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18 pages, 485 KB  
Study Protocol
SANA-Biome: A Protocol for a Cross-Sectional Study on Oral Health, Diet, and the Oral Microbiome in Romania
by Sterling L. Wright, Oana Slusanschi, Ana Cristina Giura, Ioanina Părlătescu, Cristian Funieru, Samantha M. Gaidula, Nicole E. Moore and Laura S. Weyrich
Healthcare 2025, 13(17), 2133; https://doi.org/10.3390/healthcare13172133 - 27 Aug 2025
Abstract
Periodontal disease is a widespread chronic condition linked to systemic illnesses such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Despite its global burden, population-specific studies on its risk factors remain limited, particularly in Central and Eastern Europe. The SANA-biome Project is a [...] Read more.
Periodontal disease is a widespread chronic condition linked to systemic illnesses such as cardiovascular disease, diabetes, and adverse pregnancy outcomes. Despite its global burden, population-specific studies on its risk factors remain limited, particularly in Central and Eastern Europe. The SANA-biome Project is a cross-sectional, community-based study designed to investigate the biological and social determinants of periodontal disease in Romania, a country with disproportionately high oral disease rates and minimal microbiome data. This protocol will integrate metagenomic, proteomic, and metabolomic data of the oral microbiome from saliva and dental calculus samples with detailed sociodemographic and lifestyle data collected through a structured 44-question survey. This study is grounded in two complementary frameworks: the IMPEDE model, which conceptualizes inflammation as both a driver and a consequence of microbial dysbiosis, and Ecosocial Theory, which situates disease within social and structural contexts. Our aims are as follows: (1) to identify lifestyle and behavioral predictors of periodontal disease; (2) to characterize the oral microbiome in individuals with and without periodontal disease; and (3) to evaluate the predictive value of combined microbial and sociodemographic features using statistical and machine learning approaches. Power calculations based on pilot data indicate a target enrollment of 120 participants. This integrative approach will help disentangle the complex interplay between microbiological and structural determinants of periodontal disease and inform culturally relevant prevention strategies. By focusing on an underrepresented population, this work contributes to a more equitable and interdisciplinary model of oral health research and supports the development of future precision public health interventions. Full article
(This article belongs to the Special Issue Oral Health in Healthcare)
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14 pages, 713 KB  
Article
Maternal Vitamin D Status and Its Association with Neonatal Health: Clinical Implications and Influencing Factors
by Andreea Bianca Stoica, Maria Oana Săsăran and Claudiu Mărginean
Nutrients 2025, 17(17), 2761; https://doi.org/10.3390/nu17172761 - 26 Aug 2025
Abstract
Introduction: Adequate maternal vitamin D status during pregnancy is essential for fetal skeletal development and neonatal vitamin D reserves. Evidence from Central and Eastern Europe on maternal deficiency, its determinants, and supplementation effectiveness in late pregnancy is limited. This study assessed the impact [...] Read more.
Introduction: Adequate maternal vitamin D status during pregnancy is essential for fetal skeletal development and neonatal vitamin D reserves. Evidence from Central and Eastern Europe on maternal deficiency, its determinants, and supplementation effectiveness in late pregnancy is limited. This study assessed the impact of 2000 IU/day and 4000 IU/day maternal vitamin D supplementation during the third trimester, compared to no supplementation, on maternal and neonatal 25-hydroxyvitamin D [25(OH)2D] levels at birth, and explored sociodemographic, obstetric, dietary, and lifestyle factors affecting vitamin D status. Methods: In a cross-sectional study at Târgu Mureș County Clinical Hospital, Romania, 322 term mother–newborn pairs (37–41 weeks) from January 2021 to July 2023 were evaluated. The maternal and umbilical cord 25(OH)2D was measured via electrochemiluminescence immunoassay. Data on socioeconomic status, parity, sun exposure, diet, and supplementation were collected through questionnaires and records. Statistical analysis included chi-square, linear regression, and multivariate modeling. Results: Vitamin D insufficiency and deficiency affected 32.3% and 18.9% of mothers, respectively. Supplementation was the strongest predictor of sufficiency (p < 0.01), showing a dose–response effect (r = 0.84, p < 0.01). Maternal and neonatal 25(OH)2D levels were strongly correlated (r = 0.99, p < 0.01). Although several factors correlated with deficiency in univariate analyses, only supplementation remained significant in multivariate models. No link was found between 25(OH)2D status and neonatal anthropometrics or early complications. Conclusions: A high prevalence of vitamin D deficiency has been documented among pregnant women in Romania. High-dose supplementation during late pregnancy is critical to ensure sufficient maternal and neonatal vitamin D, highlighting the need for standardized antenatal supplementation protocols, especially in disadvantaged groups. Full article
(This article belongs to the Section Micronutrients and Human Health)
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10 pages, 215 KB  
Article
Factors Associated with Post-Traumatic Stress Disorder in Women Treated for Miscarriage in the Emergency Department of a Peruvian National Hospital
by Sofia Laura L. Zafra-Pachas and Miguel A. Arce-Huamani
Healthcare 2025, 13(17), 2121; https://doi.org/10.3390/healthcare13172121 - 26 Aug 2025
Abstract
Background/Objectives: Miscarriage (spontaneous abortion) can precipitate post-traumatic stress disorder (PTSD). In Peru, post-loss mental healthcare is limited. We aimed to identify factors associated with PTSD symptoms persisting ≥ 3 months among women who experienced miscarriage and were treated in the emergency department (ED) [...] Read more.
