Search Results (2,081)

Background: Myelomeningocele (MMC) is a severe neural tube defect resulting from primary neurulation failure. Despite advanced multidisciplinary paradigms, long-term morbidity remains substantial. Population-based longitudinal data from small European cohorts are scarce. This study evaluates long-term clinical and functional outcomes within a complete national cohort in Slovenia. Methods: A retrospective cohort study was conducted on all children born with MMC in Slovenia between 2007 and 2023. Patients were managed via a centralized, standardized multidisciplinary program. Phenotypic severity was stratified by anatomical lesion levels, and outcomes were assessed using standardized functional measures. Results: Over an 18-year period, 32 children were treated (prevalence: ~1 per 10,000 live births; mean follow-up: 13.2 years). All underwent anatomical closure within 24 h of birth. Hydrocephalus developed in 71.8% (n = 23), with 65.6% requiring ventriculoperitoneal shunting. Independent ambulation was achieved by 28.1%, while 46.8% were wheelchair-dependent and paraplegic. Neurogenic bladder dysfunction occurred in 87.5%. Subgroup analysis demonstrated that thoracolumbar lesions were significantly associated with lower ambulation rates and higher shunt dependency compared to lumbosacral lesions (p < 0.05). Long-term survival was 96.9%. Conclusions: This study represents the first comprehensive national analysis of myelomeningocele outcomes in Slovenia. Despite the relatively small number of patients, complete national coverage and centralized multidisciplinary management provide a unique overview of long-term outcomes. The findings demonstrate that outcomes achieved within the Slovenian healthcare system are comparable to those reported internationally, thereby establishing an important national benchmark for future evaluation of preventive measures and evolving treatment strategies. Full article

Background/Objectives: Short interdelivery interval (IDI) is associated with adverse perinatal outcomes, but its relationship with objective neonatal acid–base markers, postpartum anemia, and early postnatal depression remains poorly characterized. We examined IDI < 24 months across four pre-specified outcome domains: neonatal acid–base status, maternal composite morbidity, postpartum anemia, and early postnatal depression. Methods: This single-center retrospective cohort study included 851 women with two consecutive singleton live births at Ankara Etlik City Hospital between 2023 and 2025. Women were classified by IDI as short (<24 months; n = 635) or standard (≥24 months; n = 216). Multivariable logistic regression provided the primary inference. Sensitivity analyses included inverse probability of treatment weighting (IPTW), restricted cubic splines (4 df), within-mother paired analysis, multiple imputation by chained equations (MICE × 20), Firth penalization, E-values, and Benjamini–Hochberg false discovery rate (FDR) correction across 13 outcomes. Results: After FDR correction, short IDI was associated with postpartum anemia (adjusted odds ratio [aOR] 1.84, 95% confidence interval (CI) 1.26–2.68; q = 0.022) and with an Edinburgh Postnatal Depression Scale score ≥13 (aOR 1.93, 95% CI 1.20–3.10; q = 0.042); umbilical-artery pH < 7.10 did not cross the FDR threshold (aOR 2.37, 1.17–4.82; q = 0.075) and is reported as an exploratory, hypothesis-generating signal. Postpartum anemia did not mediate the IDI–depression association (proportion mediated 0.6%, 95% CI −13.1% to +13.5%). Conclusions: Short IDI was associated with maternal hematologic and psychosocial signals; the IDI–depression link appears non-hematologic. Neonatal acid–base findings did not meet the FDR threshold and are exploratory. Multicenter validation is warranted. Full article

