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17 pages, 679 KB  
Article
Early Initiation of rhGH Therapy Significantly Improves Height Gain and Reduces the Gap to Target Height in Children Born Small for Gestational Age: A Multicenter Retrospective Study
by Letteria Anna Morabito, Malgorzata Wasniewska, Cecilia Lugarà, Emanuela Pignatone, Domenico Corica, Renato Vaiasuso, Alessandra Cipriani, Giovanni Luppino, Roberto Coco, Giorgia Pepe, Tiziana Abbate, Stefano Stagi and Tommaso Aversa
Children 2026, 13(5), 641; https://doi.org/10.3390/children13050641 (registering DOI) - 3 May 2026
Abstract
Background: Treatment with recombinant human growth hormone (rhGH) is approved for children born small for gestational age (SGA) who fail to show postnatal catch-up growth; however, optimizing its efficacy remains a challenge. Aim: to evaluate the impact of rhGH therapy on growth trajectory [...] Read more.
Background: Treatment with recombinant human growth hormone (rhGH) is approved for children born small for gestational age (SGA) who fail to show postnatal catch-up growth; however, optimizing its efficacy remains a challenge. Aim: to evaluate the impact of rhGH therapy on growth trajectory (GT) and adult height (AH) in SGA children and to identify factors influencing height gain (HG). Methods: A total of 49 SGA children (24 males, 25 females) without postnatal growth recovery and treated with rhGH were enrolled. Clinical and anthropometric data were collected at treatment initiation (T0), after 1 (T1) and 2 years (T2) of therapy, at pubertal onset (P0), during the first (P1) and second year (P2) of puberty, and at attainment of AH. Parameters included age, bone age, H, weight, BMI (all expressed as SDS), HG, and the difference between H and target height (Δ H-TH). Results: a significant increase in HG at all evaluated stages was observed (p < 0.05). The H–TH difference progressively decreased from T0, particularly until the first two years of puberty. Nevertheless, mean AH was −1.75 ± 0.63 SDS, and it was found to fall within the TH range in 86% of cases. Univariate and multivariate regression analysis revealed that age and H at T0 were independent predictors of HG. Conclusions: rhGH treatment has a positive impact on GT in children born SGA. Pubertal growth has a limited contribution in influencing AH of these patients. H and timing of treatment initiation significantly influence HG in SGA children. Early selection of patients for rhGH therapy could further improve their GT. Full article
(This article belongs to the Section Pediatric Endocrinology & Diabetes)
19 pages, 967 KB  
Review
The Contribution of Ultrasound and Doppler Studies on Impaired Intrauterine Conditions and the Development of Future Disease
by Yossi Geron, Yinon Gilboa, Asaf Romano and Jacob Bar
Medicina 2026, 62(5), 875; https://doi.org/10.3390/medicina62050875 (registering DOI) - 3 May 2026
Abstract
The Barker hypothesis links intrauterine conditions, mainly low birth weight, subject to poor nutrition with paradoxically improved standards of living and nutrition after World War II in Western countries, to adult disease, mainly coronary heart disease. The limitations of his hypothesis include the [...] Read more.
The Barker hypothesis links intrauterine conditions, mainly low birth weight, subject to poor nutrition with paradoxically improved standards of living and nutrition after World War II in Western countries, to adult disease, mainly coronary heart disease. The limitations of his hypothesis include the fact that it is based only on human epidemiological data and animal studies, and also that it is difficult to isolate the effect of the intrauterine environment from postnatal conditions, familial and genetic background. In the last 20 years, the introduction of ultrasound and Doppler techniques in the assessment of fetal and maternal vascularity added a major contribution to the evaluation of the intrauterine environment. Studies based on ultrasound and Doppler assist in differentiating between prematurity and fetal growth restriction (FGR), mainly in those with placental insufficiency, and postnatal morbidity and even mortality. In addition, the Pedersen hypothesis regarding fetuses with overgrowth, mainly with diabetic mothers, states that they are also prone to postnatal morbidity. However, most of the studies on the issue do not emphasize the effects of the intrauterine environment on fetal organs, such as the brain, heart, liver, kidneys and pancreas in FGR and fetal overgrowth, that may impose a different prognosis in later life. This narrative review aims to summarize current evidence from animal and human studies regarding the impact of intrauterine undernutrition and overnutrition on fetal organ development, and to evaluate how ultrasound and Doppler findings may contribute to understanding the link between the intrauterine environment and postnatal morbidity. Full article
10 pages, 405 KB  
Article
Early-Onset Neonatal Sepsis: Clinical System Involvement and Maternal–Neonatal Risk Profiles in a Retrospective Cohort Study
by Anna Damatopoulou, Michail Matalliotakis, Fani Ladomenou, Christina Thomou, Marina Koropouli and Maria Polychronaki
Children 2026, 13(5), 639; https://doi.org/10.3390/children13050639 (registering DOI) - 3 May 2026
Abstract
Background/Objectives: Neonatal sepsis remains a major contributor to neonatal morbidity and mortality worldwide, yet diagnostic uncertainty and heterogeneous clinical presentation continue to challenge early recognition and management. Early-onset sepsis (EOS), typically arising within the first 72 h of life, is strongly influenced by [...] Read more.
