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10 pages, 577 KiB  
Article
Placental Polycyclic Aromatic Hydrocarbon (PAH) Levels Are Associated with Spontaneous Preterm Birth
by Gwendolynn Hummel, Sohini Banerjee, Vasanta Putluri, Inaara Malick, Grace Johnson, Abu Hena Mostafa Kamal, Chandra Shekar R. Ambati, Nagireddy Putluri, Lori Showalter, Cynthia D. Shope, Joseph Hagan, Kjersti M. Aagaard, Bhagavatula Moorthy and Melissa A. Suter
Int. J. Mol. Sci. 2025, 26(17), 8179; https://doi.org/10.3390/ijms26178179 (registering DOI) - 23 Aug 2025
Abstract
While the cause of preterm birth (PTB) (i.e., delivery before 37 weeks of gestation) is likely multifactorial, ambient exposure to environmental chemicals has been postulated to play a role in its etiology. Our prior studies of exposure to polycyclic aromatic hydrocarbons (PAHs) in [...] Read more.
While the cause of preterm birth (PTB) (i.e., delivery before 37 weeks of gestation) is likely multifactorial, ambient exposure to environmental chemicals has been postulated to play a role in its etiology. Our prior studies of exposure to polycyclic aromatic hydrocarbons (PAHs) in pregnancy have shown an increased level of placental PAH-induced bulky DNA adducts with increasing levels of PAH exposures. In this investigation, we hypothesized that higher levels of placental PAHs would be associated with an increased risk of PTB. Using gas chromatography and mass spectrometry (GC-MS/MS), we measured levels of benzo(a)pyrene (BaP), benzo(b)fluoranthene (BbF) and dibenz(a,h)anthracene (DBA) from n = 323 subjects. We found higher levels of BbF in placentae collected from preterm compared with term deliveries (mean 100.3 vs. 84.14 ng/mL, p = 0.038). Placental BbF levels negatively correlated with gestational age at delivery (rs = −0.171, p = 0.002) and placental DBA levels were higher in placentae from spontaneous PTBs compared to those that were medically indicated (mean 743.7 vs. 599.9 ng/mL, p = 0.049), suggesting a potentially causal role in spontaneous preterm birth. Lastly, we analyzed placental levels of each PAH in male (n = 164) and female (n = 159) gestations and found that levels of BaP are significantly higher in males (mean 204.4 vs. 169.9 ng/mL, p = 0.049). These studies show a potential causal role of PAH exposure in the etiology of spontaneous preterm birth. Full article
(This article belongs to the Collection New Advances in Molecular Toxicology)
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19 pages, 1068 KiB  
Article
Post-Discharge Trajectories of Romanian Premature Infants: A Cross-Sectional Analysis of Associated Factors
by Ioana Rosca, Alexandru Dinulescu, Ana Prejmereanu, Mirela-Luminita Pavelescu, Alexandru Cosmin Palcău, Daniela-Eugenia Popescu and Andreea Teodora Constantin
Children 2025, 12(9), 1107; https://doi.org/10.3390/children12091107 - 22 Aug 2025
Abstract
(1) Background: Prematurity remains a leading contributor to neonatal morbidity and mortality, with long-term consequences that extend well beyond the neonatal period. This cross-sectional study aimed to identify key maternal, perinatal, and neonatal factors that influence the short- and long-term evolution of preterm [...] Read more.