Introduction: Labor pain is among the most intense forms of acute pain, mediated in part by excitatory glutamatergic neurotransmission within central nociceptive pathways. Glutamate plays a key role in spinal dorsal horn signaling and central sensitization, yet its peripheral dynamics during labor and in response to different analgesic modalities remain unclear. This exploratory study aimed to evaluate whether maternal salivary glutamate levels differ between epidural labor analgesia and systemic morphine analgesia during normal vaginal delivery. Method: In this observational comparative study, 36 women were selected to either epidural analgesia (n = 16) or systemic morphine analgesia (n = 20). Salivary samples were collected during active labor and analyzed for glutamate concentration using a validated enzymatic colorimetric assay. Clinical and demographic data were recorded. Non-parametric tests were applied due to non-normal distribution of glutamate levels. Results: Baseline maternal and perinatal characteristics were comparable between groups. Median salivary glutamate levels were higher in the epidural group than in the morphine group (5.32 nmol/µL [IQR 2.83–8.00] vs. 3.99 nmol/µL [IQR 2.26–8.03]), but the difference was not statistically significant (p = 0.599). Glutamate concentrations showed marked inter-individual variability (0.14–29.89 nmol/µL) and a right-skewed distribution. No significant associations were observed between glutamate levels and maternal age, Body Mass Index, gestational age, birth weight, or obstetric comorbidities. Conclusion: In this exploratory cohort, maternal salivary glutamate concentrations did not differ significantly between epidural labor analgesia and systemic morphine analgesia during labor. The variability observed suggests complex and heterogeneous regulation of peripheral glutamatergic activity in parturition. Further larger-scale studies integrating central and peripheral measurements are warranted. Full article

Background: Bilastine is a long-acting, nonsedating antihistamine used to treat allergic conditions. Human pregnancy experience with bilastine remains limited. Objectives: The primary aim was to evaluate the risk of major anomalies following first-trimester bilastine exposure. Secondary endpoints included additional pregnancy outcomes. Methods: This observational, prospective cohort study included women counseled by the Israeli Teratology Information Service regarding first-trimester bilastine exposure between July 2019 and June 2023. Participants were contacted by telephone for follow-up using a structured questionnaire. Pregnancy outcomes were compared with fexofenadine-exposed pregnancies. The data analysis, comparison, and presentation followed the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guide. Results: Follow-up was obtained for 36 pregnancies with at least first-trimester bilastine exposure. The median daily bilastine dose was 20 mg, with treatment discontinued at a median gestational age of 5 + 6 weeks. First-trimester bilastine exposure was not associated with an increased risk of major anomalies [bilastine: 2/33, 6.1% vs. fexofenadine: 2/27, 7.4%; crude OR 0.81, 95% CI 0.11–6.14]. No pattern of malformations was observed. Rates of live-birth, miscarriage, and pregnancy termination were 91.7%, 5.6%, and 2.8% in the bilastine group, and 72.2%, 19.4%, and 8.3% in the fexofenadine group, respectively. Conclusions: This cohort study, although small, provides preliminary reassurance for counseling regarding inadvertent early pregnancy exposure to bilastine. Larger studies are needed to validate these findings. Full article

Despite the success of antiretroviral therapy, people living with HIV remain at heightened risk of multimorbidity spanning cardiovascular, renal, hepatic, oncologic and neuropsychiatric domains. We investigate whether routinely collected electronic health record data (30 laboratory variables plus seven demographic/social descriptors) can support early, multi-label classification of recorded comorbidities in a real-world cohort of 2200 HIV-positive patients receiving continuous care at a major London hospital. We benchmark classical machine and deep learning models under two settings: a demographic-aware configuration that includes sensitive attributes (age, gender, race and continent of birth) and a demographic-unaware configuration that excludes them. XGBoost yields the best macro-$F_1$ performance, and demographic-aware variants consistently outperform their unaware counterparts. Permutation feature importance revealed physiologically coherent drivers (e.g., creatinine/eGFR for renal and cardiometabolic labels, hemoglobin for hematologic labels, albumin for respiratory labels) and suggested that the relative contribution of demographic variables varied across comorbidity categories. These findings indicate that (i) routinely collected EHR data contain informative patterns associated with the multi-label comorbidity profiles of people living with HIV and (ii) carefully governed use of demographic context can improve accuracy while motivating transparent consideration of fairness and bias. Full article