Background/Objectives: Miscarriage (spontaneous abortion) can precipitate post-traumatic stress disorder (PTSD). In Peru, post-loss mental healthcare is limited. We aimed to identify factors associated with PTSD symptoms persisting ≥ 3 months among women who experienced miscarriage and were treated in the emergency department (ED) of a national hospital in Lima, 2021–2023. Methods: We conducted a cross-sectional analytical study of 214 women with spontaneous abortion seen in the ED (January 2021–December 2023). PTSD symptoms were measured with the PTSD Checklist for DSM-5 (PCL-5), anchored to the miscarriage index; sociodemographic and gyneco-obstetric variables were obtained with a validated questionnaire. Multivariable Poisson regression with robust variance estimated the adjusted prevalence ratios (aPRs). Results: Probable PTSD (PCL-5 ≥ 33) was present in 52.8% of participants. Independent correlates included previous miscarriage (aPR 1.75; 95% CI 1.35–2.25), ≥2 pre-gestational medical visits (aPR 1.66; 95% CI 1.21–2.27), and one (aPR 1.36; 95% CI 1.00–1.84) or multiple comorbidities (aPR 1.61; 95% CI 1.12–2.30). No other sociodemographic or obstetric variables were significantly associated. Conclusions: More than half of women assessed ≥ 3 months after miscarriage screened positive for probable PTSD. Previous pregnancy loss increased pre-gestational healthcare contact, and medical comorbidities were associated with higher prevalence. Integrating routine mental health screening and trauma-informed support within ED and reproductive health services could improve detection and care for this population. To our knowledge, this is the first ED-based study in Peru to examine factors associated with post-loss probable PTSD (PCL-5 ≥ 33) after miscarriage. Full article
(This article belongs to the Section Women's Health Care)
20 pages, 1529 KB  
Systematic Review
Pregnancy-Related Acute Kidney Injury: Causes and Its Impact on Perinatal Outcomes—A Systematic Review
by Emmanuel N. Kontomanolis, Ioannis Prokopakis, Antonios Koutras, Emmanouil Andreou, Dionysios Metaxas, Gerasimos Boulieris, Eleftherios Zachariou, Ioakeim Sapantzoglou, Dimitrios Papageorgiou, Vasileios-Chrysovalantis Palios, Charalampos Karachalios, Angeliki Papadimitriou, Konstantinos Daglas, Athanasios Chionis, Antonios Lagadas and Paraskevas Perros
J. Clin. Med. 2025, 14(17), 6031; https://doi.org/10.3390/jcm14176031 - 26 Aug 2025
Abstract
Background: Pregnancy-Related Acute kidney injury (PRAKI) is a critical complication of pregnancy, defined by the sudden deterioration in renal function during gestation or within the initial six weeks postpartum. Pregnancy is thought to increase the risk of acute kidney injury (AKI) by 51%. [...] Read more.
