Search Results (316)

Background: Hypotonic–hyporesponsive episode (HHE) is a recognised adverse event following immunisation (AEFI) in infants, characterised by sudden hypotonia, hyporesponsiveness, and pallor or cyanosis. Although considered benign, its abrupt and often dramatic presentation often leads to acute medical evaluation. Contemporary data on HHE are limited, and awareness among healthcare professionals needs attention. Methods: We conducted a retrospective analysis of all spontaneous reports of HHE submitted to the national pharmacovigilance centre Lareb between 1 January 2012 and 22 July 2025. Cases were included only when meeting Brighton Collaboration (BC) Level 1 criteria, requiring clear documentation of hypotonia, hyporesponsiveness, and pallor or cyanosis in children younger than 24 months. Demographic and clinical characteristics, vaccine combinations, latency, duration, seriousness, and medical care utilisation were described. Results: A total of 294 Level 1 HHE cases were identified. Most episodes followed combinations of hexavalent vaccines with pneumococcal conjugate vaccines. The median age at onset was 9 weeks, with slightly more reports involving boys. The median latency to onset was 5 h (range 4–8 h), and the median episode duration was 10 min (range 3–30 min), aligning with the historical literature. All children recovered fully, and no long-term sequelae were reported. Although HHE is clinically benign, 27% of cases were classified as serious, primarily due to hospital admission. Among non-serious cases, one third involved medical assessment or emergency services. Healthcare professionals submitted 44% of reports, notably community child health physicians. Conclusions: Contemporary Dutch pharmacovigilance data confirm that the clinical characteristics of HHE remain highly consistent with long-standig evidence. Despite its benign and self-limiting nature, HHE frequently triggers substantial medical care consumption. Improved awareness of the typical presentation, course, and prognosis, supported by the Brighton Collaboration criteria, may help clinicians recognise HHE more readily, reduce unnecessary medical consumption, and provide reassurance to caregivers. Full article

Background: Exogenous nucleotides are bioactive compounds involved in nucleic acid synthesis, cellular metabolism, intestinal function, immune regulation, and related physiological processes. Owing to their potential roles in supporting growth, gut health, immune function, metabolic regulation, and physiological resilience, they have attracted increasing attention as functional dietary supplements and feed additives. However, the global research landscape of exogenous nucleotides has not been systematically characterized. This study aimed to map the development of this field and identify its major contributors, knowledge structures, application domains, and emerging research hotspots. Methods: Global literature on exogenous nucleotides published between 2000 and 2025 was retrieved from the Web of Science Core Collection. After screening and data standardization, 710 records were analyzed using VOSviewer, CiteSpace, and R-based visualization tools. The bibliometric analysis included publication output, country and institutional collaboration, keyword co-occurrence, co-cited references and journals, and citation burst detection. Results: A total of 710 publications were included. Annual publication output showed an overall upward trend, with marked growth after 2017. China and the United States were the leading contributors, while the Chinese Academy of Sciences and Peking University were among the most productive institutions. Keyword and co-citation analyses identified three major research themes: basic molecular mechanisms, physiological and health-related effects, and practical applications. Aquaculture and animal nutrition represented the most prominent application areas, with studies mainly focusing on growth performance, feed utilization, intestinal morphology, immune responses, oxidative stress resistance, and disease resistance. In human nutrition, research was mainly related to infant nutrition, intestinal and immune health, nutritional recovery, metabolic regulation, and healthy aging. Burst detection indicated a shift in research attention from early topics such as human milk and receptors to intestinal morphology and, more recently, nicotinamide mononucleotide and molecular activation. Conclusions: Research on exogenous nucleotides has expanded rapidly and is moving toward more mechanism-oriented and more diverse applications. Current evidence suggests that exogenous nucleotides have potential value as functional dietary supplements and feed additives, particularly in aquaculture, animal nutrition, infant nutrition, gut and immune health, metabolic regulation, and healthy aging. Future studies should further clarify compound-specific mechanisms, effective dose ranges, bioavailability, long-term safety, and population- or species-specific benefits to support their evidence-based application in functional foods, dietary supplements, infant formula, clinical nutrition, and functional feed products. Full article

