Search Results (1,995)

Background/Objectives: Preterm birth is associated with increased risk of motor delay and broader neurodevelopmental vulnerability. Existing reviews have examined neonatal therapy, family-centered care, or early developmental intervention broadly, but the independent evidence for physiotherapy-based interventions in which parents actively deliver or support motor or sensorimotor activities remains uncertain. This review evaluated the effects of early physiotherapy with structured, guided parental involvement on motor development in preterm infants and examined intervention content, parental burden, safety, adherence, and durability of effects. Methods: The review followed PRISMA 2020 and a prespecified PICO framework. The original PubMed, Scopus, and PEDro search was updated through 9 July 2026 using PubMed/MEDLINE, PEDro, Cochrane CENTRAL, ClinicalTrials.gov, backward and forward citation tracking, and linked-report searches. Eligible studies were randomized controlled trials of early physiotherapy, motor, or structured sensorimotor intervention with an active parent-delivered or parent-supported component and a validated motor or neurodevelopmental outcome. Multiple publications from the same randomized cohort were linked and participants were counted once. Risk of bias was evaluated with Cochrane RoB 2, intervention reporting with TIDieR, and certainty with GRADE. Results: Ten reports represented five independent randomized cohorts and 393 unique randomized infants. The Norwegian Parent-Administered Physical Therapy Intervention (NOPPI) produced a moderate short-term improvement in TIMP performance at term-equivalent age, but no consistent advantage in general movements, motor performance at 3 or 24 months, or school-age motor outcomes. COPCA and a NICU-to-home physiotherapy program produced developmental improvement over time or selected short-term gains, without consistent superiority over active or developmental care comparators. A parent-administered sensorimotor intervention by Fucile et al. improved oral-feeding outcomes but not TIMP motor performance, and its linked 18-month follow-up did not demonstrate a clear developmental advantage. Badura et al. found no significant effect of a 10-week parent-delivered general-movement-based program on MOS-R or Bayley-III motor outcomes; adherence was variable, and a transient increase in maternal depressive symptoms at discharge highlighted the importance of treatment burden. Conclusions: Guided parental involvement is feasible and may enhance short-term motor performance when activities are individualized, active, cue-responsive, and closely supervised. However, current evidence does not establish sustained superiority over well-structured usual or traditional care, developmental normalization, or benefit from passive sensorimotor input alone. Clinical implementation should combine competency-based parent training, explicit infant stress cues and stopping rules, realistic dose targets, ongoing professional support, and monitoring of adherence, parental well-being, and adverse events. Full article

Background: Radon in drinking water is a potential source of ionizing radiation exposure, yet long-term monitoring data from active tectonic regions remain limited. This study investigated ²²²Rn activity concentrations in drinking-water wells along the Sultandağı Fault (Afyonkarahisar, Türkiye) and assessed age-dependent radiological risks. Methods: ²²²Rn concentrations were measured at two-week intervals in 15 drinking-water wells between June 2021 and June 2022 using a WG-1001 water–gas separation system and an AB-5R radiation monitor. Annual effective dose (AED) and excess lifetime cancer risk (ELCR) were calculated for infants, children, and adults. Results: ²²²Rn concentrations ranged from 0.05 to 26.64 Bq L⁻¹, with a mean of 6.12 ± 2.79 Bq L⁻¹. Only one well exceeded the USEPA guideline level (11.1 Bq L⁻¹), whereas all measurements remained below the WHO reference level (100 Bq L⁻¹). Seasonal mean concentrations varied between 5.48 ± 2.53 and 7.08 ± 3.32 Bq L⁻¹. Mean AED values were 35.94, 13.17, and 15.63 μSv y⁻¹ for infants, children, and adults, respectively. Corresponding ELCR values were 1.26 × 10⁻⁴, 0.46 × 10⁻⁴, and 0.55 × 10⁻⁴. Conclusions: The results indicate generally low radiological risk from radon in drinking water within the study area, although elevated values were observed in some wells. Higher age-specific dose and risk estimates were obtained for infants. These findings provide long-term data on groundwater ²²²Rn variability in an active fault zone and support regional radiological risk assessment. Full article

