 to 2023, requires validation. The downward trend in mortality needs ongoing surveillance to monitor the impact of new management strategies on mortality rates.
Open Access
Prenatal maternal stress and long-term neurodevelopmental outcomes: a narrative review

September 17, 2025

Dimitris Baroutis, Ioanna Myrto Sotiropoulou, Rafail Mantzioros, Marianna Theodora, George Daskalakis, Panagiotis Antsaklis

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Introduction Maternal stress during pregnancy has been increasingly recognized as a significant factor influencing fetal development, with potential long-term effects on neurodevelopmental outcomes in offspring. Understanding the mechanisms and implications of prenatal stress exposure is crucial for informing preventative and interventional strategies in perinatal care. Content This narrative review synthesizes findings from epidemiological, neurobiological, and clinical research on the long-term consequences of prenatal maternal stress. It explores a broad spectrum of stressors – including psychological distress, depression, anxiety, and acute traumatic events such as natural disasters – and their associations with cognitive, behavioral, and emotional outcomes in offspring from infancy through adolescence. Key biological mechanisms are discussed, including alterations in the maternal-placental-fetal axis, HPA axis dysregulation, placental gene expression changes, epigenetic modifications, and neuroinflammatory responses. Neuroimaging and biomarker studies are highlighted to provide evidence for stress-related changes in brain structure and function. Summary Current literature supports a robust association between maternal stress during pregnancy and a heightened risk of neurodevelopmental challenges in children. These include deficits in executive function, increased anxiety and depressive symptoms, emotional dysregulation, and susceptibility to psychiatric disorders. The effects appear to be moderated by timing of exposure, genetic predispositions, and the postnatal environment. Outlook While the evidence base is growing, methodological limitations such as variability in stress assessment and inconsistent follow-up durations persist. Future research should emphasize longitudinal, biomarker-informed designs and evaluate interventions aimed at reducing prenatal stress. Integrating maternal mental health support into routine prenatal care may offer a promising pathway to improving both maternal and child outcomes.
Open Access
Nutriepigenomics in perinatal medicine: maternal nutrition as a modulator of fetal gene expression and long-term health

September 17, 2025

Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, Sri Sulistyowati, I Nyoman Hariyasa Sanjaya, Milan Stanojevic, Asim Kurjak

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Introduction Maternal nutrition during pregnancy can influence fetal development through epigenetic modifications, affecting gene expression without altering DNA sequence. Nutriepigenomics – the study of nutrient-driven epigenetic regulation – provides critical insights into how prenatal nutritional exposures can shape immediate and lifelong health outcomes. Content This narrative review synthesizes evidence from human cohort studies and experimental animal models on how macro- and micronutrients, including folate, vitamin B12, choline, vitamin D, omega-3 fatty acids, and bioactive compounds such as polyphenols and resveratrol, modify key epigenetic processes. These include DNA methylation, histone modifications, and non-coding RNA regulation, particularly within the placenta and developing fetal tissues. Summary Maternal diet-induced epigenetic changes influence fetal metabolic programming, neurodevelopment, immune maturation, and organogenesis, with impacts detectable at birth and persisting into adulthood. Evidence indicates associations with altered birthweight trajectories, increased risk of childhood obesity and immune dysregulation, and potential elevation in lifelong cardiometabolic and neuropsychiatric disease risk. Outlook Integrating nutriepigenomic insights into perinatal care offers opportunities for early preventive strategies and personalized nutrition interventions. Translational application of epigenetic biomarkers, coupled with population-level nutritional policies, could reduce disease risk across generations and improve long-term population health outcomes.
Open Access
Gestational diabetes and fetal macrosomia: a dissenting opinion

September 16, 2025

Renata Košir Pogačnik, Maja Krajec, Marija Batkoska, Andreja Trojner Bregar

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Objectives To examine the effect of interaction between parity, overweight/obesity, gestational weight gain, and gestational diabetes mellitus (GDM) on the incidence of fetal macrosomia. Methods We used a population-based dataset to establish the incidence of macrosomia (birth weight >4000 g) in singleton births at ≥38 weeks’ gestation. The cohort included women who were (1) overweight/obese or had normal body mass index (BMI) before pregnancy, (2) nulliparous or multiparous, (3) with appropriate or excessive weight gain, and (4) without GDM, with GDM controlled by nonpharmacological treatment (GDM0), or with GDM requiring insulin treatment (GDM1). Results We examined 129 686 births at ≥38 weeks. The mean gestational age at birth for all subgroup was similar. When compared with a reference incidence for nulliparas with normal pregravid BMI, appropriate weight gain, and without GDM, all variables, except GDM, independently and significantly increased the incidence of neonates weighing >4000 g. The logistic regression analysis found that excessive weight gain, pregravid BMI >25, and parity were the only independent factors associate with birth weight >4000 g. Conclusions Well-managed GDM is not significantly associated with macrosomia, whereas pre-pregnancy obesity, excessive gestational weight gain, and parity appear to be significant risk factors. These results emphasize the need for effective weight management before and during pregnancy to reduce the risk of fetal overgrowth.
Open Access
First-trimester maternal serum PAPP-A levels and hyperemesis gravidarum: unraveling the link – a meta-analysis

September 1, 2025

Antonia Varthaliti, Vasilios Pergialiotis, Vasilios Lygizos, Panos Antsaklis, Marianna Theodora, Dimitrios-Efthymios Vlachos, Maria Anastasia Daskalaki, Nikolaos Thomakos, George Daskalakis

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Objectives Hyperemesis gravidarum is a severe form of nausea and vomiting that affects approximately 0.3–2 % of pregnancies, leading to significant perinatal complications. This systematic review and meta-analysis aims to investigate the potential link between hyperemesis gravidarum and maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels in the first trimester. Methods A thorough literature search of PubMed/MEDLINE, ScienceDirect, the Cochrane Library, and Google Scholar was conducted to identify relevant studies comparing PAPP-A levels in pregnant women diagnosed with hyperemesis gravidarum compared to healthy controls. Six studies met the inclusion criteria, with a total of 1,049 participants. Meta-analysis was performed to estimate the pooled mean difference in PAPP-A levels between hyperemesis gravidarum and control groups. A p-curve analysis and funnel plot assessment were conducted to evaluate publication bias and statistical power. Results The meta-analysis demonstrated a pooled mean difference of 0.16 (95 % CI: 0.07–0.25), indicating that PAPP-A levels were significantly higher in pregnancies affected by HG. The heterogeneity statistic (I 2 =46 %) suggested moderate variability among studies. P-curve analysis showed a right-skewed distribution of significant p-values (p=0.033), suggesting evidential value and ruling out selective reporting bias. However, the prediction interval (−0.08–0.4) indicated that some future studies might yield non-significant or even negative findings. Funnel plot analysis revealed minimal publication bias, though a slight asymmetry suggested potential underrepresentation of small, non-significant studies. Conclusions This study provides evidence that PAPP-A levels are elevated in pregnancies complicated by hyperemesis gravidarum, implicating potential placental dysfunction and hormonal influences in its pathogenesis. While the findings are statistically significant and robust against publication bias, moderate heterogeneity highlights the need for larger prospective studies with standardized methodologies to confirm this association and explore possible underlying mechanisms. Understanding the role of PAPP-A in hyperemesis gravidarum may contribute to improved screening and management strategies for affected pregnancies and as a result, improved perinatal care.
Open Access
Fetoception: a window into maternal interoception?