(1) Background: Prematurity remains a leading contributor to neonatal morbidity and mortality, with long-term consequences that extend well beyond the neonatal period. This cross-sectional study aimed to identify key maternal, perinatal, and neonatal factors that influence the short- and long-term evolution of preterm infants. It also seeks to evaluate the level of post-discharge follow-up care, parental involvement during NICU hospitalization, access to supportive therapies such as physiotherapy and RSV prophylaxis, and the impact of breastfeeding practices. Additionally, the study explores parental awareness and use of recent national initiatives in Romania, such as the “Premature and Vulnerable Newborn’s Notebook”. (2) Methods: A total of 360 mothers of preterm infants born between 2001 and 2025 responded to a structured questionnaire assessing clinical characteristics, NICU care, parental involvement, and post-discharge support. (3) Results: The findings indicate that assisted reproduction and pregnancy plurality were associated with higher maternal age, while vaginal delivery was associated with lower gestational age at birth. Notably, only 25% of infants were enrolled in structured follow-up programs, and a large proportion of families relied on private services for physical therapy. Kangaroo mother care was reported by just 16.4% of mothers. While breastfeeding rates improved after discharge, access to multidisciplinary follow-up and public physiotherapy remains limited. Encouragingly, most mothers endorsed the proposed national initiative for a “Premature and Vulnerable Newborn’s Notebook.” (4) Conclusions: This study underscores the urgent need for a comprehensive national follow-up strategy to ensure equitable and continuous care for Romania’s vulnerable preterm population. Full article
(This article belongs to the Section Pediatric Neonatology)
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22 pages, 819 KiB  
Review
The Role of Oral Microbiota and Glial Cell Dynamics in Relation to Gender in Cardiovascular Disease Risk
by Devlina Ghosh and Alok Kumar
Neuroglia 2025, 6(3), 30; https://doi.org/10.3390/neuroglia6030030 - 22 Aug 2025
Abstract
The oral microbiota, long recognized for their role in local pathologies, are increasingly implicated in systemic disorders, particularly cardiovascular disease (CVD). This review focuses on emerging evidence linking oral dysbiosis to neuroglial activation and autonomic dysfunction as key mediators of cardiovascular pathology. Pathogen-associated [...] Read more.
The oral microbiota, long recognized for their role in local pathologies, are increasingly implicated in systemic disorders, particularly cardiovascular disease (CVD). This review focuses on emerging evidence linking oral dysbiosis to neuroglial activation and autonomic dysfunction as key mediators of cardiovascular pathology. Pathogen-associated molecular patterns, as well as gingipains and leukotoxin A from Porphyromonas gingivalis, Fusobacterium nucleatum, Treponema denticola, Aggregatibacter actinomycetemcomitans, etc., disrupt the blood–brain barrier, activate glial cells in autonomic centers, and amplify pro-inflammatory signaling. This glia driven sympathetic overactivity fosters hypertension, endothelial injury, and atherosclerosis. Crucially, sex hormones modulate these neuroimmune interactions, with estrogen and testosterone shaping microbial composition, glial reactivity, and cardiovascular outcomes in distinct ways. Female-specific factors such as early menarche, pregnancy, adverse pregnancy outcomes, and menopause exert profound influences on oral microbial ecology, systemic inflammation, and long-term CVD risk. By mapping this oral–brain–heart axis, this review highlights the dual role of oral microbial virulence factors and glial dynamics as mechanistic bridges linking periodontal disease to neurogenic cardiovascular regulation. Integrating salivary microbiome profiling with glial biomarkers [e.g., GFAP (Glial Fibrillary Acidic Protein) and sTREM2 (soluble Triggering Receptor Expressed on Myeloid cells 2)] offers promising avenues for sex-specific precision medicine. This framework not only reframes oral dysbiosis as a modifiable cardiovascular risk factor, but also charts a translational path toward gender tailored diagnostics and therapeutics to reduce the global CVD burden. Full article
19 pages, 788 KiB  
Review
Letrozole at the Crossroads of Efficacy and Fetal Safety in Ovulation Induction: A Narrative Review
by Aris Kaltsas, Anna Efthimiou, Christos Roidos, Vasileios Tzikoulis, Ioannis Georgiou, Alexandros Sotiriadis, Athanasios Zachariou, Michael Chrisofos, Nikolaos Sofikitis and Fotios Dimitriadis
Biomedicines 2025, 13(9), 2051; https://doi.org/10.3390/biomedicines13092051 - 22 Aug 2025
Abstract
Letrozole, a third-generation aromatase inhibitor initially developed for breast cancer, has become the preferred first-line agent for ovulation induction (OI), particularly in women with polycystic ovary syndrome (PCOS). This narrative review critically evaluates the efficacy, safety, and clinical applications of letrozole across diverse [...] Read more.