COVID-19 remains a challenge to the global healthcare despite the end of the pandemic, including due to the significant involvement of children in the epidemic process. During the pandemic period, an increase in the incidence of Sudden Unexpected Infant Death (SUID) and Sudden Infant Death Syndrome (SIDS) was observed. Currently, their rates remain elevated compared to the prepandemic period. The pathogenetic mechanisms underlying the fulminant course of infection in infants leading to fatal outcomes remain insufficiently understood. In this study, we report for the first time the results of histological and immunohistochemical examination of the lungs in a case of COVID-19-associated SUID in a 2-month-old infant. The absence of similar studies in the available literature limits opportunities for analyzing the pathogenesis of SUID. Our data allow a detailed characterization of the histological changes in the lungs, the localization and range of SARS-CoV-2 nucleocapsid protein expression, the identification of molecular mechanisms underlying apoptosis in the pulmonary microvascular endothelium, and the elucidation of the role of endothelial dysfunction. Particular attention in this article is devoted to the role of cytokines (IL-6, TNF-α, and IFN-γ) in the pathogenesis of hyperacute viral infection. The obtained data demonstrate substantial differences between the observed changes and the classic presentation of COVID-19 in older children. These findings offer prospects for improving prevention strategies and developing targeted therapy for fulminant forms of COVID-19, while also contributing to the understanding of SIDS pathogenesis. Full article

Congenital heart disease (CHD) is the most common anatomical malformation occurring in live-born infants and an increasing cause of morbidity and mortality all over the world. Population-based observations have described associations between maternal cardiometabolic disorders and the risk of CHD in offspring. The present article is a narrative review. The aim of this study was to review the epidemiological evidence and clinical observations relating maternal obesity and diabetes mellitus to the risk of CHD in offspring, with particular attention paid to first trimester disturbances of fetal cardiac development and the influence of genetic, epigenetic and environmental factors. Studies have shown that maternal diabetes is a risk factor associated with nearly all subtypes of CHDs in offspring, while obesity and overweight are associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. Diabetes and obesity share several phenotypes, which could be transmissible from mother to fetus via the placenta. This means that an increase in maternal glucose could be responsible for the prevalence of CHD in newborns of obese women. On the other hand, maternal diabetes may induce epigenetic modifications in the developing fetus. DNA methylation changes can impact gene expression patterns relevant to heart development. The abovementioned studies are heterogenous, express different opinions and are often difficult to compare. Therefore, the results from these meta-analyses must be interpreted with caution. Optimal diabetes control is responsible for the prevention of oxidative stress in diabetic pregnancies, and a deeper understanding of maternal risk factors holds the potential to improve both prenatal detection of CHDs by identifying at-risk pregnancies and primary prevention of diseases by improving preconception management. Full article

Background: Early detection of developmental disorders in infants is an important topic for scientists and clinicians, but above all for children and their families. Early detection of changes in the mechanical properties of muscles is crucial for starting therapeutic processes. This study aims to fill the research gap regarding the use of myotonometry in the infant patient group (aged 0–3 months). The study aimed to evaluate the test–retest repeatability of myotonometric measurements in infants at three time points, with particular attention to potential age-related differences. Methods: The study group consisted of healthy newborns born from physiological pregnancies with an Apgar score of 8–10 points. The studies began on the 1st–3rd day of life and lasted until the 12th week in cycles every 6 weeks. Results: In the study conducted on the 1st–3rd day of life, the repeatability of the studied parameters can be described as moderate (muscle tone, elasticity, relaxation, and creep) or poor (stiffness). Measurements conducted in the 6th week of life show high repeatability of muscle stiffness and elasticity or moderate repeatability of muscle tone, creep, and relaxation time. Measurements in the 12th week of life of the infants may be considered as high repeatability of muscle tone, stiffness, relaxation time, and the creep parameter, and moderate muscle elasticity. Conclusions: The study demonstrated the usefulness of using myotonometric measurement for infants from the 6th and 12th week of age in the studied parameters, confirmed by the high repeatability of measurements. Whereas in the group of newborns aged 1–3 days, the repeatability of all analyzed parameters can be described as moderate or low. Full article

Background: Daily, perhaps for hours at a time, pacifiers are put in baby’s mouths for the primary purpose of soothing. A causal relationship exists between the use of pacifiers and the development of malocclusions and disturbances to the cranio-facial-respiratory complex (CFRC). Finite element analysis (FEA) has enabled us to understand how pacifier bulbs behave under negative pressure and tongue movement in the mouth. It is now realized that the design and size of pacifiers should be based on infant and toddler biometrics of the maxillary palatal width and should contribute to proper oral function and development. Attention has shifted toward the interaction between the pacifier shield, the lips, chin and developing tempro-mandibular joint (TMJ). Free mandibular motion is essential to normal TMJ development, essential to maintaining airway space and promoting forward mandibular growth. This is especially relevant in infants with retrognathia, when shield pressure may restrict free movement of the jaw and anterior mandibular advancement. Conclusions: When the pacifier shield interacts with the chin, it impacts the growth and development of the infant mandible and airway physiology. Interference with free movement of the mandible must be made a functional concern in design of the pacifier shield. Technological advances in smartphone photogrammetry now make development of non-invasive diagnostic tools that can advantage the future oral health of children. Full article