September 1, 2025

Marion Imbault, Caroline Sévoz-Couche, Emmanuelle Corruble, Hugo Bottemanne

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Fetoception refers to the maternal detection and integration of signals originating from the fetus, particularly the perception of fetal movements. This process reflects a specific form of maternal interoception, the central nervous system’s capacity to process internal bodily signals. As such, fetoception offers a unique window into maternal interoceptive processing during pregnancy, a period marked by profound physiological and sensory changes. Exploring the mechanisms underlying fetoception may provide novel insights into the dynamic interactions between interoceptive systems and the maternal adaptation to pregnancy. Furthermore, potential links between fetoception, interoception, and perinatal mental health remain largely unexplored and warrant further investigation.
Open Access
Rationale for the use of fetal ventriculosubgaleal shunts for the treatment of aqueduct stenosis

September 1, 2025

Shohra Qaderi, Weston T. Northam, Ramen H. Chmait, Mark Krieger, Yves Ville, Benjamin C. Warf, Amos Grünebaum, Frank A. Chervenak, Alireza A. Shamshirsaz

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Fetal hydrocephalus causes irreversible neural injury in utero , yet no prenatal therapy currently exists. Postnatal treatments such as ventriculoperitoneal shunts and endoscopic third ventriculostomy with choroid plexus cauterization cannot reverse pre-existing brain injury. We propose that the ventriculosubgaleal shunt (VSGS), widely used as a temporizing measure in severely premature neonates, may offer a feasible and ethically justifiable approach for in utero treatment. VSGS placement avoids the complications of ventriculoamniotic shunts and leverages a closed system that can relieve intracranial pressure and potentially preserve brain tissue integrity. Given its technical simplicity, established safety profile, and alignment with core ethical principles – including maternal autonomy and proportional risk-benefit, we argue for consideration of VSGS as an investigational fetal therapy in selected cases of progressive hydrocephalus. Given its investigational status, implementation should be limited to clinical trials with stringent IRB supervision and ethical safeguards.
Open Access
Antenatal shunting and outcomes in fetuses with non-immune hydrops fetalis

August 26, 2025

Valentina Fragala, Sanjeev Sabale, Ghalia Ashoor, Christopher Harris, Carolina Zorro, Anne Greenough

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Objectives Hydrops fetalis is associated with high morbidity and perinatal mortality. The aim of our study was to compare the outcomes of infants who had non-immune hydrops fetalis (NIHF) who did or did not undergo antenatal shunting . Methods Between January 2014 and June 2023, 20 infants with the diagnosis of NIHF were admitted to the neonatal intensive care unit (NICU) at King’s College Hospital NHS Foundation Trust. The criteria for antenatal shunt placement were development of hydrops fetalis, polyhydramnios due to oesophageal compression by a pleural effusion that would likely result in preterm labour or a large pleural effusion (no hydrops at presentation) resulting in likely inferior vena cava compression and significant risk of development of hydrops. Results The 20 infants had a median gestational age of 34 (27–40) weeks of gestation at delivery and were diagnosed at a median gestational age of 29 (17–40) weeks. Eight infants had a shunt inserted antenatally (six pleuro amniotic and two abdominal amniotic) and they delivered at a significantly later median gestational age (36 vs. 32.5 weeks, p=0.025). After adjustment for gestational age at delivery and antenatal severity, those who had a shunt placed were not more likely to be oxygen dependent at 36 weeks post menstrual age (PMA) and had a lower length of stay (23 vs. 95 days, p=0.019). Conclusions Infants who had NIHF and had antenatal shunting had favourable outcomes compared to those who did not, despite a more severe antenatal presentation.
Open Access
Sonographic surveillance and perinatal outcomes among pregnancies with periviable fetal growth restriction

August 22, 2025

Felicia V. LeMoine, Angela C. Ranzini, Marisa R. Imbroane, Esha V. Ghosalkar, David N. Hackney, Emily J. Hamburg-Shields

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Objectives This study compared adverse perinatal outcomes between pregnancies complicated by periviable fetal growth restriction (pFGR) that underwent weekly sonographic surveillance vs. serial growth surveillance. Methods In this retrospective cohort study, pFGR was defined as a 22 0/7–27 6/7-week singleton, <500 g, and ≤10 % for gestational age. The surveillance group initiated weekly Doppler surveillance while the serial growth (SG) group underwent growth assessment every 3–4 weeks between 22 and 27 6/7 weeks. Adverse perinatal outcomes were compared. Results Eighty-one (36.2 %) underwent weekly Doppler surveillance. Chronic hypertension (18.5 % vs. 9.1 %, p=0.04), a prior history of fetal demise (8.6 % vs. 2.1 %, p=0.02), and an estimated fetal weight <3 % (22.2 % vs. 10.5 %, p=0.02) and any abnormal umbilical artery Doppler pattern at diagnosis (25.8 % vs. 12.9 %, p=0.046) occurred more frequently in the weekly Doppler surveillance group than the SG group. Despite no difference in perinatal death, the surveillance group demonstrated a higher rate of obstetric (65.4 % vs. 42.7 %, p<0.05) and neonatal (60.8 % vs. 28.4 %, p<0.05) adverse outcome composites compared to the SG group. Conclusions The surveillance group experienced increased rates of obstetric and neonatal morbidity without difference in perinatal death though interpretation is limited by the observational nature of this study.
Open Access
Amniotic Fluid Embolism: a comprehensive review of diagnosis and management

August 22, 2025

Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, Caroline Setiawan, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak

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Introduction Amniotic Fluid Embolism (AFE) is a rare but catastrophic obstetric emergency characterized by the sudden entry of amniotic fluid or fetal debris into the maternal circulation. This triggers acute cardiopulmonary collapse, disseminated intravascular coagulation (DIC), and multi-organ failure. Despite its low incidence, AFE remains a significant contributor to maternal mortality worldwide. The pathophysiology is poorly understood, involving immune-mediated anaphylactoid reactions and mechanical vascular obstruction. Content This review provides a comprehensive synthesis of current knowledge on AFE, examining its epidemiology, pathophysiology, risk factors, clinical manifestations, diagnostic challenges, and management strategies. A systematic literature review was conducted following PRISMA guidelines, incorporating peer-reviewed articles and clinical protocols published from 2000 to 2024. Clinical tools such as diagnostic algorithms and resuscitation frameworks were developed from aggregated evidence and thematic analysis. Summary AFE typically presents intrapartum or in the immediate postpartum period with sudden hypoxia, hypotension, and coagulopathy. Diagnosis is clinical, as no single confirmatory biomarker currently exists. Management is primarily supportive, focusing on rapid resuscitation, hemodynamic stabilization, and aggressive coagulopathy correction. Emerging strategies such as the A-OK regimen (Atropine, Ondansetron, Ketorolac) are discussed as investigational approaches under consideration. Outlook AFE continues to challenge obstetric and critical care teams due to its abrupt onset and high fatality. Future priorities include the development of validated diagnostic biomarkers, refinement of therapeutic interventions, and establishment of standardized multidisciplinary response protocols to improve maternal and neonatal outcomes.
Open Access
Correlation of serum miR-203a-3p with the severity of neonates with necrotizing enterocolitis and analysis of its molecular mechanism

August 8, 2025

Fengna Zhu, Zhengjiang Jin, Weiyu Liu, Hongyan Liu

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Objectives The objective of this study was to examine the role of microRNA-203a-3p (miR-203a-3p) in the pathogenesis of necrotizing enterocolitis (NEC). Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and receiver operating characteristic (ROC) curve analysis were employed to evaluate the relative abundances of miR-203a-3p as well as its diagnostic capacity. Logistic regression was applied to search for influential risk factors associated with NEC in neonates. Cell behaviors were assessed with flow cytometry and CCK-8 detection. The target genes of miR-203a-3p and its potential biological functions were analyzed via bioinformatic analysis. Results A significant reduction in serum levels of miR-203a-3p was observed in neonates with NEC. Notably, this miRNA exhibited exceptional diagnostic precision for differentiating NEC from non-NEC cases, as evidenced by an area under the curve (AUC) of 0.928. Furthermore, miR-203a-3p was established as an independent indicator for assessing the severity of NEC. In an NEC cell model, levels of miR-203a-3p were distinctly diminished; however, this decrease was significantly reversed following transfection with miR-203a-3p (p<0.001). Correspondingly, findings were noted regarding cell apoptosis, cell viability, inflammatory indicators, and antioxidant enzyme activities. MiR-203a-3p-related genes predominantly clustered within inflammatory-associated signaling pathways and proteins, particularly ataxia telangiectasia mutated (ATM). Notably, miR-203a-3p was found to directly target ATM. Importantly, heightened levels of ATM were detected in both neonates with NEC and LPS-triggered fetal human colon (FHC) cells (p<0.001). Conclusions MiR-203a-3p alleviates LPS-induced inflammatory damage in FHC cells through regulating ATM, thereby presenting a promising avenue for the development of novel therapeutic strategies for neonates with NEC.
Open Access
From exencephaly to anencephaly: a catastrophic continuum of neural tube defects from embryogenesis to ultrasonographic diagnosis