Background: Pregnancy-Related Acute kidney injury (PRAKI) is a critical complication of pregnancy, defined by the sudden deterioration in renal function during gestation or within the initial six weeks postpartum. Pregnancy is thought to increase the risk of acute kidney injury (AKI) by 51%. This is linked to the anatomical alterations that occur during pregnancy and special conditions, such as preeclampsia/eclampsia. PRAKI’s epidemiology and outcome vary between developed and developing nations. PRAKI is an uncommon entity in high-income countries; however, its incidence has recently increased. The aim of this systematic review is to evaluate the maternal and perinatal outcomes and risk factors affecting pregnancies affected by AKI. Methods: Comprehensive research was performed in PubMed/Medline, Scopus, and Google Scholar electronic databases from 2015 up to January 2025, using the terms AKI, PRAKI, sepsis, preeclampsia/eclampsia, liver enzymes, low platelet count (HELLP) syndrome, and pregnancy. After a thorough assessment, 25 full-text articles were obtained. Results: Our results revealed that preeclampsia, eclampsia, HELLP syndrome, and antepartum and postpartum hemorrhage predispose women to PRAKI. Other unusual factors, like disseminated intravascular coagulation (DIC) or hemolytic uremic syndrome (HUS), should not be underestimated. Furthermore, the latest published data showed unfavorable maternal and fetal outcomes in pregnancies affected by AKI compared to the general population. Conclusions: PRAKI constitutes a serious pregnancy complication that requires immediate treatment. The higher prevalence of PRAKI in developing countries (4–26%) versus wealthy nations (1.0–2.8%) has considerably indicated the impact of socioeconomic status and the accessibility of health services. Full article
(This article belongs to the Special Issue Management of Pregnancy Complications: 2nd Edition)
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16 pages, 386 KB  
Article
Iodine Deficiency and Excess in Brazilian Pregnant Women: A Multicenter Cross-Sectional Study (EMDI-Brazil)
by Aline Carare Candido, Francilene Maria Azevedo, Sarah Aparecida Vieira Ribeiro, Anderson Marliere Navarro, Mariana de Souza Macedo, Edimar Aparecida Filomeno Fontes, Sandra Patricia Crispim, Carolina Abreu de Carvalho, Nathalia Pizato, Danielle Góes da Silva, Franciane Rocha de Faria, Jorge Gustavo Velásquez Meléndez, Barbosa Míriam Carmo Rodrigues, Naiara Sperandio, Renata Junqueira Pereira, Silvia Eloiza Priore and Sylvia do Carmo Castro Franceschini
Nutrients 2025, 17(17), 2753; https://doi.org/10.3390/nu17172753 - 26 Aug 2025
Abstract
Background/Objectives: Iodine is an important nutrient for the human body, used in the production of thyroid hormones. During pregnancy, a deficiency can cause miscarriage and hypothyroidism, while an excess can cause thyroid dysfunction. Therefore, the objective of this study was to evaluate the [...] Read more.
Background/Objectives: Iodine is an important nutrient for the human body, used in the production of thyroid hormones. During pregnancy, a deficiency can cause miscarriage and hypothyroidism, while an excess can cause thyroid dysfunction. Therefore, the objective of this study was to evaluate the factors associated with the iodine nutritional status of pregnant Brazilian women. Methods: This was a cross-sectional, multicenter study conducted with pregnant women over 18 years of age, users of the Unified Health System (SUS). A semi-structured questionnaire was used to obtain sociodemographic information. Iodine status was assessed by urinary iodine concentration (UIC). The iodine content of salt and homemade and industrial seasonings was determined by the titrimetric method. Dietary intake was estimated through a 24-hour dietary recall. The chi-square test and hierarchical multinomial logistic regression were used for statistical analysis. The significance level was set at p ≤ 0.05. Results: Among Brazilian pregnant women, the median UIC was 186.7 µg/L (P25: 118.05 µg/L-P75: 280.93 µg/L). Regarding iodine nutritional status, the prevalence of deficiency was 36.7% (n = 694), above the requirement was 28.7% (n = 543), and excess iodine intake was 3.6% (n = 68). We observed that non-white pregnant women were more likely (OR = 1.83; 95% CI: 1.27–2.64) to have iodine deficiency, and those who did not work were less likely (OR = 0.71; 95% CI: 0.52–0.98). Pregnant women in the last trimester of pregnancy were less likely to have iodine intake above the requirements (OR = 0.52; 95% CI: 0.31–0.88). Conclusions: A substantial proportion of pregnant women had iodine deficiency or intake above the required level. Iodine deficiency is more chance among non-white pregnant women and less chance among those not employed during pregnancy. On the other hand, pregnant women who were in their third trimester of pregnancy were less likely to have iodine intake above the required level. Full article
(This article belongs to the Special Issue Selenium and Iodine in Human Health and Disease)
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18 pages, 1241 KB  
Review
Pregnancy Under Pressure: Oxidative Stress as a Common Thread in Maternal Disorders
by Alexandru-Dan Assani, Lidia Boldeanu, Isabela Siloși, Mihail Virgil Boldeanu, Anda Lorena Dijmărescu, Mohamed-Zakaria Assani, Maria-Magdalena Manolea and Constantin-Cristian Văduva
Life 2025, 15(9), 1348; https://doi.org/10.3390/life15091348 - 26 Aug 2025
Abstract
Oxidative stress, defined as the imbalance between reactive oxygen species (ROS) and antioxidant defenses, plays a pivotal role in the pathogenesis of several pregnancy complications, notably preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and recurrent pregnancy loss (RPL). During normal [...] Read more.