The milk fat globule membrane (MFGM) wraps around the surface of the milk fat globule, separating the internal lipid core from the external environment. MFGM is a complex trilayer membrane structure composed of polar lipids, sphingolipids, and functional proteins. In recent years, research on the biological characteristics of MFGM has been continuously deepening. It has triggered an exploration of the relationship between MFGM composition, structure, and functional mechanisms. This reveals the potential applications of MFGM in human health and production practices. This review systematically summarizes the composition and structure of MFGM, extraction and preparation techniques, functional mechanisms and the latest research progress in its applications in various fields. This study comprehensively compares the application scope of the MFGM extraction preparation technology. The mechanism of the biological activity of MFGM was further analyzed. Its application value in infant formula, dairy processing, functional foods, drug delivery systems, and cosmetics was evaluated. Nowadays, existing research needs to face numerous challenges, such as some components being unknown and the functional mechanisms not being clear enough. In the future, it is still essential to continuously pay attention to the research progress of MFGM. Further research is needed to accelerate the transformation of MFGM from by-products of dairy processing to multifunctional biomaterials. The purpose is to fully tap its enormous potential in nutrition, health care, and application fields. Full article

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

Groundwater plays an indispensable role in daily life. However, with the continuous advancement of industrialization, more attention should be paid to the quality of groundwater and the associated potential health risks in areas surrounding industrial parks. In this study, groundwater samples collected in the city of the Tibetan Plateau during the wet season (WS) and dry season (DS) were analyzed using Piper diagrams, Gibbs diagrams, and correlation analysis. The results elucidated the hydrochemical characteristics, formation mechanisms, and controlling factors of groundwater in the area. Groundwater potability was assessed using the Entropy-weighted Water Quality Index (EWQI) method. In addition, the health risk assessment model was applied to evaluate potential risks for four population groups, with NO₃⁻ and F⁻ selected as representative groundwater pollutants. The findings revealed that groundwater in the study zone was typically moderately alkaline and characterized primarily as soft–fresh and hard–fresh. The groundwater in both seasons mainly exhibited HCO₃–Ca chemical facies. Water–rock interactions involving silicate and carbonate minerals were identified as key processes controlling the hydrochemical composition in both seasons. EWQI results showed that groundwater quality for drinking purposes was excellent in the seasons. Sensitivity analysis further showed that Cl− exerted the greatest influence on the drinking water quality evaluation in both seasons. Health risk assessments revealed that the risks posed by NO₃⁻ and F⁻ to infants, children, adult females, and adult males remained within acceptable limits (with max values of 0.63, 0.39, 0.28, and 0.33 in the WS, and 0.59, 0.36, 0.26, and 0.31 in the DS, respectively). However, infants exhibited greater susceptibility than the other groups across seasons, with a risk index approximately twice that of adults. Overall, the findings contribute valuable insights for the sustainable management and planning of groundwater resources in the study zone. Future research could refine the risk assessment model with localized data and explore mitigation strategies for elevated risks in specific seasons or regions. Full article

Iodine is an essential micronutrient required for the synthesis of thyroid hormones and the maintenance of metabolic, neurodevelopmental and immune function. As iodine cannot be synthesized endogenously, adequate intake depends on dietary sources and environmental availability. Despite decades of progress in improving iodine supply, both iodine deficiency and excess remain significant global public health challenges. This review summarizes iodine physiology, covering both its role in thyroid hormone synthesis and emerging evidence for extrathyroidal immunomodulatory and antioxidant actions. It summarizes major dietary sources, global intake patterns and current approaches to iodine status assessment, including urinary biomarkers, salivary iodide measurement and dietary screening tools. The clinical consequences of iodine imbalance are examined, ranging from goiter, hypothyroidism and impaired neurocognitive development associated with deficiency, to iodine-induced thyroid dysfunction, autoimmunity and adverse systemic effects linked to excess intake. Special attention is given to vulnerable populations, particularly pregnant women and infants. This review further evaluates public health strategies, including salt iodization and targeted supplementation, while addressing the emerging challenge posed by salt-reduction initiatives. Achieving optimal iodine intake remains essential for thyroid health and population well-being, underscoring the need for coordinated monitoring and policy adaptation. Full article