August 5, 2025

Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak

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Introduction Neural tube defects (NTDs) are severe congenital anomalies arising from incomplete closure of the neural tube during early embryogenesis. Among cranial NTDs, exencephaly, acrania, and anencephaly represent a progressive developmental continuum, leading to major cerebral destruction and absence of cranial structures. Content This narrative integrative review synthesizes embryological mechanisms, historical documentation, epidemiology, genetic and environmental risk factors, and advances in prenatal imaging for acrania, exencephaly, and anencephaly. Special focus is placed on the sequential ultrasonographic findings from the first to third trimester, highlighting the transformation across this continuum. Future research possibilities, including predictive artificial intelligence models, noninvasive genetic risk profiling, and experimental in utero therapies, are also discussed. Summary Drawing on data from over 50 peer-reviewed studies, this review integrates knowledge across embryology, teratology, maternal-fetal medicine, genetics, imaging, and bioethics. It aims to guide fetal medicine specialists, radiologists, genetic counsellors, and researchers in understanding, diagnosing, and counselling for these cranial neural tube defects. Outlook Future directions emphasize precision prevention strategies, including optimized maternal folate supplementation, enhanced prenatal screening, and potential genomic therapies for high-risk pregnancies.
Open Access
Quo vadis neonatologia? Where is neonatology heading in the 21st century?

July 10, 2025

Milan Stanojević, Bożena Kociszewska-Najman, Amos Grünebaum, Frank Chervenak, Asim Kurjak

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Introduction This comprehensive narrative review examines current paradigms, emerging trends, and future directions in neonatology through systematic analysis of contemporary literature, clinical practice patterns, and expert consensus. We synthesized evidence from recent publications, international guidelines, and clinical innovations to identify key transformation areas. Content Several critical areas are reshaping neonatology. Gestational age has emerged as a lifelong health determinant with implications extending far beyond the neonatal period, affecting cardiovascular, metabolic, and neurodevelopmental outcomes throughout life. Global disparities in neonatal care remain unconscionably large, with survival rates for 28-week infants exceeding 90 % in high-income countries while similar infants in low-resource settings often die from preventable causes. Artificial intelligence applications are revolutionizing predictive analytics, real-time monitoring, and decision support systems, though implementation requires careful attention to bias, transparency, and human oversight. The neonatal microbiome’s crucial role in immune development and long-term health has prompted interventions targeting healthy colonization. Salutogenic approaches emphasizing health promotion rather than disease treatment are gaining recognition. Most significantly, the systematic marginalization of mothers in neonatal care is being challenged, with growing recognition of the mother-infant dyad as the fundamental unit of care. Summary and Outlook Future neonatal care must balance technological advancement with humanistic values, addressing global disparities while maintaining scientific rigor. Success requires committing to global health equity, embracing ethical complexity at viability margins, recognizing maternal centrality, thoughtfully integrating emerging technologies, implementing salutogenic principles, and adopting lifelong health perspectives. The field’s future depends on interdisciplinary collaboration, ethical reflection, and unwavering commitment to ensuring every newborn receives compassionate, high-quality care.
Open Access
The fetus as a patient: professional responsibility in contemporary Perinatal Medicine

July 7, 2025

Frank A. Chervenak, Asim Kurjak, Milan Stajonevic, Joachim Dudenhausen, Amos Grünebaum

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The concept of the fetus as a patient has evolved over the past several decades, driven by advances in fetal medicine, neonatology, and bioethics. Pioneering international work by Erich Saling, Ian Donald, William Liley, L. Stanley James, and Roberto Caldeyro-Barcia transformed the fetus from a passive presence into an active subject of medical diagnosis and intervention, laying the groundwork for a dual-patient ethical model in obstetric care. The Society “The Fetus as a Patient,” established in the early 1990s, galvanized international collaboration among clinicians and ethicists, promoting the recognition of the fetus as a patient. Since its inception, the Journal of Perinatal Medicine has served as the official and essential publication of the Society for the Fetus as a Patient, disseminating many of its most influential papers. Central to this evolution is the professional responsibility model, which delineates clinicians’ ethical obligations to both pregnant and fetal patients, emphasizing evidence-based advocacy and beneficence while respecting maternal autonomy. The model defines the fetus as a patient when the pregnant woman seeks care and when interventions can reasonably benefit the fetus, with viability as an inflection point serving as a key ethical threshold. Technological advances in the 21st century, such as fetal surgery and gene therapy, have further advanced the ethical landscape, necessitating nuanced, preventive ethics and transparent communication. The 2009 and 2024 International Academy of Perinatal Medicine New York declarations have reinforced the global commitment to equitable, ethically sound perinatal care, balancing maternal rights and fetal interests. As maternal-fetal medicine continues to advance, ongoing ethical reflection, institutional support, and interdisciplinary international collaboration remain essential for aligning clinical innovation with professional integrity and justice in perinatal care.
Open Access
Feasibility and reproducibility of speckle tracking echocardiography in routine assessment of the fetal heart in a low-risk population: a letter reply

July 7, 2025

Adalina Sacco, Ayisha Kazi, Diane Lambo, Victoria Jowett, Pranav Pandya

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Open Access
Urinary immune biomarkers for late-onset sepsis in preterm very low birth weight neonates – a diagnostic accuracy study

January 1, 2000

Gayatri Morajker, Ashwini Ankush Patil, Prashanth Ranya Raghavendra, Anuja Datar, Sruthi Nair, Prajakta Dandekar Jain, Haribalakrishna Balasubramanian, Anitha Haribalakrishna, Medha Goyal, Nandkishor S. Kabra

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Objectives To evaluate diagnostic accuracy of urinary immune biomarkers (IBM) for late-onset sepsis (LOS) in very preterm infants. Methods This multicenter, prospective diagnostic accuracy study, included preterm infants <32 weeks of gestation and birth weight <1,500 g, needing evaluation for suspected LOS. Urine samples obtained concurrent to blood culture and sepsis screen were evaluated for interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) levels using enzyme immunoassay. Positive blood and/or CSF culture served as reference standards. Receiver operating characteristic curves were used to evaluate performance of urinary IBM for detection of LOS. Results During September 2021–September 2023, we evaluated 136 preterm, very low birth weight infants (mean gestational age: 28.2 weeks, mean birth weight: 933 g) for sepsis after 72 h of postnatal age and prior to 37 weeks postmenstrual age. Twenty four infants had culture-positive sepsis. Median IL-8 and MCP-1 levels in neonates with LOS were 86.5 pg/mL and 230.2 pg/mL and those in non-infected neonates were 66.5 pg/mL and 212.1 pg/mL. Urinary IL-8 had sensitivity and specificity of 42 and 51 % [AUC: 0.46 (0.35–0.57)] and urinary MCP-1 had sensitivity and specificity of 46 and 53 % [AUC: 0.49 (0.38–0.60)] for detection of LOS. Conclusions Urinary IL-8 and MCP-1 had low sensitivity and specificity for diagnosis of LOS in very preterm infants. These findings underscore the need to establish reference ranges for urinary IBM in preterm neonates.
Open Access
McDonald vs. Shirodkar cerclage for the prevention of preterm birth in patients with obesity

January 1, 2000

Sarah H. Abelman, Frank I. Jackson, Nathan A. Keller, Julie Chen, Luis A. Bracero, Matthew J. Blitz