Background/Objectives: Neonatal sepsis remains a major contributor to neonatal morbidity and mortality worldwide, yet diagnostic uncertainty and heterogeneous clinical presentation continue to challenge early recognition and management. Early-onset sepsis (EOS), typically arising within the first 72 h of life, is strongly influenced by maternal and perinatal factors. Limited data exist on the temporal evolution of clinical system involvement during the first week of life. This study aimed to identify the predominant clinical systems involved in preterm and term neonates with suspected or confirmed sepsis and to determine maternal and neonatal risk factors associated with early disease severity, persistent sepsis, and adverse outcomes. Methods: A total of 297 neonates met the inclusion criteria. Most infants (99.3%) were admitted before 72 h of life. Clinical system involvement was recorded daily, and maternal–neonatal risk factors were analyzed to identify predictors of advanced sepsis at presentation, persistent sepsis at Day 7, and mortality. Results: Respiratory involvement was the predominant clinical system affected on Day 1 (57.2%) and remained common through Day 3. CNS, gastrointestinal, and skin involvement were infrequent. Lower gestational age (p = 0.035) and prolonged rupture of membranes >18 h (p = 0.043) independently predicted sepsis at Day 1. Advanced sepsis at admission was associated with lower birth weight, lower gestational age, older maternal age, and absence of intrapartum antibiotics (all p ≤ 0.001). Persistent sepsis at Day 7 was linked to prematurity (p = 0.008), higher mortality (p < 0.001), and prolonged hospitalization (p = 0.001). Conclusions: Respiratory involvement was the most common clinical system affected in neonates with EOS. Prematurity, low birth weight, prolonged rupture of membranes, and maternal intrapartum infection significantly increased the risk of severe disease. Understanding the evolution of clinical system involvement during the first days of life may support more precise risk stratification and reduce unnecessary antibiotic exposure. Full article
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13 pages, 1500 KB  
Article
Association of Maternal and Cord Blood Choline and Betaine Concentrations with Birthweight: A Prospective Mother–Infant Cohort Study
by Sumiya Aihemaitijiang, Jiaxing Wen, Kai Li, Haoran Ren, Hongtian Li, Yubo Zhou and Jianmeng Liu
Nutrients 2026, 18(9), 1456; https://doi.org/10.3390/nu18091456 - 1 May 2026
Abstract
Background: Experimental studies indicated that maternal choline and betaine status have the potential to alter fetal growth, but epidemiological data remain sparse. Objective: We aimed to investigate the association of maternal and cord blood choline and betaine concentrations with birthweight outcomes. Methods: This [...] Read more.
Background: Experimental studies indicated that maternal choline and betaine status have the potential to alter fetal growth, but epidemiological data remain sparse. Objective: We aimed to investigate the association of maternal and cord blood choline and betaine concentrations with birthweight outcomes. Methods: This prospective cohort study involved 988 mother–infant dyads from Hebei and Shandong provinces. Plasma concentrations of choline and betaine in maternal late pregnancy and cord blood were quantified using ultra-performance liquid chromatography–mass spectrometry. Multivariable linear or logistic regression was performed to examine their association with continuous or binary birthweight outcomes. Results: Maternal plasma choline and betaine concentrations in late pregnancy (median [interquartile range]; 12.34 [10.13, 14.78] and 14.99 [12.01, 18.36] μmol/L) were significantly lower than those in cord blood (29.98 [24.74, 35.93] and 31.14 [25.56, 37.28] μmol/L). Each 1 μmol/L increase of late-pregnancy and cord blood betaine concentrations were associated with 9.87 g (95% confidence interval [CI]: −16.08, −3.66 g) and 5.29 g (95% CI: −8.52, −2.06 g) lower birthweight, respectively. Compared with the lowest quintile, the highest quintiles of late-pregnancy and cord blood betaine concentrations were associated with lower risks of large-for-gestational-age (adjusted odds ratios [ORs] = 0.47 [95% CI: 0.24, 0.90] and 0.31 [95% CI: 0.17, 0.56]) and macrosomia (adjusted ORs = 0.12 [95% CI: 0.03, 0.43] and 0.15 [95% CI: 0.05, 0.40]). These associations, particularly for cord blood, persisted and appeared more pronounced in pregnancies with maternal overweight/obesity or gestational diabetes mellitus (GDM), but the interaction effect did not reach statistical significance. No significant associations were observed for choline in any periods. Conclusions: Higher plasma concentrations of betaine in maternal late-pregnancy and cord blood were associated with lower birthweight. These findings emphasize the importance of sufficient betaine status during pregnancy, especially among mothers with obesity or GDM. Full article
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17 pages, 464 KB  
Article
Psychiatric and Functional Outcomes in Preterm School-Aged Children in Greece
by Symeon Dimitrios Daskalou, Theodoros N. Sergentanis, Nikolaos Gerosideris, Christina Ouzouni, Elpida Stratou and Ioanna Giannoula Katsouri
Psychiatry Int. 2026, 7(3), 92; https://doi.org/10.3390/psychiatryint7030092 - 1 May 2026
Abstract
Background: Preterm birth is a significant early-life stressor associated with increased psychiatric vulnerability and long-term functional impairments in school-aged children. Objective: To compare behavioral–emotional outcomes and functional competence between school-aged preterm and term-born children, examining perinatal, cognitive, and socioeconomic predictors. Methods: 140 children [...] Read more.
