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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Due to the flip to the new publication model, the first three issues of the new volume will not be published in the first three months of the new year, but in February, March and April.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
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
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
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
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
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
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
Maternal and neonatal outcomes of ultrasound-guided percutaneous nephrostomy for symptomatic hydronephrosis in pregnancy: a retrospective cohort study

January 1, 2000

Ozan Karadeniz, Bugra Tunc, Alperen Ince, Ecem Oksen, Ali Dablan

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Objectives To evaluate the maternal and neonatal outcomes of pregnant patients who underwent ultrasound-guided percutaneous nephrostomy for the management of symptomatic hydronephrosis. Methods This retrospective cohort study evaluated 85 pregnant patients with symptomatic hydronephrosis (≥ Grade 2) managed at a tertiary center between January 2020 and February 2025. Participants were stratified into ultrasound-guided PCN (n=43) and conservative management (n=45) groups. The primary outcome of this study was to evaluate the safety and efficacy of ultrasound-guided PCN in pregnant patients with symptomatic hydronephrosis. Results Demographic characteristics were similar between groups. Abdominal pain was more common in the conservative group (45.5 % vs. 26.8 %, p=0.062), while other clinical and laboratory parameters showed no significant differences. Antibiotic use differed significantly (p=0.016), though urine culture results were comparable. Pregnancy and neonatal outcomes, including gestational age at delivery, birth weight, Apgar scores, cesarean delivery rates, and neonatal intensive care unit (NICU) admission rates, did not differ significantly between groups (all p>0.05). Kaplan–Meier survival analysis demonstrated no statistically significant difference in cumulative live birth rates between the PCN and conservative treatment groups (log-rank test, p=0.665), with hazard ratios indicating comparable reproductive outcomes over time. Conclusions This study demonstrates that ultrasound-guided PCN is a safe and effective intervention for managing symptomatic hydronephrosis during pregnancy, with favorable maternal and neonatal outcomes. Further prospective studies with larger cohorts are warranted to validate these findings and refine clinical guidelines.
Open Access
Detection of isolated fetal limb anomalies using 3D/4D ultrasound

January 1, 2000

Eberhard Merz, Sonila Pashaj

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Objectives Demonstration of the advantage of 3D/4D ultrasound compared to 2D imaging in the precise detection and parental counseling of isolated fetal limb defects. Methods Prospective observational study of 201 fetal limb defects over a 30-year period (1994–2023) in a level III center. Results Comparison of 2D and 3D ultrasound showed a benefit in the precise demonstration of isolated limb abnormalities in 154 of the 201 cases (76.6 %), particularly in subtle malformations. In the demonstration of the defects to the parents-to-be, 3D/4D ultrasound was superior to 2D ultrasound in 100 % of cases by the fact that the abnormalities could be better understood by the parents when using a spatial presentation. Conclusions 3D/4D ultrasound is superior to 2D sonography in the demonstration of isolated limb defects, particularly in subtle limb defects.
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
Abnormal Doppler and perinatal outcomes according to the placental lesions of maternal and fetal vascular malperfusion in preterm fetal growth restriction

January 1, 2000

Young Eun Chung, You-Ri Lee, Sooji Ham, Boram Park, Kyunga Kim, Ji-Hee Sung, Yun Dan Kang, Suk-Joo Choi, Soo-Young Oh, Jung-Sun Kim, Cheong-Rae Roh

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Objectives We aimed to identify the associations between specific pathologic placental findings and abnormal Doppler results as well as perinatal outcomes in preterm fetal growth restriction (FGR). Methods This retrospective study included 465 consecutive singleton pregnancies with FGR delivered between 22+0 and 36+6 weeks of gestation. Abnormal Doppler was defined as absent or reversed end-diastolic flow in the umbilical artery (UA) and a pulsatility index less than the 10th percentile in the middle cerebral artery (MCA). Placental pathology was evaluated focusing on villous or vascular findings of maternal (MVM) and fetal vascular malperfusion (FVM) based on Amsterdam criteria. Results The average gestational age at delivery and neonatal birth weight were 32 weeks (±4 weeks) and 1,299 g (±575 g), respectively. Placental MVM lesions were observed in the majority of cases (90.3 %) and were significantly related to abnormal UA and MCA Doppler. Meanwhile, FVM lesions was observed in about half of the cases (44.8 %) and were significantly related to abnormal MCA Doppler, but not abnormal UA Doppler. Both villous and vascular lesions of MVM and FVM were associated with lower neonatal birth weight. Among specific key findings of MVM and FVM, distal villous hypoplasia was highly associated with abnormal UA Doppler (crude OR 5.01, 95 % CI 1.27–19.68), while intramural fibrin deposition in large fetal vessels was significantly associated with abnormal MCA Doppler (crude OR 2.49, 95 % CI 1.01–6.13). Of note, intramural fibrin deposition of large fetal vessels was associated with neonatal mortality (crude OR 3.25, 95 % CI 1.52–6.92). Conclusions We identified key findings among placental MVM and FVM associated with abnormal UA and MCA Doppler as well as neonatal mortality in preterm FGR.
Open Access
Ureaplasma parvum detected in umbilical cord tissues diagnosed with funisitis associated with adverse pregnancy outcomes and neonatal pneumonia

