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Search Results (2,836)

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17 pages, 931 KB  
Review
The Effect of Maternal Stress on 11beta-Hydroxysteroid Dehydrogenase Activity During Pregnancy: Evidence for Potential Pregnancy Complications and Consequences on Fetal Development and Metabolism
by Polina Pavli, George Mastorakos, Makarios Eleftheriades and Georgios Valsamakis
Int. J. Mol. Sci. 2025, 26(22), 11071; https://doi.org/10.3390/ijms262211071 (registering DOI) - 16 Nov 2025
Abstract
Τhe intrauterine environment has a strong connection with the growing fetus and possible effects that can continue up to adulthood. Currently, stress is conceptualized as a modern teratogen. The overwhelming majority of studies indicate that maternal stress during pregnancy may have effects on [...] Read more.
Τhe intrauterine environment has a strong connection with the growing fetus and possible effects that can continue up to adulthood. Currently, stress is conceptualized as a modern teratogen. The overwhelming majority of studies indicate that maternal stress during pregnancy may have effects on pregnancy outcomes and fetal development, with long-lasting consequences on child and adult vulnerability to disease. Glucocorticoids are essential for regulating fetal development, growth, and metabolism. The two isoforms of 11beta-hydroxysteroid dehydrogenase enzyme (11β-HSD) mediate and regulate glucocorticoid actions and biological activity. It has not yet been fully elucidated whether maternal stress during pregnancy affects 11β-HSD isoenzyme activity and expression and results in possible adverse effects on fetal development, metabolism, and pregnancy outcomes. This review examines a possible pathophysiological mechanism by which maternal stress during pregnancy affects placental 11β-HSD isoenzyme activity, thereby causing adverse effects on the physiological status of pregnancy, fetal development, and metabolism. Furthermore, the main outcome of the review is the following: chronic and acute maternal stress during pregnancy affects the activity and the expression of placental 11β-HSD isoenzymes and has possible subsequent unfavorable results on preeclampsia, preterm birth, and fetuses with intrauterine growth restriction (IUGR) or small for gestational age (SGA) fetuses. Full article
(This article belongs to the Special Issue Endocrinology of Pregnancy)
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16 pages, 1874 KB  
Article
Association of Prenatal Ozone Exposure with Fetal Growth and Birth Outcomes: Roles of Maternal Inflammation and Metabolic Dysregulation
by Zexin Yu, Chunyan Wang, Yueyi Lv, Mengjun Chang, Hao Wang, Yunyun Du, Xianjia Li, Jin Ji and Suzhen Guan
Toxics 2025, 13(11), 983; https://doi.org/10.3390/toxics13110983 (registering DOI) - 15 Nov 2025
Abstract
Prenatal ozone (O3) exposure may trigger systemic inflammation and oxidative stress. These effects could contribute to adverse pregnancy outcomes. We conducted a prospective cohort study involving 235 pregnant women in Ningxia, China. Maternal O3 exposure during pregnancy and prior to [...] Read more.
Prenatal ozone (O3) exposure may trigger systemic inflammation and oxidative stress. These effects could contribute to adverse pregnancy outcomes. We conducted a prospective cohort study involving 235 pregnant women in Ningxia, China. Maternal O3 exposure during pregnancy and prior to conception was assessed using high-resolution spatiotemporal models. Multivariable logistic and linear regression analyses were employed to evaluate the associations between O3 exposure and adverse pregnancy outcomes. Mediation and interaction models were further applied to examine the potential modifying roles of gestational diabetes mellitus (GDM) and inflammatory biomarkers. In multivariable analyses adjusted for maternal and environmental covariates, higher prenatal O3 exposure was significantly associated with an increased risk of preterm birth (PTB) (OR = 1.24, 95% CI: 1.05~1.45, p = 0.010) and low birth weight (LBW) (OR = 1.29, 95% CI: 1.09~1.54, p = 0.004). Similarly, elevated maternal SAA and CRP levels were positively associated with these adverse pregnancy outcomes (p < 0.05). Notably, higher TNF-α levels were inversely associated with the risks of PTB (OR = 0.15, 95% CI: 0.03~0.85, p = 0.032) and LBW (OR = 0.05, 95% CI: 0.01~0.39, p = 0.005). IL-17A levels were inversely associated with neonatal length-for-age Z scores (β = −0.28, 95% CI: −0.55~−0.01, p = 0.043). Our findings suggest that prenatal O3 exposure is associated with increased risks of PTB and LBW. Alterations in systemic inflammatory markers and metabolic dysfunction during pregnancy were related to adverse pregnancy outcomes and fetal growth deficits, but they did not mediate these associations, with O3 remaining an independent predictor after adjustment. Full article
(This article belongs to the Section Air Pollution and Health)
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13 pages, 874 KB  
Review
Facial Clefts and the Trigeminal Nerve: A Narrative Review of the Literature and Clinical Considerations in the Era of Personalized Medicine
by Natalia Lucangeli, Matilde S. Cannistrà, Domenico Scopelliti, Pasquale Parisi, Domenico Tripodi, Patrick Barbet and Claudio Cannistrà
J. Pers. Med. 2025, 15(11), 556; https://doi.org/10.3390/jpm15110556 (registering DOI) - 15 Nov 2025
Abstract
Background Facial clefts are rare congenital malformations, occurring in approximately 1 in 700 live births for cleft lip and palate and fewer than 1 in 100,000 for atypical Tessier clefts. They pose significant diagnostic and surgical challenges. While genetic, vascular, and environmental factors [...] Read more.