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Objectives Transvaginal cervical cerclage is a common intervention to prevent preterm birth in high-risk patients. This study aimed to compare McDonald and Shirodkar cerclage techniques in preventing preterm birth among patients with obesity, a group at increased risk for adverse pregnancy outcomes. Methods This was a retrospective study of singleton pregnancies complicated by pre-pregnancy obesity (BMI≥30 kg/m 2 ) and transvaginal cerclage placement between 2018 and 2023 within a large health system in New York. The primary exposure was type of cerclage, McDonald or Shirodkar. Primary outcomes were preterm birth <37 weeks and <34 weeks. Secondary outcomes were spontaneous preterm birth <37 and <34 weeks, and gestational age at delivery. Subgroup analyses were performed by cerclage indication (history-, ultrasound-, or exam-indicated). Multivariate logistic regression and linear mixed model analyses were utilized to evaluate these outcomes while controlling for potential confounders. Results Of 495 patients included, 375 (76 %) underwent McDonald and 120 (24 %) underwent Shirodkar cerclage. In adjusted and unadjusted analyses, there was no significant difference in preterm birth at <37 or <34 weeks (p=0.98 and p=0.30 respectively) or spontaneous preterm birth at <37 or <34 weeks (p=0.75 and p=0.36) between the groups. There was no significant difference in mean gestational age at delivery (36.4 ± 4.3 vs. 35.9 ± 4.7 weeks, p=0.50). Subgroup analyses confirmed similar findings across cerclage indications, though with a benefit for the McDonald technique for ultrasound-indicated cerclages (36.6 ± 4.2 vs. 35.0 ± 5.1 weeks, p=0.02). Conclusions McDonald and Shirodkar cerclages are equally effective in prolonging pregnancy in patients with obesity.
Open Access
Association of discordance in birth weights of dichorionic twins with the incidence of preeclampsia in pregnant women

January 1, 2000

Sara Čebron, Anja Rupar, Ivan Verdenik, Tanja Premru-Sršen

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Objectives Preeclampsia (PE) is more common in multiple pregnancies, especially dichorionic twins, which often show birthweight discordance. The threshold of birthweight discordance linked to increased risk remains unclear, based largely on the Delphi consensus method. This study examines whether discordance independently predicts PE and identifies the most predictive threshold to guide prenatal care. Methods We conducted a retrospective population-based cohort study of 2,546 women with dichorionic twins who delivered in Slovenia between 2013 and 2022, using data from the National Perinatal Information System. The association between twin birthweight discordance, the main independent variable, and PE, the main outcome variable, was determined using multivariate logistic regression. We calculated the crude odds ratio (OR) and adjusted odds ratio (aOR) with a 95 % confidence interval. ROC analysis determined the area under the curve (AUC), the sensitivity, and the false positive rate for predicting PE. Two-sided p-values <0.05 were considered statistically significant. Results In our cohort PE occurred in 5.38 %. Compared with a birthweight discordance of <10 %, a discordance >25 % was identified as a statistically significant independent risk factor for PE development (aOR=1.66; 95 % CI 1.10–2.52; p=0.016). Birthweight discordance between 10 and 25 % was not significantly associated with PE. The AUC for predicting PE with birthweight discordance was significant at 55.2 % (51.6–58.8 %). However, at a birthweight discordance threshold of >25 %, only 10.2 % of pregnant women with PE could be identified with 5.8 % false-positive results. Conclusions This study revealed that a birthweight discordance >25 % in dichorionic twins significantly increases PE risk.
Open Access
Structured stillbirth management in Slovenia: outcomes and comparison with international guidelines

January 1, 2000

Maja Dolanc Merc, Tanja Premru-Sršen

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Background Stillbirth remains a major public health issue with long-lasting psychological impacts. Despite advancements in prenatal diagnostics, many stillbirths remain unexplained. Slovenia has implemented a structured, centralized algorithm for stillbirth investigation and care. Content This mini-review analyzes a decade of clinical data (2013–2023) from the Department of Perinatology at University Medical Centre Ljubljana (UMC Ljubljana), assessing the outcomes of Slovenia’s stillbirth management algorithm. The Slovenian approach is also compared with international guidelines from ACOG, RCOG, CNGOF, PSANZ, SOGC, and FOGSI. Slovenia reports one of the lowest stillbirth rates in Europe – 2 per 1,000 births at ≥24 weeks and 1.4 per 1,000 at ≥28 weeks. At UMC Ljubljana, fetal death rates remained stable between 0.4 % and 0.6 %. The structured algorithm includes maternal history, laboratory testing, placental and fetal pathology, and genetic evaluation. Active induction is preferred over expectant management, and routine TORCH screening and centralized committee oversight are emphasized. Summary Slovenia’s structured, algorithm-based system has led to notably low stillbirth rates, supported by uniform clinical care and systematic investigations. Although Slovenia’s experience is encouraging, these results derive from a single-center national registry without comparative cohort analysis, limiting attribution of outcomes to specific elements of the algorithm. Outlook Future progress will involve the expansion of WES access and full ICD-PM implementation by 2027, enhancing data comparability and facilitating broader international research.
Open Access
Effect of antenatal betamethasone on fetal heart rate short-term variability in growth restricted fetuses

January 1, 2000

Tjaša Šikonja, Zala Sršen, Ivan Verdenik, Renata Košir Pogačnik, Miha Lučovnik, Gabrijela Bržan Šimenc, Tanja Premru-Sršen

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Objectives The study aimed to evaluate the magnitude and duration of the effect of antenatal betamethasone on fetal heart rate short-term variability (STV) in growth-restricted (FGR) fetuses in comparison with appropriate-for-gestational age (AGA) fetuses. Methods A prospective observational study was conducted at the UMC Ljubljana between June 2023 and June 2024, including 21 FGR and 20 AGA fetuses. We measured STV before applying betamethasone and at regular intervals for seven days after the first application or until delivery. Confounding variables were fetal and maternal demographic and clinical characteristics. Analysis was done using linear regression, paired-sample t-tests and one-way and two-way analysis of variance. Results The increase in STV 6–12 h after the first application was significant compared to baseline in both groups (p < 0.001). STV remained significantly elevated the first 24 h after the first application in the FGR group (p=0.018) but not in the AGA group. There was no significant difference in STV between baseline and 48 and 72 h after the first application in either group. When adjusted for gestational age, STV was significantly lower in the group of FGR compared to AGA fetuses at all times of cCTG recordings (p=0.031). Conclusions Following the initial increase in STV after the first dose of betamethasone, STV declines and returns to levels that doesn’t differ significantly from baseline after 24 h in AGA and 48 h in FGR fetuses. Longer-lasting response of FGR fetuses to betamethasone merits further investigation.
Open Access
Measurements of the fetal heart and prenatal biomarkers in children born with an isolated ventricular septum defect – a large, prospective, multicenter cohort study

January 1, 2000

Cathrine Vedel, Christian Pihl, Finn Stener Jørgensen, Olav Bjørn Petersen, Line Rode, Karin Sundberg, Helle Zingenberg, Henning Bundgaard, Kasper Iversen, Anne-Sophie Sillesen, Anna Axelsson Raja, Niels Vejlstrup, Ann Tabor, Charlotte Kvist Ekelund

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Objectives To compare 2nd-trimester cardiac and fetal biometries, 1st-trimester biomarkers, and obstetric outcome between children with an isolated ventricular septum defect (iVSD) and healthy children in a large cohort of children with neonatal echocardiography. Methods The Copenhagen Baby Heart Study offered all neonates born in Copenhagen an echocardiography within the 60 days of life between 2016 and 2018. The mothers were recruited at the 2nd-trimester scan (18+0 to 22+6). The documentation from the 2nd-trimester anomaly scan was supplemented with the four-chamber view with Doppler flow, the sagittal view of the aortic arch, the mid-umbilical artery flow, and the ductus venosus flow. All prenatal images were evaluated and cardiac biometries measured by two blinded investigators. VSDs were classified as muscular or as “other type” (perimembranous, inlet, and outlet VSDs). We compared cardiac biometries, biomarkers, and pregnancy outcome between fetuses with a neonatally diagnosed iVSD and controls. Results We included 25,556 neonates for an echocardiography, of which 9,155 fetuses were scanned in the period with extended cardiac imaging prenatally. We identified 294 fetuses with a postnatal VSD. Fetal measurements were similar between those with an iVSD compared to those without, and obstetric outcome were similar. Conclusions Our results indicate that children diagnosed with an iVSD through neonatal echocardiography in an unselected population have an otherwise structurally normal heart prenatally and a normal pregnancy outcome.
Open Access
Placenta-oriented counseling: challenges and opportunities in obstetric practice