Oxidative stress, defined as the imbalance between reactive oxygen species (ROS) and antioxidant defenses, plays a pivotal role in the pathogenesis of several pregnancy complications, notably preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and recurrent pregnancy loss (RPL). During normal pregnancy, low to moderate ROS levels support essential placental functions such as angiogenesis and trophoblast differentiation. However, excessive ROS production overwhelms antioxidant systems, leading to lipid peroxidation, protein and DNA damage, and impaired placental function. This review synthesizes current evidence linking oxidative stress to adverse pregnancy outcomes, highlighting key biomarkers such as malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-iso-prostaglandin F2α (8-iso-PGF2α). While antioxidant therapies—particularly vitamins C and E, selenium, and folic acid—have shown promise in reducing oxidative markers, their impact on clinical outcomes remains inconsistent. The variability in results underscores the need for standardized biomarker protocols and personalized treatment strategies based on genetic predispositions and baseline oxidative status. Future research may better harness antioxidant interventions to improve maternal–fetal health by addressing these gaps. Full article
(This article belongs to the Special Issue Prevention, Diagnosis, and Treatment of Gestational Diseases)
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18 pages, 1535 KB  
Review
Scientific and Public Health Challenges in Folic Acid Supplementation: Insights from Brazil and Global Implications
by Marília Körbes Rockenbach, Ricardo Rohweder, Lavinia Schuler-Faccini, Maria Teresa Vieira Sanseverino and Thayne Woycinck Kowalski
Nutrients 2025, 17(17), 2752; https://doi.org/10.3390/nu17172752 - 26 Aug 2025
Abstract
Folic acid supplementation during the periconceptional period is a well-established strategy to prevent neural tube defects (NTDs). However, emerging uncertainties surrounding optimal dosage, alternative folate forms, duration of use, and the role of genetic variability have sparked scientific and policy debates. In Brazil, [...] Read more.
Folic acid supplementation during the periconceptional period is a well-established strategy to prevent neural tube defects (NTDs). However, emerging uncertainties surrounding optimal dosage, alternative folate forms, duration of use, and the role of genetic variability have sparked scientific and policy debates. In Brazil, these challenges are amplified by unique contextual factors, including the routine distribution of high-dose folic acid (5000 µg) through the public health system, social vulnerability, low adherence, and limited population-specific evidence for the country’s highly admixed population. This narrative review critically examined the scientific evidence and public health policies surrounding folic acid supplementation, with a focus on Brazil. We examined historical developments, international recommendations, and emerging controversies, including the emerging influence of misinformation. Despite the worldwide progress in NTD prevention, both local and global challenges persist, including delayed initiation, inconsistent adherence, and uncertainty regarding alternative supplementation regimens. Addressing these demands requires the development of context-specific guidelines, alongside coordinated strategies in provider training, public education, monitoring, and research investments to ensure effective, safe, and equitable folic acid supplementation. Full article
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12 pages, 513 KB  
Article
Maternal and Birth Characteristics Are Relevant to the Consumption of Ultra-Processed Foods in Young Adults: Results from the Nutritionists’ Health Study
by Sthefani C. Penha, Ilana N. Bezerra, Daniela V. Azevedo, Helena A. C. Sampaio and Antonio A. F. Carioca
Int. J. Environ. Res. Public Health 2025, 22(9), 1321; https://doi.org/10.3390/ijerph22091321 - 25 Aug 2025
Viewed by 834
Abstract
Background: One’s dietary pattern throughout life is established during the perinatal period, especially in the intrauterine environment. This study aims to analyze whether maternal and birth characteristics are associated with food consumption in young adults using baseline data from the Nutritionists’ Health Study [...] Read more.