Background Facial clefts are rare congenital malformations, occurring in approximately 1 in 700 live births for cleft lip and palate and fewer than 1 in 100,000 for atypical Tessier clefts. They pose significant diagnostic and surgical challenges. While genetic, vascular, and environmental factors are well documented, growing embryological evidence suggests that the trigeminal nerve may also contribute to craniofacial development. This narrative review explores the association between trigeminal nerve development and facial clefts, aiming to provide a neurodevelopmental perspective with clinical implications, particularly in the context of personalized medicine, where patient-specific neuroanatomical and developmental factors can guide tailored care. Methods A narrative review of embryological, anatomical, and clinical data was conducted. Histological analyses of malformed fetuses and normal human embryos were integrated with published studies. Clinical findings were compared with Paul Tessier’s facial cleft classification and mapped against trigeminal innervation territories. Results Two groups of facial clefts emerged according to the timing of trigeminal disruption. Early embryonic damage (before 10 weeks of gestation) produces superficial epidermal continuity with fibrotic tissue replacing normal deep structures. Later fetal damage results in complete clefts with full tissue discontinuity. The distribution of these clefts corresponds to trigeminal nerve terminal branch territories, supporting the hypothesis that trigeminal innervation exerts trophic effects on craniofacial morphogenesis through neurohormonal signaling. Conclusions Early impairment of trigeminal development may play a pivotal role in the pathogenesis of certain clefts. The spatial and temporal relationship between nerve development and morphogenesis should be considered in classification and surgical planning. However, limitations of this narrative approach include selective literature coverage and lack of quantitative synthesis. Future directions include single-cell transcriptomics, organoid models, and fetal MRI tractography to clarify trigeminal–mesenchyme interactions and inform therapeutic strategies. These advances may foster a personalized medicine approach, enabling more precise prenatal diagnosis, individualized surgical planning, and optimized long-term outcomes. Full article
(This article belongs to the Special Issue Personalized Medicine for Oral and Maxillofacial Surgery)
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8 pages, 592 KB  
Article
Timing Matters? Impact of Early Sperm Processing on Motile Sperm Recovery, Fertilization, Blastocyst Rate, and Pregnancy Outcomes in IUI and IVF
by Kiana Loo, Isabelle Mason, Rebecca Chung, Samantha Sechler, Kathryn Coyne, Joseph Findley, Rachel Weinerman, Rebecca Flyckt and Sung Tae Kim
J. Clin. Med. 2025, 14(22), 8094; https://doi.org/10.3390/jcm14228094 (registering DOI) - 15 Nov 2025
Abstract
Background/Objectives: Efficient sperm separation is critical for Assisted Reproductive Technology (ART). This study evaluates how assisted liquefaction (AL), a faster sperm preparation technique, affects motile sperm recovery and ART outcomes. Methods: A prospective pair analysis to address the efficiency of AL and retrospective [...] Read more.
Background/Objectives: Efficient sperm separation is critical for Assisted Reproductive Technology (ART). This study evaluates how assisted liquefaction (AL), a faster sperm preparation technique, affects motile sperm recovery and ART outcomes. Methods: A prospective pair analysis to address the efficiency of AL and retrospective cohort analysis of IUI and IVF/ICSI cycles were performed. Results: The average time to perform AL was 3 min, in comparison to the 15 to 30 min for traditional liquefaction (TL) until initiating sperm preparation. The total motility (p = 0.252) and progressive motility (p = 0.227) of the sperm samples were about 4% higher in the AL group although there was no significant difference. No significant differences were observed between AL and TL in fertilization (80.0% vs. 81.9%, p = 0.297), blastocyst rates (48.2% vs. 48.1%, p = 0.595), positive pregnancy (70.5% vs. 75.0%, p = 0.667), clinical pregnancy (65.9% vs. 68.4%, p = 0.841), or live birth (52.3% vs. 51.3%, p = 0.831) outcomes in IVF. The Positive pregnancy (p = 0.669) and clinical pregnancy (p = 0.841) of IUI were not significantly different between both groups. Conclusions: AL offers similar results to TL while reducing preparation time without interrupting ART outcomes. AL may have benefit to asthenozoospermia cases for ART due to reduced exposure time of sperm to semen that may prevent sperm quality impact. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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45 pages, 20005 KB  
Review
Congenital Scoliosis: A Comprehensive Review of Diagnosis, Management, and Surgical Decision-Making in Pediatric Spinal Deformity—An Expanded Narrative Review
by Paweł Grabala
J. Clin. Med. 2025, 14(22), 8085; https://doi.org/10.3390/jcm14228085 - 14 Nov 2025
Abstract
Congenital scoliosis is a complex spinal deformity caused by abnormal vertebral development during embryogenesis, occurring in roughly 0.5–1.0 per 1000 live births. It encompasses a wide spectrum of anomalies that arise from failures in vertebral formation or segmentation, or mixed defects during the [...] Read more.