January 1, 2000

Polona Pečlin

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Placental histopathology is an invaluable yet underutilized resource in obstetric care. While it offers unique insights into the etiology of adverse pregnancy outcomes, its clinical integration is often limited by inconsistencies in placenta submission, reporting delays, lack of standardized interpretation, and limited interdisciplinary dialogue. Certain placental abnormalities provide immediate clinical insights, guiding acute management decisions, while others indicate an increased risk of recurrence in future pregnancies. Additionally, many lesions help contextualize antenatal findings or clarify postnatal complications, offering valuable diagnostic and prognostic information. The article reviews the spectrum of placental lesions, ranging from common findings to rare high-risk entities, and their implications for future pregnancy outcomes. It examines both the persistent challenges and emerging opportunities associated with placenta-oriented counseling in modern obstetric practice. It also explores strategies for translating placental findings into actionable care, emphasizing the importance of implementing structured, multidisciplinary review processes. Furthermore, it highlights how placental histologic findings must be interpreted within the broader clinical context, considering maternal history, laboratory investigations, microbiological cultures, genetic analyses, and neonatal outcomes, to ensure their diagnostic relevance and support informed patient-centered decision-making focused on the maternal–placental–fetal triad.
Open Access
Diagnostic yield and clinical impact of prenatal whole exome sequencing (WES) – four-year single center experience

January 1, 2000

Katleen Janssens, Marjan De Rademaeker, Joke Muys, Bettina Blaumeiser, Katrien Janssens

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Objectives This study evaluates the diagnostic yield of prenatal whole exome sequencing (WES) and its impact on outcome, such as termination of pregnancy (TOP) or neonatal management. Methods A retrospective analysis of more than 4 years of prenatal WES at a single genetic center was performed. Inclusion criteria included normal genome-wide deletion/duplication analysis and ≥1 ultrasound anomaly. Trio analysis was performed, filtering for de novo , compound heterozygous, homozygous, and hemizygous variants, complemented by a genome-wide phenotype-driven analysis. Results (Likely) pathogenic variants fitting the phenotype were identified in 36 of 171 cases (21.1 %), of which 19 were de novo , 14 autosomal recessive, one autosomal dominant, and 2 X-linked dominant. Median turnaround time was 16 days. Parents opted for TOP in 21 cases, three resulted in intrauterine death, 11 were carried to term and one was lost to follow-up. Among the neonates, the diagnosis led to optimized postnatal management in 8/11 (72.7 %), abstinence of care in two (18.2 %) and exclusion of syndromic disorders in one (9.1 %). Conclusions Our findings indicate that in 1/5 pregnancies with ultrasound anomalies and normal deletion/duplication analysis, a (likely) pathogenic variant explaining the phenotype can be identified. The high proportion (17/36 or 47.2 %) of inherited variants highlights the importance of WES for recurrence risk assessment.
Open Access
The use of laser therapy in fetal medicine: a narrative review

January 1, 2000

Janina Semmler, Wolfgang Henrich, Christian Bamberg

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Introduction Fetal therapy has evolved into an established clinical specialty in fetal medicine, offering life-saving interventions for conditions with high intrauterine morbidity and mortality. Among various approaches, laser therapy has played a significant role in advancing fetal procedures. Content The most established application of laser is fetoscopic laser coagulation for twin-twin transfusion syndrome, which significantly reduces perinatal mortality and neurological complications. Other indications include twin anemia-polycythemia sequence and, as an intrafetal application, twin reversed arterial perfusion sequence. As an experimental approach, intrafetal laser therapy can be used to close the feeding blood vessel of unwanted tissue, thus preventing further tissue growth. Despite the advantages of fetal laser therapy, it presents challenges such as preterm premature rupture of membranes, preterm birth, technical difficulties, and the need for specialized expertise. Summary Laser therapy has become a cornerstone of fetal medicine, demonstrating significant clinical benefits. While laser therapy for TTTS is supported by high-level evidence, other applications rely on observational or experimental data. Outlook Future advancements, including improved imaging technologies, artificial intelligence, and robotic-assisted techniques, are expected to further enhance the precision, safety, and accessibility of fetal laser therapy. Large-scale studies through international collaborations will be essential to standardize protocols and improve outcomes.
Open Access
Implementation of a universal low-dose aspirin protocol for the prevention of preeclampsia in a federally qualified health center

January 1, 2000

Jaclyn Del Pozzo, Insaf Kouba, Frank Jackson, Jamie Green, Kristen Demertzis, Quratulain Zeeshan, Matthew J. Blitz

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Objectives Low-dose aspirin (LDA) prophylaxis is an evidence-based intervention that reduces preeclampsia risk, yet adherence remains suboptimal in underserved populations due to inconsistent risk assessment and communication gaps. This study evaluated the impact of a universal LDA protocol at a Federally Qualified Health Center (FQHC) serving a socially vulnerable population. Methods Patients initiating prenatal care between 12 and 28 weeks of gestation were included. A retrospective cohort from 2021 (pre-intervention) was compared to a prospective cohort from 2022 (post-intervention). The intervention prescribed daily LDA to all eligible patients. Adherence was defined as provider-documented patient use during at least one follow-up visit and at delivery, an indirect measure relying on patient report and provider documentation. The primary outcome was LDA adherence. Secondary outcomes included preeclampsia with and without severe features and postpartum hemorrhage requiring blood transfusion. Multivariable logistic regression adjusted for maternal age, pregestational diabetes, and chronic hypertension. Results Among 775 patients, LDA adherence increased from 8.7 % pre-intervention to 75.0 % post-intervention (p<0.001). The incidence of preeclampsia with severe features decreased significantly (OR 0.14, 95 % CI 0.04–0.37). In high-risk patients, adherence rose from 8.9 to 70.9 % (p<0.001) with a similar reduction in severe preeclampsia (OR 0.16, 95 % CI 0.05–0.44). No significant changes were observed in preeclampsia without severe features or postpartum hemorrhage requiring transfusion. Conclusions Implementation of a universal LDA protocol in a high-risk, underserved population markedly improved adherence and reduced severe preeclampsia without increasing hemorrhage risk, offering a practical, low-cost strategy to improve maternal outcomes.
Open Access
Antepartum cerebroplacental ratio in low risk pregnancy and its relationship with adverse perinatal outcome: a prospective cohort study

January 1, 2000

Neha Rathore, Manu Goyal, Pratibha Singh, Taruna Yadav, Shashank Shekhar

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Objectives To assess the relationship of cerebroplacental ratio (CPR) with non-reassuring/abnormal cardiotocography (CTG) tracing and perinatal outcomes like operative delivery, birth weight, NICU admission, meconium-stained liquor, and APGAR score in low-risk pregnancy. Methods This was a prospective cohort study at tertiary center in western India which included low risk singleton pregnancies between 35 and 37+6 weeks with cephalic presentation. Ultrasound was done between 35 and 37+6 weeks gestation including fetal biometry and Doppler for CPR calculation. Patients were divided into two groups, with normal CPR (>10th centile) and abnormal CPR (≤10th centile), and maternal and neonatal outcomes were compared. Results Out of 172 cases enrolled, CPR was abnormal in 55 (31.97 %) patients and normal in 117 (68.02 %) patients. In abnormal CPR group, CTG tracing was reassuring in 61.81 %, non-reassuring in 18.18 %, and abnormal in 20 %. While in normal CPR group, CTG tracing was reassuring in 81.19 %, non-reassuring in 11.11 %, and abnormal in 7.69 %. This was significant difference between the two groups (p=0.027). Cesarean and operative vaginal delivery rates were comparable in both groups, (p value=0.63, 0.33). Lower birth weight was observed in 45.45 % of women in the abnormal CPR group, while 21.36 % of women had low birth weight in the normal CPR group (p value=0.006). No significant difference was found in APGAR score and NICU admissions between the two groups (p-value-0.94, 0.87). Conclusions We conclude that CPR measurement has good negative predictive value for fetal outcome in low risk pregnancy.
Open Access
Outcomes in early term neonates requiring extracorporeal membrane oxygenation