Background: One’s dietary pattern throughout life is established during the perinatal period, especially in the intrauterine environment. This study aims to analyze whether maternal and birth characteristics are associated with food consumption in young adults using baseline data from the Nutritionists’ Health Study (NutriHS). Methods: We employed cross-sectional analysis of data from 386 undergraduate nutrition students and nutritionists. Current food consumption was evaluated as per the NOVA classification. The maternal and birth factors included maternal age, parity, type of childbirth, health problems during pregnancy, prematurity, and birth weight, and multiple correspondence analysis of these variables was performed to identify patterns in them. Results: The energy contribution of ultra-processed foods was positively associated with the pattern characterized by participants whose mothers were 19 years of age or younger, primiparous, and had a vaginal delivery (β = 0.48; 95% confidence interval = 0.02, 1.66). Conclusions: We concluded that maternal age at birth was associated with the dietary patterns of adult children. Participants whose mothers were 19 or younger at birth had significantly higher consumption of ultra-processed foods in adulthood compared to those whose mothers were older. Full article
15 pages, 2813 KB  
Article
Thermal Imaging as a New Perspective in the Study of Physiological Changes in Pregnant Women—A Preliminary Study
by Karolina Rykała, Agnieszka Szurko, Daria Wziątek-Kuczmik, Agnieszka Kiełboń, Manuel Sillero-Quintana, Armand Cholewka and Teresa Kasprzyk-Kucewicz
J. Clin. Med. 2025, 14(17), 5998; https://doi.org/10.3390/jcm14175998 - 25 Aug 2025
Viewed by 185
Abstract
Background/Objectives: This study aimed to examine the dynamic thermal variations that occur in the posterior body regions of pregnant women by employing thermal imaging techniques. Methods: The study involved the participation of 34 women in various stages of pregnancy. The skin [...] Read more.
Background/Objectives: This study aimed to examine the dynamic thermal variations that occur in the posterior body regions of pregnant women by employing thermal imaging techniques. Methods: The study involved the participation of 34 women in various stages of pregnancy. The skin temperature (Tsk) distribution in specific body areas, including the spinal region and lower limbs, was analyzed under standard conditions. Results: The most considerable increase in body temperature (Tsk) recorded in female volunteers was achieved during the second trimester of pregnancy in physiologically stressed areas, such as the upper back (0.4 °C), lower back (0.77 °C), thighs (0.94 °C) and calves (0.32 °C). Contrastingly, a decrease in Tsk of noteworthy magnitude was observed in all body regions during the third trimester, with an average decrease of 1.7 °C. The lower back’s most substantial decrease was observed (1.95 °C). Furthermore, a disparity was observed in the Tsk distribution of the calves, with the highest ∆Tmean value recorded at approximately 0.5 °C, and the thighs exhibiting a ∆Tmean value of 0.25 °C. Conclusions: Preliminary studies have demonstrated the potential of thermal imaging as a reliable and safe method to support prenatal diagnosis. Its application can facilitate the early detection of health complications, including inflammatory states or posture and circulatory system disorders, thereby enhancing the standard of prenatal care. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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32 pages, 1161 KB  
Review
Understanding Preeclampsia: Cardiovascular Pathophysiology, Histopathological Insights and Molecular Biomarkers
by Kaltrina Kutllovci Hasani, Nurxhan Ajeti and Nandu Goswami
Med. Sci. 2025, 13(3), 154; https://doi.org/10.3390/medsci13030154 - 25 Aug 2025
Viewed by 187
Abstract
Preeclampsia (PE) is not merely a pregnancy complication but a clinical manifestation of underlying vascular dysfunction with long-term health implications. It is diagnosed after 20 weeks of gestation as new-onset hypertension with proteinuria or organ involvement. The condition arises from impaired placental development, [...] Read more.
Preeclampsia (PE) is not merely a pregnancy complication but a clinical manifestation of underlying vascular dysfunction with long-term health implications. It is diagnosed after 20 weeks of gestation as new-onset hypertension with proteinuria or organ involvement. The condition arises from impaired placental development, particularly defective spiral artery remodeling, which leads to placental ischemia and the release of antiangiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). These circulating factors contribute to systemic endothelial dysfunction, resulting in hypertension, inflammation, and multiorgan stress. Histopathological findings, including acute atherosis and abnormal vascular remodeling, further reflect the cardiovascular damage underlying PE. This review synthesizes emerging evidence on the vascular and histological mechanisms of PE, highlighting novel biomarkers such as microRNAs and neprilysin, and the potential of advanced diagnostic tools, including machine learning. Importantly, PE is now recognized not only as an obstetric disorder but also as an early marker of future cardiovascular disease. This paradigm shift emphasizes the need for personalized prevention strategies, close surveillance of high-risk women, and long-term cardiovascular follow-up. Pregnancy thus represents a critical window for early detection and intervention in women’s cardiovascular health. Full article
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14 pages, 633 KB  
Review
A Systematic Review on Biomarkers for Gestational Diabetes Mellitus Detection in Pregnancies Conceived Using Assisted Reproductive Technology: Current Trends and Future Directions
by Angeliki Gerede, Efthymios Oikonomou, Anastasios Potiris, Christos Chatzakis, Peter Drakakis, Ekaterini Domali, Nikolaos Nikolettos and Sofoklis Stavros
Int. J. Mol. Sci. 2025, 26(17), 8234; https://doi.org/10.3390/ijms26178234 - 25 Aug 2025
Viewed by 218
Abstract
Gestational diabetes mellitus (GDM) is a frequently encountered medical complication during pregnancy that is increasing at a rapid pace globally, posing significant public health concerns. Similarly, there is a rising trend in the number of women who have utilized assisted reproductive technology (ART). [...] Read more.