Medical cannabis use is steadily increasing worldwide, including among pregnant and breastfeeding women. This Perspective provides an overview of current evidence regarding cannabis exposure during pregnancy and lactation and its implications for clinical decision-making. The available literature indicates relatively consistent evidence linking prenatal Δ⁹-tetrahydrocannabinol (THC) exposure with adverse perinatal outcomes, including reduced birth weight, increased risk of preterm delivery, and potential neurodevelopmental effects, although the findings remain heterogeneous and often confounded. In contrast, evidence regarding cannabis exposure during breastfeeding is sparse, and long-term infant outcomes associated with postnatal exposure through breast milk remain insufficiently characterized. Data on isolated cannabidiol (CBD) exposure during pregnancy and lactation are particularly limited, and most available evidence derives from preclinical studies or pharmacokinetic modeling rather than clinical outcome studies. Current recommendations from major health organizations uniformly advise avoiding cannabis and cannabinoid use during pregnancy and breastfeeding. This Perspective highlights the need to interpret the evidence according to cannabinoid type, exposure period, route and pattern of use, and the distinction between recreational exposure and regulated medical use. Such distinctions are particularly important because evidence is relatively stronger for prenatal THC exposure, whereas data on CBD and lactational exposure remain limited and are derived largely from indirect clinical, pharmacokinetic, and preclinical sources. Within this evidence landscape, individualized clinical interpretation may be needed when exposure has already occurred, cessation is not immediately feasible, or maternal treatment decisions remain complex, while remaining anchored in current avoidance recommendations. Full article

Objectives: Preterm infants confront multiple coexistent health risks and may not receive human milk (HM), which contains human milk oligosaccharides (HMOs), among other biologically active, beneficial components. 2′-Fucosyllactose (2′-FL) is the most abundant HMO in most HM. Interventional studies of formula with added HMOs have demonstrated multiple beneficial outcomes in healthy, term infants. Methods: This double-blind, randomized, placebo-controlled pilot study (NCT03306316) evaluated the effect of a 2′-FL supplement on growth, tolerance, and neurobehavior, as assessed by the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS), in preterm infants. Eligible neonates born between 26 0/7 and 31 6/7 weeks gestational age (GA) were enrolled from three NICUs in the United States. Preterm infants consuming mother’s own milk or donor human milk were randomized to receive a supplement of 0.135 g/mL of 2′-FL or 0.05 g/mL dextrose (placebo) twice daily until 36 weeks corrected GA, NNNS assessment, or hospital discharge, whichever came first. Results: Of 42 participating preterm infants, 23 (55%) received 2′-FL and demonstrated no significant differences in growth in weight, length, or head circumference over 5 weeks. There were also no differences in stool frequency, adverse (AEs) or serious adverse events (SAEs), or neurobehavior (NNNS) between groups. Conclusions: This pilot study found that 2′-FL supplementation in preterm infants through 36 weeks corrected GA was safe and well-tolerated and supported adequate growth and neurobehavior. Full article

Magnetic resonance imaging (MRI) has become the gold standard for evaluating brain injury and development in newborn infants, providing structural, metabolic, and functional information without ionizing radiation. This review comprehensively examines the principal MRI modalities used in current neonatal neuroimaging for a novice/intermediate-level reader—including conventional T1- and T2-weighted imaging, diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping, diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), susceptibility-weighted imaging (SWI), volumetric analysis, arterial spin labeling (ASL), and functional connectivity MRI—with particular attention to their applications in preterm and term populations. Additionally, validated MRI scoring systems for quantifying brain injury severity and predicting neurodevelopmental outcomes are reviewed and summarized. Understanding the technical principles, clinical applications, and limitations of these modalities is essential for optimal interpretation of neonatal brain MRI, and for advancing prognostication and therapeutic decision-making in this vulnerable population. Full article

