Search Results (630)

Introduction: Cow’s milk protein allergy (CMPA) is one of the most common food allergies in early infancy and poses important clinical and economic challenges for affected children, their families, and healthcare systems. In Latin America, variability in diagnostic and therapeutic approaches remains substantial. Objective: We aim to systematically review the available evidence on CMPA, with emphasis on clinical characteristics, diagnosis, management, and economic impact, and to provide a complementary cost analysis of specialized formulas in the Colombian context. Methods: A systematic review was conducted according to PRISMA guidelines to synthesize current evidence on CMPA in pediatric populations. Studies published between 2010 and 2023 were screened using predefined eligibility criteria, and 46 studies were included in the qualitative synthesis. A complementary cost analysis was also performed to estimate the six-month costs associated with specialized infant formulas in Colombia, based on average age-specific formula consumption and standardized 2025 market prices. Results: The reviewed evidence confirms that CMPA is a heterogeneous condition with variable clinical manifestations and persistent diagnostic challenges, particularly in non-IgE-mediated presentations. Elimination of cow’s milk protein followed by oral food challenge remains the reference diagnostic approach. Breastfeeding with maternal dairy exclusion is consistently recommended as the preferred first-line strategy, whereas extensively hydrolyzed and amino-acid-based formulas are used when breastfeeding is not feasible or is insufficient. Estimated six-month costs ranged from COP 4,337,640 to COP 14,480,700 (approximately USD 1100–3600), depending on formula type. Conclusions: CMPA requires early recognition, careful clinical evaluation, individualized nutritional management, and improved access to effective and affordable treatment strategies. Full article

Background/Objectives: Sufficient sleep quantity/quality in infancy is crucial for healthy development, so it is important to identify early associated predictive factors. Research findings highlight salient endogenous (infant temperament) and exogenous (breastfeeding) influences, though no known studies have examined nuanced and interactive relations among these variables from early to late infancy/toddlerhood. Thus, the current study examined the main and interaction effects of these variables on infant sleep at 6 and 14 months while controlling for prenatal cortisol exposure. Methods: Data from a subsample (n = 79) of the Infant Development and Healthy Outcomes in Mothers Study were used, including prenatal maternal saliva samples assayed for cortisol and maternal questionnaires that included retrospective reporting of infant temperament, sleep quality and quantity, and breastfeeding frequency. Results: Multiple linear regression results include a statistically significant negative relation between prenatal maternal cortisol area under the curve and 6-month infant sleep quantity. A greater breastfeeding frequency at 6 months was associated with decreased 6-month sleep quality via conditional but not interaction effects. Greater 6-month infant Surgency was associated with better sleep quality at 14 months. There were no statistically significant interaction effects. Conclusions: The findings suggest that maternal psychophysiological stress has a significant influence on infant sleep duration, while research should further investigate the role of infant temperament and breastfeeding in shaping infant sleep quality. Significant conditional effects highlight patterns that should be re-examined with a larger sample to determine whether infant temperament may buffer against negative associations between breastfeeding frequency and infant sleep quality in early and late infancy in a developmental stage-consistent manner. Future replication studies should include a multi-method, longitudinal assessment of all key study variables, as well as a larger, more sociodemographically diverse sample of maternal–infant dyads. Full article

Background/Objectives: Appetite-regulating hormones are bioactive components of human milk. We tested the associations of leptin and adiponectin with infant growth and eating behaviors to age 6 months. Methods: In a cohort of 70 healthy, full-term infants and their mothers, human milk adiponectin and leptin were assayed at age 2 months (m). At infant ages 2, 4, and 6 m, infant anthropometry was obtained, mothers reported feeding frequency, duration, and breastfeeding intensity and completed the Baby Eating Behavior Questionnaire (Enjoyment of Food, Food Responsiveness, and General Appetite), and infant sucking vigor using an artificial nipple (burst duration and sucking frequency) was measured. Mothers reported demographics, gestational diabetes and pre-pregnancy body mass index (BMI), gestational age, and infant birthweight. Multivariate models evaluated predictors of leptin and adiponectin, and associations of leptin and adiponectin with infant growth and eating behaviors. Results: Human milk leptin was predicted by maternal BMI (β = 0.02) and breastfeeding intensity (β = −0.32). Regarding infant growth, infant weight-for-age and weight-for-length z-scores at 6 m were predicted by leptin (β = 0.91 and β = 1.22, respectively) and adiponectin (β = 0.01 and β = 0.01, respectively). Regarding infant eating behaviors, feeding duration at 2 m and feeding frequency at 4 m were predicted by adiponectin (β = 0.03 and β = −0.02, respectively). Conclusions: Human milk leptin and adiponectin may contribute to weight gain in early infancy, but the effect does not appear to be mediated substantially by infant eating behaviors. Further investigation into the metabolic programming of early infant weight gain is warranted. Full article