Congenital scoliosis is a complex spinal deformity caused by abnormal vertebral development during embryogenesis, occurring in roughly 0.5–1.0 per 1000 live births. It encompasses a wide spectrum of anomalies that arise from failures in vertebral formation or segmentation, or mixed defects during the fourth to sixth weeks of gestation. Managing this condition requires careful consideration of growth dynamics, associated systemic anomalies, and individualized decisions regarding surgical timing. In this review, current evidence on the epidemiology, pathophysiology, diagnostic strategies, and treatment of congenital scoliosis is synthesized, with special attention to surgical decision-making between hemivertebrectomy and growth-preserving methods such as growing rods. Recent surgical techniques—including magnetically controlled growing rods and posterior vertebral column resection—have expanded therapeutic options, while greater recognition of the psychosocial impacts has underscored the importance of family-centered care. Successful management relies on striking a balance between early deformity correction and preserving long-term spinal and thoracic growth. Multidisciplinary collaboration and thorough family counseling remain central to optimizing both structural and psychosocial outcomes. Full article
(This article belongs to the Section Clinical Neurology)
9 pages, 420 KB  
Commentary
Universal Decentralized Cord Blood TSH Screening Should Be Offered as Routine Delivery Care in Limited-Resource Settings
by Nitash Zwaveling-Soonawala, Anju Virmani, Aman B. Pulungan, Joseph Haddad, Sirisha Kusuma Boddu, Feyza Darendeliler and A. S. Paul van Trotsenburg
Int. J. Neonatal Screen. 2025, 11(4), 105; https://doi.org/10.3390/ijns11040105 - 14 Nov 2025
Abstract
Newborn screening (NBS) for congenital hypothyroidism (CH) facilitates early diagnosis and treatment and prevents permanent intellectual disability. Sadly, 50 years after the first introduction of NBS for CH, only 29.6% of newborns worldwide are screened. Africa and Asia, the continents with the highest [...] Read more.
Newborn screening (NBS) for congenital hypothyroidism (CH) facilitates early diagnosis and treatment and prevents permanent intellectual disability. Sadly, 50 years after the first introduction of NBS for CH, only 29.6% of newborns worldwide are screened. Africa and Asia, the continents with the highest birth rates, have very limited screening coverage. Most NBS programs measure TSH in a dried-blood spot taken from a heel-prick on a filter paper after 24 to 72 h of life. Implementing national NBS programs is logistically complex and expensive, requiring parental consent, specialized laboratories, and excellent infrastructure. In limited-resource settings, introducing such a complex program is often impossible. We propose universal decentralized cord blood TSH screening, offered as routine delivery care for all newborns in limited-resource settings. TSH measurement may be performed by local laboratories using widely available, inexpensive radioimmunoassay kits, with the report available within a few hours. Since the TSH report would be available before discharge, suitable clinical decision making would be possible, with a minimal need for recall, thus minimizing the parental, medical, and financial burden and improving developmental outcomes. The most important requirement is to change to a grassroots approach, with the education of obstetricians and pediatricians worldwide to perform routine cord blood TSH and make sure the TSH result is available before the baby is discharged. Full article
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19 pages, 1396 KB  
Article
Long-Term Reproductive Outcomes After Palmer-Type Neosalpingostomy in Hydrosalpinx: A Seven-Year Real-World Cohort Study
by Laurențiu Augustus Barbu, Nicolae-Dragoș Mărgăritescu, Liliana Cercelaru, Tiberiu Stefăniță Țenea Cojan, Mădălina Costinela Stănică, Irina Enăchescu, Ana-Maria Țenea Cojan, Valentina Căluianu, Gabriel Florin Răzvan Mogoș and Liviu Vasile
J. Clin. Med. 2025, 14(22), 8043; https://doi.org/10.3390/jcm14228043 - 13 Nov 2025
Abstract
Background: Hydrosalpinx is a major cause of female infertility, but the long-term outcomes of Palmer-type neosalpingostomy remain insufficiently documented. Methods: We retrospectively analyzed 160 women with primary or secondary infertility and laparoscopically confirmed hydrosalpinx who underwent Palmer-type neosalpingostomy at a single specialized center [...] Read more.
