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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
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
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 (registering DOI) - 28 Apr 2026
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
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 182
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 140
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 133
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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16 pages, 1067 KB  
Systematic Review
The Role of Maternal Homocysteine Concentration in Pregnancy Complications: A Systematic Review and Meta-Analysis
by Ahmed Abu-Zaid, Saeed Baradwan, Majed Saeed Alshahrani, Khalid Khadawardi, Neveen Awadh, Hedaya Albelwi, Heba M. Adly, Saleh A. K. Saleh, Mohammed Abuzaid, Maha Tulbah and Osama Alomar
J. Clin. Med. 2026, 15(9), 3216; https://doi.org/10.3390/jcm15093216 - 23 Apr 2026
Viewed by 184
Abstract
Background: Adverse pregnancy outcomes such as preeclampsia (PE), preterm birth, low birth weight (LBW), small for gestational age (SGA), and stillbirth are major contributors to maternal and neonatal morbidity and mortality. Elevated maternal homocysteine (Hcy) levels, influenced by genetic, dietary, and lifestyle factors, [...] Read more.
Background: Adverse pregnancy outcomes such as preeclampsia (PE), preterm birth, low birth weight (LBW), small for gestational age (SGA), and stillbirth are major contributors to maternal and neonatal morbidity and mortality. Elevated maternal homocysteine (Hcy) levels, influenced by genetic, dietary, and lifestyle factors, have been increasingly associated with placental dysfunction and adverse pregnancy outcomes. This review aims to evaluate the link between hyperhomocysteinemia and pregnancy complications to inform clinical practice. Methods: A comprehensive search of PubMed, Scopus, Web of Science, and Cochrane Central Library was conducted up to December 2024. Observational studies assessing maternal Hcy levels in relation to pregnancy complications were included. Heterogeneity was measured using the I2 statistic, and a random-effects model using the DerSimonian–Laird method was applied to account for study variability. Effect sizes were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results: Thirteen studies were included in this meta-analysis. Elevated maternal Hcy was significantly associated with: PE (OR: 2.49; 95% CI: 1.41–4.40; I2 = 96.03%; n = 9), preterm birth (OR: 4.01; 95% CI: 1.84–8.72; I2 = 91.08%; n = 6), fetal loss (OR: 1.76; 95% CI: 1.22–2.52; I2 = 41.47%; n = 6), SGA (OR: 1.69; 95% CI: 1.35–2.11; I2 = 0.00%; n = 3), and LBW (OR: 2.46; 95% CI: 1.37–4.43; I2 = 77.71%; n = 3). Conclusions: This review highlights a significant association between elevated maternal Hcy levels and various pregnancy complications. However, given the substantial heterogeneity and reliance on observational evidence, these findings should be interpreted with caution. Future well-designed prospective cohort studies with standardized definitions of hyperhomocysteinemia, consistent timing of exposure assessment across pregnancy trimesters, and adjustment for key confounders are needed to better clarify these associations and underlying mechanisms. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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23 pages, 6924 KB  
Review
The KISS1/KISS1R Axis in Human Placentation: Molecular Mechanisms and Implications for Foetal Growth Restriction and Pre-Eclampsia
by Elitsa Gyokova, Eleonora Hristova-Atanasova and Kamelia Dimitrova
Int. J. Mol. Sci. 2026, 27(9), 3748; https://doi.org/10.3390/ijms27093748 - 23 Apr 2026
Viewed by 130
Abstract
Pre-eclampsia and foetal growth restriction (FGR) are major pregnancy complications primarily driven by placental dysfunction, and remain leading causes of maternal and perinatal morbidity. Ultrasound imaging, Doppler studies, and angiogenic biomarkers like placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) constitute [...] Read more.