January 1, 2000

Sourabh Verma, Bryn H. S. Seltzer, Jason C. Fisher, Erin Cicalese

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Objectives To evaluate ECMO-related morbidity and mortality between Early-term (ET) and Full-term (FT) infants. Methods We performed a retrospective review of 3,831 neonatal ECMO runs for meconium aspiration syndrome (MAS) and/or persistent pulmonary hypertension of the newborn (PPHN) in the Extracorporeal Life Support Organization (ELSO) Registry from 2007 to 2017. Neonates born at 37 0/7 –38 6/7 weeks were classified as ET and those born at 39 0/7 –40 6/7 weeks were classified as FT. Primary outcomes were ECMO survival and survival to discharge. Secondary outcomes were complications while on ECMO. Data were analyzed using Mann-Whitney U and Fisher’s Exact testing. Logistic regression was performed to assess odds of ECMO survival for factors noted to be significantly different between groups. Results Of 2,551 infants who met inclusion criteria based on gestational age, we identified 805 (32 %) ET and 1,746 (68 %) FT infants. ET infants had significantly lower ECMO survival (90 vs. 94 %, p<0.01) and survival to discharge (80 vs. 88 %, p<0.01), more neurologic complications on ECMO (15 vs. 12 %, p=0.024), and increased need for hemofiltration (33 vs. 29 %, p=0.033). There were no statistically significant differences between groups in mechanical, hemorrhagic, infectious, metabolic, renal, pulmonary, limb, or cardiovascular complications while on ECMO. Multiple logistic regression showed that ET gestational age, development of neurologic complications on ECMO, and need for hemofiltration are independent negative predictors of ECMO survival. Conclusions ET gestational age is an independent risk factor for worse ECMO outcomes and survival in comparison to FT infants, highlighting the vulnerability of this population.
Open Access
Hemorrhage-related maternal morbidity of secondary compared to primary postpartum hemorrhage

January 1, 2000

Matthew R. Carroll, Sarah Tounsi, Jessica L. Gerard, Susan M. Leong-Kee, Laurie S. Swaim, Mark A. Turrentine

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Objectives To compare a composite hemorrhage-related maternal morbidity in individuals with secondary to primary postpartum hemorrhage and treatment interventions utilized. Methods A retrospective case-control study of deliveries complicated by secondary postpartum hemorrhage was performed at a tertiary care center. To estimate a clinically relevant increase of 50 % in the composite maternal hemorrhage-related maternal morbidity (35–53 % absolute increase) in individuals with secondary postpartum hemorrhage, a correlation coefficient of 0.2, at an 80 % power with a p < 0.05 with a two-sided test would require 95 individuals with secondary postpartum hemorrhage be matched to 95 individuals with a primary postpartum hemorrhage. Logistic regression analysis was used to evaluate the outcome of the composite of hemorrhage-related maternal morbidity. Results From January 2018 through December 2022, 33,026 deliveries occurred, and 94 individuals were identified that were admitted with secondary postpartum hemorrhage, 0.28 % of deliveries, 95 % confidence interval (CI) 0.21–0.35 %. The composite hemorrhage-related maternal morbidity was increased in individuals with secondary compared to primary postpartum hemorrhage, adjusted odds ratio (OR) 14.0, 95 % CI 4.6 to 42.2. Most individuals with secondary postpartum hemorrhage had a dilation and curettage 91.5 % (86/94). In individuals with secondary postpartum hemorrhage that underwent uterine evacuation, histology revealed 45.2 % (38/84) had retained placenta, and 20.2 % (17/84) subinvolution. Conclusions A composite maternal hemorrhage-related outcome is associated more often with secondary compared to primary postpartum hemorrhage and nearly all individuals with secondary postpartum hemorrhage undergo a dilation and curettage.
Open Access
Virtual fetal holography for parental counseling and education: applications, limitations, and future directions

January 1, 2000

Wiku Andonotopo, Muhammad Adrianes Bachnas, Efendi Lukas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak

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Introduction Effective prenatal counseling relies on clear communication of fetal development and potential complications. Conventional 2D and 3D ultrasound images often fail to intuitively convey complex anatomy to expectant parents, limiting engagement and informed decision-making. Content Virtual fetal holography combines advanced image processing and 3D/4D ultrasound data to generate interactive, life-like fetal models. This review synthesizes current literature on its technological basis, clinical applications, and patient-centered outcomes. Evidence from cardiology, surgical planning, and anatomy education demonstrates how holography improves spatial understanding, supports multidisciplinary counseling, and enhances patient experience compared to standard imaging. Applications in anomaly counseling, maternal–fetal bonding, and clinical training are highlighted, alongside workflow models integrating mixed reality headsets and AI algorithms. Summary Virtual fetal holography shows potential for improving prenatal education and emotional engagement. Current evidence is largely descriptive and feasibility-based, with limited empirical validation of its impact on clinical decision-making or patient outcomes. Outlook Future research should address cost, technical complexity, ethical considerations, and standardized clinical protocols. Large-scale trials and cost-effectiveness analyses are needed to define its role in routine prenatal care.
Open Access
Generative artificial intelligence for counseling of fetal malformations following ultrasound diagnosis

January 1, 2000

Amos Grünebaum, Frank A. Chervenak

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Objectives To explore the potential role of generative artificial intelligence (GenAI) in enhancing patient counseling following prenatal ultrasound diagnosis of fetal malformations, with an emphasis on clinical utility, patient comprehension, and ethical implementation. Background The detection of fetal anomalies during the mid-trimester ultrasound is emotionally distressing for patients and presents significant challenges in communication and decision-making. Generative AI tools, such as GPT-4 and similar models, offer novel opportunities to support clinicians in delivering accurate, empathetic, and accessible counseling while preserving the physician’s central role. Methods We present a narrative review and applied framework illustrating how GenAI can assist obstetricians before, during, and after the fetal anomaly scan. Use cases include lay summaries, visual aids, anticipatory guidance, multilingual translation, and emotional support. Tables and sample prompts demonstrate practical applications across a range of anomalies.
Open Access
Complications in monochorionic twin pregnancies

January 1, 2000

Philipp Klaritsch

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Monochorionic placentas occur in two-thirds of identical (monozygotic) twin pregnancies and typically feature inter-fetal vascular anastomoses on their surface. These anastomoses can cause very specific complications including twin-to-twin transfusion syndrome (TTTS) in about 10 %, TAPS in 5 %, twin reversed arterial perfusion (TRAP) sequence in 2.5 % and spontaneous intrauterine fetal death (IUFD) in 2 % of monochorionic-diamniotic twin pregnancies. Moreover, unequal sharing of placental territories can lead to selective fetal growth restriction (sFGR) in about 15 %. Monochorionic multiples affected by such complications are at increased risk of mortality, brain abnormalities and neurodevelopmental disorders. This narrative review provides insight into prenatal detection and management of specific complications of monochorionic twin pregnancies.
Open Access
Advantages of fully automated AI-enhanced algorithm (5D CNS+™) for generating a fetal neurosonogram in clinical routine

January 1, 2000

Jann Lennard Scharf, Michael Gembicki, Achim Rody, Amrei Welp, Jan Weichert

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Objectives The objective was to demonstrate superiority of a fully vs. semi-automated approach (5D CNS+™) and to verify operators could handle and benefit from a fully automated rendering volumetric datasets to generate a complete fetal neurosonogram. Methods A total of 136 stored three-dimensional (3D) volumes of the brain of unselected, structurally normal fetuses were examined. Two operators applied both software versions for detailed assessment of the fetal central nervous system (CNS). The procession time was measured for each operator and for both program versions. The number of correctly calibrated planes were evaluated and necessity for manual adjustment of the planes was registered. Results The intraclass correlation coefficient was 0.507 (0.307–0.648) for semi-automated and 0.782 (0.693–0.846) for fully automated 5D CNS+™. The acquisition time of application for semi-automated 5D CNS+™ was 27.70 s ± 6.28 s for operator 1 and 33.20 s ± 9.67 s for operator 2, for fully automated 5D CNS+™ 10.89 s ± 0.85 s for operator 1 and 10.79 s ± 0.60 s for operator 2 (p<0.0001). The statistical analysis for manually corrected planes by both operators between both software algorithms showed a Bland-Altman-Bias of 1.44/9 planes for operator 1 and 1.45/9 planes for operator 2. Conclusions The fully automated 5D CNS+™ algorithm applied on 3D volume datasets provides examiners regardless their expertise not only enormous time efficiency, but also diagnostic confidence in evaluating details of the fetal CNS. This tremendously simplifies application in clinical routine.
Open Access
RNA biomarkers in hypertensive disorders of pregnancy: systematic review