Background: COVID-19 during pregnancy has been associated with various obstetric complications; however, epidemiological evidence regarding its relationship with hypertensive disorders of pregnancy (HDP) and preterm birth remains inconclusive. Therefore, we aimed to evaluate the association between COVID-19 during pregnancy and the risk of HDP and preterm birth among Mexican pregnant women. Methods: We conducted a retrospective cohort study based on a review of 3710 medical records of women treated at a tertiary hospital between 2020 and 2023. COVID-19 was diagnosed by real-time reverse transcription polymerase chain reaction (RT-PCR) assay. We estimated adjusted risk ratios (aRRs) using robust Poisson regression models, controlling for potential confounders. Results: The COVID-19 rate was 2.5%. We observed that women with COVID-19 had a higher risk of HDP (aRR = 1.59; 95% CI = 1.07–2.36). When HDP subgroups were analyzed separately, COVID-19 was associated with an increased risk of preeclampsia (aRR = 2.04; 95% CI = 1.34–4.20) and preterm birth (aRR = 1.50; 95% CI = 1.02–2.19). The association with gestational hypertension lost statistical significance after adjustment. Conclusions: Our findings suggest that COVID-19 during pregnancy may be associated with hypertensive disorders of pregnancy and preterm birth. However, the observed association with preeclampsia should be interpreted cautiously because diagnostic overlap between severe COVID-19 and preeclampsia cannot be excluded. Full article

Background: Maternal postpartum hospital readmissions represent profound implications for maternal health outcomes and potential gaps in quality of maternal care. Objective: This study aims to synthesise evidence on risk factors for maternal postpartum hospital readmissions within 42 days of discharge following birth hospitalisation. Methods: An electronic database search utilised CINAHL, EMBASE (Ovid), and MEDLINE for relevant studies published from 1 January 2010 to 30 June 2024. The studies that investigated the prevalence and risk factors for 42-day postpartum maternal readmission and reported risk estimates, published in English, were included. The risk of bias was assessed using the Newcastle–Ottawa Scale (NOS) for case-control studies and cohort studies. The PRISMA guidelines were followed in reporting this review. The review protocol was registered on PROSPERO (CRD42023442269). Results: A total of 7758 articles were retrieved, ultimately including 60 studies. The rate of maternal postpartum readmissions varied from 0.1236‰ to 26%. Significant risk factors were extracted and categorised into five groups: maternal demographic and socio-economic factors; behavioural and lifestyle factors; health institution structural factors; obstetric and delivery characteristics; as well as maternal morbidity The most frequently cited risk factors which contributed to maternal postpartum hospital readmissions were age, race/ethnicity, substance use, caesarean delivery, length of maternal hospital stay, premature birth, and all maternal morbidities, especially mental health disorders, severe maternal morbidity, and hypertensive disorders of pregnancy. Conclusions: This systematic review identified complex and diverse risk factors associated with maternal postpartum hospital readmissions within 42 days after discharge following birth hospitalisation. This helps our understanding of the risk factors and the strength of association with maternal postpartum hospital readmissions. Future research should develop a multidimensional risk assessment framework to guide clinical practice in adopting holistic individualised approaches for postpartum risk evaluation, thereby reducing readmission rates and improving maternal health outcomes. Full article

Background/Objectives: Preterm infants have higher fat mass and lower lean mass at term-corrected age; however, whether these differences persist into preschool age remains unclear. This prospective observational cohort study aimed to compare body composition between very-low-birth-weight (VLBW) preterm (gestational age < 33 weeks) children and their term-born counterparts aged 5–6 years. Methods: Anthropometric data, body composition, blood biochemical parameters, and insulin resistance (HOMA-IR index) were compared between the preterm and term groups. Results: The study included 96 children (57 preterm and 39 term-born). Although lean mass index and fat mass index were comparable between groups, preterm children exhibited significantly higher insulin levels and HOMA-IR values after adjustment (p = 0.003 and p = 0.004, respectively). Within the preterm cohort, overweight/obesity was associated with higher trunk and total fat percentages, as well as higher HOMA-IR, compared with those of normal-weight or underweight children (all adjusted p < 0.001). Weight growth velocity from 2 to 5 years was positively associated with serum insulin, HOMA-IR, and both trunk and total body fat percentages. Additionally, girls in both groups displayed significantly higher trunk and total body fat percentages than boys. Conclusions: Children born very preterm with VLBW had higher fasting insulin levels and HOMA-IR, despite generally comparable DXA-derived LMI, FMI, and fat distribution at preschool age. Overweight status and rapid early childhood weight gain may contribute to increased metabolic risk in this population, highlighting the need for early metabolic monitoring and growth management. Future large-scale, long-term studies are required to confirm these findings. Full article