Background: Hydrosalpinx is a major cause of female infertility, but the long-term outcomes of Palmer-type neosalpingostomy remain insufficiently documented. Methods: We retrospectively analyzed 160 women with primary or secondary infertility and laparoscopically confirmed hydrosalpinx who underwent Palmer-type neosalpingostomy at a single specialized center in Romania (2018–2024). Patients were enrolled consecutively, and disease severity was classified intraoperatively using standardized criteria. The primary outcome was clinical pregnancy; secondary outcomes included live birth, miscarriage, ectopic pregnancy, recurrence, and time to conception. Results: The clinical pregnancy rate was 33.8%, intrauterine/live birth rate 25.6%, miscarriage rate 3.8%, and ectopic pregnancy rate 4.4%. Recurrence occurred in 21.2% of cases. Outcomes were strongly influenced by hydrosalpinx severity and pelvic adhesions: women with mild disease achieved the highest pregnancy rates, whereas those with severe adhesions had poor prognosis. Neither age, AMH, nor laterality were independent predictors. Median time to pregnancy was 9 months. Conclusions: Palmer-type neosalpingostomy can achieve satisfactory reproductive outcomes in selected women, particularly those with mild hydrosalpinx and no adhesions. This study provides long-term real-world evidence from Eastern Europe, complementing international literature and emphasizing the importance of individualized patient selection. Full article
(This article belongs to the Special Issue Advances in Gynecological Diseases (Second Edition))
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13 pages, 627 KB  
Systematic Review
Intermittent Fasting During Pregnancy and Neonatal Birth Weight: A Systematic Review and Meta-Analysis
by Alice Giorno, Concetta De Simone, Giovanni Lopez, Maria L. Pisaturo, Ludovica Niccolini, Maurizio Guida, Laura Sarno and Sergio C. A. Schettini
Nutrients 2025, 17(22), 3546; https://doi.org/10.3390/nu17223546 - 13 Nov 2025
Abstract
Background/Objectives: Intermittent fasting (IF), such as Ramadan fasting, is common among pregnant women despite religious exemptions. The possible impact of fasting on pregnancy outcome and, in particular, on birthweight is uncertain and was documented with conflicting evidence. Methods: The aim of this meta-analysis [...] Read more.
Background/Objectives: Intermittent fasting (IF), such as Ramadan fasting, is common among pregnant women despite religious exemptions. The possible impact of fasting on pregnancy outcome and, in particular, on birthweight is uncertain and was documented with conflicting evidence. Methods: The aim of this meta-analysis and systematic review was to investigate the association between intermittent fasting during pregnancy and neonatal birthweight, along with low birthweight (LBW, <2500 g) risk. Studies evaluating fasting during pregnancy with reported neonatal outcomes were included. We searched (PubMed, Scopus, Web of Science) from 2004 through June 2025. All contributing studies were observational in design; no randomized trials were identified. The risk of bias was assessed using the Newcastle-Ottawa Scale. The pooled relative risks (RR) and mean differences (MD) were calculated according to random-effects models (DerSimonian–Laird method) and heterogeneity was quantified with the I2 statistic. Results: Nineteen studies, all observational in design, were included for qualitative synthesis, and six studies yielded quantitative data to conduct meta-analyses. No randomized controlled trials were identified. Intermittent fasting during pregnancy, encompassing more than 1.3 million pregnancies, was associated with a small but statistically significant reduction in neonatal birth weight. The pooled mean difference was −94 g (95% CI: −176 to −12 g; p = 0.03; I2 = 70%), indicating a minor but statistically significant effect that is unlikely to be clinically meaningful. The pooled RR for LBW was 0.96 (95% CI: 0.88–1.05; p = 0.38; I2 < 10%), showing no association between fasting and low birthweight risk. Sensitivity analyses reduced heterogeneity (I2 ≈ 55%) and confirmed the robustness of these findings. According to the GRADE approach, the certainty of evidence was moderate for birthweight and high for LBW. Conclusions: Intermittent fasting during pregnancy, including Ramadan fasting, was associated with a minor but statistically significant reduction in neonatal birthweight without increasing the risk of low birthweight. This difference was small and clinically negligible. Further prospective studies are needed to clarify trimester-specific effects and long-term developmental outcomes. Full article
(This article belongs to the Section Nutrition in Women)
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17 pages, 3329 KB  
Article
Cumulative Hydrocortisone Exposure and Early Brain Volumetrics in Very Low Birth Weight Infants: Associations with Neurodevelopmental Outcomes
by Min Soo Kim, Moon-Yeon Oh, Emi Tomita, Soo-Ah Im, Young-Ah Youn and Sae Yun Kim
Biomedicines 2025, 13(11), 2765; https://doi.org/10.3390/biomedicines13112765 - 12 Nov 2025
Viewed by 109
Abstract
Background/Objectives: Systemic hydrocortisone (HCS) in very low birth weight (VLBW) infants is commonly used to treat early hypotension or prevent bronchopulmonary dysplasia. This study evaluated the associations between postnatal HCS exposure and neurodevelopment in VLBW infants by comparing regional brain volume at [...] Read more.