January 1, 2000

Wen Lei, Leijun Huo, Qiuping Chen, Yanxia Liao, Mi Li, Xiangcheng Zhou, Jiali Zhang, Shuai Zhou, Liang Zhang, Hongyi Gao, Hua Deng

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Objectives Existing studies yielded conflicting evidence regarding the associations between genital tract microbial and funisitis, chorioamnionitis and adverse pregnancy outcomes. This study aims to provide additional evidence for their association through systematic investigation. Methods A total of 98 FFPE umbilical cord specimens confirmed as funisitis and chorioamnionitis through histopathological examination were tested for seven genital tract microorganisms using quantitative polymerase chain reaction (qPCR). Electronic medical records of mothers and neonates were retrieved to analyze the risk associations between microorganism-positive cases and chorioamnionitis as well as adverse pregnancy outcomes. The umbilical cord samples with Ureaplasma parvum positive had been sequenced for serovars analysis. Results Ureaplasma parvum (UP), Ureaplasma urealyticum (UU), Group B Streptococcus (GBS) and Mycoplasma homini s (MH) were all detected in the study with prevalence of 36.5 %, 7.9 %, 18.6 %, and 5.8 %, respectively, while Mycoplasma genitalium (MG), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) were not detected. Ureaplasma spp. were identified as the predominant microorganisms detected in 98 umbilical cord cases by using qPCR, demonstrating concordance with clinical vaginal swab findings from pregnant women. Genital microorganisms infection was associated with high stage chorioamnionitis (p = 0.0254) and adverse pregnant outcomes (p = 0.0053). In addition, the prevalence of U. parvum demonstrated a strong significant association with neonatal pneumonia (p = 0.0037). Conclusions Umbilical cord specimens tested positive for U. parvum demonstrated a significant association with adverse perinatal outcomes and neonatal pneumonia. Additional studies are warranted to investigate the determinants enabling commensal U. parvum in the genital tract to ascend and induce intrauterine infection, thereby leading to adverse clinical outcomes.
Open Access
Ten years of experience with screening for diabetes in pregnancy according to IADPSG criteria in Slovenia

January 1, 2000

Lili Steblovnik, Renata Košir Pogačnik, Mateja Sladič

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This review presents analysis of gestational diabetes mellitus (GDM) in Slovenia based on national data and published research over a decade. Slovenia adopted the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations in 2011 and integrated them into routine antenatal care by 2023. Universal screening has increased the prevalence of GDM from 4 % before 2010 to 21 % in 2023. The analysed perinatal outcomes improved: the overall rates of large for gestational age (LGA) neonates and Erb’s palsy decreased (AOR 0.93, 95 % CI 0.91–0.96 and AOR 0.72, 95 % CI 0.60–0.86 respectively) as did rates of preeclampsia (AOR 0.72, 95 % CI 0.68–0.76) and gestational hypertension (AOR 0.80, 95 % CI 0.77–0.83). The population of pregnant women changed, mean age at delivery, pre-pregnancy body mass index (BMI), proportion of obesity and parity increased. A dose-response relationship was found between pre-pregnancy BMI and GDM as there was synergistic effect of parity and maternal obesity on excessive fetal growth. Despite the nutrition interventions and tight control of blood glucose levels LGA infants could not be completely prevented. Beyond metabolic effects, GDM imposes a significant psychological burden; distinct psychological profiles were identified, emphasizing the need for tailored psychosocial support.
Open Access
The intrauterine microbiome–neurodevelopment axis: decoding the prenatal microbial imprint on lifelong mental health

January 1, 2000

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

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Introduction The traditional view of a sterile intrauterine environment has been challenged by sequencing studies detecting low-biomass microbial DNA in placenta, amniotic fluid, and fetal tissues. These findings suggest that maternal microbiota-derived signals may contribute to fetal brain development and influence long-term neuropsychiatric outcomes. Content This narrative review synthesizes evidence from over 90 preclinical and clinical studies examining maternal microbiota–fetal brain interactions. Maternal immune activation – characterized by elevated cytokines such as interleukin (IL)-6 and IL-17A – has been shown in mouse models to disrupt cortical layering and synaptic organization, while human cohort studies involving more than 250,000 pregnancies link maternal inflammatory markers to increased autism spectrum disorder (ASD) risk. Microbial metabolites, including short-chain fatty acids (butyrate, acetate, propionate), bile acids, and tryptophan derivatives, regulate microglial maturation, blood–brain barrier integrity, and hippocampal neurogenesis. Epigenetic mechanisms – DNA methylation, histone acetylation, and chromatin remodeling – have been observed in placenta and cord blood from pregnancies affected by obesity or dysbiosis. Large-scale epidemiological studies also associate prenatal infection and antibiotic exposure with higher rates of ASD and attention-deficit/hyperactivity disorder (ADHD). Summary Collectively, the evidence indicates that maternal microbiota influence fetal brain development through converging immune, metabolic, epigenetic, and hormonal pathways. Strong mechanistic insights come from animal models, whereas human data remain largely observational, limiting causal interpretation. Outlook Recognizing the maternal microbiome as a modifiable prenatal factor highlights opportunities for prevention. Early translational approaches – including maternal microbiota profiling, dietary optimization, and probiotic supplementation – are under investigation, but require rigorous clinical validation before integration into prenatal care.
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
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
Community births in the United States, 2016–2024: post-pandemic patterns across racial and ethnic groups