Background: Preterm birth is a significant early-life stressor associated with increased psychiatric vulnerability and long-term functional impairments in school-aged children. Objective: To compare behavioral–emotional outcomes and functional competence between school-aged preterm and term-born children, examining perinatal, cognitive, and socioeconomic predictors. Methods: 140 children aged 6–10 (70 preterm, 70 age-matched controls) were assessed using the Child Behavior Checklist (CBCL) and Strengths and Difficulties Questionnaire (SDQ). Functional competence—defined as participation in daily activities, social interactions, and school performance—was examined alongside behavioral–emotional outcomes. Predictors included gestational age, birth weight, SES, and cognitive ability. Results: Preterm birth was associated with higher SDQ scores in emotional problems, hyperactivity, and peer problems. CBCL results showed lower total functional competence scores, specifically in activities, social participation, and school performance. Longer NICU stay predicted higher internalizing problems and lower social participation. Cognitive ability was linked to lower SDQ externalizing and internalizing scores. SES was not a significant predictor. Conclusions: Preterm birth and prolonged NICU hospitalization are linked to persistent behavioral–emotional and functional vulnerabilities. These findings underscore the need for early, integrated developmental monitoring within a preventive psychiatry framework to identify psychiatric vulnerability and support functional participation. Full article
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9 pages, 279 KB  
Article
Prenatal Selective Serotonin Reuptake Inhibitor Exposure and Its Impact on Neonatal Gastrointestinal and Urinary System: A Retrospective Matched Cohort Study
by Ronella Marom, Laurence Mangel, Addy S. BrandStetter, Jacky Herzlich, Dror Mandel and Yuval Bar-Yosef
Children 2026, 13(5), 630; https://doi.org/10.3390/children13050630 - 30 Apr 2026
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Abstract
Objective: Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) has been associated with altered neonatal adaptation, but its relationship with early elimination patterns remains unclear. Given the role of serotonin in gastrointestinal and urinary physiology, we aimed to evaluate the association between maternal [...] Read more.
Objective: Prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) has been associated with altered neonatal adaptation, but its relationship with early elimination patterns remains unclear. Given the role of serotonin in gastrointestinal and urinary physiology, we aimed to evaluate the association between maternal SSRI use during pregnancy and time to first stool and time to first void in healthy neonates. Methods: In this retrospective matched cohort study, neonates exposed to SSRIs in utero were matched 1:1 with unexposed controls by gestational age (GA) and weight-for-gestational-age category. The primary outcomes were time to first void and time to first stool. Multivariable linear regression was performed using log10-transformed time to first stool, adjusting for maternal age, GA, and neonatal sex. Sensitivity analyses included size-for-gestational-age and time to first feeding. Results: A total of 266 neonates were included (133 SSRI-exposed, 133 unexposed). Time to first stool was shorter in SSRI-exposed neonates compared with unexposed neonates (median 7.4 vs. 8.6 h, p = 0.023), while the time to first void did not differ. In adjusted analysis, SSRI exposure remained associated with shorter time to first stool (β = −0.08, 95% CI −0.16 to −0.001, p = 0.035), corresponding to an approximate 17% reduction. The association was consistent across sensitivity analyses. Meconium-stained amniotic fluid was associated with shorter time to first stool among SSRI-exposed neonates but not in unexposed neonates. The overall model explained a limited proportion of variance. Conclusions Prenatal SSRI exposure was associated with modest but consistent reduction in time to first stool, without affecting time to first void. While the clinical significance remains uncertain, these findings suggest a potential influence of in utero SSRI exposure on early neonatal gastrointestinal adaptation, which may be influenced by intrapartum conditions. Full article
(This article belongs to the Section Pediatric Drugs)
14 pages, 712 KB  
Review
Neurodevelopmental Trajectories in Preterm Neonates: Integrating Neuroimaging Modalities with Clinical Neurological Outcomes
by Andreea Ioana Necula, Roxana Pavalache-Stoiciu, Larisa Nicoleta Andrasoaie and Al Jashi Isam
Diagnostics 2026, 16(9), 1356; https://doi.org/10.3390/diagnostics16091356 - 30 Apr 2026
Viewed by 130
Abstract
This narrative review aims to demonstrate how integrating neuroimaging with functional assessments and standardized protocols enhances the identification of long-term motor and psychiatric risks. This review synthesized 12 studies from the last 5 years. The analysis focused on preterm infants (<37 weeks’ gestational [...] Read more.