Background and objectives: A migraine is a highly prevalent and disabling neurological disorder that mainly affects women of childbearing age. Treatment options for migraine prevention are limited during pregnancy and breastfeeding. Although OnabotulinumtoxinA (OnabotA) has proven efficacy and safety in chronic migraine prophylaxis in adults, its safety in pregnancy and breastfeeding remains understudied. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, this review systematically appraised the evidence on the use of OnabotA for chronic migraines and other neurological conditions during pregnancy and breastfeeding across four electronic databases between January 2000 and December 2025. Results: In summary, of the 555 OnabotA-exposed pregnancies, 80.2% resulted in full-term births, with a 17.5% loss rate (73 spontaneous, 21 elective, three unspecified) and 1.6% reporting foetal anomalies. These findings align with general population baselines for miscarriages (12.5–18.7%) and foetal anomalies (3–5%), respectively. Among 94 cases of reported breastfeeding, no adverse infant events or developmental delays were observed at 1 year. Maternal outcomes showed favourable symptom control without adverse effects. Conclusions: Although there is limited data on the use of OnabotA in pregnancy and breastfeeding, no significant adverse effects have been identified in pregnant mothers or neonates. OnabotA should therefore be considered on a case-by-case basis for treatment of various neurological conditions, including migraines, when there are no better safe alternatives. Full article

Background: Neonatal encephalopathy (NE) is a major cause of neonatal mortality and long-term neurological disability. Although hypoxic–ischaemic encephalopathy (HIE) is the most common cause, several genetic disorders may mimic or coexist with hypoxic–ischaemic injury. Next-generation sequencing has emerged as a promising diagnostic tool in this setting. This systematic review evaluated the current evidence on genomic sequencing in NE. Material and methods: A systematic review was conducted according to PRISMA 2020 guidelines and prospectively registered in PROSPERO. PubMed/MEDLINE, Embase, and Scopus were searched from inception to June 2026. Eligible studies included neonates (≤28 days) with NE, suspected or confirmed HIE, HIE mimics, or unexplained NE who underwent genomic sequencing. Whole-exome sequencing (WES), whole-genome sequencing (WGS), clinical exome sequencing (CES), rapid genomic sequencing, and targeted next-generation sequencing panels were considered. Study quality was assessed using the Newcastle–Ottawa Scale. Results: Seven studies met the inclusion criteria. Considerable heterogeneity was observed regarding patient selection, sequencing strategies, and reported outcomes. Among diagnostic sequencing studies, diagnostic yield ranged from 23.5% to 53.1%. Pathogenic and likely pathogenic variants were identified in genes associated with developmental and epileptic encephalopathies, metabolic disorders, mitochondrial diseases, and neurodevelopmental syndromes, including SCN2A, KCNQ2, CACNA1A, STXBP1, PTPN11, BCOR, MMUT, COQ2, and GBE1. Genomic sequencing frequently refined or changed the initial diagnosis, improved prognostic assessment and genetic counselling, and, in selected cases, guided disease-specific treatment. One study investigated genetic susceptibility to hypoxic–ischaemic injury rather than diagnostic sequencing. Conclusions: Genomic sequencing provides clinically meaningful diagnoses in a substantial proportion of neonates with unexplained NE or atypical HIE presentations. Current evidence supports integrating genomic sequencing into the diagnostic evaluation of selected infants, although larger prospective studies are needed to define its optimal timing, clinical utility, and cost-effectiveness. Full article

Background/Objectives: Isolated Left Ventricular Apical Hypoplasia (ILVAH) is a rare congenital anomaly characterized by a truncated, spherical left ventricle (LV) with fibro-fatty apical replacement. Historically considered a benign condition of asymptomatic adults, its hemodynamic behavior under physiological stress remains poorly characterized. We present two distinct cases and a comprehensive literature review (n = 59) to redefine the clinical spectrum of ILVAH. Methods: To contextualize our findings, a comprehensive review of the literature was performed up to February 2026. We searched the PubMed/MEDLINE database using the terms “Isolated Left Ventricular Apical Hypoplasia”, “ILVAH”, “truncated left ventricle”, and “left ventricular apical hypoplasia”. The literature search and study selection were conducted in accordance with the PRISMA guidelines. Case presentations: Case 1 describes a male infant with ILVAH and muscular ventricular septal defects who unexpectedly developed transient systolic heart failure at one month of life, requiring prompt medical therapy (ACE inhibitors and diuretics) for functional recovery. Case 2 describes a 33-year-old woman with a known diagnosis of ILVAH. Serial echocardiography during her first pregnancy revealed progressive left atrial dilation and the onset of mild post-capillary pulmonary hypertension. Immediately following an elective cesarean section at 37 weeks, she experienced acute heart failure. She was successfully managed with pre-emptive volume offloading. Conclusions: ILVAH is not a universally benign anomaly. The morphologically deficient and rigid ventricle is vulnerable to afterload shifts in infancy and rapid volume expansion in adulthood. A review of all previously reported pregnancies in ILVAH reveals a consistent pattern of severe, unrecognized postpartum pulmonary edema. Proactive, multidisciplinary management is suggested to prevent clinical decompensation. Our findings suggest that ILVAH may act as a stress-sensitive restrictive congenital left ventricle disease rather than a universally benign anatomical variant, a hypothesis that warrants further investigation. Full article