January 1, 2000

Damilya Salimbayeva, Gulfairuz Urazbayeva, Almagul Kurmanova, Makhambet Smailov, Altynay Nurmakova

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Objectives The purpose of the study is to explore the potential of novel genetic markers in predicting and diagnosing hypertensive conditions during pregnancy, focusing on their role in key pathological processes. The relevance of this study is determined by the necessity to improve methods for the early detection and effective management of pregnancy complications, particularly those associated with elevated blood pressure, which pose a threat to the health of both mother and foetus. Methods The research methodology involves a systematic analysis of scientific literature from the past five years, specifically from 2019 to 2024, emphasising the integration of data from various populations and research approaches within the field of molecular medicine. Results The main findings demonstrate that certain molecular markers reflecting gene activity exhibit high accuracy in predicting the risks of complications associated with hypertension of pregnancy. It is established that these markers can detect disturbances in the regulation of vascular tone, angiogenesis processes, and inflammatory responses long before the onset of clinical symptoms. This opens up opportunities for timely medical intervention and a personalised approach to pregnancy management. Conclusions The results of the study confirm the potential of utilising genetic markers in clinical practice to improve pregnancy outcomes and reduce risks for both mother and child. The practical value lies in the possibility of developing new screening programmes and therapeutic strategies based on the individual characteristics of patients, contributing to more effective management of hypertensive disorders during pregnancy.
Open Access
Fetal neurobehavior and consciousness: a systematic review of 4D ultrasound evidence and ethical challenges

January 1, 2000

Mochammad Besari Adi Pramono, Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, I Nyoman Hariyasa Sanjaya, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak

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Introduction Recent advancements in four-dimensional (4D) ultrasonography have enabled detailed observation of fetal behavior in utero , including facial movements, limb gestures, and stimulus responses. These developments have prompted renewed inquiry into whether such behaviors are merely reflexive or represent early signs of integrated neural function. However, the relationship between fetal movement patterns and conscious awareness remains scientifically uncertain and ethically contested. Content A systematic review was conducted in accordance with PRISMA 2020 guidelines. Four databases (PubMed, Scopus, Embase, Web of Science) were searched for English-language articles published from 2000 to 2025, using keywords including “fetal behavior,” “4D ultrasound,” “neurodevelopment,” and “consciousness.” Studies were included if they involved human fetuses, used 4D ultrasound or functional imaging modalities, and offered interpretation relevant to neurobehavioral or ethical analysis. A structured appraisal using AMSTAR-2 was applied to assess study quality. Data were synthesized narratively to map fetal behaviors onto developmental milestones and evaluate their interpretive limits. Summary and Outlook Seventy-four studies met inclusion criteria, with 23 rated as high-quality. Fetal behaviors such as yawning, hand-to-face movement, and startle responses increased in complexity between 24–34 weeks gestation. These patterns aligned with known neurodevelopmental events, including thalamocortical connectivity and cortical folding. However, no study provided definitive evidence linking observed behaviors to conscious experience. Emerging applications of artificial intelligence in ultrasound analysis were found to enhance pattern recognition but lack external validation. Fetal behavior observed via 4D ultrasound may reflect increasing neural integration but should not be equated with awareness. Interpretations must remain cautious, avoiding anthropomorphic assumptions. Ethical engagement requires attention to scientific limits, sociocultural diversity, and respect for maternal autonomy as imaging technologies continue to evolve.
Open Access
Shaping the future: advancing maternal-fetal medicine through educational standards and innovations

January 1, 2000

Ivica Zalud

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The field of maternal-fetal medicine (MFM) stands at a transformative crossroads. Rising maternal morbidity and mortality in the United States, coupled with increasing clinical complexity driven by advanced maternal age, chronic diseases, and evolving reproductive technologies, demand a reimagining of MFM training. This review provides a comprehensive overview of current educational standards and innovations shaping MFM fellowship programs, drawing heavily from the frameworks of the American Board of Obstetrics and Gynecology (ABOG), the Accreditation Council for Graduate Medical Education (ACGME), and professional societies. Special attention is given to the MFM fellowship program in Hawai’i, which since its establishment in 2008, has emerged as a model of educational innovation, cultural responsiveness, and geographic adaptability. The integration of telemedicine, cultural competency, research, simulation, mentorship, and global health perspectives into MFM education is explored, culminating in a discussion on preparing the next generation of perinatal subspecialists for an evolving landscape of maternal and fetal health.
Open Access
Artificial wombs in perinatal medicine: a transformative frontier in neonatal care and bioethics

January 1, 2000

Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, I Nyoman Hariyasa Sanjaya, Dudy Aldiasnyah, Cut Meurah Yeni, Nuswil Bernolian, Waskita Ekamaheswara Kasumba Andanaputra, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak

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Objectives To evaluate the current state and translational readiness of artificial womb technology (AWT), focusing on its technical feasibility, preclinical validation, and ethical, legal, and clinical implications for perinatal medicine. Methods We conducted an integrative narrative review of the scientific literature from January 2000 to May 2025. Searches were performed in PubMed, Scopus, and Web of Science using terms such as “artificial womb,” “extrauterine fetal incubation,” “artificial placenta,” “preterm birth,” and “bioethics.” A total of 65 peer-reviewed studies were included, spanning domains of bioengineering, preclinical models, clinical frameworks, and normative analysis. Data were synthesized thematically, with supplemental visual mapping and comparative tables to illustrate platform characteristics and ethical considerations. Results Advanced AWT systems, including EXTEND and the Perinatal Life Support (PLS) platform, have demonstrated success in sustaining extremely preterm lambs and goat fetuses, preserving physiological development in fluid-based environments. Key innovations include pumpless oxygenators, modular system architecture, and AI-assisted monitoring. Despite progress, unresolved challenges include umbilical cannulation, sterility, endocrine simulation, and long-term neurodevelopmental outcomes. Ethical tensions surround maternal autonomy, fetal personhood, informed consent, and global equity in access. Conclusions Artificial wombs represent a paradigm shift in neonatal care, offering the potential to extend viability and reduce preterm morbidity. As AWT approaches clinical translation, interdisciplinary coordination across medicine, ethics, and law will be essential to guide responsible integration. This analysis provides a foundational roadmap for advancing AWT from preclinical innovation to ethical clinical application.
Open Access
Patient education materials: improving readability to advance health equity

January 1, 2000

Amos Grünebaum, Susan L. Pollet, Renee McLeod-Sordjan, Gloria Bachman, Frank A. Chervenak

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Objectives To assess the readability of American College of Obstetricians and Gynecologists (ACOG) patient education pamphlets and evaluate changes over 25 years to determine their role as a social determinant of health affecting maternal health disparities. Methods Cross-sectional descriptive analysis of 134 English-language ACOG patient pamphlets using five validated readability metrics (Flesch Reading Ease Score, SMOG Index, Gunning Fog Index, Coleman-Liau Index, and Bormuth Grade Placement). Materials were categorized into five groups: Pregnancy & Childbirth, Gynecologic Conditions, Other, Cancer & Screening, and Infections & STIs. A random subset of 20 pamphlets underwent quality assessment using the DISCERN tool. Results were compared with historical data from 1999. Results The mean DISCERN score was 65.6/75, indicating excellent content quality. However, readability analysis revealed concerning accessibility barriers. The mean Flesch Reading Ease score was 58.4 ± 6.2, with only 35.1 % of pamphlets meeting plain language standards (≥60 score, equivalent to 8th grade or below). Most materials (57.5 %) required 10th-12th grade reading ability. Across all readability metrics, the average grade level was 9.5, with only 2.2–6.7 % of pamphlets meeting recommended standards (≤8th grade). Comparison with 1999 data showed worsening readability, with scores increasing 1.0–3.7 grade levels across all metrics. Conclusions ACOG patient education materials consistently exceed recommended readability levels and have become more complex over 25 years. This inaccessibility perpetuates health disparities, particularly affecting marginalized populations with lower health literacy. Implementing plain language policies, AI-driven text simplification, and readability audits are essential for advancing maternal health equity and ensuring all patients can access comprehensible reproductive health information.
Open Access
Early unfavorable outcomes of second-trimester selective feticide for complicated monochorionic twins: single-operator experiences