This narrative review aims to demonstrate how integrating neuroimaging with functional assessments and standardized protocols enhances the identification of long-term motor and psychiatric risks. This review synthesized 12 studies from the last 5 years. The analysis focused on preterm infants (<37 weeks’ gestational age) and evaluated the correlation between neuroimaging (head ultrasound (HUS) and Magnetic Resonance Imaging (MRI)), head circumference (HC), and functional assessments like Prechtl General Movements (GMs). While HUS remains the primary bedside tool, its sensitivity for subtle, non-cystic white matter injury is limited compared to MRI. Both modalities demonstrate high negative predictive values at term-equivalent age (TEA) for excluding severe motor deficits. Structural markers, including increased ventricular midbody size, immature gyration, and bilateral lesion laterality, were strongly associated with Cerebral Palsy (CP) and gross motor delays. Furthermore, TEA assessments provided superior prognostic accuracy compared to early neonatal scans. Optimal outcomes were linked to the integration of neuroimaging with functional assessments (GMs) and reliable parental support to ensure follow-up compliance. A tiered HUS/MRI protocol combined with routine GMs assessment enables precise prognostic counseling. Correlating TEA imaging with long-term findings necessitates follow-up beyond 24 months. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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16 pages, 709 KB  
Review
β-Thalassemia Minor and Pregnancy Outcomes: Pathophysiology, Clinical Implications, and Management
by Angeliki Gerede, Sofoklis Stavros, Efthymios Oikonomou, Anastasios Potiris, Maria Danavasi, Vasiliki Kourti, Ismini Anagnostaki, Ekaterini Domali, Nikoletta Koutlaki and Makarios Eleftheriadis
Med. Sci. 2026, 14(2), 225; https://doi.org/10.3390/medsci14020225 - 30 Apr 2026
Viewed by 73
Abstract
β-thalassemia minor, often referred to as the β-thalassemia trait, is among the most prevalent hemoglobinopathies globally, impacting around 80–90 million carriers, with a prevalence of up to 15% among Mediterranean, Middle Eastern, and Asian populations. Although traditionally regarded as clinically benign, pregnancy imposes [...] Read more.
β-thalassemia minor, often referred to as the β-thalassemia trait, is among the most prevalent hemoglobinopathies globally, impacting around 80–90 million carriers, with a prevalence of up to 15% among Mediterranean, Middle Eastern, and Asian populations. Although traditionally regarded as clinically benign, pregnancy imposes hematologic and metabolic stressors that may unmask latent vulnerabilities. This review combines the latest data and findings about the pathophysiology of β-thalassemia minor during pregnancy, its short-term outcomes on the mother and fetus, and its long-term impact on the child, as well as management techniques. A narrative review of PubMed-indexed studies (2000–2025) was conducted, including cohort and case–control studies, systematic reviews, meta-analyses, and international guidelines. Outcomes were organized by theme, and quantitative findings (prevalence, relative risks, odds ratios) were combined when available. Anemia is a common health issue for mothers. Literature mentions that the pooled incidence is between 30% and 40% during the third trimester, with ~5%of carriers needing a blood transfusion (mainly in iron-deficient or baseline Hb 6–8 g/dL cases). Meta-analyses have shown elevated risks of pre-eclampsia (odds ratio (OR) ~ 1.4, 95% confidence interval (CI) 1.1–1.8) and postpartum hemorrhage (PPH); however, estimates differ by region. The odds of preterm delivery (OR ~ 1.4), small-for-gestational-age (SGA) (OR ~ 1.5), and low birth weight (LBW) are slightly increased for carriers, and neonatal intensive care unit (NICU) admission rates are also higher for carriers. However, the risk of stillbirth is not always increased. The usual approach is iron supplementation guided by ferritin levels to prevent overload, personalized transfusion thresholds, and regular folate support. There is not much evidence for long-term consequences for children of carrier mothers since no research has followed more than 200 children born to carrier mothers into adulthood. However, maternal anemia is linked to slower growth, neurodevelopmental issues, and a higher risk of cardiometabolic problems in larger groups of pregnant women. However, maternal anemia is associated with slower growth, neurodevelopment, and higher cardiometabolic risk in larger groups of pregnant women. β-thalassemia minor during pregnancy usually has a mild, though significant, impact. While most pregnancies proceed without complications, this condition is associated with a significantly higher prevalence of anemia and other adverse postnatal outcomes. Consequently, the implementation of risk-stratified monitoring, smart supplementation, and standardized management protocols is essential. Prospective registries, mechanistic placental research, and long-term offspring cohorts are necessary to better understand long-term trends. Full article
(This article belongs to the Section Gynecology)
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13 pages, 884 KB  
Article
Refeeding Syndrome May Increase the Risk of Anemia of Prematurity: Is Early Enteral Nutrition the Solution?