Necrotizing enterocolitis (NEC) remains one of the most devastating gastrointestinal disorders affecting preterm infants, with substantial mortality and long-term morbidity despite advances in neonatal care. Increasing evidence implicates intestinal dysbiosis, impaired intestinal barrier function, and dysregulated immune responses as central drivers of NEC pathogenesis, making microbiome-targeted interventions a promising preventive strategy. Collectively termed “biotics,” these interventions include probiotics, prebiotics, synbiotics, and postbiotics, each aimed at modulating the developing gut ecosystem. This narrative review summarizes current evidence on the efficacy, safety, and clinical applicability of biotics for NEC prevention in very preterm and very-low-birth-weight infants. Randomized controlled trials and meta-analyses involving more than 10,000 infants demonstrate that specific multi-strain probiotic formulations, particularly those combining Lactobacillus and Bifidobacterium species, reduce NEC incidence and all-cause mortality, although benefits are less consistent in extremely low-birth-weight infants. Prebiotics alone showed a limited impact on NEC prevention, while emerging evidence suggests synbiotics may offer additive or superior protection compared with probiotics alone. Postbiotics represent a novel and potentially safer alternative, especially for the most vulnerable infants, though clinical data remain limited. Despite favorable effectiveness in meta-analyses, probiotics adoption remains variable due to strain heterogeneity, variable product quality, regulatory challenges, and rare but serious safety concerns. Precision microbiome approaches, pharmaceutical-grade formulations, personalized therapies informed by multi-omics profiling, and next-generation delivery systems may drive the future in this field. Full article

Background/Objectives: Breast pumps are essential tools when breastfeeding dyads are separated or there are breastfeeding challenges that prevent or reduce effective milk removal. Hospital-grade and personal-use pumps offer different features and performance characteristics. Direct comparative studies evaluating pump efficacy and maternal satisfaction are limited in this area, hampering healthcare professionals in their support of lactating women. We compared the efficacy and maternal perceptions of a hospital-grade breast pump (Symphony; Medela AG) and an electric personal-use pump (Pump in Style Pro; Medela AG). Methods: In total, 28 lactating mothers with healthy-term infants participated in an unblinded randomised crossover trial. Participants attended two pumping sessions using either the hospital-grade pump or personal-use pump. Effectiveness of milk removal and maternal perception were measured. Participants completed a 24 h milk profile to enable calculation of the percentage of available milk removed from the breast. Results: There were no significant differences for milk removal efficacy parameters after accounting for pre-expression degree of fullness of the breast between pumps. Similarly, there was no difference in comfort ratings. However, mothers perceived the hospital-grade breast pump vacuum as smoother than the personal-use pump (p = 0.003) and rated the hospital-grade breast pump as having a more pleasant sound (p < 0.001). Both findings remained significant after adjustment for pre-expression degree of fullness (p < 0.001 and p = 0.030, respectively). Conclusions: The hospital-grade pump and the personal-use pump did not differ with respect to milk removal efficacy and comfort. However, participants did perceive differences in vacuum application. Full article