Aim: Retinopathy of prematurity (ROP) is the leading cause of blindness in preterm infants. In this study, we evaluated the potential role of anemia and packed red blood cell (RBC) transfusions as risk factors in ROP development. Methods: A retrospective cohort study was conducted on premature infants who met the following inclusion criteria: infants with gestational age (GA) ≤ 32 weeks and very low birth weight (VLBW) who were admitted to the Neonatology-Preterm Department of Emergency Pediatric Hospital Cluj-Napoca during a two-year period (from 1 January 2023 to 31 December 2024). We investigated differences in the following perinatal characteristics between the two groups, those with ROP and those without: GA, birth weight (BW), severe respiratory distress syndrome, early-onset and late-onset sepsis, hemoglobin (Hb) levels, and RBC transfusions. We used the statistically significant variables to perform binary logistic regression. Results: A total of 124 newborns were recruited, with the following inclusion criteria: GA ≤ 32 weeks and BW ≤ 1500 g, of whom 79 received at least one RBC transfusion prior to 36 weeks corrected GA. Of them, 48 developed ROP with an incidence of 38.7%. In 20 cases, ROP required treatment. To adjust for clinical illness, a binary logistic regression model was created, including known risk factors for ROP and illness severity (GA, severe respiratory distress syndrome, and early- and late-onset sepsis) that were closely related to the risk of ROP development. For this regression model, Nagelkerke R-squared = 0.358, p < 0.001, and the AOR was 4.812 (95% CI: 1.374–16.847). Conclusions: RBC transfusions increased the risk of ROP. Full article

Background: Human breast milk (HBM), as the initial food for humans, is quite essential for infant development and also for health throughout the lifespan. Exosomes are bioactive components in HBM, yet their nutritional role remains poorly recognized. Objectives: This study investigates how HBM exosomes change with lactation and their potential role in infant growth and development. Methods: HBM samples were obtained at 2 and 6 months postpartum from a well-established birth cohort. Purified exosomes were detected using transcriptomic, lipidomic, and proteomic approaches. Then, multi-omics data were analyzed to compare differentially expressed miRNAs, lipids, and proteins along with different lactation periods and their association with the infant growth process. Results: Compared with the 2-month postpartum group, the expression levels of miR-214-3p, miR-199a-5p, miR-126-3p, miR-127-5p, miR-144-3p, and miR-4787-5p were down-regulated in the 6-month postpartum group. In addition, 190 lipids and 269 proteins were up-regulated in the 6-month postpartum group, whereas 15 lipids and 244 proteins were down-regulated. Enrichment analysis revealed that the predicted target genes of differentially expressed miRNAs were primarily involved in cell communication and axon guidance. In parallel, the differentially expressed proteins were enriched in biosynthesis of unsaturated fatty acids and fatty acid metabolism pathway, implying a potential role in adipogenesis and neurodevelopment. Conclusions: This study reveals that the cargo contents of HBM exosomes change with the lactation period and may adapt to the needs of infant growth and development, particularly adipogenesis and neurodevelopment. HBM exosomes may play an important role in transferring genetic information from mothers to infants and be related to infants’ development. The underlying mechanisms warrant further investigation and validation. Full article

The Cambodian genocide occurred between April 1975 and January 1979. Over one-third of Cambodia’s population perished, and many survivors suffer physical and mental health consequences. This study examines lasting influences of the Cambodian genocide on Cambodia’s population structure and on adult health and health behavior. To illustrate the legacy of decreased fertility and increased mortality during the genocide, population pyramids (1975, 1985, 2014, 2022) were generated using data from the United Nations Population Division. For comparison, population pyramids for the neighboring country of Thailand were generated. To examine the enduring health sequelae of the genocide, nationally representative Demographic and Health survey data (2014, 2021–2022) were used to compare smoking behaviors and stunted growth of women born shortly before and during the genocide (1972–1979) with women born shortly after the genocide (1980–1987). Cambodia’s population pyramids reveal a long-term paucity of individuals in the 1970s birth cohorts not observed for Thailand. Compared to women born shortly after the genocide, women with early-life exposure to the genocide were more likely to report smoking in adulthood and to have experienced stunted growth. The genocide impacted Cambodia’s population structure and affected the health and health behaviors of early childhood genocide survivors into adulthood. These findings imply life course and intergenerational impacts. Full article