Pre-eclampsia and foetal growth restriction (FGR) are major pregnancy complications primarily driven by placental dysfunction, and remain leading causes of maternal and perinatal morbidity. Ultrasound imaging, Doppler studies, and angiogenic biomarkers like placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) constitute the main diagnostic modalities; however, these predominantly reflect established disease rather than early molecular disturbances underlying placentation. The identification of biomarkers directly associated with trophoblast signalling pathways has the potential to improve early risk stratification and enable mechanistic classifications. Kisspeptin signalling via its receptor (KISS1R) regulates trophoblast invasion, extracellular matrix remodelling, ERK1/2 activation, and angiogenic balance, thereby modulating spiral artery transformation. Kisspeptin-10 (KP-10), the minimal bioactive fragment of KISS1, is highly expressed in placental syncytiotrophoblasts and exerts its effects through the G-protein-coupled receptor KISS1R. Core features of early-onset FGR and pre-eclampsia (PE)—including defective placentation, maternal vascular malperfusion, and angiogenic imbalance—have been linked to dysregulation of this pathway. During normal gestation, maternal circulating kisspeptin concentrations rise exponentially. In contrast, pregnancies subsequently complicated by FGR or PE, particularly in the early gestation, are associated with reduced levels. However, the comparability of existing studies and their translational applicability are limited by a substantial methodological heterogeneity, including assay variability, gestational age dependence, and inadequate adjustment for maternal confounders. These limitations hinder robust conclusions regarding the role of kisspeptin in placental pathology. This review critically integrates molecular, pathophysiological, and clinical evidence relating to the role of KP-10 in placental dysfunction. The key question is whether KP-10 represents a mechanistic biomarker of trophoblast signalling dysfunction or merely a secondary marker of reduced placental mass; resolving this distinction is essential. Full article
(This article belongs to the Special Issue Molecular Insights into Placental Pathology)
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19 pages, 1549 KB  
Review
GLP-1 Receptor Agonists, Fertility Restoration, and Reproductive Safety in Women of Reproductive Age: A Narrative Review
by Malak Moones Abedi, Mohamedanas Mohamedfaruk Patni, Arshiya Nasreen Bint Shajahan, Rajani Dube, Liyan Khadeeja, Ibrahim Alabid, Ahmad Kharoufeh, Subhranshu Sekhar Kar, Biji Thomas George, Shadha Nasser Bahutair and Thilakavathy Pandurangan
J. Clin. Med. 2026, 15(9), 3204; https://doi.org/10.3390/jcm15093204 - 22 Apr 2026
Viewed by 329
Abstract
Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for the management of obesity and type 2 diabetes, particularly among women of reproductive age. Emerging evidence suggests potential effects on ovulation, fertility, and pregnancy outcomes. This narrative review aims to synthesize current evidence [...] Read more.
Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for the management of obesity and type 2 diabetes, particularly among women of reproductive age. Emerging evidence suggests potential effects on ovulation, fertility, and pregnancy outcomes. This narrative review aims to synthesize current evidence on the reproductive safety of GLP-1RAs, with a focus on their implications for conception, unintended pregnancy, and maternal–fetal outcomes. Methods: A narrative literature review was conducted using PubMed and relevant bibliographic sources to identify studies published between 2020 and 2025. The search included clinical trials, observational studies, registry data, case reports, and selected preclinical evidence. Studies addressing reproductive outcomes, including ovulation, fertility, pregnancy exposure, and fetal safety, were included. Evidence was synthesized descriptively in accordance with recommended approaches for narrative reviews. Results: Available evidence indicates that GLP-1RAs may improve ovulatory function and menstrual regularity, particularly in women with obesity or polycystic ovary syndrome, potentially increasing the likelihood of conception. However, human data on pregnancy exposure remain limited. While current evidence does not consistently demonstrate a strong teratogenic signal, findings are based on small samples and heterogeneous study designs. Concerns persist regarding unintended pregnancies due to improved fertility and the absence of robust safety data during early gestation. Conclusions: GLP-1RAs present a complex clinical scenario in women of reproductive age, with potential benefits for metabolic and reproductive health but uncertain safety during pregnancy. Clinicians should exercise caution, provide appropriate contraceptive counseling, and carefully weigh the risks and benefits when prescribing these agents. Further large-scale, prospective studies are needed to clarify reproductive safety and inform evidence-based clinical guidelines. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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13 pages, 358 KB  
Article
Effects of a Prolonged Exclusive Human Milk-Based Diet on Structural and Functional Brain Maturation in Very Preterm Infants: An Ancillary Analysis of the NEOVASC Trial
by Wolfgang Mitterer, Christoph Hochmayr, Maria Waltner-Romen, Maria Sappler, Marlene Hammerl, Lena Gatterer, Vera Neubauer and Ursula Kiechl-Kohlendorfer
Nutrients 2026, 18(9), 1321; https://doi.org/10.3390/nu18091321 - 22 Apr 2026
Viewed by 137
Abstract
Background/Objectives: Early postnatal nutrition is a modifiable determinant of brain maturation in preterm infants. Exclusive human milk-based diets (EHMD) are associated with improved neurodevelopmental outcomes. The objective of this exploratory ancillary analysis of the NEOVASC randomized controlled trial was to determine whether prolonging [...] Read more.