Letrozole, a third-generation aromatase inhibitor initially developed for breast cancer, has become the preferred first-line agent for ovulation induction (OI), particularly in women with polycystic ovary syndrome (PCOS). This narrative review critically evaluates the efficacy, safety, and clinical applications of letrozole across diverse infertility contexts. Compared to clomiphene citrate, letrozole is associated with higher ovulation and live birth rates, a lower risk of multiple gestation, and a more favorable endometrial environment. Its pharmacokinetics—marked by transient estrogen suppression and a short half-life—limit embryonic exposure, supporting its favorable safety profile. Emerging data from large, randomized trials and meta-analyses demonstrate no increase in congenital anomalies, miscarriage, or adverse perinatal outcomes in letrozole-conceived pregnancies. Moreover, maternal side effects are generally mild, and the risk of ovarian hyperstimulation syndrome is low. Letrozole has also shown utility in mild stimulation protocols, fertility preservation for estrogen-sensitive malignancies, and clomiphene-resistant PCOS. Key clinical strategies—such as early-cycle initiation, lowest effective dosing, and individualized monitoring—optimize therapeutic outcomes while minimizing potential risks. While long-term offspring data remain limited and mechanistic concerns persist, current evidence robustly supports letrozole as a safe and effective option for OI, balancing reproductive success with maternal–fetal safety across a range of infertility indications. Full article
(This article belongs to the Special Issue Maternal-Fetal and Neonatal Medicine)
9 pages, 448 KiB  
Article
Re-Evaluating the Contraction Stress Test for Term Fetal Growth Restriction Fetuses: A Retrospective Study
by Roie Alter, Hagar Herz, Adiel Cohen, Naama Lessans, Yossef Ezra and Doron Kabiri
J. Clin. Med. 2025, 14(16), 5899; https://doi.org/10.3390/jcm14165899 - 21 Aug 2025
Abstract
Background: Fetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality, yet optimal intrapartum management remains debated. The contraction stress test (CST) has been proposed as a tool to assess fetal tolerance to labor, but its prognostic value in FGR pregnancies [...] Read more.
Background: Fetal growth restriction (FGR) is associated with increased perinatal morbidity and mortality, yet optimal intrapartum management remains debated. The contraction stress test (CST) has been proposed as a tool to assess fetal tolerance to labor, but its prognostic value in FGR pregnancies is unclear. This study aimed to evaluate the utility of CST in predicting perinatal outcomes among term fetuses with FGR and to compare these outcomes with those of small-for-gestational-age (SGA) fetuses. Methods: We conducted a retrospective cohort study of term singleton deliveries at a tertiary care center over a two-year period. FGR was defined as birthweight below the 3rd percentile or, prenatally, below the 10th percentile with abnormal Doppler findings. SGA fetuses were defined as birthweights between the 3rd and 10th percentiles. Participants were stratified into the following three groups: (1) FGR with a negative CST result, (2) FGR without CST, and (3) SGA without FGR. The primary outcome was the rate of emergency cesarean delivery. Secondary outcomes included a composite of neonatal adverse events (Apgar score < 7 at 5 min, umbilical cord pH < 7.1, NICU admission, prolonged neonatal hospitalization, intubation, or intraventricular hemorrhage) and a combined metric of neonatal and maternal adverse events. Results: A total of 1688 term singleton pregnancies were included in this analysis, comprising 33 cases of FGR with negative CST results, 275 cases of FGR without CST, and 1123 cases classified as SGA. Emergency cesarean delivery rates were comparable between FGR with negative CST (15.2%) and FGR without CST (14.9%), both were significantly higher than in the SGA group (9.7%, p = 0.025). Composite neonatal adverse events did not differ significantly between the FGR groups (21.2% vs. 24.7%) but were more frequent than in the SGA group (8.1%, p < 0.001). Similarly, the incidence of combined neonatal and maternal adverse events was not different between the FGR groups (30.3% vs. 33.5%) yet exceeded that of the SGA group (15.1%, p < 0.001). Conclusions: In this cohort, a negative CST performed prior to labor induction did not reduce the risk of adverse maternal or neonatal outcomes in pregnancies complicated by FGR. These findings indicate that routine use of CST may offer limited prognostic benefit in the evaluation of term FGR, highlighting the necessity for further studies to establish evidence-based surveillance and management strategies for this high-risk group. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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16 pages, 5420 KiB  
Case Report
Severe Aortic Stenosis and Pre-Excitation Syndrome in Pregnancy—A Multidisciplinary Approach
by Miruna Florina Ştefan, Lucia Ştefania Magda, Catalin Gabriel Herghelegiu, Doru Herghelegiu, Oana Aurelia Zimnicaru, Catalin Constantin Badiu, Maria Claudia Berenice Suran, Andreea Elena Velcea, Calin Siliste and Dragoș Vinereanu
Diagnostics 2025, 15(16), 2099; https://doi.org/10.3390/diagnostics15162099 - 20 Aug 2025
Viewed by 148
Abstract
Background/Objectives: Heart disease affects 0.1% to 4% of pregnant women, with congenital heart defects being the leading cause in developed countries. While maternal mortality is generally low, pre-existing cardiac conditions substantially increase adverse outcome risks. This report describes the multidisciplinary management of [...] Read more.