Background/Objectives: We aimed to report three novel MAGED2 variants associated with transient antenatal Bartter syndrome (TABS) and to summarize the prenatal and postnatal features of MAGED2-related TABS through case analysis and literature review. Methods: Three unrelated Chinese families with polyhydramnios-affected pregnancies underwent genetic testing. Clinical data, including prenatal imaging, delivery details, and postnatal outcomes were reviewed. A literature review of reported MAGED2 variants and associated phenotypes was conducted. Results: Three previously unreported MAGED2 variants were identified: two frameshift variants (c.1511del [p.Gly504Alafs*72] and c.338del [p.Pro113ArgfsTer4]) and one deletion (chrX:54,820,664–54,839,053 [GRCh37]). All fetuses presented with polyhydramnios; two were large for gestational age (LGA). Additional findings included ventriculomegaly and scrotal enlargement. Two male infants were delivered at 33 weeks following repeated amnioreduction, with transient postnatal electrolyte abnormalities and normal neurodevelopment at 3 and 4 years. One fetus with a frameshift variant died in utero at 26 + 1 weeks. A literature review of 53 cases revealed 38 distinct MAGED2 variants, predominantly null variants (65.8%). Polyhydramnios was the most consistent antenatal sign. No intellectual disability was reported in surviving individuals. Conclusions: These findings expand the MAGED2 mutational spectrum. Polyhydramnios and LGA represents the most frequent features in TABS. In fetuses presenting with early-onset severe polyhydramnios (around 19–20 weeks of gestation), particular attention should be paid to possible exon-level or partial deletions involving MAGED2 during genetic evaluation. Full article

Liquid infant formula has garnered increasing attention due to its mild thermal processing and superior retention of bioactive nutrients. Within such matrices, the lipid source is a critical determinant of protein digestion behavior, yet its influence on peptide bioavailability and intestinal homeostasis remains undefined. Given that efficient peptide absorption is vital for the systemic delivery of bioactivity in infants, understanding the lipid–protein synergy is essential for formula optimization. Moreover, excessive oxidative stress is closely associated with impaired intestinal health and developmental disorders in infants, making the regulation of oxidative stress crucial for maintaining intestinal function. The present study evaluated the effects of three distinct lipid sources—soybean oil (SM), bovine milk fat (BM), and goat milk fat (GM)—on the physicochemical stability, proteolytic digestion, peptide release, intestinal absorption, and oxidative stress modulation of goat-milk-based infant formula. An integrated approach combining physicochemical characterization, in vitro simulated infant digestion, and a Caco-2 intestinal epithelial cell model was employed. we demonstrate that all three lipids (3% w/w) formed stable emulsions with uniform spherical structures and mean particle diameters of 117–300 nm, as visualized by laser confocal microscopy. Following in vitro simulation of infant gastrointestinal digestion, the SM group exhibited the most extensive protein hydrolysis, yielding the highest total peptide content (4.28 ± 0.10 mg/mL) and generated the highest number of peptides identified by LC-MS/MS (474 types). Bioinformatic analysis predicted that peptides from all groups possess potential antihypertensive, hypoglycemic, and immunomodulatory activities. The Caco-2 monolayer cell model demonstrated that although the GM group produced fewer identified peptide species than the SM group (365 types), it achieved significantly higher intestinal peptide absorption rate (55.34 ± 1.05%). Furthermore, the GM digests provided superior protection against H₂O₂-induced oxidative stress in Caco-2 cells, markedly reducing reactive oxygen species levels and suppressing the expression of pro-inflammatory cytokines TNF-α and IL-6. Collectively, these findings reveal that while soybean oil promotes more extensive proteolysis, the use of homologous goat milk lipid enhances peptide bioaccessibility and confers potential cytoprotective effects on intestinal epithelial cells, underscoring its potential as a preferred lipid source in infant formula formulations. Full article

Background/Objectives: Breastfeeding represents a critical developmental window during which maternal biology, environmental exposures, and nutrition converge to influence infant gastrointestinal health and long-term developmental trajectories. From a One Health perspective, breastfeeding can be conceptualized not as a static nutritional act, but as a dynamic and modifiable biological system in which maternal factors shape early-life microbiota assembly and immune programming. This narrative review explores how microbiota-oriented strategies during breastfeeding may foster a favorable trajectory of infant health, potentially extending to transgenerational outcomes. Methods: This narrative review is structured around a ten-point decalogue addressing interconnected domains relevant to the maternal–milk–infant microbiota axis, including maternal diet, microbial diversity, environmental exposures, psychological stress and probiotic use. Current mechanistic and clinical evidence was examined to evaluate how these domains may modulate microbiota composition and function during breastfeeding. Attention was given to probiotic supplementation, including strain specificity, timing of administration, and clinical context, as well as to the broader implications of a One Health framework. Results: Available evidence suggests that maternal nutritional patterns, environmental and psychosocial exposures, and targeted microbiota-modulation strategies may influence the composition and functional properties of human milk and the developing infant microbiota. Probiotic use during breastfeeding appears to have strain-specific and context-dependent effects, with potential benefits in selected clinical scenarios. However, findings remain heterogeneous, and uncertainties persist regarding optimal strains, timing, and long-term outcomes. Conclusions: Breastfeeding can be understood as a dynamic biological interface shaped by maternal and environmental factors. Integrating microbiota-oriented strategies within a One Health framework may support infant gastrointestinal health and possibly contribute to longer-term developmental trajectories. Nevertheless, careful interpretation of the current evidence is warranted to avoid reductionist, supplement-centered approaches and to prevent maternal overmedicalization or blame. Full article

