Search Results (363)

Background and Clinical Significance: Sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD) syndrome is a rare autosomal recessive disorder caused by biallelic variants in the TRNT1 gene, which encodes tRNA nucleotidyltransferase 1. The disease typically presents early in life with microcytic anemia, recurrent febrile episodes, developmental delay, and immune dysfunction. Because of its rarity and variable clinical expression, diagnosis may be challenging, and broad genetic testing can identify additional variants whose clinical significance requires careful interpretation. Case Presentation: We report a 4-month-old male infant with recurrent febrile episodes, severe recurrent microcytic anemia, recurrent infections, mild psychomotor developmental delay, and multisystem involvement. Genetic analysis identified two heterozygous TRNT1 variants inherited from different parents and confirmed to be in trans: a maternally inherited pathogenic frameshift variant, c.428_431del, p.(Asp143Glyfs12), and a paternally inherited missense variant, c.1246A>G, p.(Lys416Glu), initially classified as a variant of uncertain significance and subsequently interpreted as likely pathogenic in the context of the clinical phenotype and segregation findings. These findings supported the diagnosis of TRNT1-related SIFD syndrome. An additional heterozygous pathogenic C7 variant, c.633_643del, p.(Ser212Hisfs4), was identified. No second pathogenic C7 allele was detected, and functional complement testing was not performed; therefore, complement component 7 deficiency could not be established. Conclusions: This case highlights the importance of early genetic evaluation in infants with recurrent fever, microcytic anemia, immune abnormalities, and multisystem involvement. It also emphasizes the need for cautious interpretation of additional monoallelic pathogenic variants detected by broad genetic panels when functional confirmation and a compatible inheritance pattern are lacking. Full article

Background/Objectives: Breastfeeding confers important health benefits for mothers and children. The coronavirus disease 2019 (COVID-19) pandemic disrupted childcare practices and maternal behaviors, with some effects persisting beyond the acute phase. This study aimed to evaluate the impact of the COVID-19 pandemic on breastfeeding. Methods: This retrospective single-center study included full-term infants born at Tokyo Metropolitan Toshima Hospital between January 2019 and January 2024. Data was routinely collected. The participants were categorized into those born before, during, and after the pandemic. The rates of exclusive breastfeeding and volume of formula milk at 1-month health checkups were compared across the groups using the chi-square test and regression analysis. Results: A total of 812 (30.1%), 1602 (61.0%), and 214 (8.1%) infants born before, during, and after the pandemic, respectively, were analyzed. The rates of exclusive breastfeeding differed significantly among the groups, (42.2%, 28.1%, and 22.9%, respectively). Concurrently, formula milk consumption increased during the study period, with significant differences observed between those born before and during the pandemic and between those born before and after the pandemic. Conclusions: Breastfeeding rate declined during the COVID-19 pandemic and the effect persisted after the pandemic. We speculate this trend may be attributed to the loss of educational opportunities and reduced interactions among mothers. Another contributing factor was the shift in the sources of information for maternal decision-making. After the pandemic, reliance on social media as a primary source of guidance increased; however, much of this information was less evidence-based and potentially inaccurate. Healthcare providers should recognize these challenges and prepare for future pandemics. Full article

Early childhood dental caries (ECC) remains one of the most prevalent and preventable chronic diseases affecting young children globally, yet behavioral and contextual determinants of its onset during the first 1000 days of life remain poorly understood and infrequently modeled in Latin American populations. This study presents a novel application of the PRECEDE diagnostic framework to conceptualize Early Childhood Dental Caries during the first 1000 days (1000ECDC) as a behaviorally rooted, socio-ecologically conditioned health problem. Drawing on a formative longitudinal pilot study (n = 10 mother–infant dyads, Caracas, Venezuela) and a complementary narrative literature review, we develop the first PRECEDE-based conceptual model linking maternal prenatal and postnatal behaviors to dental caries risk in a Latin American context. The model identifies dietary and feeding behaviors, oral health care practices, and healthcare service utilization as primary behavioral risk factors, modulated by predisposing factors (low oral health knowledge, limited self-efficacy, cultural norms), enabling factors (socioeconomic constraints, fragmented health systems), and reinforcing factors (social norms, family influence). Exploratory pilot findings indicated that more than 60% of children had advanced dental caries lesions at 24-month follow-up, consistent with regional estimates and underscoring the urgency of early intervention. This model provides practitioners and policymakers with a structured, evidence-informed diagnostic tool to guide the design of early-life oral health promotion programs, with particular relevance for low-resource Latin American settings. Future validation through expert consensus and prospective studies is warranted. Full article