Background/Objectives: Heart disease affects 0.1% to 4% of pregnant women, with congenital heart defects being the leading cause in developed countries. While maternal mortality is generally low, pre-existing cardiac conditions substantially increase adverse outcome risks. This report describes the multidisciplinary management of a pregnant patient with a bicuspid aortic valve, severe aortic stenosis, and ascending aortic ectasia. Case Presentation: A 34-year-old pregnant woman, asymptomatic but at high risk (World Health Organization Class III) for hemodynamic decompensation, was closely monitored throughout gestation. At 36 weeks, intrauterine growth restriction was detected, prompting an elective cesarean delivery at 38 weeks. Postpartum, the patient developed pre-eclampsia, which was managed successfully. Imaging revealed progressive aortic dilation, leading to surgical aortic valve replacement and ascending aorta reduction plasty. Post-operatively, atrioventricular reentrant tachycardia from an unrecognized accessory pathway developed; medical therapy effectively controlled the arrhythmia after failed catheter ablation. One year later, both mother and child remained in good health. Discussion: This case illustrates the complexity of managing pregnancy in women with congenital heart disease and significant aortic pathology. The physiological changes of pregnancy can exacerbate underlying lesions, necessitating individualized risk assessment, vigilant monitoring, and timely intervention. Conclusions: A multidisciplinary approach involving cardiology, obstetrics, anesthesiology, and genetics is essential to optimize outcomes for pregnant women with significant heart disease. As advances in care allow more women with congenital heart defects to reach childbearing age, structured care pathways remain vital for ensuring safe pregnancies and long-term cardiovascular health. Full article
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21 pages, 563 KiB  
Review
Addressing Patient–Provider Communication Gaps in Vanishing Twin Syndrome: Implications for Patient Care and Clinical Guidelines
by Nichole M. Cubbage, Samantha L. P. Schilit, Allison Groff, Stephanie Ernst and Marc A. Nascarella
Healthcare 2025, 13(16), 2048; https://doi.org/10.3390/healthcare13162048 - 19 Aug 2025
Viewed by 376
Abstract
Background: Vanishing twin syndrome (VTS) represents a complex and under-recognized phenomenon in multifetal pregnancies, associated with both clinical uncertainty and significant psychosocial impact. Despite its frequency, gaps remain in diagnostic clarity, international guidelines, and communication strategies with patients and families. Materials and [...] Read more.
Background: Vanishing twin syndrome (VTS) represents a complex and under-recognized phenomenon in multifetal pregnancies, associated with both clinical uncertainty and significant psychosocial impact. Despite its frequency, gaps remain in diagnostic clarity, international guidelines, and communication strategies with patients and families. Materials and Methods: This hybrid review integrates narrative and systematic elements to assess the diagnostic, clinical, and psychosocial gaps in VTS. A systematic literature search was conducted across Medline/PubMed, CINAHL, PsycINFO, EBM Reviews, and Scopus using terms such as “vanishing twin syndrome,” “patient-provider communicat*,” and “bereave* care.” Sources included systematic reviews, randomized controlled trials, cohort studies, and qualitative studies. Exclusion criteria were outdated publications (>10 years old). Results: Evidence revealed multiple domains of concern. Clinical risks and diagnostics remain poorly defined, with inconsistent recognition of maternal and neonatal complications. Psychosocial impacts were prominent, encompassing grief, identity disruption, and unmet support needs. Patient–provider communication was frequently inadequate, with insufficient training and lack of standardized language. International guidelines varied widely in scope, with only a few of them providing clear recommendations for bereavement care in multifetal loss contexts. Discussion: Emerging discourse highlights the limitations of the traditional fission model and alternative conceptual frameworks, such as Herranz’s model, for understanding VTS. These theoretical differences underscore the need for precise terminology and consistent diagnostic practices. Clinical implications extend to prenatal screening, obstetric management, and the integration of psychosocial support. Patient-centered communication and structured support initiatives (e.g., the Butterfly Project) demonstrate the potential to bridge communication gaps and improve care experiences. Conclusions: VTS requires recognition as both a medical and psychosocial condition. Improved clinical definitions, harmonized international guidelines, and emphasis on empathetic communication are essential to address the current gaps. Integrating these elements into practice may enhance patient outcomes and provide families with validation and support following multifetal loss. Full article
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10 pages, 495 KiB  
Article
Evidence for Extracellular Superoxide Dismutase (SOD3), Glutathione and Redox Dynamics in Amniotic Fluid Throughout Gestation
by Leah Knieps, Ebru Aileen Alsat, Tamene Melaku, Andreas Mueller and Soyhan Bagci
Children 2025, 12(8), 1086; https://doi.org/10.3390/children12081086 - 19 Aug 2025
Viewed by 153
Abstract
Introduction: Amniotic fluid (AF) plays a pivotal role in foetal gastrointestinal development by delivering bioactive factors that support intestinal maturation. However, the redox environment of AF and its potential contribution to foetal intestinal homeostasis remain insufficiently characterised. This study aimed to quantify key [...] Read more.