Background/Objectives: Systemic hydrocortisone (HCS) in very low birth weight (VLBW) infants is commonly used to treat early hypotension or prevent bronchopulmonary dysplasia. This study evaluated the associations between postnatal HCS exposure and neurodevelopment in VLBW infants by comparing regional brain volume at term-equivalent age (TEA) with neurodevelopmental outcomes in early infancy. Methods: This retrospective cohort study included VLBW infants admitted to a neonatal intensive care unit (NICU) between 2013 and 2019. The cumulative HCS dose during hospitalization was recorded, and regional brain volumes were analyzed using magnetic resonance imaging at TEA. Neurodevelopmental outcomes were assessed at a corrected age for prematurity of 18–24 months. Results: Among 146 infants, 57 were classified in the high HCS group (>90 mg/kg) and 89 in the low HCS group (≤90 mg/kg HCS). Bronchopulmonary dysplasia, periventricular leukomalacia, and sepsis were more frequent in the high HCS group. Ninety-five infants underwent magnetic resonance imaging, which revealed reduced brain volumes in the high HCS group. At follow-up, cerebral palsy (35.9% vs. 9.1%, p = 0.003), neurodevelopmental impairment (54.0% vs. 23.6%, p = 0.002), and head circumference <10th percentile (64.3% vs. 19.5%, p < 0.001) were more common in the high HCS group. After adjustment, HCS > 90 mg/kg remained independently associated with cerebral palsy (adjusted odds ratio [aOR] 5.44, p = 0.016) and reduced head circumference (aOR 4.45, p = 0.016). Conclusions: High cumulative HC exposure correlated with reduced brain volume at TEA and adverse neurodevelopmental outcomes at 24 months of age. Careful monitoring of dose and treatment duration is essential to balance therapeutic benefits against potential risks. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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10 pages, 5192 KB  
Article
Clinical Outcomes After Hysteroscopic Removal of Retained Products of Conception with or Without Prior Uterine Artery Embolization
by Eva Skuk, Polona Vihtelič, Peter Popovič, Kaja Kovač, Ivan Verdenik and Nataša Kenda Šuster
J. Clin. Med. 2025, 14(22), 8020; https://doi.org/10.3390/jcm14228020 - 12 Nov 2025
Viewed by 91
Abstract
Purpose: Retained products of conception (RPOC) are a common complication after pregnancy. While hysteroscopic resection is the standard treatment when RPOC does not resolve spontaneously, highly vascular tissue can lead to severe bleeding during the procedure. This study assessed clinical outcomes, procedural [...] Read more.
Purpose: Retained products of conception (RPOC) are a common complication after pregnancy. While hysteroscopic resection is the standard treatment when RPOC does not resolve spontaneously, highly vascular tissue can lead to severe bleeding during the procedure. This study assessed clinical outcomes, procedural safety, and reproductive performance in patients with highly vascular RPOC treated with uterine artery embolization (UAE) prior to hysteroscopy, compared to those treated with hysteroscopy alone. Methods: This retrospective study included 42 women diagnosed with RPOC at University Medical Centre Ljubljana, Slovenia (2010–2020). Patients were divided into two groups: UAE followed by hysteroscopic resection (UAE + HSC, n = 21) and hysteroscopic resection alone (HSC-only, n = 21). Data on clinical outcomes, complications, and reproductive history were analyzed using Fisher’s exact and t-tests (p < 0.05). Results: Groups were similar in baseline characteristics, except for greater vascularity in the UAE + HSC group (100% vs. 4.8%, p < 0.05). Bleeding >300 mL occurred more often in the UAE + HSC group, but all cases were managed conservatively and only one patient required transfusion. No uterine perforations occurred. Residual RPOC was found in one patient per group. Rates of endometritis, menstrual changes, and pelvic pain were comparable. Among those who attempted conception, live birth and miscarriage rates did not differ significantly. Conclusions: UAE prior to hysteroscopic surgery appears to be a safe and effective option for highly vascular RPOC, especially in patients at risk of hemorrhage, with no adverse impact on fertility. Further prospective studies are recommended. Full article
(This article belongs to the Special Issue Advanced Hysteroscopic Technology for Gynecological Disease)
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13 pages, 379 KB  
Article
Cost-Effectiveness Analysis of Universal Rotavirus Vaccination Schedules in Syria
by Mania Mershed, Razan Altarabishi, Rasha Mohamed, Lamia Abu ajaj, Dima Alrashee, Manar Kamel and Salah Al Awaidy
Vaccines 2025, 13(11), 1157; https://doi.org/10.3390/vaccines13111157 - 12 Nov 2025
Viewed by 125
Abstract
Background: Rotavirus (RV) continues to be the leading cause of acute gastroenteritis (AGE) globally among children under five. National RV vaccination efforts have lowered morbidity and mortality. Vaccination is a key public health tool to alleviate this substantial burden of RV in middle- [...] Read more.