January 1, 2000

Amos Grünebaum, Frank A. Chervenak

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Objectives Community births in the United States – including planned home and freestanding birth center deliveries – have increased in recent years. Understanding how these patterns have evolved across racial and ethnic groups, particularly in the post-pandemic period, is essential for clinical practice and health policy. Objective: To analyze national trends in community births from 2016 through 2024 by race and ethnicity, and to discuss clinical, ethical, and policy implications. Methods Birth certificate data from the CDC natality database were examined for 2016–2024. Community births were defined as intended home or freestanding birth center births. Trends were assessed overall and stratified by race/ethnicity, with relative changes indexed to 2016. Results From 2016 to 2024, community births increased overall but diverged by group. Non-Hispanic White and Hispanic women demonstrated sustained increases relative to 2016, while non-Hispanic Black women showed an increase during the pandemic followed by decline, and non-Hispanic Asian women displayed a modest upward trend. These shifts occurred against the backdrop of declining total births in some groups, affecting proportional comparisons. International comparisons are limited by the distinctive U.S. context, where midwifery is less integrated and credentialing standards are variable. Conclusions Community birth patterns since the pandemic reveal both growth and divergence across racial and ethnic groups. These findings highlight the need for policy interventions to address maternity care deserts and harmonize midwifery credentialing. Clinically, professional responsibility requires fully informed consent leading to directive counseling, which should not be misinterpreted as paternalism but as an ethical duty to recommend hospital birth as the safest option while respecting patient autonomy.
Open Access
Integrating mental health into obstetric practice: a review of collaborative care models for perinatal anxiety

January 1, 2000

Julian Dewantiningrum, Wiku Andonotopo, Efendi Lukas, Mochammad Besari Adi Pramono, Wisnu Prabowo, Muhammad Adrianes Bachnas, I Nyoman Hariyasa Sanjaya, Anak Agung Gede Putra Wiradnyana, Anak Agung Ngurah Jaya Kusuma, Khanisyah Erza Gumilar, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, Dudy Aldiansyah, Aloysius Suryawan, Ridwan Abdullah Putra, Anita Deborah Anwar, Laksmana Adi Krista Nugraha, Waskita Ekamaheswara Kasumba Andanaputra, Wibisana Andika Krista Dharma, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak

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Objective Perinatal anxiety is one of the most common yet least systematically addressed complications of preg- nancy and childbirth. Despite abundant evidence that collaborative and integrated care models improve maternal outcomes, obstetric practice still lacks a defined operational standard for addressing anxiety alongside routine obstetric care. Fragmented screening, insufficient referral systems, and financing barriers continue to delay intervention, widening inequities across populations and settings. Methods This opinion article synthesizes recent evidence (2010–2025) from PubMed, Google Scholar, and professional guidelines to propose a practical framework for embedding mental health care within obstetric workflows. Drawing upon studies from high- and low-resource contexts, we outline a ten-point minimum standard for perinatal-anxiety management and a three-tier maturity model that describes the progressive integration of collaborative care—from basic screening to digitally supported, team-based systems. The model identifies measurable implementation metrics and policy levers that enable sustainability and equity. Results Rather than advocating new research, this article translates two decades of findings into a clinically actionable standard. It emphasizes the central role of ob- stetric teams in early detection, stepped care, and follow-up through coordination with mental-health professionals. Conclusions Integrating mental health into obstetric practice is both a moral and operational imperative. By adopting the proposed minimum standard and maturity model, health systems can transform perinatal anxiety care from discre- tionary innovation to routine expectation—achieving faster response, broader access, and better maternal–infant out- comes worldwide.
Open Access
Umbilical venous flow and maternal hemodynamics as predictors of impaired fetal growth in gestational diabetes: a prospective study

January 1, 2000

Daniele Farsetti, Sara Nardini, Lavinia Maffi, Giulia Gagliardi, Roberta Frantellizzi, Francesca Pometti, Barbara Vasapollo, Gian Paolo Novelli, Herbert Valensise