Background/Objectives: Gram-negative neonatal sepsis remains a cause of morbidity and mortality in preterm infants, yet the relationship between early clinical severity and long-term neurodevelopmental outcomes is incompletely defined. This study aimed to characterize Gram-negative sepsis in preterm infants and to evaluate its short-term and 18–24-month neurodevelopmental consequences. Methods: We conducted a retrospective observational cohort study of preterm infants admitted to a tertiary neonatal intensive care unit between 1 January 2022 and 31 December 2023. Infants with culture-proven Gram-negative neonatal sepsis, including both early-onset sepsis (EOS) and late-onset sepsis (LOS), were included. Clinical, microbiological, therapeutic, and laboratory data were collected, and survivors were assessed at 18–24 months’ corrected age using the Bayley Scales of Infant and Toddler Development. Results: Among infants with culture-proven Gram-negative sepsis, late-onset cases were more frequent than early-onset cases, and Klebsiella pneumoniae was the most common pathogen (38.0%). Multidrug-resistant organisms were associated with 52.0% of infections. In-hospital mortality was 26.0%. Major short-term complications included intraventricular hemorrhage (24.0%), severe intraventricular hemorrhage (20.0%), necrotizing enterocolitis (12.0%), bronchopulmonary dysplasia (20.0%), and meningitis (10.0%). Among survivors who underwent neurodevelopmental assessment, neurodevelopmental impairment was observed in 38.0%, most frequently affecting the language (22.5%) and cognitive (20.0%) domains. Infants with neurodevelopmental impairment had significantly lower gestational age and birth weight and higher inflammatory biomarker levels. In multivariable analyses, lower gestational age emerged as the strongest independent predictor of both mortality (adjusted OR 0.19, 95% CI 0.04–0.99) and neurodevelopmental impairment (adjusted OR 0.12, 95% CI 0.02–0.71). Conclusions: Gram-negative neonatal sepsis in preterm infants was associated with substantial mortality, severe neonatal complications, and a high burden of later neurodevelopmental impairment. Lower gestational age was independently associated with adverse short- and long-term outcomes. These findings support early recognition, targeted antimicrobial therapy, and structured neurodevelopmental follow-up in this high-risk population. Full article

School discipline disproportionately affects Black students and is associated with diminished academic outcomes. However, the mechanisms through which exclusionary discipline constrains college/university degree attainment—and the role of mental health in this pathway—remain underexplored with longitudinal data from a large urban birth cohort. This study examines whether depressive symptoms mediate the relationship between high school discipline and college/university degree attainment, and whether this mediation pathway varies by race and sex. Using data from the Future of Families and Child Wellbeing Study (N = 1417), I employed generalized structural equation modeling (GSEM) to test a serial mediation model: school discipline (Year 15) → depressive symptoms (Year 15) → college-going behaviors (Year 15) → college/university degree attainment (Year 22). Bootstrap confidence intervals (1000 replications) tested indirect effects. Moderation analyses examined whether the mediation pathway differed by race, sex, and depressive symptoms’ severity. School discipline significantly predicted higher depressive symptoms (b = 0.46, p = 0.001), which in turn predicted fewer college-going behaviors (b = −0.02, p = 0.001) and lower odds of college/university degree attainment (OR = 0.89, p = 0.001). The total indirect effect through depressive symptoms was significant (b = −0.06, 95% BC CI [−0.134, −0.017]). Sex, but not race (F = 0.24, p = 0.868), moderated the discipline–depressive pathway: discipline increased depressive symptoms more strongly for females (b = 0.78, p = 0.001) than males (b = 0.21, p = 0.251). Depressive symptoms amplified discipline’s effect on college/university degree attainment (interaction OR = 0.39, p = 0.037). Depressive symptoms partially mediate school discipline’s negative effect on college attainment, with the strongest effects among females. Higher education institutions must prepare to support students whose K-12 experiences were marked by exclusionary discipline. Full article