Background: Rotavirus (RV) continues to be the leading cause of acute gastroenteritis (AGE) globally among children under five. National RV vaccination efforts have lowered morbidity and mortality. Vaccination is a key public health tool to alleviate this substantial burden of RV in middle- and low-income countries. In Syria, RV morbidity accounts for 27% of severe GE. We conducted a cost-effectiveness analysis of introducing rotavirus vaccinations (RVV) into Syria’s National Immunization Program. Methods: A decision tree model was developed to assess the cost-saving of two-dose rotavirus vaccinations (Rotarix®) compared to no vaccination. A birth cohort of 573,944 newborns was simulated throughout a 5-year time frame to capture the near-term health and economic effects. The analysis adopted an incremental cost-saving approach, evaluating a hypothetical 2023 birth cohort from the government’s perspective. Outcomes included the cost per disability-adjusted life year (DALY) prevented and the cost per death averted. Model inputs were derived from local data, specifically including healthcare and vaccination costs and deaths attributable to RVGE, the scientific literature, and national/international databases. The incremental cost-effectiveness ratio (ICER) measures the cost of avoiding one disability-adjusted life year (DALY) adopted. Results: Over five years, the two-dose RV strategy would avert 77,500 RVGE cases, reduce outpatient visits by 59%, and reduce severe RV hospitalizations by 41%. The vaccination program would cost $21,817,918 USD and avert $3,239,907 USD in healthcare costs, resulting in a net cost of $18,578,011 USD. The incremental cost-effectiveness ratio (ICER) was $2098 USD per DALY averted, which is below three times Syria’s GDP per capita ($753.6 USD), indicating high cost-effectiveness according to WHO benchmarks. Conclusions: Introducing rotavirus vaccination is highly cost-saving and will result in a substantial reduction in healthcare burdens and lives lost. Policy planners must ensure its inclusion in the National Immunization Programs, ensuring sustainable financing and equitable access. Full article
(This article belongs to the Special Issue Childhood Immunization and Public Health)
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9 pages, 1034 KB  
Article
Are Dichorionic Twin Pregnancies Resulting from In Vitro Fertilization Different from Spontaneous Dichorionic Twin Pregnancies? A Retrospective Cohort Study
by Ahmet Zeki Nessar, Şebnem Karagün, Fikriye Işıl Adıgüzel, Şule Gül Aydın, Serdar Aykut, Aslıhan Kurt, Süleyman Cansun Demir, Mete Sucu and İsmail Cüneyt Evrüke
J. Clin. Med. 2025, 14(22), 8000; https://doi.org/10.3390/jcm14228000 - 11 Nov 2025
Viewed by 176
Abstract
Background: We aimed to compare the perinatal outcomes of dichorionic/diamniotic twin (DC/DA) pregnancies resulting from in vitro fertilization (IVF) with those resulting from spontaneous DC/DA pregnancies. Methods: The study group included 99 women with DC/DA pregnancies resulting from IVF, and the [...] Read more.
Background: We aimed to compare the perinatal outcomes of dichorionic/diamniotic twin (DC/DA) pregnancies resulting from in vitro fertilization (IVF) with those resulting from spontaneous DC/DA pregnancies. Methods: The study group included 99 women with DC/DA pregnancies resulting from IVF, and the control group included 92 women with spontaneous DC/DA pregnancies. Maternal demographic characteristics (age, parity, and gravidity), pre-existing conditions (chronic hypertension and pregestational diabetes mellitus), and obstetric history were recorded. Pregnancy outcomes included gestational age at delivery, number of fetuses, and mode of delivery. The antepartum complications that we evaluated include first- and second-trimester bleeding, placenta previa, preterm birth, fetal growth restriction (FGR), oligohydramnios, and tocolytic use. The obstetric complications that we assessed include prematurity, twin-to-twin transfusion syndrome (TTTS), and hydrops fetalis. Additionally, neonatal data such as 1st minute and 5th minute Apgar scores, birth weight, neonatal intensive care unit (NICU) admission, presence of congenital anomalies, and neonatal death were recorded, and comparisons were made between the groups. Results: Women in the IVF group were older (34.7 ± 6.9 vs. 32.3 ± 6.1 years, p = 0.03) and more frequently primiparous (73.7% vs. 37.0%, p < 0.001). The mean gestational age at delivery was slightly lower in the IVF group, though this was not statistically significant (34.3 ± 3.5 vs. 35.1 ± 2.5 weeks, p = 0.101). Cesarean delivery was common in both groups, with comparable overall rates (90.9% vs. 94.6%, p = 0.411), but emergency cesarean section occurred more frequently in IVF pregnancies (81.8% vs. 55.8%, p = 0.001). No significant differences were found regarding chronic hypertension or pregestational diabetes. However, several differences were demonstrated in terms of obstetric complications. For example, preterm births and fetal growth restriction (FGR) were significantly more frequent in IVF pregnancies (59.8% vs. 30.4%, p < 0.001), and tocolytic use was also more frequent (56.6% vs. 29.7%, p < 0.001). No significant differences were observed in terms of placenta previa, oligohydramnios, TTTS, hydrops fetalis, and neonatal outcomes. The logistic regression analysis revealed that IVF pregnancies were associated with an increased risk of preterm birth: OR 3.45, 95% CI 1.85–6.78 (p < 0.001); the risk of FGR was also higher in IVF pregnancies: OR 2.11, 95% CI 1.02–4.37 (p = 0.015). However, tocolytic use was not significantly associated with IVF: OR 1.49, 95% CI 0.50–4.44 (p = 0.471). Conclusions: Although DC/DA pregnancies conceived through IVF have a higher risk of preterm birth, fetal growth restriction, and greater use of tocolytic agents than spontaneous DC/DA pregnancies, their neonatal outcomes are similar. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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15 pages, 1680 KB  
Article
Effect of Slow Versus Rapid Advancement of Enteral Feeding on Intestinal Oxygenation in Preterm Infants
by Hulya Ozdemir, Sinem Gulcan Kersin, Halime Sema Can Buker, Merih Cetinkaya, Ibrahim Kandemir, Asli Memisoglu and Hulya Selva Bilgen
Children 2025, 12(11), 1527; https://doi.org/10.3390/children12111527 - 11 Nov 2025
Viewed by 142
Abstract
Background/Objectives: The optimal rate of enteral feeding advancement in preterm infants remains uncertain despite decades of clinical research. This uncertainty arises from concerns that rapid feeding progression may increase the risk of feeding intolerance and necrotizing enterocolitis (NEC), two major causes of morbidity [...] Read more.