Unbiased stereology represents the most accurate approach for estimating the total number of neurons of specific brain regions; however, its reliability critically depends on the use of rigorously defined and anatomically appropriate sampling parameters. The brain nucleus Locus Coeruleus (LC) plays a key role in several brain functions. LC impairment has been associated with a range of disorders affecting individuals across the lifespan, from infancy to adulthood. In animal models of these conditions, precise estimation of LC neuronal number is essential. The LC analysis poses specific methodological challenges due to its small size, indistinct anatomical boundaries, and age-dependent changes in neuronal density. In this study, we present a detailed and reproducible stereological workflow for the quantification of LC neurons in the mouse brain across the lifespan. Using C57BL/6J mice at postnatal, adult, and aged stages, we optimized all key components of the Optical Fractionator method, LC neurons were identified by immunoperoxidase staining for tyrosine hydroxylase (TH) and quantified using systematic-random sampling implemented in Stereo Investigator^® software. We show that age-specific adjustment of stereological parameters is necessary to obtain reliable estimates, particularly at early postnatal stages characterized by high neuronal packing density. With the optimized protocols described here, TH+ LC neuron counts consistently met accepted precision criteria, as assessed by the Gundersen coefficient of error. Full article

Background: The first 1000 days of life, from conception to 2 years of age, represent a critical window during which nutrition can exert long-lasting effects on neurodevelopment, immune maturation, and susceptibility to prematurity-related morbidity. Docosahexaenoic acid (DHA) is a key structural n-3 long-chain polyunsaturated fatty acid of the brain and retina, characterized by rapid fetal accretion during the third trimester. Methods: We conducted a narrative review of studies published from March 2015 up to December 2025, including randomized controlled trials, follow-up studies, and systematic reviews/meta-analyses about DHA supplementation during pregnancy, lactation, infancy and early childhood, and its role on development. Results: Across the first 1000 days, DHA supplementation improves biochemical DHA status, particularly in populations with low baseline levels (moderate to high level of evidence), while clinical outcomes remain heterogeneous. During pregnancy, some benefits in specific cognitive and behavioral domains have been demonstrated, whereas effects on global cognition and long-term behavior are frequently null (moderate evidence). Visual outcomes appear favorable, with improvements in visual acuity (moderate evidence). In preterm infants, enteral DHA—often combined with arachidonic acid (ARA)—is feasible and well tolerated. DHA may reduce inflammatory markers and necrotizing enterocolitis risk when in equilibrium with ARA (low to moderate evidence), while no evidence supports the link between DHA and reduced risk of bronchopulmonary dysplasia and retinopathy of prematurity (moderate evidence). Neurodevelopmental outcomes are mixed: neuroimaging studies suggest enhanced white matter maturation with DHA + ARA, whereas most trials show no clear benefit regarding standardized developmental scores (moderate evidence). Conclusions: DHA is biologically essential during the first 1000 days, but its clinical impact depends on timing, dose, baseline status, and prematurity-related context. The balance between DHA and ARA, rather than DHA supplementation alone, emerges as a key determinant of clinical efficacy, supporting a shift toward precision-based nutritional strategies in early life. Full article

Singing-Oriented Language and Music Education (SOLME) is an accessible, low-resource pedagogical and cognitive framework in which singing serves as the primary interface through which musical activities support both first and foreign language acquisition processes. Early vocalizations in infancy make the overlap between singing and speech highly perceptible, forming a continuum rather than clearly separable domains. Child-directed speech similarly shares key features with singing—such as repetition, emotional engagement, exaggerated pitch variation and rhythm—and both input forms inherently combine musical and linguistic elements. Research has shown that the overlap between singing and language abilities persists throughout the lifespan, positioning singing as a valuable facilitator of language learning processes. Singing, integrated as a musical tool, has proven effective in enhancing key abilities for (foreign) language learning—including phonological awareness, pronunciation, and verbal memory, among others—and in supporting language functioning across diverse communication disorders, from developmental fluency challenges to acquired impairments. This entry outlines the benefits of singing as an integrated means to support musical development as well as first and second language acquisition processes. It outlines functional and structural similarities between singing and language development, from early caregiver–infant interaction to formal foreign-language instruction, and then discusses the many advantages of embedding singing as a musical tool in the (foreign) language learning process. Full article