Acute hepatitis B virus (HBV) infection is rare during infancy, and severe symptomatic HBV-associated hepatitis is even less common. We describe two siblings who developed severe HBV-associated liver injury during infancy, two years apart, but experienced markedly divergent clinical outcomes. Clinical, laboratory, virological, microbiological, imaging, therapeutic, and follow-up data were retrospectively reviewed. Household members were subsequently tested for HBV and HDV. The first infant, a 5-month-old girl, presented with HBsAg positivity, negative serological markers for HAV, HCV, and HEV, and severe acute liver injury with a fulminant clinical course that resulted in death. Because anti-HBc IgM, HBV DNA, repeat HBsAg testing, and follow-up serology were unavailable, acute HBV infection could not be confirmed, and the episode was therefore classified as presumed HBV-associated fulminant hepatitis. The rapidly fatal clinical course precluded a comprehensive etiological evaluation, and the available medical records did not fully document the diagnostic work-up. The second patient, a 4-month-old boy, presented with serological and molecular evidence of acute HBV infection, including low-level HBV DNA, total anti-HDV positivity of uncertain clinical significance, and positive CMV IgM/IgG serology. He also had a urinary tract infection (UTI) caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. Without HDV RNA and CMV DNA testing, active HDV infection and clinically significant CMV disease could not be definitively confirmed, while passive transfer of maternal anti-HDV antibodies could not be excluded. The patient required prolonged hospitalization, during which he received supportive, replacement, and antimicrobial therapy. He recovered, and long-term follow-up demonstrated HBsAg clearance with undetectable HBV DNA. Testing of household members revealed chronic HBV infection in the mother and maternal grandmother, both of whom had detectable HDV RNA, consistent with ongoing HBV/HDV circulation within the family. However, without viral sequence data from the infants, the source, route, timing, and direction of transmission could not be established. These cases illustrate the potential severity of HBV-associated hepatitis during infancy and its highly variable clinical outcomes. They also underscore the importance of antenatal HBV screening, timely immunoprophylaxis, and cautious interpretation of suspected viral coinfections when molecular confirmation is unavailable. Full article

Background: Perinatal deaths remain a major public health concern and present unique medico-legal challenges. Forensic autopsy plays a crucial role in determining the cause of death, distinguishing live birth from stillbirth, assessing fetal viability, and identifying traumatic or non-natural causes of death. Methods: This retrospective study included all perinatal cases referred to the Gaziantep Forensic Medicine Group Presidency between 2021 and 2024. Demographic characteristics, gestational age, autopsy findings, histopathological and toxicological examinations, hydrostatic lung test results, and final forensic diagnoses were evaluated. Results: Seventeen of 339 infant forensic cases met the inclusion criteria. Fourteen underwent complete forensic autopsy, whereas three were evaluated by external postmortem examination and medical records. Despite a multidisciplinary forensic investigation that included external examination, complete forensic autopsy, systematic macroscopic organ evaluation, routine histopathological examination, hydrostatic lung flotation testing, toxicological analysis when indicated, review of maternal medical and obstetric records, judicial investigation records, and placental and umbilical cord histopathology whenever available, no definitive cause of death could be established in six cases. Advanced decomposition prevented determination in two cases. One case was classified as an undiagnosed natural death, whereas no specific cause of death could be assigned in the remaining three cases. Placental examination was available in only a minority of cases, whereas umbilical cord histopathology was performed in nearly all autopsied cases. Causes of death included traumatic injury, pulmonary immaturity, intrauterine infection, congenital anomalies, maternal drug exposure, placental abruption, maternal disease, and umbilical cord pathology. Conclusions: Perinatal death investigations require a multidisciplinary forensic approach integrating autopsy, histopathology, toxicology, placental examination, and clinical information. Beyond determining the cause of death, forensic evaluation is essential for assessing live birth, fetal viability, suspected abuse, maternal violence, medical malpractice, and criminal investigations. Full article