Gestational diabetes mellitus (GDM) is a frequently encountered medical complication during pregnancy that is increasing at a rapid pace globally, posing significant public health concerns. Similarly, there is a rising trend in the number of women who have utilized assisted reproductive technology (ART). Numerous studies have been carried out to investigate the relationship between GDM and ART. This comprehensive systematic review seeks to identify potential biomarkers for the early diagnosis of GDM in pregnancies conceived through ART. We conducted a PubMed search covering the past five years to identify studies that explore biomarkers associated with the development of GDM in pregnancies conceived through ART. The outcome measures included human chorionic gonadotropin (HCG), the body mass index (BMI), the Follicle Stimulating Hormone to Luteinizing Hormone (FSH/LH) ratio, increased hemoglobin A1c levels, fasting insulin concentrations, homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride levels, total cholesterol levels, low-density lipoprotein cholesterol concentrations, low-density lipoprotein/high-density lipoprotein (LDL/HDL), total cholesterol to high-density lipoprotein (TC/HDL), the estradiol/follicle ratio, soluble fms-like tyrosine kinase-1 (sFlt-1), Placental Growth Factor (PLGF), endometrial thickness, and psychological stress. Seventeen studies were included. The identification and development of serum or ultrasound biomarkers for the early detection of GDM in pregnancies conceived through ART pose considerable challenges. These challenges arise from the multifactorial nature of GDM, the methodological variations in ART, and the limited availability of relevant studies. The most promising biomarker identified was the estradiol/follicle ratio. Women with a higher estradiol/follicle ratio exhibited significantly lower rates of GDM. There is a pressing necessity for biomarkers to enable the early detection of GDM in pregnancies conceived through ART. E2 levels, β-hCG, and the E2/F ratio, along with the TC/HDL and LDL/HDL ratios, show potential as reliable biomarkers for identifying GDM. Full article
(This article belongs to the Special Issue Molecular Biomarkers for Targeted Therapies)
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21 pages, 991 KB  
Review
The Emerging Roles of Ferroptosis and NETosis in Pregnancy Complications: Insights into Preeclampsia and Gestational Diabetes Mellitus
by Vasiliki Katsi, Angeliki Alifragki, Konstantinos Fragkiadakis, Nikolaos Kopidakis, Eleutherios Kallergis, Evangelos Zacharis, Emmanouil Kampanieris, Emmanouil Simantirakis, Konstantinos Tsioufis and Maria Marketou
Curr. Issues Mol. Biol. 2025, 47(9), 685; https://doi.org/10.3390/cimb47090685 - 25 Aug 2025
Viewed by 89
Abstract
Gestational complications, such as preeclampsia and gestational diabetes mellitus (GDM), pose significant risks to maternal and fetal health and increase long-term cardiovascular disease risk in offspring. This review aims to synthesize current knowledge on the roles of ferroptosis and neutrophil extracellular trap formation [...] Read more.