Preterm birth interrupts critical phases of lung development and is associated with long-term alterations in respiratory structure and function. While bronchopulmonary dysplasia (BPD) has traditionally been considered the principal determinant of adverse outcomes, accumulating evidence indicates that prematurity per se contributes substantially to persistent pulmonary impairment. Lung function trajectories in preterm-born children frequently track along lower percentiles from infancy into adolescence and early adulthood, with limited catch-up growth and increased vulnerability to chronic airflow limitation. Assessment of lung function requires a developmentally tailored approach, as feasibility and interpretability vary across age groups. In infancy, non-volitional techniques such as tidal breathing flow-volume loop analysis and raised-volume rapid thoracoabdominal compression allow early evaluation of respiratory mechanics. During toddlerhood, methodological limitations persist, although emerging technologies may expand feasibility. In preschool children, impulse oscillometry enables detection of small airway dysfunction, often preceding spirometric abnormalities. From school age onward, spirometry, body plethysmography, diffusing capacity, and multiple breath washout provide complementary information on obstructive, restrictive, and gas-exchange impairments. Longitudinal studies demonstrate that reduced lung function is not confined to children with BPD and may predispose to early-onset chronic obstructive pulmonary disease-like phenotypes. Early identification of abnormal trajectories and modifiable risk factors supports structured long-term follow-up and preventive strategies. Standardization of age-specific assessment protocols and harmonization of reference values are essential to improve risk stratification and optimize long-term respiratory outcomes in this vulnerable population. Full article

Changes in microbial composition during early infancy by various factors (mode of delivery, nutritional practices, antibiotic usage, and environmental influences) have been correlated with observable variances in cognitive abilities, temperament, stress response, and the predisposition to neurodevelopmental disorders. Consequently, microbiota-targeted interventions such as probiotics, prebiotics, and synbiotics are being explored as avenues to enrich beneficial microbial taxa, enhance short-chain fatty acid production, fortify mucosal immunity, and mitigate inflammatory responses during these critical periods. Preclinical research, primarily in experimental animal models, has demonstrated a causal link between microbiota composition and developmental processes such as myelination, synaptic plasticity, and socio-emotional behaviors, whereas human evidence remains largely associative and heterogeneous. A notable gap exists in the current literature, which typically centers on gastrointestinal, psychiatric, or preterm outcomes, without a focused investigation into neurodevelopmental assessments within the first three years. To bridge this gap, we conducted a systematic review and meta-analysis of randomized controlled trials assessing the impact of probiotics, prebiotics, and synbiotics on neurodevelopment and behavior in infants aged 0–36 months. Our primary objective was to establish whether microbiota-targeted strategies confer discernible neurodevelopmental benefits, alongside elucidating the mechanisms underpinning the relationship between microbial modulation and early brain development. Full article

Background: Secondary pseudohypoaldosteronism (PHA) is a rare, transient condition caused by renal tubular resistance to aldosterone, most commonly associated with urinary tract infection (UTI) and/or congenital anomalies of the kidney and urinary tract (CAKUT). It mimics primary adrenal disorders, presenting with life-threatening electrolyte disturbances in early infancy. Case Presentation: We report a male infant admitted twice within the first four months of life with severe dehydration, hyponatremia, hyperkalemia, metabolic acidosis, and acute kidney injury (AKI). Urine cultures grew Klebsiella pneumoniae and later Escherichia coli. Imaging studies demonstrated obstructive CAKUT, including posterior urethral valves, bilateral megaureters, hydronephrosis, and bladder diverticulosis. Congenital adrenal hyperplasia was excluded. Further evaluation showed markedly elevated plasma renin and aldosterone levels, confirming secondary PHA. The patient was successfully treated with intravenous fluids, electrolyte correction, and antibiotic therapy. Subsequently, oral sodium chloride and bicarbonate supplementation were added. Stepwise surgical correction of the urinary tract anomalies was initiated. Conclusions: Secondary PHA should be considered in infants presenting with failure to thrive, dehydration, hyponatremia, and hyperkalemia, particularly in the presence of UTI or CAKUT. Early recognition and differentiation from primary adrenal disorders are essential to prevent life-threatening complications. Prompt correction of electrolyte imbalance and management of the underlying urinary tract pathology are crucial for favorable outcomes. Full article