Background/Objectives: The optimal rate of enteral feeding advancement in preterm infants remains uncertain despite decades of clinical research. This uncertainty arises from concerns that rapid feeding progression may increase the risk of feeding intolerance and necrotizing enterocolitis (NEC), two major causes of morbidity and mortality in this population. The feeding rate may also influence intestinal oxygenation due to mesenteric hemodynamic changes during feeding. This study aimed to evaluate whether the rate of enteral feeding advancement (slow vs. rapid) affects intestinal oxygenation and its association with feeding intolerance (FI) or necrotizing enterocolitis in very low birth weight preterm infants. Methods: This prospective, randomized, two-center study included infants born at 28–32 weeks of gestation. Group 1 received slow advancement (20 mL/kg/day) and Group 2 rapid advancement (30 mL/kg/day) of enteral feeds. Splanchnic (srSO2) and cerebral (crSO2) oxygenation were monitored daily using the FDA-approved INVOS NIRS device during feeding periods (08:00–16:00). Monitoring was performed during minimal enteral nutrition (Phase 1), advancement phases (Phase 2), and for two days after achieving full enteral feeding (Phase 3). The splanchnic-to-cerebral oxygenation ratio (SCOR) was also calculated. Percentage changes in srSO2 and SCOR during and after feeding were calculated from baseline (prefeeding) values and analyzed. Results: Sixty infants were enrolled. Mean gestational age and birth weight were 29.76 ± 1.33 weeks and 1375.05 ± 271.19 g, respectively. Group 2 achieved full enteral feeding significantly earlier (p = 0.001), with no other demographic differences between groups. No cases of NEC were observed. Feeding intolerance occurred in 14 infants (23.3%): 8 in Group 1 and 6 in Group 2 (p = 0.192). Both groups exhibited increased srSO2 and SCOR during feeding; however, the between-group differences were not statistically significant (Phase 2 srSO2 and SCOR: p = 0.07, 0.08; Phase 3 srSO2 and SCOR: p = 0.069, 0.071). However, the percentage change from baseline in srSO2 and SCOR during and after feeding was significantly greater in Group 2 during the advancement and full enteral feeding phases (Phase 2 srSO2 and SCOR: p = 0.03, 0.022; Phase 3 srSO2 and SCOR: p = 0.015, 0.048). Infants with feeding intolerance demonstrated significantly lower srSO2 and SCOR values compared to tolerant infants, and this reduction persisted even after reaching full enteral feeding. ROC analysis suggested gestational age < 30 weeks, birth weight < 1180 g, srSO2 < 52, and SCOR < 0.6 were associated with feeding intolerance. Conclusions: Intermittent bolus feeding increased intestinal oxygenation, with a more pronounced effect in the rapid advancement group. No difference in gastrointestinal adverse outcomes was observed between groups. Lower intestinal oxygenation was associated with feeding intolerance, and the suggested predictive criteria may help guide individualized feeding strategies. Full article
(This article belongs to the Section Pediatric Neonatology)
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23 pages, 2780 KB  
Article
Prematurity and Epigenetic Regulation of SLC6A4: Longitudinal Insights from Birth to the First Month of Life
by Aline de Araújo Brasil, Leo Travassos Vieira Milone, Paulo Victor Barbosa Eleutério dos Santos, Stephanie Cristina Alves de Oliveira Saide, Vitor Barreto Paravidino, Georgia Chalfun, Letícia Santiago da Silva Ferreira, Mariana Berquó Carneiro Ferreira, Anna Beatriz Muniz Ferreira, Geovanna Barroso de Farias, Jaqueline Rodrigues Robaina, Mariana Barros Genuíno de Oliveira, Maria Clara de Magalhães-Barbosa, Arnaldo Prata-Barbosa and Antonio José Ledo Alves da Cunha
Biomedicines 2025, 13(11), 2753; https://doi.org/10.3390/biomedicines13112753 - 11 Nov 2025
Viewed by 175
Abstract
Background/Objectives: Prematurity is a significant global health concern, often associated with neurodevelopmental challenges. Solute Carrier Family 6 Member 4 (SLC6A4), the gene encoding the serotonin transporter, a key component in serotonin reuptake in the synaptic cleft, plays a key role in [...] Read more.