Gestational complications, such as preeclampsia and gestational diabetes mellitus (GDM), pose significant risks to maternal and fetal health and increase long-term cardiovascular disease risk in offspring. This review aims to synthesize current knowledge on the roles of ferroptosis and neutrophil extracellular trap formation (NETosis)—two regulated cell death pathways—in these pregnancy-related conditions. We performed a comprehensive analysis of preclinical and clinical studies that investigate the involvement of dysregulated iron metabolism, oxidative stress, inflammation, and endothelial dysfunction mediated by ferroptosis and NETosis in gestational pathologies. Evidence indicates that disturbances in maternal iron homeostasis and enhanced formation of lipid peroxides and NETs contribute to placental dysfunction and systemic inflammation, exacerbating disease severity. Therapeutic strategies targeting these pathways are emerging but require further validation. Our review also identifies key gaps in mechanistic understanding, biomarker development, and translational research needs. We conclude that modulation of ferroptosis and NETosis offers promising avenues for improving diagnosis and treatment of pregnancy complications, though carefully designed clinical studies are essential to confirm their clinical utility and safety. Full article
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24 pages, 2057 KB  
Review
Drugs, Mother, and Child—An Integrative Review of Substance-Related Obstetric Challenges and Long-Term Offspring Effects
by Atziri Alejandra Jiménez-Fernández, Joceline Alejandra Grajeda-Perez, Sofía de la Paz García-Alcázar, Mariana Gabriela Luis-Díaz, Francisco Javier Granada-Chavez, Emiliano Peña-Durán, Jesus Jonathan García-Galindo and Daniel Osmar Suárez-Rico
Drugs Drug Candidates 2025, 4(3), 40; https://doi.org/10.3390/ddc4030040 - 25 Aug 2025
Viewed by 207
Abstract
Substance use during pregnancy is an increasingly important yet under-recognized threat to maternal and child health. This narrative review synthesizes the current evidence available on the epidemiology, pathophysiology, clinical management, and policy landscape of prenatal exposure to alcohol, tobacco, opioids, benzodiazepines, cocaine, cannabis, [...] Read more.
Substance use during pregnancy is an increasingly important yet under-recognized threat to maternal and child health. This narrative review synthesizes the current evidence available on the epidemiology, pathophysiology, clinical management, and policy landscape of prenatal exposure to alcohol, tobacco, opioids, benzodiazepines, cocaine, cannabis, methamphetamines, and other synthetic drugs. All major psychoactive substances readily cross the placenta and can remain detectable in breast milk, leading to a shared cascade of obstetric complications (hypertensive disorders, placental abruption, pre-term labor), fetal consequences (growth restriction, structural malformations), and neonatal morbidities such as neonatal abstinence syndrome and sudden infant death. Mechanistically, trans-placental diffusion, oxidative stress, inflammatory signaling, and placental vascular dysfunction converge to disrupt critical neuro- and cardiovascular developmental windows. Early identification hinges on the combined use of validated screening questionnaires (4 P’s Plus, CRAFFT, T-ACE, AUDIT-C, TWEAK) and matrix-specific biomarkers (PEth, EtG, FAEE, CDT), while effective treatment requires integrated obstetric, addiction, and mental health services. Medication for opioid use disorders, particularly buprenorphine, alone or with naloxone, confers superior neonatal outcomes compared to methadone and underscores the value of harm-reducing non-punitive care models. Public-health strategies, such as Mexico’s “first 1 000 days” framework, wrap-around clinics, and home-visiting programs, demonstrate the potential of multisectoral interventions, but are hampered by structural inequities and punitive legislation that deter care-seeking. Research gaps persist in polysubstance exposure, culturally tailored therapies, and long-term neurodevelopmental trajectories. Multigenerational, omics-enabled cohorts, and digital longitudinal-care platforms represent promising avenues for closing these gaps and informing truly preventive perinatal health policies. Full article
(This article belongs to the Section Clinical Research)
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21 pages, 2457 KB  
Article
BthTX-II, an Asp49 PLA2 from Bothrops jararacussu, Impairs Toxoplasma gondii Infection: In Vitro and Ex Vivo Approaches
by Vinícius Queiroz Oliveira, Emanuelle Lorrayne Ferreira, Lorena Pinheiro Morais, Leonardo Alves Garcia, Gabriel de Oliveira Sousa, Marcos Paulo Oliveira Almeida, Guilherme de Souza, Joed Pires de Lima Júnior, Natália Carine Lima dos Santos, Rafael Martins de Oliveira, Tássia Rafaela Costa, Andreimar Martins Soares, Luísa Carregosa Santos, Daiana Silva Lopes, Emidio Beraldo-Neto, Angelica Oliveira Gomes, Jovita Eugênia Gazzinelli Cruz Madeira, Bellisa Freitas Barbosa, Eloisa Amália Vieira Ferro, Samuel Cota Teixeira and Veridiana de Melo Rodrigues Ávilaadd Show full author list remove Hide full author list
Pharmaceuticals 2025, 18(9), 1260; https://doi.org/10.3390/ph18091260 - 25 Aug 2025
Viewed by 194
Abstract
Background/Objectives: Toxoplasma gondii, an obligate intracellular parasite, poses a major global health concern owing to its potential for congenital transmission, particularly during pregnancy. Current pharmacological treatments, including spiramycin and pyrimethamine, exhibit limitations in both efficacy and safety, underscoring the need for [...] Read more.