Background: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and hospitalization in infancy. Reliable biomarkers reflecting host antiviral responses and disease dynamics are still lacking. Methods: We evaluated the expression of the interferon-stimulated genes IFI44L, IFI27, and RSAD2 in peripheral blood of infants hospitalized with RSV bronchiolitis at admission and discharge, and in healthy controls, using multiplex RT-qPCR. A composite interferon-based Viral Score was derived from coordinated ISG expression. Results: All three ISGs and the Viral Score were markedly elevated during acute RSV infection at hospital admission compared with discharge and healthy controls. Following clinical recovery, ISG expression and Viral Score declined significantly and approached baseline levels. The Viral Score clearly discriminated acute infection from recovery and healthy states, reflecting dynamic systemic interferon activation. Conclusions: A Viral Score based on IFI44L, IFI27, and RSAD2 captures systemic antiviral immune responses in infants with RSV bronchiolitis and declines with disease resolution. This interferon-based host-response signature represents a promising biomarker for defining viral infection status and monitoring disease dynamics in pediatric respiratory infections. Full article

Background: Vitamin B12 deficiency is a recognized but frequently under-integrated cause of global developmental delay (GDD) in infancy and early childhood. Early diagnosis is critical because neurological impairment may be partially or completely reversible with timely treatment. Objective: This narrative review aims to synthesize current evidence on the role of vitamin B12 deficiency in the diagnostic evaluation of GDD, with a focus on clinical phenotype, risk factors, biomarkers, treatment outcomes, and practical integration into contemporary diagnostic algorithms. Methods: A structured, non-systematic search of PubMed/MEDLINE, Embase, and Web of Science was performed to identify clinical studies, case series, reviews, and guideline documents addressing pediatric vitamin B12 deficiency and neurodevelopmental delay. Results: Vitamin B12 deficiency in early childhood is most commonly associated with maternal deficiency and exclusive breastfeeding without adequate supplementation. Evidence from recent clinical and observational studies indicates that vitamin B12 deficiency may present with nonspecific neurological symptoms, including developmental regression, hypotonia, and feeding difficulties. Incorporating vitamin B12 assessment—using serum vitamin B12, holotranscobalamin, methylmalonic acid, and homocysteine—into early diagnostic algorithms for GDD may facilitate timely identification of a treatable cause of neurodevelopmental impairment. The proposed diagnostic framework emphasizes early biochemical evaluation in infants with unexplained developmental delay, thereby supporting prompt treatment during a critical window of neurological reversibility. Conclusions: Targeted assessment of vitamin B12 status in children with GDD, together with evaluation of maternal status, represents a clinically relevant approach to identifying a potentially preventable and treatable cause of neurodevelopmental impairment. Integration of functional biomarkers into diagnostic pathways and the development of pediatric-specific reference standards are key priorities for future research and clinical practice. Full article

Introduction: Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is a rare autosomal recessive disorder caused by biallelic variants in the tartrate-resistant acid phosphatase 5 (ACP5) and characterized by variable skeletal, immunological, and neurological manifestations. Because early skeletal abnormalities may be subtle, diagnosis can be challenging in infancy. Materials and methods: We conducted a detailed clinical, immunological, radiological, and molecular evaluation of an infant with early-onset cytopenia, recurrent infections, seizures, and developmental delay. Genomic analysis was performed using whole exome sequencing (WES) and copy number variation sequencing (CNV-seq). In addition, we performed a structured narrative review of published ACP5-related SPENCDI cases to summarize the clinical spectrum and the currently reported use of Janus kinase (JAK) inhibitors. Results: Genomic analysis identified an ACP5 stop-gain variant (c.311G>A; p.Trp104*) with an apparently homozygous signal on WES. Re-evaluation of the copy-number data demonstrated an overlapping heterozygous 19p13.2–p13.13 deletion encompassing ACP5, indicating biallelic ACP5 defects consisting of a sequence variant on one allele and deletion of the other allele. Clinically, the patient showed prominent extra-osseous manifestations, including impaired T- and NK-cell cytotoxicity, before the emergence of definite radiographic skeletal abnormalities. Our literature review showed that skeletal abnormalities were repeatedly documented across published ACP5-related SPENCDI reports, although radiographic changes were often subtle and could be preceded by immune manifestations. Reported use of JAK inhibitors suggests potential benefit for immune dysregulation in selected patients, whereas the neurological response remains uncertain. Conclusions: This study reports a novel ACP5 variant and expands the known phenotypic spectrum of SPENCDI. SPENCDI should be considered in children with unexplained immune dysfunction and developmental delay, and suggestive neuroimaging findings, even when overt skeletal deformities are absent. Early genetic testing and targeted skeletal imaging may facilitate diagnosis. Full article