Background/Objectives: Early postnatal nutrition is a modifiable determinant of brain maturation in preterm infants. Exclusive human milk-based diets (EHMD) are associated with improved neurodevelopmental outcomes. The objective of this exploratory ancillary analysis of the NEOVASC randomized controlled trial was to determine whether prolonging an exclusive human milk-based diet, specifically through continued human milk-based fortification until 36 weeks postmenstrual age, is associated with differences in early brain structure and functional motor development compared with earlier introduction of bovine milk-based fortifier or formula at 32 weeks postmenstrual age. Methods: This ancillary study of the NEOVASC trial included preterm infants (<32 gestational weeks and birthweight of 500–1250 g) randomized to either prolonged EHMD until 36 weeks PMA or a diet introducing bovine milk-based fortifier or formula from 32 weeks. Quantitative brain metrics, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were analyzed at 40 weeks PMA. Functional maturation was assessed repetitively using the General Movement Optimality Score (GMOS) (34, 36, and 40 weeks PMA) and Motor Optimality Score (52 weeks PMA). Results: Fifty-four infants were included. Groups did not differ in brain growth metrics. After adjustment for imbalances in clinical characteristics, no FA or ADC differences remained statistically significant. GMOS at 40 weeks PMA was higher in the intervention group, with no differences at other time points. Conclusions: In this exploratory ancillary analysis of the NEOVASC trial, prolonging an exclusive EHMD until 36 weeks postmenstrual age was not associated with consistent differences in early brain maturation or motor performance. Given the high overall exposure to human milk in both groups, subtle effects may have been attenuated. These findings require confirmation in larger, adequately powered studies with long-term follow-up. Full article
(This article belongs to the Special Issue Early Nutrition and Neurodevelopment)
14 pages, 280 KB  
Article
Morbidity, Mortality, and Short-Term Outcomes of Preterm Infants ≤ 25 Weeks of Gestation
by Melinda Matyas, Florica Ramona Dorobantu, Madalina Valeanu, Monica G. Hasmasanu, Nicoleta Grosu, Adelina Tutu, Anna D. Jakab and Gabriela Zaharie
J. Clin. Med. 2026, 15(9), 3198; https://doi.org/10.3390/jcm15093198 - 22 Apr 2026
Viewed by 260
Abstract
Background: Short-term morbidities and mortality decreased significantly in the past decade at preterm born < 25 weeks of gestation. Severe lifelong morbidities affect an important part of these patients. Objective: to investigate the in-hospital morbidity, mortality, and short-term complications of preterm neonates born [...] Read more.