Background/Objectives: Toxoplasma gondii, an obligate intracellular parasite, poses a major global health concern owing to its potential for congenital transmission, particularly during pregnancy. Current pharmacological treatments, including spiramycin and pyrimethamine, exhibit limitations in both efficacy and safety, underscoring the need for novel therapeutic strategies. In this study, we investigated the antiparasitic potential of BthTX-II, an Asp49 phospholipase A2 (PLA2) isolated from Bothrops jararacussu venom, in human trophoblast cells (BeWo) and third-trimester human placental explants infected with T. gondii. Methods: In vitro assays were performed using BeWo cells infected with T. gondii tachyzoites and treated with non-cytotoxic concentrations of BthTX-II (3.125, 1.56, and 0.78 µg/mL). An ex vivo model employing third-trimester human placental villous explants was used under similar conditions. Parasite proliferation, adhesion, and invasion were assessed alongside host immune response modulation. Results: Our findings demonstrate that BthTX-II reduces T. gondii proliferation in BeWo cells at all tested non-cytotoxic concentrations. The toxin also significantly impaired parasite adhesion and invasion while modulating host immune response by upregulating interleukin (IL)-6, IL-8, and macrophage migration inhibitory factor (MIF), and downregulating vascular endothelial growth factor—potentially disrupting parasite proliferation. In placental villous explants, BthTX-II (1.56 μg/mL) reduced T. gondii proliferation and modulated IL-8, MIF, and tumour necrosis factor-alpha levels without compromising tissue viability. Conclusions: These findings highlight BthTX-II as a potential candidate in toxoplasmosis treatment. Further investigation should focus on its dual role in limiting parasite development and modulating immune responses at the maternal–fetal interface. Full article
(This article belongs to the Special Issue Recent Research in Therapeutic Potentials of Venoms)
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22 pages, 615 KB  
Systematic Review
Effectiveness of the Internet of Things for Improving Pregnancy and Postpartum Women’s Health in High-Income Countries: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
by Etsuko Nishimura, Noyuri Yamaji, Kiriko Sasayama, Md. Obaidur Rahman, Katharina da Silva Lopes, Citra Gabriella Mamahit, Mika Ninohei, Phyu Phyu Tun, Rina Shoki, Daichi Suzuki, Aya Nitamizu, Daisuke Yoneoka, Eiko Saito and Erika Ota
Healthcare 2025, 13(17), 2103; https://doi.org/10.3390/healthcare13172103 - 23 Aug 2025
Viewed by 412
Abstract
Background/Objectives: The Internet of Things (IoT), integrated with application software, has increasingly been used to support health management through monitoring indicators like physical activity, sleep, and heart rate, in pregnant and postpartum women. However, limited evidence exists regarding its effectiveness in improving [...] Read more.
Background/Objectives: The Internet of Things (IoT), integrated with application software, has increasingly been used to support health management through monitoring indicators like physical activity, sleep, and heart rate, in pregnant and postpartum women. However, limited evidence exists regarding its effectiveness in improving health outcomes for pregnant and postpartum women. The objective of this systematic review and meta-analysis was to evaluate and synthesize the role of IoT in enhancing the health outcomes of pregnant and postpartum women. Methods: A systematic search was conducted on 13 February 2023, across CENTRAL, CINAHL, ClinicalTrials.gov, Embase, MEDLINE, PsycINFO, PubMed, and WHO ICTRP to identify all randomized controlled trials. Studies were included if they involved pregnant or postpartum women in high-income countries and used sensor-based data collection via smartphones or wearable devices. Two reviewers independently selected the studies, extracted data, and assessed the risk of bias using the Cochrane Collaboration’s risk of bias assessment tool 2.0. We performed a pairwise meta-analysis using a random effects model. The findings were reported according to PRISMA guidelines. Results: Seven studies with 1638 pregnant and postpartum women were included in this review. Of the seven included studies, half targeted women with gestational diabetes and the other half targeted obese women. A meta-analysis revealed that IoT interventions may reduce gestational weight gain in women with obesity with a mean difference of −3.35 kg (95% confidence interval (CI): −5.23 to−1.46; I2 = 36%; two studies; 242 women; moderate certainty of evidence). Conclusions: This review suggested that IoT interventions may limit gestational weight gain in pregnant women with obesity. Future studies should evaluate the long-term effects of IoT-based interventions on maternal and neonatal health outcomes. Full article
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