Introduction: Amniotic fluid (AF) plays a pivotal role in foetal gastrointestinal development by delivering bioactive factors that support intestinal maturation. However, the redox environment of AF and its potential contribution to foetal intestinal homeostasis remain insufficiently characterised. This study aimed to quantify key antioxidant markers—superoxide dismutase isoforms (SOD1, SOD3), glutathione (GSH), and the oxidative DNA damage marker 8-hydroxy-2-deoxyguanosine (8-OHdG)—in AF across gestational ages and compare them with those in human milk (HM). Methods: AF samples (n = 60) were collected from pregnancies between 15 and 40 weeks of gestation, grouped into preterm (<37 weeks) and term (≥37 weeks). SOD1, SOD3, GSH, and 8-OHdG concentrations were quantified using ELISA. HM samples (n = 45) were similarly analysed. Results: SOD1 and SOD3 in AF concentrations decreased significantly with gestational age (GA) (p < 0.001), while 8-OHdG levels increased (p < 0.001). SOD3 showed a negative correlation with 8-OHdG (p = 0.004). HM contained significantly higher levels of both SOD isoforms compared to AF (AF vs. HM: 35.6 (1.9–172.3) vs. 267.9 (54.6–843.8), p < 0.001 for SOD1 and 1.2 ng/mL (0.1–26.5) vs. 5.5 ng/mL (0.1–300.0), p < 0.001 for SOD3), regardless of GA. Conclusions: Our findings highlight the dynamic nature of the redox environment in AF and its potential importance for foetal GIT development. The disruption of redox balance by preterm birth or inadequate AF intake during foetal life may have long-term consequences for intestinal development and function. These insights provide a foundation for future clinical studies aimed at enhancing neonatal feeding regimens, particularly for preterm infants and those with congenital gastrointestinal disorders. Full article
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24 pages, 694 KiB  
Review
Gestational Diabetes Mellitus: The Dual Risk of Small and Large for Gestational Age: A Narrative Review
by Andreea Fotă and Aida Petca
Med. Sci. 2025, 13(3), 144; https://doi.org/10.3390/medsci13030144 - 19 Aug 2025
Viewed by 304
Abstract
Background/Objectives: Gestational diabetes mellitus (GDM) complicates approximately 14% of pregnancies worldwide, its prevalence rising with increasing maternal age and obesity. While maternal hyperglycemia is traditionally associated with fetal overgrowth and large-for-gestational-age (LGA) neonates, emerging evidence indicates that GDM may also contribute to [...] Read more.