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Objectives This study aims to evaluate the association between maternal cardiovascular function, umbilical vein blood flow (UV-Q), and impaired fetal growth in pregnancies complicated by gestational diabetes mellitus (GDM). Methods In this prospective observational study, 84 singleton pregnancies complicated by GDM between 28 and 32 weeks of gestation were enrolled. All participants underwent a standardized maternal hemodynamic assessment using USCOM device and fetal ultrasound including Doppler-based measurement of UV-Q. Impaired fetal growth was defined as either small for gestational age (SGA, birthweight <10th centile) or a ≥40 centile drop between estimated fetal weight (EFW) at enrolment and actual birthweight centile (“DROP”). Predictive performance was assessed using ROC analysis and multivariate logistic regression. Results Fetuses with impaired growth (n=24) had significantly lower UV-Q centiles (median 29.50 vs. 50.00, p=0.04), higher maternal systemic vascular resistance (SVR) (1,004.50 vs. 915.00 dyn s cm −5 , p<0.01), lower cardiac output (CO) (6.5 vs. 7.2 L/min, p=0.03), and reduced oxygen delivery (DO 2 ) (1,021.22 vs. 1,131.06 mL/min, p<0.01) compared to those with normal growth. Multivariate analysis identified UV-Q centile ≤24, SVR>916 dyn s cm −5 , and DO 2 ≤1,061.4 as independent predictors of impaired growth (AUC up to 0.78). These associations remained significant after adjusting for EFW at enrolment. Conclusions In pregnancies complicated by GDM, impaired fetal growth may reflect placental dysfunction and maternal cardiovascular maladaptation. Maternal hemodynamic parameters and UV-Q may enhance fetal growth surveillance, particularly when incorporating longitudinal metrics such as DROP. These findings suggest a potential role for integrating maternal-fetal hemodynamics into standard care to identify “hidden” growth restriction phenotypes in GDM pregnancies.
Open Access
Serum vitamin D and inflammatory markers in SARS-CoV-2 positive pregnant women

January 1, 2000

Vita Andreja Mesarič, Tanja Premru Sršen, Gorazd Kavšek, Ivan Verdenik, Aleksandra Štrukelj, Mirjam Druškovič

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Objectives The SARS-CoV-2 pandemic was declared by World Health Organisation (WHO) in March 2020, causing health and economic disruptions and millions of deaths. Pregnant women represent a vulnerable group, as COVID-19 during pregnancy increases the risk of preterm birth, preeclampsia, and severe maternal illness. Nutritional status, such as vitamin D deficiency, may influence these outcomes, yet data on its status in the cohort of SARS-CoV-2 positive pregnant women as well as its association with inflammatory and angiogenic markers is scarce. The aim of this study was to evaluate the levels of vitamin D in the cohort of SARS-CoV-2 positive pregnant women and its association with inflammatory and angiogenic markers. Methods Prospective cohort study at Ljubljana Maternity Hospital (Oct 1, 2020–Mar 30, 2021) enrolled singleton pregnancies with PCR-confirmed SARS-CoV-2 within the last 14 days, delivering at our institution. Results Among 235 SARS-CoV-2-positive pregnant women 62.1 % had adequate and 21.3 % insufficient level of vitamin D and 13.6 % were vitamin D deficient. Statistical analysis revealed no significant correlations between 25-OH-vitamin D and C-reactive protein (CRP), procalcitonin (PCT), leukocyte count, soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), the sFlt-1/PlGF ratio, or body mass index (BMI). Conclusions Our prospective cohort study revealed that high proportion of pregnant women has inadequate levels of vitamin D. Although maternal insufficiency is linked to adverse outcomes, its association with inflammatory and angiogenic markers remains unclear. Rigorous studies in pregnancy are essential to clarify vitamin D’s role in COVID-19 complications in pregnancy.
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
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
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
The impact of maternal cardiovascular status prior to labor on birth outcomes: an observational study

January 1, 2000

Daniele Farsetti, Francesca Pometti, Giulio Maria Natali, Greta Carta, Livia Pieri, Benedetta Laudonio, Davide Archelao Dessì, Barbara Vasapollo, Gian Paolo Novelli, Herbert Valensise

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Objectives To evaluate the diagnostic accuracy of maternal characteristics, computerized cardiotocography (cCTG), maternal hemodynamics, and fetal Doppler in predicting adverse perinatal outcomes (APO) in healthy term pregnancies before labor onset. Methods In this prospective observational study, 395 term pregnant women were enrolled. Data on obstetric history, cCTG, maternal hemodynamics, and fetal ultrasound were collected. Women undergoing labor induction were excluded. The primary endpoint was a composite APO, defined as cesarean or operative vaginal delivery due to pathological CTG, 5-min Apgar <7, umbilical artery pH <7.1 and/or base excess >12 mmol/L, or NICU admission. A secondary outcome, “objective APO”, excluded operative delivery for pathological CTG. Logistic regression analyses were performed to assess predictors of APO. Results Among 307 women with spontaneous labor, 41 (13.36 %) experienced a composite APO. These women were less often multiparous (7.32 vs. 27.07 %, p=0.01), had higher systemic vascular resistance [SVR: 1,353 (1,209–1,498) vs. 1,249 (1,071–1,438) dyn s cm −5 , p=0.01], and lower short-term variability [STV: 7.5 (6.2–10.0) vs. 9.1 (7.6–11.0) ms, p<0.01]. Fetal Doppler indices, including cerebro-placental ratio, showed no significant differences. ROC analysis identified SVR >1,135 dyn s cm −5 (OR 6.92, 95 % CI 2.08–23.03) and STV ≤7 ms (OR 3.95, 95 % CI 1.97–7.92), as optimal predictors. Multivariate analysis confirmed STV, SVR, and parity as independent predictors. In the secondary analysis of “objective APO”, both SVR and STV remained significant predictors, and the multivariable model demonstrated excellent discrimination [AUC 0.931 (95 % CI 0.896–0.957)]. Conclusions In term pregnancies, maternal hemodynamic assessment and cCTG performed before labor may improve the identification of women at increased risk of APO.
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
Successful management of severe hemolytic disease of the fetus and newborn (HDFN) due to anti-Kell