Background: Short-term morbidities and mortality decreased significantly in the past decade at preterm born < 25 weeks of gestation. Severe lifelong morbidities affect an important part of these patients. Objective: to investigate the in-hospital morbidity, mortality, and short-term complications of preterm neonates born ≤25 weeks of gestation. Methods: A prospective longitudinal cohort study was conducted in children born 2021–2024, ≤25 weeks of gestation, admitted to a 3rd-level unit, and care till discharge. Pregnancy complications’ effect on neonatal evolution was analyzed, six main in-hospital morbidities specific for preterm birth and other aggravating circumstances, with a possible effect on the evolution were analyzed, as follows: inflammatory syndrome, early pulmonary or digestive hemorrhages, and early inotropic support. The neurological development in the first year of life was analyzed through theparticipation of premature infants in the follow-up program after discharge. Results: Forty-nine premature infants were enrolled, with a mean gestational age of 24.37 ± 0.76 weeks and an average weight of 665 ± 143 g. Most newborns required intubation at birth (42/49), and 33/49 received 2-dose surfactant therapy postnatally. NEC was present in 26.5% of the group, being more common in patients with inflammatory syndrome—increase in procalcitonin (PCT), and those who received a higher number of blood transfusions. The BPD and ROP, as well as the severity of the latter, correlated with the oxygen requirement on the 28th day of life. BPD was more common in infants associated with PDA requiring combination treatment. ROP increased with the number of transfusions required by patients. At the follow-up at the first timepoint evaluation, were 51% of the study group, and 30.6% of them had normal neurological development. At 12 months of age, however, the neurological examination was normal in only three patients (23.08%) but only 36.5% of the study group attended the follow-up. Neurodevelopmental disorders were present in 10 of the patients, one with spastic diplegia. Conclusions: In the hospital, the morbidity and survival rate of the group was like other studies. The small number of follow-up participants does not allow the generalization of the data, but as far as neurological development is concerned, it is like that of other studies. Full article
(This article belongs to the Special Issue Risk Factors in Neonatal Intensive Care)
14 pages, 252 KB  
Article
Hypoxic Ischemic Encephalopathy: Hearing Impairment and Related Risk Factors
by Francesca Serrao, Simonetta Frezza, Guido Conti, Simona Fattore, Mirta Corsello, Alessadra Lio, Chiara Di Sipio Morgia, Chiara Concilio, Angelo Tizio, Tommaso Verdolotti, Simona Gaudino, Simonetta Costa and Giovanni Vento
J. Clin. Med. 2026, 15(9), 3180; https://doi.org/10.3390/jcm15093180 - 22 Apr 2026
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Abstract
Objectives: The purpose of this study was to compare the incidence of hearing loss at three months of age in a cohort of newborns with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) with that reported in the literature. We also evaluated potential [...] Read more.
Objectives: The purpose of this study was to compare the incidence of hearing loss at three months of age in a cohort of newborns with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) with that reported in the literature. We also evaluated potential risk factors associated with audiological impairment and changes in hearing threshold during follow-up. Methods: This retrospective observational cohort study was conducted at the Neonatal Intensive Care Unit of the Fondazione Policlinico Universitario A. Gemelli, IRCCS in Rome, Italy, between January 2017 and December 2023. Infants underwent audiological screening and a full diagnostic evaluation at three months of age and were followed during the first year of life. Results: A total of 149 infants were enrolled, and hearing loss was identified in six (4.0%) at three months of age. Two of these six infants showed an improvement in their hearing threshold, resulting in a prevalence of permanent bilateral sensorineural hearing loss (SNHL) of four out of 149 infants (2.7%), with no cases of late-onset hearing loss detected. Gestational age was identified as an independent protective factor against SNHL (OR 0.49; 95% CI 0.22–0.91). Conclusions: The audiological screening program demonstrates effectiveness in early intervention for diagnosing and treating hearing loss. Infants with HIE are at high risk for hearing disorders and require increased attention in neonatological and audiological management. Management should be individualized based on specific risk factors. The association between gestational age and susceptibility to cochlear damage should be confirmed by further studies. Full article
(This article belongs to the Section Clinical Pediatrics)
12 pages, 1134 KB  
Article
Ultrasound Characteristics of an Isolated Redundant Foramen Ovale Flap in Fetuses and Its Differential Diagnosis from Aortic Coarctation
by Liya Li, Yuxin Li, Shijie Zhang, Shaozheng He, Qiuyue Chen and Guorong Lyu
J. Clin. Med. 2026, 15(8), 3166; https://doi.org/10.3390/jcm15083166 - 21 Apr 2026
Viewed by 197
Abstract
Objective: To evaluate the potential utility of the ratio of the maximal diameter of the bulging foramen ovale flap to the left atrial diameter (FOFD/LAD) for distinguishing false-positive prenatal suspicion of fetal coarctation of the aorta (CoA), and to examine its association with [...] Read more.