Background/Objectives: Gestational diabetes mellitus (GDM) complicates approximately 14% of pregnancies worldwide, its prevalence rising with increasing maternal age and obesity. While maternal hyperglycemia is traditionally associated with fetal overgrowth and large-for-gestational-age (LGA) neonates, emerging evidence indicates that GDM may also contribute to small-for-gestational-age (SGA) outcomes. Methods: A comprehensive literature search was conducted using multiple databases, including PubMed, Web of Science, and ScienceDirect, to identify studies related to gestational diabetes mellitus, fetal growth outcomes such as small for gestational age and large for gestational age, and associated pathophysiological mechanisms. Results: This narrative review explores the mechanisms by which GDM influences fetal growth, emphasizing the dual risk of excessive and restricted intrauterine growth. Fetal macrosomia typically results from chronic maternal hyperglycemia, leading to increased transplacental glucose delivery and fetal hyperinsulinemia. In contrast, SGA outcomes are a consequence of vascular and endothelial dysfunction, placental insufficiency, or excessively restrictive glycemic control that limit the availability of nutrients. Both extremes of fetal growth carry a myriad of significant perinatal and long-term metabolic risks. Conclusions: Understanding the diverse pathways through which GDM affects fetal growth is essential for developing individualized clinical strategies. Full article
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11 pages, 441 KiB  
Article
Intravenous Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia During Pregnancy: Effects on Maternal and Fetal Wellbeing—A Multicenter Retrospective Observational Study
by Eleonora Romani, Sara Zullino, Anna R. Speciale, Paola M. Villa, Veronica Bonaldo, Francesca Parisi, Chiara Lubrano, Felice Petraglia, Irene Cetin and Federico Mecacci
Nutrients 2025, 17(16), 2670; https://doi.org/10.3390/nu17162670 - 19 Aug 2025
Viewed by 351
Abstract
Objectives: To assess the impact of intravenous ferric carboxymaltose (FCM) on fetal and maternal adverse effects in pregnant women diagnosed with iron deficiency anemia (IDA). Methods: This is a multicenter retrospective study on 472 pregnant women diagnosed with moderate to severe [...] Read more.
Objectives: To assess the impact of intravenous ferric carboxymaltose (FCM) on fetal and maternal adverse effects in pregnant women diagnosed with iron deficiency anemia (IDA). Methods: This is a multicenter retrospective study on 472 pregnant women diagnosed with moderate to severe IDA undergoing treatment with FCM between 2019 and 2025 at Careggi University Hospital (Florence) and Vittore Buzzi Children Hospital (Milan). Fetal wellbeing was assessed using computerized cardiotocography (cCTG) or ultrasound, based on gestational age at treatment. Maternal side effects were evaluated through clinical evaluation. Results: cCTG was performed in 377/472 patients (80%), with a mean short-term variability of 10.2 ms. Normal cCTG criteria were met in 98.4% of cases; six patients exhibited transient reduced variability, which resolved following intrauterine resuscitation. Ultrasound assessment was performed in 95 patients (20%), revealing no fetal heart rate abnormalities. Maternal side effects occurred in seven patients (1.4%). Hemoglobin concentrations increased by a median of 1.4 g/dL after five weeks, reaching up to 2.8 g/dL in women with a baseline Hb < 8 g/dL. Conclusions: Our findings support the potential safety and efficacy of intravenous FCM for the treatment of IDA during pregnancy, demonstrating low rates of maternal side effects and no adverse fetal heart rate patterns. However, prospective studies are necessary to confirm these results. Full article
(This article belongs to the Special Issue Maternal Diet, Body Composition and Offspring Health)
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20 pages, 984 KiB  
Review
Maternal HIV Infection and Antiretroviral Therapy in Pregnancy: Implications for Vertical Transmission, Fetal Safety, and Long-Term Infant Outcomes
by Tudor Fleșeriu, Lorena Elena Meliț, Cristina Oana Mărginean, Adrian Vlad Pop and Anca-Meda Văsieșiu
Pathogens 2025, 14(8), 818; https://doi.org/10.3390/pathogens14080818 - 19 Aug 2025
Viewed by 338
Abstract
HIV mother-to-child transmission (MTCT) continues to pose a significant public health challenge, especially in regions with limited resources, although the worldwide distribution of antiretroviral therapy (ART) has drastically lowered the risk of vertical transmission to even below 1% in some regions. There are [...] Read more.
HIV mother-to-child transmission (MTCT) continues to pose a significant public health challenge, especially in regions with limited resources, although the worldwide distribution of antiretroviral therapy (ART) has drastically lowered the risk of vertical transmission to even below 1% in some regions. There are still uncertainties regarding the safety of some ART regimens during pregnancy and their longer-term effects on infants who are perinatally exposed to HIV but remain uninfected. This review explores current evidence regarding the interplay between maternal HIV infection, ART during pregnancy, and both maternal and pediatric outcomes. Particular attention is given to the risk/benefit ratio surrounding different drug classes, with integrase inhibitors seeming promising choices in MTCT due to their rapid viral suppression and favorable safety profiles. Meanwhile, regimens containing protease inhibitors or nucleoside reverse transcriptase inhibitors have been linked to some adverse outcomes such as low birth weight, growth restriction, and potential mitochondrial or metabolic disturbances. Although ART remains central in preventing MTCT, a deeper understanding of its effects on fetal development and postnatal health is needed, and it should be thoroughly monitored through future research and longitudinal surveillance. Full article
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24 pages, 393 KiB  
Review
The Health Effects of Heated Tobacco Product Use—A Narrative Review
by Małgorzata Znyk and Dorota Kaleta
Healthcare 2025, 13(16), 2042; https://doi.org/10.3390/healthcare13162042 - 18 Aug 2025
Viewed by 811
Abstract
One of the most popular currently available tobacco products is the heated tobacco product (HTP), which heats nicotine and other chemical substances into a vapor for inhalation. The aim of the present review was to clarify the effects of exposure to HTP, which [...] Read more.