Background/Objectives: Prematurity is a significant global health concern, often associated with neurodevelopmental challenges. Solute Carrier Family 6 Member 4 (SLC6A4), the gene encoding the serotonin transporter, a key component in serotonin reuptake in the synaptic cleft, plays a key role in stress response and neurodevelopment. Epigenetic regulation of stress-related genes, such as SLC6A4, influences neonatal stress adaptation and developmental outcomes. This study aimed to quantify and compare DNA methylation levels at 13 CpG sites in the promoter region of the SLC6A4 gene between preterm and term neonates at three time points. Methods: A cohort of 46 preterm infants and a cohort of 49 full-term infants were analyzed. Blood samples collected at birth (D0), the fifth day (D5), and the thirtieth day (D30) were used to analyze DNA methylation, using bisulfite conversion and pyrosequencing. Results: Significant differences in SLC6A4 methylation were observed. At D0, CpGs 12 and 13 showed higher methylation in preterm infants. CpG 9 showed lower methylation in preterm infants at D5. Extremely preterm infants had the highest values of methylation at the three time points. Longitudinal mixed-effects analysis revealed distinct temporal patterns between groups. Total and site-specific methylation at CpGs 2, 8, and 9 increased over time in full-term infants, while methylation remained stable over time in very preterm and extremely preterm infants. Conclusions: This study reveals significant differences in SLC6A4 methylation between very preterm, extremely preterm, and full-term infants, highlighting the impact of prematurity and early-life stress on the epigenome. These findings contribute to improving our understanding of the epigenetic mechanisms shaping neurodevelopment and stress adaptation in neonates. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine (2nd Edition))
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16 pages, 720 KB  
Article
Risk Factors and Predictive Parameters of Necrotizing Enterocolitis in Preterm Infants—A Single-Center Retrospective Study
by Tamas Toth, Angela Borda, Reka Borka-Balas, Manuela Cucerea, Emoke Andrea Szasz, Horea Gozar and Radu-Alexandru Prisca
Diseases 2025, 13(11), 368; https://doi.org/10.3390/diseases13110368 - 10 Nov 2025
Viewed by 201
Abstract
Background and Objectives: Necrotizing enterocolitis (NEC) represents a severe gastrointestinal emergency in preterm infants. The aim of this study was to identify risk factors and predictive parameters for NEC requiring surgery and to evaluate associated short-term outcomes. Materials and Methods: We [...] Read more.
Background and Objectives: Necrotizing enterocolitis (NEC) represents a severe gastrointestinal emergency in preterm infants. The aim of this study was to identify risk factors and predictive parameters for NEC requiring surgery and to evaluate associated short-term outcomes. Materials and Methods: We conducted a retrospective study in preterm neonates diagnosed with NEC admitted to a tertiary neonatal intensive care unit (NICU) between January 2015 and May 2025. Demographic data, perinatal events, risk factors, clinical signs, imaging findings, and outcomes were analyzed, with a particular focus on surgically managed cases. Descriptive and inferential statistical methods were applied. Results: Forty-four infants met the inclusion criterion. The mean gestational age (GA) was 29.34 ± 4.3 weeks, and the mean birth weight was 1100 ± 563 g. According to Bell’s severity index, 45.5% had Bell Stage I, 36.4% Stage II, and 18.2% Stage III. Eleven patients (25%) required surgery. All surgical patients had abdominal distension, and 63.6% had bilious gastric residue. Abdominal X-ray showed pneumoperitoneum in 72.7% and pneumatosis intestinalis in 27.3% of cases. Laboratory abnormalities, including thrombocytopenia, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and hyponatremia (45.5%; 133 ± 6.95 mmol/L), were frequently associated with surgical NEC. A lower GA and birth weight correlated with a higher Bell stage (p = 0.0085 and p = 0.0291). Overall mortality was 29.5% (13/44); surgical mortality was 9.1% (1/11). Conclusions: In this single-center lot, low gestational age and birth weight, abdominal distension with bilious residuals, systemic inflammation, and hyponatremia were frequent among infants who required surgery. Selected infants may benefit from early surgery even without perforation, but inferences are limited by this study’s sample size and retrospective design. Prospective multi-center studies are needed to validate predictors and refine surgical timing. Full article
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