by Maria Di Chiara, Caterina Spiriti, Gaia Loffredo, Fabiana Russo, Daniela Regoli, Cecilia Betto, Francesco Crispino and Gianluca Terrin
Nutrients 2026, 18(9), 1380; https://doi.org/10.3390/nu18091380 - 28 Apr 2026
Viewed by 169
Abstract
Background/Objectives: Preterm infants are particularly vulnerable to nutritional deficiencies and electrolyte imbalances during the early stages of extrauterine life. To ensure optimal metabolic support, they often require the early initiation of “aggressive” parenteral nutrition (PN), which is a known risk factor for Refeeding [...] Read more.
Background/Objectives: Preterm infants are particularly vulnerable to nutritional deficiencies and electrolyte imbalances during the early stages of extrauterine life. To ensure optimal metabolic support, they often require the early initiation of “aggressive” parenteral nutrition (PN), which is a known risk factor for Refeeding Syndrome (RS), a potentially serious metabolic condition characterized by fluid and electrolyte disturbances, the most significant of which is hypophosphatemia. Hypophosphatemia can impair the metabolism, survival, and function of red blood cells, leading to a reduction in key intracellular metabolites and the development of a metabolic block that alters their quality and decreases their stability. It is therefore hypothesized that RS may contribute to the development of anemia of prematurity (AOP). At the same time, early enteral nutrition (EN) may promote metabolic adaptation and reduce exposure to the complications of prolonged parenteral support, potentially protecting against AOP. The primary aim of this study was to determine whether preterm infants who develop RS are at increased risk of AOP. A secondary aim was to evaluate whether early EN may act as a protective factor against the development of AOP. Methods: This retrospective observational study was conducted on infants with a gestational age ≤ 34 weeks and/or birth weight ≤ 1500 g, admitted to the Neonatal Intensive Care Unit of Policlinico Umberto I—Sapienza University of Rome, between January 2015 and November 2022. Infants diagnosed with AOP were classified as cases, while those without AOP served as the control group. Results: A total of 412 preterm infants were enrolled (110 cases, 302 controls). Refeeding Syndrome was significantly more frequent in infants with AOP (30.9% vs. 11.6%, p < 0.001). In the logistic regression model adjusted for gestational age, RS was independently associated with AOP (OR = 2.81; 95% CI: 1.55–5.10; p < 0.001), along with gestational age ≤ 34 weeks (OR = 7.10; 95% CI: 2.13–24.0; p = 0.001). Early enteral nutrition during the first week of life was associated with a significantly lower risk of AOP (OR = 0.12; 95% CI: 0.029–0.52; p = 0.005). The association between RS and AOP was confirmed in the model adjusted for birth weight (OR = 2.06; 95% CI: 1.16–3.79; p = 0.021). Infants with AOP showed significantly higher parenteral nutrition intake, delayed initiation of enteral feeding, and later achievement of full enteral nutrition compared with controls (all p < 0.001). Conclusions: RS is significantly associated with AOP in preterm infants, likely through pathophysiological mechanisms related to hypophosphatemia. Importantly, early EN may be a protective factor against AOP, suggesting that timely initiation and advancement in enteral feeding may counteract the metabolic derangements associated with intensive parenteral support. These findings support a nutritional approach that prioritizes early and progressive enteral nutrition as a strategy to reduce the risk of both RS and AOP. Further prospective studies are needed to confirm these associations and to define optimal EN protocols for this population. Full article
(This article belongs to the Special Issue Enteral Nutrition—Current Insights and Future Direction)
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9 pages, 2562 KB  
Case Report
CBCT-Guided Iliosacral Screw Osteosynthesis in a Pregnant Woman: A Case Report and Literature Review
by Bastien Chalamet, Jean-Baptiste Pialat, Anthony Viste, Didier Defez, Pierre-Adrien Bolze and Nicolas Stacoffe
J. Pers. Med. 2026, 16(5), 235; https://doi.org/10.3390/jpm16050235 - 28 Apr 2026
Viewed by 221
Abstract
Objectives: Management of unstable pelvic fractures during pregnancy presents a major therapeutic challenge, requiring careful multidisciplinary evaluation to balance maternal benefits and fetal radiation risks. Methods: We report the case of a 32-year-old patient who presented with a pelvic fracture due [...] Read more.