One of the most popular currently available tobacco products is the heated tobacco product (HTP), which heats nicotine and other chemical substances into a vapor for inhalation. The aim of the present review was to clarify the effects of exposure to HTP, which currently remain unclear. A literature search of Web of Science, Scopus, ClinicalKey, and PubMed was conducted. The search identified 55 studies on humans and human cells in vitro (mostly independent, i.e., not funded by the tobacco sector) published from February 2021 to May 2025. Studies evaluating the effects of HTP use on the cardiovascular system indicate an increase in blood pressure, heart rate, platelet clot formation, and an enhanced inflammatory response, which is often followed by endothelial dysfunction. Increases in white blood cell counts, pro-inflammatory cytokines, leukocytes, eosinophils, platelets, IL-6, IL-2, IL-8, total NNAL, and 2,3-d-TXB2 were also observed. The studies suggest a positive correlation between HTP use and the occurrence of respiratory diseases, with particular negative effects observed on lung physiology, human bronchial epithelial cells, acute eosinophilic pneumonia, allergies, and asthma. Our findings indicate that the use of HTP is associated with possible adverse effects on the reproductive system. The review also identified new studies on the health effects of HTP use during pregnancy on the fetus, newborn, and mothers. Further research is needed to determine the short-term and long-term health effects of using HTP products. Full article
34 pages, 441 KiB  
Review
Rescuing Fertilization Failure in ICSI: A Narrative Review of Calcium Ionophore Activation, PLCζ Testing, and Embryo Morphokinetics
by Charalampos Voros, Despoina Mavrogianni, Diamantis Athanasiou, Ioakeim Sapantzoglou, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Georgios Papadimas, Charalampos Tsimpoukelis, Ioannis Papapanagiotou, Dimitrios Vaitsis, Aristotelis-Marios Koulakmanidis, Maria Anastasia Daskalaki, Vasileios Topalis, Nikolaos Thomakos, Marianna Theodora, Panagiotis Antsaklis, Fotios Chatzinikolaou, Dimitrios Loutradis and Georgios Daskalakis
Biomedicines 2025, 13(8), 2007; https://doi.org/10.3390/biomedicines13082007 - 18 Aug 2025
Viewed by 294
Abstract
Fertilisation failure following intracytoplasmic sperm injection (ICSI) is a significant challenge in assisted reproductive technology (ART), particularly in the absence of an identifiable cause. Artificial oocyte activation (AOA), typically with calcium ionophores, has emerged as a potential solution in scenarios characterised by a [...] Read more.
Fertilisation failure following intracytoplasmic sperm injection (ICSI) is a significant challenge in assisted reproductive technology (ART), particularly in the absence of an identifiable cause. Artificial oocyte activation (AOA), typically with calcium ionophores, has emerged as a potential solution in scenarios characterised by a deficiency of phospholipase C zeta (PLCζ). This narrative review consolidates the latest clinical and experimental data regarding the application of calcium ionophores for oocyte activation, the significance of PLCζ testing in instances of unexplained fertilisation failure, and the impact of AOA on the morphokinetics and developmental potential of embryos. AOA has demonstrated an enhancement in fertilisation, cleavage, and pregnancy outcomes in specific patient populations, including individuals with diminished ovarian reserve or those who have previously attempted conception unsuccessfully. Although AOA appears to have no impact on embryo morphokinetics, certain studies indicate slight alterations in early cleavage features. The available statistics indicate that there are no significant safety concerns about outcomes for babies. This finding underscores the significance of tailored ART methodologies that incorporate molecular diagnostics and targeted AOA therapies. It emphasises the necessity for additional prospective trials to enhance patient selection and long-term safety surveillance. Full article
(This article belongs to the Special Issue New Advances in Human Reproductive Biology)
14 pages, 2112 KiB  
Case Report
Giant Left Atrial Appendage Aneurysm in a 6-Year-Old Girl with a Prothrombotic Genetic Predisposition: A Case Report and Literature Review
by Horatiu Suciu, Emanuel-David Anitei, Valentin Ionut Stroe, Emilia Eleonora Brudan, Tudor Capilna, Hussam Al Hussein, Simina Ghiragosian, Paul Calburean, Mihaly Veres and Marius Mihai Harpa
Diagnostics 2025, 15(16), 2070; https://doi.org/10.3390/diagnostics15162070 - 18 Aug 2025
Viewed by 203
Abstract
Background: The term ‘left atrial appendage aneurysm’ (LAAA) has been recognized since 1962, when it was first described. It is an exceedingly rare pathology that can affect both adults and children. Often asymptomatic, it may be discovered incidentally. The anomaly consists of an [...] Read more.