January 1, 2000

Tuangsit Wataganara, Katika Nawapun, Kanokwaroon Watananirun, Sommai Viboonchart, Suparat Jaingam, Nisarat Phithakwatchara

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Objectives This study reviews early unfavorable outcomes following selective in-utero cord occlusion in monochorionic twin pregnancies at risk of hemodynamic accidents by a single operator. Methods The study analyzed laser ablation (LA), laser transection (LT), radiofrequency ablation (RFA), and bipolar diathermy (BD) procedures performed between 14 and 22 weeks of gestation from 2006 to 2022. Outcomes included: (1) technical failure (abandonment before cessation of Doppler flow), (2) intraoperative events (hemodynamic instability in the woman or co-twin), and (3) complications (e.g., fluid leakage, infection, abruption, co-twin demise, or miscarriage) within 1 week post-procedure. Results Ten LAs were performed at 14–15 weeks for discordant anomalies, all without complications. Two LTs were conducted at 20 weeks for umbilical cord knotting; with one procedure experienced technical failure. All twin reversed arterial perfusion sequence (TRAPS) (n=55) received RFA, with one procedure experienced technical failure. All twin-to-twin transfusion syndrome (TTTS) (n=25) received BD, with one procedure experienced technical failure. Selective intrauterine growth restriction (sIUGR) (n=30) received RFA (n=5) and BD (n=25), with 1 RFA (25 %) and 1 BD (4 %) experienced technical failure. (p<0.01) All four technical failure cases had extensive anterior placenta. There were no intraoperative events. McDonald cervical cerclage was performed in 8/25 TTTS cases with pre-operative cervical length of ≤25 mm and/or funneling of the internal cervical os. Early procedure-related complications were experienced in two sIUGR cases receiving BD, both of which had extensive anterior placenta. Conclusions Early unfavorable outcomes were associated with sIUGR as an indication.
Open Access
The incidence and outcomes of perinatal asphyxia in spontaneous extreme preterm birth: a retrospective cohort study

January 1, 2000

Zohal Faiz, Eline van ’t Hof, Marjon de Boer, Timo de Haan, Mirjam Weissenbruch, Arthur Klautz, Pien Lippes, Ben Willem Mol, Christianne de Groot, Petra Bakker

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Objectives To determine the incidence and outcome of perinatal asphyxia (PA) in spontaneous extreme preterm birth (PTB) between 24 and 28 weeks gestation. Methods We conducted a retrospective cohort study (2010–2019) at a Dutch tertiary center, including singleton spontaneous PTBs with active neonatal management. PA was defined as a 5-min Apgar score ≤5, umbilical artery pH≤7.00, base deficit >12 mmol/L, and need for ongoing resuscitation. Cases were classified as proven PA (all criteria met), suspected PA (Apgar≤5 only if blood gas data missing), or no PA. Neurodevelopment was assessed at 2 years corrected age. Multiple imputation addressed missing data. Logistic regression, adjusted for gestational age (GA), was used to evaluate associations with infant mortality, cerebral injury, and neurodevelopmental impairment (NDI). Results Among 138 neonates, 84 % had no PA, 12.3 % suspected PA, and 3.6 % proven PA. After imputation, the estimated incidence of PA was 5.0 %. PA was not significantly associated with infant mortality (aOR 1.07; 95 % CI 0.13–8.87; p=0.95) or intraventricular hemorrhage (aOR 1.62; 95 % CI 0.26–10.39; p=0.61). NDI occurred in two infants with PA. Conclusions PA occurred more frequently in this extreme preterm cohort than in term neonates, yet did not independently influence mortality or morbidity. A major limitation is the use of ACOG criteria, originally developed for term births, which may have led to over- or underestimation of PA’s true incidence and impact. Although based on few confirmed cases, findings suggest PA, may not be a major independent predictor of adverse outcome in extreme PTB.
Open Access
The fetal occiput-spine angle measurement during first stage of labor as a predictor for vaginal delivery, a systematic review and meta-analysis

January 1, 2000

Potsanop Kassayanan, Kasidis Nontaprom, Prame Chantabal, Monchai Suntipap

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Objectives To evaluate the diagnostic utility of the fetal occiput-spine angle (OSA) measured by transabdominal ultrasonography in predicting successful vaginal delivery (VD) during the first stage of labor. Methods A systematic search of MEDLINE, Scopus, EMBASE databases, and Google Scholar was conducted from January 15, 2025, to February 1, 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses for diagnostic test accuracy guidelines. Two independent reviewers selected studies according to inclusion criteria, extracted data, and assessed risk of bias assessed by the Quality Assessment of Diagnostic Accuracy Studies-2. Results Six studies with 1,129 participants were included. The pooled sensitivity and specificity of OSA for predicting VD were 86 % (95 % confidence interval (CI): 73–93 %) and 80 % (95 % CI: 37–97 %), respectively. The DOR was 23.71 (95 % CI: 2.5–223.36 %). The mean OSA of women with successful VD was 10.44° wider than that of women who underwent cesarean delivery, although not significant (p=0.16). High heterogeneity (I 2 >88.2 %) was observed. The risk of bias was low across most domains. Conclusions The fetal OSA demonstrated moderate diagnostic value in predicting successful VD. Furthermore, additional high-quality, large-scale studies with standardized cut-offs are necessary to verify its clinical utility.
Open Access
Reference ranges for fetal tricuspid and mitral annular plane systolic excursions

January 1, 2000

Jakkapop Kanjak, Ratana Komwilaisak, Piyamas Saksiriwuttho, Kiattisak Kongwattanakul, Sukanya Chaiyarach, Chatuporn Duangkum, Termtem Waidee

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Objectives Echocardiography is the standard tool for assessing fetal cardiac function. Tricuspid annular plane systolic excursion (TAPSE) and mitral annular plane systolic excursion (MAPSE) are simple, reliable indicators of systolic function. Many studies have established reference ranges in adult and pediatric populations; however, data remain limited in fetuses, especially in Southeast Asia. The aim of the study was to establish normal reference ranges for TAPSE and MAPSE in fetuses born between 18 + 0 and 37 + 6 weeks’ gestation in a Southeast Asian population. Methods This prospective, cross-sectional study was conducted between January 2024 and February 2025. Data from 280 singleton pregnancies with normal fetal growth and no maternal comorbidities were included in the study. TAPSE and MAPSE were measured using M-mode imaging in a four-chamber view. Percentile reference values were determined using quantile regression models, with gestational age (GA) and estimated fetal weight (EFW) as predictors. The intraclass correlation coefficient (ICC) was used to assess intra- and interobserver reliability. Results TAPSE and MAPSE were significantly and positively correlated with GA and EFW. Mean TAPSE ranged from 3.76 to 9.08 mm (GA) and 3.42 to 9.30 mm (EFW), while MAPSE ranged from 3.10 to 6.34 mm (GA) and 2.71 to 6.60 mm (EFW). The TAPSE values consistently exceeded the MAPSE values across all GAs. The inter- and intra-observer ICCs were high (TAPSE, 0.94/0.91; MAPSE, 0.91/0.88). Conclusions This study established the first normal TAPSE and MAPSE reference ranges for a Southeast Asian population and provided reliable tools for fetal cardiac assessment.

Special Issue: Perinatal Responsibility in a Fragmented World: Reflections from the 2024 IAPM Meeting; Issue Editors: Milan Stanojević, Frank A. Chervenak and Ivica Zalud

Journal Impact Factor	1.4	2024, Journal Citation Reports (Clarivate, 2025)
5-year Journal Impact Factor	1.8	2024, Journal Citation Reports (Clarivate, 2025)
Journal Citation Indicator	0.71	2024, Journal Citation Reports (Clarivate, 2025)
CiteScore	3.5	2024, Scopus (Elsevier B.V., 2025)
SCImago Journal Rank	0.592	2024, SJR (Scimago Lab, 2025; Data Source: Scopus)
Source Normalized Impact per Paper	0.733	2024, CWTS Journal Indicators (CWTS B.V., 2025; Data Source: Scopus)

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