January 1, 2000

Erika Hrastar, Irena Bricl, Tanja Premru-Sršen, Jakob Gubenšek, Lilijana Kornhauser Cerar, Polona Pečlin

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Objectives Hemolytic disease of the fetus and newborn (HDFN) is a potentially life-threatening condition, caused by maternal alloimmune antibodies targeting fetal red blood cells. This report aims to present a case of severe early-onset anti-K-mediated HDFN, managed successfully with intravenous immunoglobulin (IVIG), therapeutic plasma exchange (TPE) and intrauterine transfusion (IUT), and to discuss comparable alternative approaches reported in the literature. Methods We treated a 32-year old woman in her third pregnancy with a high titer of anti-K alloantibodies (1:2048), detected in the first trimester. Weekly IVIG therapy of 1 g/kg was initiated at 15 weeks of gestation, followed by four TPEs and two IUTs. Due to suspected fetal anemia at 33 weeks of gestation, we opted for delivery. The newborn required phototherapy and erythropoietin treatment, with normal development at age two. Results To contextualize our approach, we reviewed published cases of anti-K-mediated HDFN and compiled a comparative table of treatment strategies and outcomes. Analysis showed that treatment protocols varied in IVIG dosing, TPE use, and timing, reflecting the absence of standardized approaches. These strategies were associated with delayed IUT and improved neonatal outcomes following prior fetal losses. Conclusions Our case, along with the review of published cases, supports the use of IVIG, with or without TPE, in managing anti-K alloimmunized pregnancies. The variability in treatment approaches underscores the need for individualized care based on maternal antibody titers, fetal antigen status, and disease progression, while emphasizing the importance of standardized protocols and prospective studies to guide optimal management.
Open Access
Management and outcomes of periviable infants in Slovenia: a decade of experience

January 1, 2000

Polona Rajar, Tamara Čopi, Mateja Sladič, Marijana Vidmar Šimic, Lilijana Kornhauser Cerar

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Objectives To determine rates of active approach, mortality, and morbidity for periviable infants at level 3 maternity hospital between 2013 and 2022. Methods Single center retrospective cohort study including mothers and their liveborn infants at gestational age from 22 +0 weeks to 24 +6 weeks during a ten-year period. Clinical data regarding pregnancy, delivery, neonatal mortality, and morbidity were collected from the Vermont Oxford Network (VON) database. Results 185 liveborn infants with gestational age (GA) from 22 +0 to 24 +6 weeks were included. A high proportion of the most immature infants were not treated actively (92 % infants born at 22 weeks of GA died in delivery room). Survival rates according to GA were 4 % (22 weeks), 40.7 % (23 weeks), and 65.1 % (24 weeks). Of the infants admitted to the neonatal intensive care unit (n=142), 25.3 % had severe intraventricular hemorrhage (grade III or IV) or periventricular leukomalacia, 13.4 % underwent abdominal surgery (due to necrotizing enterocolitis), and 17.6 % required laser treatment for retinopathy of prematurity. Supplemental oxygen at 36 weeks postmenstrual age was required by 40.8 % infants. Conclusions At our center, which cares for more than 90 % of periviable newborns born in Slovenia, we achieved comparable survival and morbidity outcomes for actively approached liveborn periviable infants compared to those from developed countries reported in the literature. In the future, we aim to implement active antenatal care for pregnant women and infants born after completed 22 weeks of gestation and monitor the long-term outcomes of all infants born at the limit of viability.
Open Access
Sonographic surveillance and perinatal outcomes among pregnancies with periviable fetal growth restriction

January 1, 2000

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
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
Amniotic Fluid Embolism: a comprehensive review of diagnosis and management

January 1, 2000

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
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
The fetal exposome and Preterm Birth: a systematic synthesis of environmental exposures and multi-omics evidence

January 1, 2000

Wiku Andonotopo, Muhammad Adrianes Bachnas, Julian Dewantiningrum, Mochammad Besari Adi Pramono, Nuswil Bernolian, Cut Meurah Yeni, Anak Agung Gede Putra Wiradnyana, I Nyoman Hariyasa Sanjaya, Muhammad Ilham Aldika Akbar, Ernawati Darmawan, Sri Sulistyowati, Milan Stanojevic, Asim Kurjak