Background: The term ‘left atrial appendage aneurysm’ (LAAA) has been recognized since 1962, when it was first described. It is an exceedingly rare pathology that can affect both adults and children. Often asymptomatic, it may be discovered incidentally. The anomaly consists of an exaggerated dilation of the primitive portion of the left atrium, resulting from pectinate muscle dysplasia or as a consequence of an obstructive lesion between the left atrium and the mitral valve. Surgical intervention represents a reliable strategy for preventing catastrophic complications such as stroke, thromboembolism, and rupture. This is a very rare condition, which is why we aimed to present a case report along with a review of the literature. Case presentation: We report the case of a 6-year-old asymptomatic girl in whom a giant left atrial appendage aneurysm was incidentally detected during a routine transthoracic echocardiogram, associated with a small atrial septal defect and a prothrombotic genetic profile. The aneurysm was successfully excised, and the atrial septal defect was closed. The postoperative course was uneventful, and the patient was discharged home on the 8th postoperative day. Conclusions: Left atrial appendage aneurysm is rare in children and often asymptomatic, yet it may be life-threatening due to stroke or thromboembolism. Fetal echocardiography may be considered in selected high-risk pregnancies, and routine postnatal assessment is advised, with surgical intervention recommended particularly for patients with risk factors for thrombus formation in the left atrium or its appendage. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Heart Disease, 2nd Edition)
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Systematic Review
A Systematic Review and Meta-Analysis of Single-Dose GnRH Agonist on the Day of Frozen Embryo Transfer in Artificial Cycles: Preliminary Evidence from Randomized Trials
by Luz Franco Pire, Laura Morales López, María Hernández Hernández, Raquel Campos Romero, Ignacio Cristóbal García and Ignacio Cristóbal Quevedo
J. Clin. Med. 2025, 14(16), 5763; https://doi.org/10.3390/jcm14165763 - 14 Aug 2025
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Abstract
Background/Objectives: GnRH agonists may offer potential benefits when used for luteal phase support in assisted reproductive treatments. This systematic review and meta-analysis of randomized controlled trials evaluates the effect of a single-dose administration of gonadotropin-releasing hormone (GnRH) agonist on the day of [...] Read more.
Background/Objectives: GnRH agonists may offer potential benefits when used for luteal phase support in assisted reproductive treatments. This systematic review and meta-analysis of randomized controlled trials evaluates the effect of a single-dose administration of gonadotropin-releasing hormone (GnRH) agonist on the day of frozen-thawed embryo transfer (FET) in artificial cycles, in terms of reproductive outcomes. Methods: A comprehensive literature search was performed using the PubMed and Cochrane databases to identify relevant studies. The outcomes assessed were live birth rate, clinical pregnancy rate, positive pregnancy test, implantation rate, and miscarriage rate. Three randomized controlled trials were included in the analysis. Results: The clinical pregnancy rate (56.5% vs. 47.4%; OR 1.27; 95% CI: 1.01–1.60; p = 0.0426) and live birth rate (34.3% vs. 23.9%; OR 1.71; 95% CI: 1.00–2.91; p = 0.0483) were significantly higher in the treatment group compared to the control group. No statistically significant differences were observed between the groups in terms of positive pregnancy test, implantation rate, or miscarriage rate, although the analysis revealed a trend toward improved outcomes in the intervention group. Conclusions: In summary, although our meta-analysis indicates that a single dose of GnRH agonist in artificial FET cycles may be associated with improved clinical pregnancy and live birth rates, these findings are based on a limited number of available trials. Larger, well-designed randomized controlled trials are urgently needed before any changes to clinical recommendations can be justified. Full article
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