Background/Objectives: Total parenteral nutrition (TPN) is essential for neonates unable to receive adequate enteral feeding, but its long-term metabolic effects remain uncertain. This study evaluated associations between neonatal TPN exposure, exposure duration, and later endocrinologic or metabolic disorders. Methods: This nationwide cohort included 2,424,716 infants born in South Korea between 2005 and 2010. TPN exposure was identified during the first 28 days of life. The primary outcome was the first occurrence of type 2 diabetes mellitus (T2DM), essential hypertension, dyslipidemia, or obesity during follow-up of up to 18 years. The primary analysis used inverse probability of treatment-weighted (IPTW) Cox models, whereas duration-based associations were evaluated using secondary exploratory multivariable Cox regression. Results: The final cohort included 2,303,567 infants, of whom 7656 received TPN. In the primary IPTW analysis, any neonatal TPN exposure was not associated with either the primary composite outcome (HR 1.01, 95% CI 0.94–1.09; p = 0.801) or T2DM (HR 1.12, 95% CI 0.93–1.35; p = 0.215). In secondary exploratory multivariable analyses, TPN exposure for ≥3 days was associated with T2DM (adjusted HR 2.14, 95% CI 1.34–3.41; p = 0.001), whereas exposure for 1–2 days was not. Conclusions: The primary IPTW analysis showed no significant association between any neonatal TPN exposure and the primary composite outcome or T2DM. The association observed for ≥3 days in secondary exploratory analyses should be regarded as hypothesis-generating. Full article

Background: Unplanned paediatric hospital readmissions are key indicators of healthcare quality, often reflecting issues in discharge planning and continuity of care. The COVID-19 pandemic significantly disrupted healthcare delivery and utilisation, yet its impact on paediatric readmission patterns in Australia remains unclear. Methods: A 5-year single-centre retrospective cohort study of 21,262 paediatric admissions and unplanned readmissions at a non-tertiary metropolitan Australian hospital between 21 March 2017 and 20 March 2023 was conducted. Admissions up to 20 March 2020 were classified as pre-pandemic, and those from 21 March 2020 as during the COVID-19 pandemic. We analysed patient characteristics, including gender, age, First Nations status, primary diagnosis, and socio-economic status, to identify UHR trends. Results: During the COVID-19 period, total paediatric admissions declined by nearly 30%, and the readmission rate decreased from 7.5% to 4.6% compared with the pre-pandemic period. Across both cohorts, higher readmission rates were observed among male patients, infants aged 0–12 months, and children from more socio-economically advantaged areas. Readmissions among First Nations children and those with communicable diseases declined during the pandemic period. Conclusions: A higher proportion of males and patients under 12 months of age had higher readmission rates across both periods. These findings highlight the need for targeted early intervention, age-specific discharge planning, and strengthened follow-up care for high-risk groups. Further research should extend the study period beyond the pandemic and include larger cohorts to better characterise long-term trends and improve generalisability. Full article

Introduction: Bronchopulmonary dysplasia (BPD) remains the most significant complication of extreme prematurity, affecting long-term respiratory outcomes. Because current diagnostic criteria identify only established lesions at 36 weeks postmenstrual age, early non-invasive biomarkers are needed. This pilot study aimed to identify a candidate salivary miRNA panel associated with BPD risk and to explore its pathogenetic relevance through in silico analysis. Methods: Saliva was collected from 20 preterm infants (10 with BPD and 10 controls), and miRNA expression was profiled using the GeneChip™ miRNA 4.1 Array Plate. Discriminatory performance was explored by ROC analysis within this discovery cohort, together with power and Spearman correlation analyses. Results: Expression of hsa-let-7b-5p, hsa-let-7c-5p, and hsa-miR-4454 was significantly elevated in the BPD group (p < 0.05, log₂FC ≥ 1.0), with no significant correlation with gestational age or birth weight. Bootstrap-corrected AUC values ranged from 0.905 to 0.937 and were supported by leave-one-out cross-validation. All three miRNAs showed very large effect sizes exceeding the minimum detectable effect at 80% power. Conclusions: In this pilot study, salivary miRNAs represent a hypothesis-generating candidate biomarker signal for BPD that requires external validation in larger, independent cohorts before any diagnostic or prognostic application can be considered. Full article