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Objectives Preterm birth (PTB), defined as delivery before 37 weeks of gestation, is a leading cause of neonatal mortality and long-term developmental impairment. Its complex etiology, spanning environmental, genetic, psychosocial, and socio-economic domains, limits effective prediction and prevention. We systematically synthesized evidence on how environmental exposures influence PTB risk through multi-omic disruptions within a fetal exposome framework. Methods A comprehensive literature search was conducted in major biomedical databases, following PRISMA guidelines. Ninety-five human studies published through May 2025 were included, encompassing exposures such as ambient air pollution, endocrine-disrupting chemicals, maternal stress, nutrition, occupational hazards, climate variability, and microbiome alterations. Two reviewers independently extracted data (exposure type, omics platform, biospecimen, PTB subtype) with inter-rater reliability assessment, and study quality was evaluated using the Newcastle–Ottawa Scale. Findings were narratively stratified by exposure category, study design, and spontaneous vs. indicated PTB. Results Environmental exposures were consistently associated with disruptions in oxidative stress, inflammation, immune regulation, hormonal signaling, placental aging, and microbial ecology, mediated by multi-omic signatures in maternal, placental, and fetal tissues. Candidate biomarkers show promise for early risk stratification but lack validation and population-level predictive performance due to heterogeneous exposure assessment and study design. Conclusions Integrating fetal exposome concepts with multi-omics enhances mechanistic insight into PTB risk and may support biomarker discovery and precision-guided prenatal interventions. Clinical translation requires standardized exposure measurement, biomarker validation, and equity-focused implementation.
Open Access
Associations between previous cesarean section and maternal and neonatal complications: the modification of long inter-pregnancy interval

January 1, 2000

Yuxin Xiang, Qing Zhao, Wenbin Dong, Yujiao Zhang, Xiaoping Lei

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Objectives We aim to explore whether the long inter-pregnancy interval (IPI) modifies the association between previous cesarean section (CS) and adverse maternal and neonatal outcomes in a population with a high rate of CS and a long IPI. Methods Adverse maternal and neonatal outcomes were compared between the previous CS and previous vaginal delivery groups. Logistic models were used to adjust for potential confounding factors and calculate the Odds Ratios (ORs) and 95 % confidence intervals (CIs). The interaction model and stratified analyses were used to evaluate the modifications of IPIs on the associations between previous CS and maternal and neonatal outcomes. Results Compared with previous vaginal delivery, previous CS was associated with increased risks of uterine-related complications (a OR=1.57, 95 % CI 1.25–1.98), but with decreased risks of preterm birth (a OR=0.73, 95 % CI 0.63–0.85) and severe neonatal adverse outcomes (a OR=0.59, 95 % CI 0.46–0.78). There are synergistic biological interaction effects of previous CS and a long IPI (>60 months) on the risks of placental-related complications (RERI=0.32, 95 % CI 0.05–0.58; AP=0.39, 95 % CI 0.03–0.76) but an antagonistic biological interaction effect on the risk of preterm birth (RERI=−0.35, 95 % CI -0.68 to −0.01; AP=−0.09, 95 % CI -0.68 to −0.03). Conclusions Previous CS was associated with increased risks of adverse maternal outcomes but decreased risks of certain adverse neonatal outcomes. Prolonged IPIs might not attenuate the adverse effects of previous CS on mothers, and might adversely exert harm on newborns.
Open Access
Comparative effectiveness of oxytocin, carbetocin, and tranexamic acid for postpartum hemorrhage prevention in cesarean deliveries: a prospective cohort analysis

January 1, 2000

Beyzanur Kahyaoğlu, Rezzan Berna Temoçin, Mehmet Güçlü, Mehmet Mete Kırlangıç, Elif Ünlügedik Sayın, Ahmet Özkul

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Objectives To evaluate the comparative effectiveness of four pharmacologic regimens – oxytocin, carbetocin, oxytocin plus tranexamic acid (TXA), and carbetocin plus TXA – for postpartum hemorrhage (PPH) prophylaxis in cesarean deliveries. Methods This prospective cohort study was conducted at a tertiary center in Istanbul, Turkey, between March 2024 and January 2025. A total of 400 women undergoing cesarean delivery at 34+0–39+6 weeks of gestation were sequentially assigned to one of four prophylactic intervention groups (n=100 each): oxytocin, oxytocin+TXA, carbetocin, or carbetocin+TXA. Medications were administered post-placental delivery. Third-stage labor management was standardized. Primary outcomes included estimated blood loss (EBL), 24-h hemoglobin change (ΔHb), and need for transfusion or intravenous iron. Baseline neonatal characteristics, including birthweight and Apgar scores, were recorded to ensure comparability across groups. Results Baseline characteristics were similar across groups. Hemoglobin decline differed significantly (p=0.015), being lowest in the carbetocin+TXA group (7.73 ± 6.68 %) and highest in the oxytocin group (10.70 ± 7.23 %). Although mean EBL was lowest in the carbetocin+TXA group, the difference was not statistically significant (p=0.172). Transfusion and iron supplementation rates were low and comparable. No adverse neonatal outcomes were observed. Conclusions Carbetocin combined with TXA was associated with the most favorable hematologic profile. These findings support the use of multimodal pharmacologic strategies for PPH prevention in cesarean births and may inform future protocol development.
Open Access
Pregnancy-associated anemia and its effects in term neonates