Background: The first 1000 days of life represent a critical window for developmental programming, during which specific nutritional exposures, such as vitamin D levels, may influence long-term health trajectories. Vitamin D plays a central role in skeletal development, but increasing evidence also supports its possible involvement in immune, metabolic, and neurodevelopmental processes during early life. In this narrative review, we summarize current evidence on the biological functions of vitamin D across the first 1000 days, focusing on its roles in skeletal, immune, metabolic, and neurodevelopmental processes, and its potential role as a programming factor. Methods: We conducted our research using the PubMed, Scopus, and Cochrane databases. We included systematic reviews, randomized controlled trials, and high-quality observational studies published from 2015 onward, focusing on pregnancy, neonatal life, and early childhood. Results: Vitamin D acts through placental, epigenetic, skeletal, immune, metabolic, and neurodevelopmental pathways that are particularly active during early development. Low maternal or early-life vitamin D status has been associated with adverse birth outcomes and impaired bone health. It has also been linked to increased susceptibility to infections and allergic diseases, altered metabolic trajectories, and mild neurodevelopmental differences. Evidence from supplementation trials remains heterogeneous, with benefits appearing more consistent in populations with baseline deficiency. Conclusions: Vitamin D fulfills several biological plausibility criteria for a potential early-life programming factor, although current human evidence remains heterogeneous. Full article

Inherited distal renal tubular acidosis (dRTA) is a rare but clinically significant disorder of renal acid–base regulation that frequently presents in infancy or early childhood. Among the genetic causes of autosomal recessive dRTA, mutations in the ATP6V1B1 gene are particularly important due to their association with early-onset disease and sensorineural hearing loss. Failure to recognize and treat this condition promptly can result in growth retardation, bone disease, nephrocalcinosis, chronic kidney disease, and permanent auditory impairment. This article presents a comprehensive review of the pediatric literature concerning dRTA. We focus on the pathophysiology, pediatric presentation, renal and audiological outcomes, genetic architecture, and management implications of ATP6V1B1-associated dRTA in children. We highlight evolving genotype–phenotype correlations, the emerging recognition of autosomal recessive disease mechanisms, and the importance of early diagnosis and long-term multidisciplinary follow-up. Full article

Early life represents a critical developmental programming window during which nutrition and microbial exposures shape long-term physiological function. Feeding mode is a major determinant of infant gut microbiota assembly and metabolic activity. This narrative review synthesizes current evidence comparing breastfeeding (BF) and formula feeding in relation to microbial composition, functional capacity, and immune programming during the preweaning and early postweaning periods. BF may support a relatively stable, bifidobacteria-dominated microbiota enriched in pathways involved in carbohydrate utilization, vitamin biosynthesis, and immune modulation. Human milk oligosaccharides, secretory IgA, lactoferrin, and milk-associated microbes collectively guide microbial succession, enhance barrier integrity, and support immune tolerance. In contrast, formula-fed infants typically exhibit greater microbial diversity, earlier transition toward adult-like profiles, and increased abundance of facultative anaerobes, alongside the enrichment of pathways related to bile acid and amino acid metabolism. Microbiota patterns in formula-fed infants are further influenced by formula composition, including protein load, lipid structure, and supplementation with prebiotics, probiotics, and human milk oligosaccharide analogues. Although advances in formula design have reduced compositional gaps, functional differences in microbial stability and immune programming persist. Recognizing early infancy as a sensitive programming window underscores the need for microbiome-informed nutritional strategies and longitudinal, multi-omics research to clarify causal mechanisms and optimize early-life interventions. Full article