Background/Objectives: Since the establishment of the Korean Neonatal Network (KNN) in 2013, numerous studies have been conducted using its nationwide registry of very low birth weight infants (VLBWIs). Beyond serving as a clinical database, the KNN has evolved into a national healthcare research infrastructure supporting multicenter collaboration, evidence generation, and quality improvement in neonatal care. This study aimed to evaluate the scientific productivity, collaborative structure, and knowledge-generation capacity of the KNN through bibliometric network analysis and to identify future research directions in Korean neonatal research. Methods: Publications from 1 January 2015 to 5 June 2024 were retrieved from the Web of Science Core Collection. Literature searches were performed using Medical Subject Headings (MeSH), Emtree terms, and related keywords associated with very low birth weight infants, extremely low birth weight infants, and the Korean Neonatal Network. A total of 7060 global publications and 86 KNN-related publications were identified for analysis. Co-authorship and keyword co-occurrence analyses were conducted using VOSviewer to evaluate international collaborations, research themes, and temporal trends in keyword emergence. Scimago Graphica was used to visualize keyword evolution, and burst detection analysis was performed using CiteSpace to identify emerging research topics. Results: Among global publications on VLBWIs, South Korea ranked 13th worldwide with 226 publications and demonstrated substantial international collaboration, particularly with researchers in the United States. Analysis of the 86 KNN-related publications revealed the rapid development of observational and topic-focused research areas within a relatively short period. Keyword clustering and temporal analyses demonstrated a progressive expansion of research interests as the database matured. Burst analysis identified emerging themes related to mortality and morbidity risk factors, neurodevelopmental outcomes, and predictive modeling using machine learning techniques. Conclusions: Bibliometric analysis demonstrated that research based on the KNN has largely followed global trends in neonatal research despite its relatively recent establishment. The KNN has successfully functioned as a nationwide research infrastructure facilitating collaborative knowledge generation and scientific productivity. Nevertheless, several underrepresented research areas and opportunities for broader international collaboration were identified. These findings may help guide future research strategies and maximize the impact of national neonatal registry-based healthcare systems. Full article

Background and Objectives: Advances in perinatal and neonatal care have improved survival in preterm infants, yet neurodevelopmental impairment remains a major concern. A considerable proportion of preterm infants with normal or only mildly abnormal neuroimaging findings still develop neurodevelopmental difficulties, highlighting the need for more sensitive imaging markers beyond the detection of major brain lesions. Cranial ultrasound is a widely used bedside imaging tool that enables both detection of brain injury and quantitative assessment of brain growth. This study aimed to evaluate the association between early and term-equivalent cranial ultrasound morphometric parameters, head circumference, and neurodevelopmental outcomes assessed by the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4). Materials and Methods: This exploratory observational study included 22 preterm infants admitted to a neonatal intensive care unit. Cranial ultrasound examinations were performed within the first 72 h of life and at term-equivalent age (37–40 weeks postmenstrual age). Measured parameters included the Levene index, lateral ventricular width, third ventricle width, subarachnoid space, and interhemispheric fissure. Head circumference was analyzed as an additional marker of postnatal brain growth. Neurodevelopment was assessed at 12–14 months corrected age using Bayley-4. Associations were analyzed using Spearman’s rank correlation. Results: Significant correlations were more frequent at term-equivalent age than in the early neonatal period. Early measurements showed positive associations between ventricular parameters and motor outcomes, as well as between head circumference and receptive communication (p < 0.01). Third ventricle width was also associated with receptive communication. At term-equivalent age, lateral ventricular width demonstrated consistent negative correlations with motor and language outcomes, with strong associations in motor domains (p < 0.01). Head circumference showed limited positive associations, reaching significance only for personal–social skills, while third ventricle width was associated with play and leisure activities. Conclusions: Morphometric cranial ultrasound measurements, particularly those obtained at term-equivalent age, may provide valuable additional information about early neurodevelopment in preterm infants. Head circumference reflected postnatal brain growth but showed less consistent associations with neurodevelopmental outcomes than ventricular morphometric parameters. Larger prospective studies with longer follow-up are needed to confirm these findings and define the prognostic value of individual cranial ultrasound morphometric parameters and head circumference for predicting neurodevelopmental outcomes in preterm infants. Full article