Postnatal corticosteroids are frequently administered to extremely preterm infants to support respiratory management, yet their effects on the immature cardiovascular system are complex and underexplored. As the second installment in a series on physiology-informed steroid use, this narrative review focuses on the cardiovascular consequences of systemic corticosteroid therapy in preterm neonates. We examine how corticosteroids influence key aspects of cardiovascular physiology, including ductal closure, systemic and pulmonary vascular resistance, myocardial remodeling, and autonomic regulation. Attention is given to the hemodynamic transition of early postnatal life and how steroid exposure may interact with patency of the ductus arteriosus and vascular development. The potential for corticosteroids to contribute to reactive myocardial hypertrophy, systemic hypertension, and pulmonary hypertension is also reviewed in the context of both short- and long-term outcomes. Emerging diagnostic and monitoring tools are discussed for their potential to guide individualized therapy. These include targeted neonatal echocardiography (TnECHO) to assess cardiac function and structure, electrocardiography (ECG) for rhythm and conduction abnormalities, heart rate variability analysis for autonomic function, and circulating biomarkers to evaluate myocardial stress and inflammation. Together, these tools may inform tailored steroid timing and dosing, especially in the research context, while monitoring for signs of cardiovascular side effects in real time. By synthesizing mechanistic insights with evolving clinical evidence, this review highlights the need for a more nuanced understanding of how corticosteroids affect the developing cardiovascular system. It underscores the importance of integrating cardiovascular monitoring into routine care to optimize therapeutic benefit while minimizing unintended harm. Alongside companion reviews addressing respiratory and growth impacts, this installment contributes to a broader framework for individualized, physiology-driven steroid use in extremely preterm infants. Full article

Over the years, the impact of music on the prenatal and neonatal stages of human life has gained significant scientific attention. This study provides a comprehensive bibliometric review of research investigating how music influences fetal and newborn development. Using the Scopus and Web of Science databases, a search of relevant studies published in English between January 2006 and July 2025 was conducted, whose basic criterion was the use of the following keywords: “music” and “fetus” or “fetal”. Additional terms such as “fetus development”, “fetus heart rate”, “fetus movement”, “mother–fetus relationship”, “newborn”, etc., were also utilized. In result, 75 publications were selected, and their bibliographic data and full sources were retrieved. The included studies were grouped according to two perspectives that consider the impact of music (1) on the development of the fetus and the newborn, and (2) on maternal health and mother–fetus bonding. Using VOSviewer, bibliometric mapping was performed, which allowed to obtain keyword co-occurrence network and co-authorship network. The chosen literature was then quantitatively and qualitatively analyzed. The analysis revealed a sharp upward trend in publications starting in 2015, with a temporary decline in 2020 due to the COVID-19 pandemic. The highest number of publications were from Iran. The most investigated topics were related to the fetus heart and maternal health. The most common publication type and research methodology were, respectively, article and experiment. While the key authors Lordier, L., Filippa, M., Grandjean, D., and Monaci, M.G. lead the field, the co-authorship network remains fragmented into isolated and relatively small research groups. The Journal of Maternal–Fetal and Neonatal Medicine emerged as the leading publication outlet, while the study by Graven et al. entitled “Auditory Development in the Fetus and Infant” remains the most cited work. The keyword co-occurrence network allowed the identification of three main thematic clusters indicating the physiological, clinical, and therapeutic aspects of the impact of music on fetal and neonatal development. A qualitative analysis revealed that music plays a vital role in early human development and maternal well-being, demonstrating positive effects of auditory stimuli on fetal and newborn physiology, as well as on the mother–fetus relationship, while being a non-invasive and non-pharmacological method of intervention. However, the lack of a fully connected global research community and standardized protocols for, e.g., choosing the musical repertoire, sound administration, and the duration of exposure suggests the need for increased international collaboration to further integrate music therapy into standard clinical practices for prenatal and neonatal care. Full article