Objectives: Management of unstable pelvic fractures during pregnancy presents a major therapeutic challenge, requiring careful multidisciplinary evaluation to balance maternal benefits and fetal radiation risks. Methods: We report the case of a 32-year-old patient who presented with a pelvic fracture due to a road traffic accident at three months of pregnancy. A left sacroiliac osteosynthesis was performed to treat a left sacroiliac diastasis with pelvic osteosynthesis using a trans-iliosacral approach under cone-beam CT (CBCT) guidance using a very-low-dose protocol. Radiation parameters and fetal dose estimates were calculated in advance in collaboration with a medical physicist. Tight beam collimation, a reduced field of view, and minimization of fluoroscopic checks were applied to keep fetal exposure as low as reasonably achievable. This article aims to demonstrate the feasibility of managing a complex pelvic fracture using interventional radiology and to review the literature on management options and gestational age-dependent fetal risks. Results: The estimated cumulative fetal dose from initial imaging, open surgery, and CBCT-guided osteosynthesis remained below 70 mGy using a pregnant phantom (Duke Organ Dose–Dosewatch–General Electric system), which is below thresholds associated with deterministic effects. The procedure achieved optimal screw positioning with less than 40 s of fluoroscopy. Maternal postoperative recovery was favorable, and follow-up revealed normal fetal development. Conclusions: This case demonstrates that CBCT-guided percutaneous iliosacral screw fixation can be safely performed during pregnancy with meticulous planning, dose-reduction strategies, and multidisciplinary collaboration, maintaining fetal radiation exposure below accepted safety thresholds. Full article
(This article belongs to the Special Issue Exploring Interventional Radiology: New Advances and Prospects)
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12 pages, 1064 KB  
Article
Sleep-Related Breathing Disorders and Pregnancy: Where We Stand and Where to Go
by Jorge Montês, Mónica Grafino, Miguel Ângelo-Dias, Jorge Lima and Sofia Tello Furtado
Medicina 2026, 62(5), 835; https://doi.org/10.3390/medicina62050835 - 28 Apr 2026
Viewed by 156
Abstract
Background and Objectives: Pregnancy causes various physiological and hormonal changes that disrupt sleep architecture and modify respiratory patterns, increasing the risk of sleep-related breathing disorders (SBDs) such as obstructive sleep apnea (OSA) and potentially exacerbating pre-existing conditions. These disorders have been linked [...] Read more.
Background and Objectives: Pregnancy causes various physiological and hormonal changes that disrupt sleep architecture and modify respiratory patterns, increasing the risk of sleep-related breathing disorders (SBDs) such as obstructive sleep apnea (OSA) and potentially exacerbating pre-existing conditions. These disorders have been linked to adverse maternal and fetal outcomes. However, current screening tools remain inadequate, and data, including from Portugal, remain limited. This study aimed to assess the prevalence of SBD symptoms suggestive of sleep-disordered breathing during pregnancy, characterize the population, and explore associations with demographic and anthropometric parameters. Materials and Methods: A prospective observational study was conducted from July to December 2024 at Hospital da Luz Lisboa, involving pregnant women ≥ 18 years attending routine consultations. Participants completed a structured questionnaire that assessed demographic and anthropometric data, comorbidities, ten SBD symptoms, and the Epworth Sleepiness Scale (ESS). Results: The cohort included 289 participants, with a mean age of 34.4 years and pre-pregnancy body mass index (BMI) of 23.6 kg/m2. On average, women reported 3.1 SBD symptoms, with fatigue (65.4%), memory/concentration impairment (52.2%), and non-restorative sleep (50.5%) being the most common. Excessive daytime sleepiness (ESS >10) was present in 22.8% of the population. Snoring was significantly associated with older age and higher BMI (p = 0.0009 and p < 0.0001, respectively). Both the number of symptoms and ESS scores tended to increase with gestational age, particularly in the third trimester. Women with diabetes had higher odds of reporting snoring, nocturnal dyspnea, and witnessed apneas, with odds ratios of 4.65, 8.77, and 11.38, respectively. Conclusions: SBD symptoms and daytime sleepiness are highly prevalent in pregnancy and typically increase with advancing gestation. These findings emphasize the need for improved clinical strategies to enable early identification and management of SBD in pregnant women, thereby reducing maternal-fetal complications. Full article
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14 pages, 591 KB  
Article
Hearing Assessment in HIV-Exposed-Uninfected Infants
by Amanda Zanatta Berticcelli, Andréa Lúcia Corso, Pâmela Panassol, Leticia Petersen Schmidt Rosito, Roberta Rahal de Albuquerque, Letícia de Paula e Souza, Milena Lessa da Silva, Sady Selaimen da Costa and Luciana Friedrich
Trop. Med. Infect. Dis. 2026, 11(5), 115; https://doi.org/10.3390/tropicalmed11050115 - 27 Apr 2026
Viewed by 165
Abstract
Background: Among the complications caused directly or indirectly by the Human Immunodeficiency Virus (HIV) are alterations in the auditory system. Children who are HIV-exposed but uninfected (HEU) appear to have a higher risk of hearing loss (HL) compared to their unexposed peers, but [...] Read more.