Background and Objectives: Appendectomy during pregnancy is associated with preterm birth, but downstream neonatal outcomes, neonatal intensive care resource use, and caregiver-reported psychological symptom burden remain insufficiently characterized. We aimed to compare neonatal infection rates, NICU resource utilization, and caregiver psychosocial outcomes between preterm infants born after maternal appendectomy during pregnancy and preterm controls frequency-matched by gestational-age strata without antecedent non-obstetric surgery. Methods: In this single-center prospective cohort study (March 2023–December 2025), 121 preterm infants were enrolled: 54 born after maternal appendectomy during pregnancy (31 laparoscopic, 23 open) and 67 non-surgical preterm controls. Neonatal outcomes included culture-confirmed infection, death, or major neonatal morbidity, and neonatal intensive care resource metrics. Caregiver outcomes were assessed near discharge using the 36-Item Short Form Survey, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 scale, and Hospital Anxiety and Depression Scale. Group comparisons used normality-guided parametric or non-parametric tests and multivariable logistic regression; subgroup and mediation analyses were exploratory. Mediation analyses explored indirect pathways. Results: Culture-confirmed infection was numerically more frequent in appendectomy-group neonates than in controls (35.2% versus 20.9%; p = 0.078), but this difference was not statistically significant. NICU length of stay was significantly longer (47.3 ± 14.8 vs. 41.2 ± 12.6 days; p = 0.014), and caregiver Patient Health Questionnaire-9 depressive symptom scores were higher (12.4 ± 4.3 vs. 9.6 ± 3.8; p < 0.001). Open appendectomy and negative histopathology subgroups showed the strongest adverse signals. Exploratory mediation analysis suggested that a substantial portion of the appendectomy-caregiver depression association statistically co-varied with prolonged hospitalization (Sobel p = 0.008); this exploratory pathway analysis does not establish a causal mediation pathway. Conclusions: Preterm infants born after maternal appendectomy during pregnancy showed non-significant numerical increases in infection outcomes, significantly higher neonatal intensive care resource use, and higher caregiver-reported psychological symptom scores compared with non-surgical preterm controls, with open surgery and negative appendectomy representing clinically complex subgroups with less favorable exploratory signals. Full article

Background: Vitamin D-binding protein (DBP) is the principal carrier of circulating 25-hydroxyvitamin D [25(OH)D] and is independently synthesized by the neonate. Whether neonatal DBP at birth adds predictive value beyond baseline 25(OH)D for supplementation response remains unclear. Methods: This single-center prospective cohort study enrolled 101 neonates. Neonates with 25(OH)D < 20 ng/mL (supplementation-response cohort; n = 59: 29 preterm, 30 term) received 800 IU/day oral cholecalciferol for 8 weeks; neonates with 25(OH)D ≥ 20 ng/mL served as baseline reference controls (n = 42). Serum 25(OH)D and DBP were measured at baseline and week 8 in the supplementation-response cohort. Results: Median baseline 25(OH)D was 8.6 [6.7–12.0] ng/mL and median baseline DBP was 4.9 [3.7–8.1] µg/mL. After supplementation, 25(OH)D increased significantly (median Δ = 17.7 ng/mL; p < 0.001), with 55/59 (93.2%) achieving sufficiency. In multivariable regression, gestational age was the strongest independent predictor of Δ25(OH)D (β = −0.440, p = 0.001), followed by baseline 25(OH)D (β = −0.314, p = 0.015); baseline DBP was not significant (β = 0.072, p = 0.551). Conclusions: Baseline DBP did not independently predict supplementation response. Lower gestational age and lower baseline 25(OH)D were associated with greater increases in 25(OH)D after supplementation, whereas baseline DBP provided no additional predictive value. Supplementation with 800 IU/day for 8 weeks was effective across gestational-age categories. Routine DBP measurement does not appear to provide additional clinical value for guiding neonatal vitamin D supplementation. Full article