January 1, 2000

Rita P. Verma, Neeti Luke, Zhe Zhou

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Objectives To investigate the implications of maternal anemia in term neonates. Methods In a population-based retrospective cohort study, standard demographic and clinical variables noted during post-birth hospitalization in term neonates were compared across groups stratified by maternal anemia in a racially diverse population. Results Of 474 maternal-neonatal dyads, 66.03 % were Hispanic (H), 15.8 % Black (B), 7.3 % non-hispanic white (NHW), and 10.7 % Asian/pacific islanders (AP). 39.6 % of H, 57.3 % of B, 65.7 % of NHW, and 37 % of AP mothers were anemic, with significantly higher prevalence in NHW and B compared to H. 12.8 % of all anemia cases had moderately severe anemia (Hematocrit<30 %). Body mass index was lower, and gravidity, hypertension, and Cesarean-section rates were higher in anemic mothers, while feeding difficulty, hospitalization duration, and Neonatal intensive care unit admission rate were higher in the neonates born to them. Mothers with moderately severe anemia were younger, had higher parity, and a higher prevalence of antepartum hemorrhage compared to the mild anemia group. Their offspring, although not small for gestational age, had lower birth weights. The adverse maternal-neonatal outcomes associated with anemia were less common in the Hispanic mother-infant dyads compared to the B and NHW. Conclusions Maternal anemia is associated with significant complications in term neonates and their mothers. There is a racial disparity in its prevalence and associated maternal-neonatal complications. The cultural-biological etiopathogenesis of this observation warrants further investigation. Optimization of antenatal care and targeted interventions could improve the outcomes and prevalence in at-risk populations.
Open Access
Longitudinal changes of left ventricular hypoplasia and ventricular disproportion in congenital diaphragmatic hernia neonates

January 1, 2000

Flaminia Pugnaloni, Bartolomeo Bo, Judith Leyens, Irma Capolupo, Andrea Dotta, Pietro Bagolan, Andreas Mueller, Neil Patel, Florian Kipfmueller

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Objectives Ventricular disproportion, defined as a ratio of right ventricle (RV) end-diastolic diameter to left ventricle (LV) end-diastolic diameter (RV D /LV D ) ≥ 1.1 is commonly observed in neonates with congenital diaphragmatic hernia (CDH) and it is independently associated with adverse outcome. Longitudinal postnatal data on ventricular disproportion of CDH neonates are poorly studied and we aimed to evaluate changes in RV D /LV D through serial echocardiographic studies at selected timepoints in the neonatal period. Methods This retrospective observational study included CDH neonates admitted to the University Children’s Hospital of Bonn between January 2011 and March 2021. RV D /LV D was measured via apical 4-chamber echocardiographic views at admission, 48 h of life, pre-surgical repair, pre-extubation, and on day 5 of ECMO support, if applicable. Patients receiving palliative care, experiencing early death, or lacking follow-up echocardiographic data were excluded. Results Of 248 CDH neonates, 80 were excluded, leaving 168 in the final cohort. At baseline, 41.7 % had an RV D /LV D ≥1.1. Mortality (34.3 %) and ECMO rates (62.9 %) were significantly higher in these patients compared to those with RV D /LV D <1.1. Ventricular disproportion decreased over time: 41.7 % at admission, 23.1 % at 48 h, 15.7 % pre-repair, and 9.1 % pre-extubation. For ECMO patients, RV D /LV D ≥1.1 was found in 62.9 % at admission, decreasing over time. Non-survivors had significantly higher RV D /LV D at 48 h (p=0.020) and pre-extubation (p=0.001). Conclusions In CDH neonates, ventricular disproportion improves over time, but RV D /LV D ≥1.1 remains strongly associated with mortality, particularly in ECMO patients, where non-survivors exhibit persistently elevated RV D /LV D .
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
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
Assessment of fetal adrenal gland and thymothoracic ratio in preterm premature membrane rupture: a prospective case-control study

January 1, 2000

Burcu Bozkurt Ozdal, Atakan Tanacan, Betul Akgun Aktas, Huseyin Kayaalp, Gulnihal Reyhan Toptas, Esra Karatas, Ozgur Kara, Dilek Sahin

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Objectives This study aims to investigate the role of fetal thymus and adrenal medulla dimensions in the pathogenesis of preterm prelabor rupture of membranes (PPROM). Methods A prospective, case-control study was conducted involving 45 pregnant women with PPROM between 28 and 37 weeks of gestation and 45 matched healthy controls. Ultrasonographic measurements of fetal thymus (width, length, TTR) and adrenal glands (length, width, depth, volume), including the adrenal medulla, were performed. Biochemical markers (WBC, CRP) and neonatal outcomes were recorded. Statistical analyses included comparisons between groups, correlation assessments, and ROC curve analysis to evaluate predictive parameters. Results The fetal thymus dimensions and TTR ratio were significantly smaller in the PPROM group. The adrenal medulla volume, length, and depth were notably reduced, while total adrenal gland size showed no significant difference. Moderate negative correlations were observed between inflammatory markers and TTR. ROC analysis indicated that TTR and adrenal medulla volume could predict NICU admission with moderate sensitivity and specificity. Conclusions The findings suggest that alterations in fetal thymus and adrenal medulla sizes are associated with PPROM and may serve as potential biomarkers for its diagnosis and prognosis. Further large-scale studies are warranted to validate these parameters and explore their clinical applications.
Open Access
Antenatal shunting and outcomes in fetuses with non-immune hydrops fetalis

January 1, 2000

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
Revisiting KANET in the context of fetal connectomics: defining optimal gestational windows for neurodevelopmental screening