Background: Among the complications caused directly or indirectly by the Human Immunodeficiency Virus (HIV) are alterations in the auditory system. Children who are HIV-exposed but uninfected (HEU) appear to have a higher risk of hearing loss (HL) compared to their unexposed peers, but a lower risk than those infected with HIV. However, the literature remains inconclusive regarding this association. This study aims to evaluate the hearing function of HEU infants during the first months of life and to correlate these findings with maternal, gestational, and neonatal variables. Methods: This prospective cohort study included all HIV-exposed infants born in a quaternary hospital in southern Brazil between 2021 and 2023. Maternal, gestational, and neonatal data were collected, as well as the results of neonatal auditory screening. At approximately 6 months of age, otolaryngological and audiological assessments were performed, including wideband tympanometry and electrophysiological evaluation using Auditory Brainstem Response with frequency-specific stimuli. The prevalence of hearing loss refers to the number of infants affected. Results: Thirty-eight infants, with a mean age of 8 months (±3.3), completed the study. Of these, 1 (2.6%) presented with bilateral sensorineural HL, and 13 (34.2%) presented with conductive HL, with 6 cases being unilateral and 7 bilateral. No associations were found between hearing loss and maternal, gestational, or neonatal variables, except for maternal CD4 count, where higher CD4 cell counts were associated with an increased risk of conductive HL. Conclusion: The findings provide relevant data on auditory alterations in HEU infants, demonstrating a high prevalence of conductive HL. These results highlight the importance of monitoring the hearing of these children during the first years of life. Full article
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17 pages, 1553 KB  
Article
Regulation of Human Renal Transporters by Pregnancy-Related Hormones in Primary Proximal Tubular Epithelial Cells
by Yik Pui Tsang, Kai Wang, Edward J. Kelly, Qingcheng Mao and Jashvant D. Unadkat
Metabolites 2026, 16(5), 292; https://doi.org/10.3390/metabo16050292 - 24 Apr 2026
Viewed by 260
Abstract
Background/Objectives: Pregnancy is associated with increased renal secretory clearance of drugs mediated by organic anion transporters (OATs) and organic cation transporter 2 (OCT2). Circulating concentrations of pregnancy-related hormones (PRHs) increase with gestational age, providing a plausible mechanism for renal OAT and OCT2 [...] Read more.
Background/Objectives: Pregnancy is associated with increased renal secretory clearance of drugs mediated by organic anion transporters (OATs) and organic cation transporter 2 (OCT2). Circulating concentrations of pregnancy-related hormones (PRHs) increase with gestational age, providing a plausible mechanism for renal OAT and OCT2 regulation. Methods: Using primary human proximal tubular epithelial cells (PTECs), we quantified the effects of PRHs, at trimester-specific concentrations, on the mRNA expression of renal drug transporters (apical and basal) and metabolizing enzymes (DMETs), as well as endocytic receptors. PTECs from three female, premenopausal donors were cultured in an optimized Transwell system that maintains measurable OAT activity. PTECs were then exposed for 72 h to trimester-matched PRH cocktails at physiologic (1×) or supraphysiologic (10×) concentrations, with medium replaced every 24 h. DMET and endocytic receptor mRNA were quantified by RT-qPCR, and uptake activities of OAT1/2/3, OCT2, OAT4, and OCTN1 were measured with selective substrates or substrate–inhibitor pairs. Results: At 1× PRHs, renal DMET and endocytic receptor mRNA expression was unchanged across trimester-related PRH concentration except for consistent downregulation of PEPT2. Uptake activity for all measured transporters was unchanged. At 10× PRHs, selective changes in mRNA expression of transporters were observed (e.g., induction of OAT1), but these changes did not translate into changes in activity. Conclusions: Our data argue against PRHs as the main driver of the increase in OAT-mediated drug secretion during pregnancy. Alternative mechanisms (e.g., flow-dependent mechanotransduction and untested hormones [e.g., prolactin, hCG]) should be evaluated to explain gestation-dependent changes in renal secretory clearance of drugs. Full article
(This article belongs to the Special Issue Recent Advances in Drug Metabolism and Transport)
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10 pages, 298 KB  
Article
Machine-Learning Models Outperform Clinicians in Predicting Postnatal Growth Failure Among Very Low Birth Weight Infants
by Joohee Lim, Sook Hyun Park, Teahyen Cha, So Jin Yoon, Jung Ho Han, Jeong Eun Shin, In Gyu Song, Soon Min Lee, Ho Seon Eun and Min Soo Park
Diagnostics 2026, 16(9), 1282; https://doi.org/10.3390/diagnostics16091282 - 24 Apr 2026
Viewed by 195
Abstract
Background/Objectives: Early detection of postnatal growth failure (PGF) is essential for optimizing nutritional management in preterm infants, as PGF is associated with adverse neurodevelopmental outcomes. Early prediction remains difficult because postnatal growth is influenced by multiple clinical factors including gestation age, birth [...] Read more.