Objective: To evaluate the potential utility of the ratio of the maximal diameter of the bulging foramen ovale flap to the left atrial diameter (FOFD/LAD) for distinguishing false-positive prenatal suspicion of fetal coarctation of the aorta (CoA), and to examine its association with fetal cardiac structural parameters. Materials and Methods: This retrospective study included a selected referral cohort of 44 fetuses with prenatal suspicion of CoA, who were classified postnatally into the false-positive prenatal suspicion group (n = 29) or the true CoA group (n = 15), along with 50 gestational age-matched controls. FOFD, LAD, atrial and ventricular diameters, great-vessel diameters, and aortic isthmus Z-scores were measured. Associations were assessed using Spearman rank correlation, and intergroup differences were evaluated using the Kruskal–Wallis test with Bonferroni-adjusted Mann–Whitney U tests. Results: FOFD/LAD was significantly higher in the false-positive prenatal suspicion group than in the true CoA and control groups (all p < 0.001), whereas no difference was observed between the true CoA and control groups (p = 0.059). In the false-positive and control groups, FOFD/LAD was positively associated with RAD/LAD, RVD/LVD, and PAD/AoD (all p < 0.001). Both suspected CoA groups showed higher right-to-left cardiac structural ratios and aortic isthmus Z-scores than controls (all p < 0.001), but these indices did not differ between false-positive prenatal suspicion and true CoA cases. Conclusions: In a selected cohort of fetuses with prenatal suspicion of CoA, an increased FOFD/LAD may reflect the presence of a redundant foramen ovale flap and may serve as a promising adjunctive parameter for distinguishing RFOF-related CoA mimicry from true CoA. However, given the limited sample size and moderate reproducibility, these findings should be considered exploratory and require validation in larger independent cohorts. Full article
(This article belongs to the Special Issue Clinical Update on Prenatal Diagnosis and Maternal Fetal Medicine)
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17 pages, 4538 KB  
Article
Improving LISA Practice: An Ongoing Observational Quality Improvement Initiative Following Initiation of Less-Invasive Surfactant Administration in a Level IV NICU
by Tynisha Koenigsaecker, Shreya Patel, Stephanie C. Martinez, Kevin Ives, Julie Bodie, Chad Weagraff, Monika Bhola and Rita M. Ryan
Children 2026, 13(4), 571; https://doi.org/10.3390/children13040571 - 20 Apr 2026
Viewed by 259
Abstract
Background/Objectives: Surfactant has been delivered via less-invasive surfactant administration (LISA) in our neonatal intensive care unit (NICU) since 2020. Data have been monitored and the literature regularly reviewed to improve our LISA practice. The purpose of this project is to share the [...] Read more.
Background/Objectives: Surfactant has been delivered via less-invasive surfactant administration (LISA) in our neonatal intensive care unit (NICU) since 2020. Data have been monitored and the literature regularly reviewed to improve our LISA practice. The purpose of this project is to share the clinical practice changes made to help other NICU providers fine-tune their LISA practice. Methods: The original LISA criteria included babies with GA 27–36 6/7 w, on > 21% O2, on continuous positive airway pressure (CPAP), pCO2 < 70 if a blood gas was obtained, and radiographic and/or clinical evidence of respiratory distress syndrome (RDS). Current criteria include GA 25–35 6/7 w and minimum CPAP + 6. This manuscript highlights the changes made since 2023. To monitor these changes, targeted data from the entire cohort were examined before and after each change. Results: LISA was attempted on 399 babies (average (SD) GA 31.7 (2.7), birth weight 1752 (590), with a procedural success rate of 97%. Overall, 18% required intubation within 7 days after LISA. The median (IQR) for FiO2 was 32 (28, 40) prior to LISA and 23 (21, 30) post-LISA and the hour of age of LISA was 4 (2.5, 9.9). LISA procedure success rate was increased by the use of video laryngoscopy as well as reinforcement of the use of sucrose sedation and swaddling; our first attempt success increased overall from 39% to 52%. After the introduction of a clinical RDS score (Downes), there was an expected and logical increase in the number of infants requiring intubation within 7 days of LISA indicating likely over-treatment prior to this change. After implementation of a clearly described plan for babies <28 w gestation there was a decrease in the hour of age of LISA from 3 (2.5, 4.5) to 2 (0.8, 3) h. Conclusions: It is critical to continually evaluate a new practice and identify strategic changes. We offer our changes to assist others starting or using LISA. Full article
(This article belongs to the Special Issue Advances in Neonatal Cardiorespiratory Care)
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