January 1, 2000

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

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Objectives To introduce the KANET-connectome matrix (KANET-Con) as a conceptual framework linking fetal behaviors observed on four-dimensional (4D) ultrasound to underlying neural network maturation, and to evaluate optimal gestational timing for functional neurodevelopmental screening. Methods A narrative review was conducted using a PRISMA-guided literature identification and screening process. PubMed, Scopus, and Web of Science were searched (January 2000–March 2025) for studies addressing fetal connectomics, fetal neurobehavior, KANET scoring, and developmental neuroimaging. Forty-two peer-reviewed studies met inclusion criteria. Observed fetal behaviors—including facial mimicry, eye blinking, limb movement, and overall gestalt coordination—were aligned with their most plausible neural substrates using evidence from developmental neuroscience and imaging. Results Findings demonstrated clear temporal associations between specific fetal behaviors and neural circuit development. Eye blinking and facial expressions (24–26 weeks) correlated with brainstem-cortical integration; hand-to-face gestures (26–30 weeks) reflected emerging interhemispheric pathways; and complex limb coordination (28–32 weeks) was linked to corticospinal and basal ganglia maturation. Collectively, these data indicate that 24–32 weeks of gestation represents an optimal window for KANET-based neurobehavioral screening. Additionally, emerging artificial intelligence applications show potential to enhance scoring objectivity by detecting subtle movement features such as behavioral entropy, asymmetry, and latency. Conclusions KANET, interpreted through a fetal connectomic lens, provides a functional window into early neural integration. The KANET-Con offers a clinically relevant, globally accessible conceptual model to support early detection of neurodevelopmental deviations and inform risk stratification, particularly in resource-limited settings.
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
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
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
Second pregnancy vaginal birth after cesarean- impact of maternal age on outcomes from a retrospective cohort study

January 1, 2000

Syed Mariyam, Fathima Minisha, Salwa Abu Yaqoub, Nader AlDewik, Thomas Farrell

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Objectives The rate of cesarean delivery (CD) in Qatar is rising at an alarming rate. Vaginal birth after cesarean section (VBAC) is associated with lower maternal morbidity and is an important option for younger mothers. This study compared the pregnancy outcomes of second pregnancies in women with prior CD, according to their age groups, with the aim of individualising VBAC counselling. Methods This retrospective study divided women in their second pregnancies based on age: young group (YG<25 years), control group (CG, 25–35 years), and advanced age group (AG>35 years). The primary outcome was the mode of delivery. Results Out of 2,729 women, 18.2 % had a VBAC (27.4 % in YG vs. 9.5 % in AG). Nearly 48 % agreed to a TOLAC (57.9 % in YG and 41.8 % in AG), 38 % of whom had a successful VBAC. Among those who opted for TOLAC, 47.3 % in YG had a successful VBAC, compared to only 22.8 % in AG (p<0.001). While hypertension, diabetes, macrosomia and preterm birth reduced VBAC, postdated and uncomplicated pregnancies increased the rates. Compared to CG, YG had 35 % lower odds of repeat CD (aOR=0.64, CI=0.49–0.85, p=0.002), while AG had nearly two times higher odds (CI=1.26–2.95, p=0.003), after adjusting for confounders. Conclusions Maternal age emerged as an important predictor of repeat cesarean, with younger mothers having a much higher chance of successful VBAC. More than half with uncomplicated pregnancies opted for an elective CD, highlighting the requirement for improving counselling services that motivate women to take up VBAC and improve their confidence in the healthcare system.
Open Access
Clinical factors in SARS-CoV-2 antibody response in unvaccinated mothers

January 1, 2000

Mirjam Druškovič, Gorazd Kavsek, Vita Andreja Mesarič, Aleksandra Strukelj, Tatjana AvšiČ Županc, Alojz Ihan, Tanja Premru Sršen

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Objectives Understanding the clinical factors influencing the SARS-CoV-2 antibody response during and after pregnancy is critical for optimizing maternal care and vaccination strategies. This prospective cohort study aimed to evaluate associations between maternal clinical characteristics and SARS-CoV-2-specific IgG and IgA antibody levels at delivery and 42 days postpartum in unvaccinated pregnant women. Methods A total of 387 pregnant women with confirmed SARS-CoV-2 infection during pregnancy were included. SARS-CoV-2 infection was confirmed using real-time RT-PCR. Clinical data, including age, body mass index (BMI), smoking status, pre-existing morbidities, and obstetric complications, were recorded. SARS-CoV-2-specific IgG and IgA antibodies were quantified using ELISA at delivery and 42 days postpartum. Results Higher preconception BMI significantly correlated with increased odds of detecting IgG and IgA antibodies at both delivery and postpartum assessments (p<0.05), independently of maternal age and chronic diseases. Women without chronic systemic diseases exhibited lower antibody levels at delivery, whereas smokers had significantly lower odds of IgG antibody presence at delivery. Additionally, pre-existing cardiovascular diseases were associated with reduced antibody presence at six weeks postpartum. Other clinical parameters did not show significant associations. Conclusions Preconception BMI and pre-existing systemic diseases may modulate SARS-CoV-2 antibody responses in pregnant women. These clinical factors should inform assessments of maternal and neonatal infection risks and guide vaccination strategies in pregnant populations. Further research is needed to elucidate the mechanisms underlying these associations.

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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