Background/Objectives: Early detection of postnatal growth failure (PGF) is essential for optimizing nutritional management in preterm infants, as PGF is associated with adverse neurodevelopmental outcomes. Early prediction remains difficult because postnatal growth is influenced by multiple clinical factors including gestation age, birth weight, nutritional status, and comorbidities. Machine-learning approaches have been proposed to predict complex neonatal outcomes. This study compared the predictive performance of neonatologists with that of a machine-learning model for predicting PGF. Methods: PGF was defined as a decrease in weight z-score greater than 1.28 at discharge compared with birth. A machine-learning model based on extreme gradient boosting (XGBoost) was trained using a dataset of 7954 very low birth weight (VLBW) infants. Nine neonatologists independently assessed 100 clinical cases through a questionnaire-based evaluation, including 50 patients with PGF. Predictive performance was evaluated using seven metrics: area under the receiver operating characteristic curve (AUROC), accuracy, error rate, positive predictive value (PPV), sensitivity, specificity, and F1 score. Results: The neonatologists had a median of 5 years (range: 4–10 years) of clinical experience. The median prediction score among the neonatologists was 52/100 (range, 44–60), whereas the XGBoost model achieved 79/100. The XGBoost model achieved an AUROC of 0.79, accuracy of 0.79, error rate of 0.21, sensitivity of 0.82, and an F1 score of 0.80, demonstrating superior overall performance compared to the neonatologists. In addition, the XGBoost model had a lower error rate than the neonatologists (0.21 vs. 0.49), whereas specificity (0.76 vs. 0.86) and PPV (0.77 vs. 0.53) did not differ significantly. Conclusions: The machine-learning model demonstrated superior or comparable predictive performance to that of neonatologists in detecting PGF. Machine-learning-based prediction models may support early risk stratification and targeted nutritional management in VLBW infants. Full article
(This article belongs to the Special Issue Artificial Intelligence in Clinical Decision Support—2nd Edition)
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14 pages, 719 KB  
Article
The Relationship Between Maternal Serum Afamin Levels and Intrahepatic Cholestasis of Pregnancy and Neonatal Outcomes
by Kubilay Çanga, Bengisu Elüstü, İbrahim Buğra Bahadır, Ümran Özcan, Seyit Ahmet Erol and Şevki Çelen
J. Clin. Med. 2026, 15(9), 3241; https://doi.org/10.3390/jcm15093241 - 24 Apr 2026
Viewed by 192
Abstract
Objective: This study aimed to evaluate maternal serum afamin levels in women with intrahepatic cholestasis of pregnancy (ICP), examine their relationship with fasting bile acid concentrations, and assess their association with perinatal outcomes. Methods: This prospective case-–control study included 80 singleton [...] Read more.
Objective: This study aimed to evaluate maternal serum afamin levels in women with intrahepatic cholestasis of pregnancy (ICP), examine their relationship with fasting bile acid concentrations, and assess their association with perinatal outcomes. Methods: This prospective case-–control study included 80 singleton pregnancies followed at a tertiary perinatology center between October 2025 and March 2026. Forty women with ICP, defined by pruritus and fasting bile acids > 10 μmol/L, were compared with 40 healthy pregnant controls. Women with ICP were further stratified according to fasting bile acid levels as <40 and ≥40 μmol/L. Maternal serum afamin concentrations were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Maternal characteristics, liver biochemistry, fetal biometric and Doppler parameters as well as obstetric and neonatal outcomes were compared. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of afamin for ICP, and logistic regression analysis was used to assess its association with ICP. Results: Baseline maternal characteristics were comparable between groups. Maternal serum afamin levels were significantly higher in the ICP group than in controls (6.18 ± 4.24 vs. 3.98 ± 1.95 ng/mL, p = 0.004). Afamin correlated positively with fasting bile acids (r = 0.372, p = 0.018), but not with transaminases, gestational age at delivery, birth weight, or neonatal outcomes. In logistic regression, afamin was independently associated with ICP (adjusted odds ratio [aOR] 1.260; 95% confidence interval [CI] 1.059–1.500; p = 0.009). ROC analysis showed poor discrimination for ICP (area under the curve [AUC] 0.634, 95% CI 0.51–0.76, p = 0.039), whereas afamin did not discriminate between subgroups defined by fasting bile acid levels (<40 vs. ≥40 μmol/L). The optimal cut-off value of 4.93 ng/mL predicted ICP with 55% sensitivity, 67.5% specificity, a positive likelihood ratio of 1.69, and a negative likelihood ratio of 0.67. Conclusions: Maternal serum afamin levels are elevated in ICP and show a modest association with fasting bile acid burden. Its discriminatory performance is limited, and it does not reliably distinguish patients defined by a ≥40 μmol/L threshold. These findings suggest that afamin reflects the maternal response to cholestasis rather than disease severity and may serve as a complementary biomarker. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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