Acute bronchiolitis is the leading cause of infant hospitalization worldwide, with respiratory syncytial virus (RSV) historically predominating. Prospective virological data for the 2025–2026 epidemic season in Morocco were lacking. A prospective observational cohort study was conducted at the Department of Pediatric Infectious Diseases and Clinical Immunology, Casablanca Mother-Child Hospital, from August 2025 through March 2026. Consecutive infants aged 1–24 months hospitalized with acute viral bronchiolitis underwent nasopharyngeal sampling and multiplex rapid antigen testing for RSV, influenza A, influenza B, and SARS-CoV-2. A total of 131 infants were enrolled (median age 4.8 months; male-to-female ratio 0.84:1). At least one virus was identified in 63 patients (48.1%; 95% CI 39.1–57.3%). RSV predominated: 49 sole infections and 2 co-infections with influenza A, totaling 51 positives (80.9% of virus-positive cases; 38.9% of the cohort). Influenza A totaled 8 cases (12.7%), including the 2 co-infections; influenza B accounted for 2 further cases (3.2%). SARS-CoV-2 was not detected. Epidemic activity peaked in January 2026 (65 admissions), declining through February (34) and March (12). All detected pathogens have licensed preventive options, supporting the introduction of nirsevimab, maternal RSV vaccination, and seasonal influenza vaccination as public health priorities in Morocco. Full article

Background: Neonates and young infants are susceptible to vaccine-preventable diseases because of immature immune responses and delayed acquisition of vaccine-induced protection. As household members and caregivers are a major source of exposure, international organizations recommend cocooning, i.e., vaccination of susceptible individuals who are in regular contact with infants, to provide complementary indirect neonatal protection. To evaluate cocooning implementation, we assessed influenza and pertussis vaccination uptake among mothers and close contacts of hospitalized neonates and identified factors associated with vaccine uptake. Methods: Mothers of neonates hospitalized in a Neonatal Intensive Care Unit (NICU) between 1 January 2022 and 31 December 2024 were invited to complete a structured questionnaire. Mothers reported their own vaccination status and that of the neonate’s close contacts. Associations between maternal characteristics and vaccine uptake were examined using logistic regression. Results: In total, 405 mothers participated. Influenza vaccination uptake was 47.6% among mothers, and at least one adult close contact was vaccinated in 53.6% of families. Pertussis vaccination uptake was 40.5% among mothers, and at least one adult close contact was vaccinated in 32.3% of families. The most frequently reported reason for non-vaccination was low perceived need among unvaccinated mothers (74.1% for influenza and 83.4% for pertussis) and among families with incompletely vaccinated adult close contacts (81.8% for influenza and 89.7% for pertussis). In multivariable analyses, higher maternal education was associated with increased uptake of both influenza (OR 2.36, 95% CI: 1.47–3.80, p < 0.001) and pertussis vaccination (OR 4.25, 95% CI 2.02–8.94, p < 0.001), whereas younger maternal age (≤25 years) was associated with lower influenza vaccine acceptance (OR 0.24, 95% Cl: 0.1–0.60, p = 0.002). Conclusions: Vaccination uptake among mothers and adult close contacts of NICU-admitted neonates was suboptimal for both influenza and pertussis vaccines. Targeted counseling before delivery, reinforced during maternity or NICU hospitalization as a catch-up opportunity, and system-level implementation measures aligned with the dominant barrier of low perceived need are needed to strengthen cocooning in this high-risk population. Full article

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infection in young infants and accounts for substantial morbidity, hospitalization, and mortality worldwide, with the highest burden concentrated in the first months of life, when immunological and anatomical immaturity favors severe disease. Maternal vaccination has emerged as a strategy to bridge this window of vulnerability through the transplacental transfer of neutralizing antibodies. This integrative review synthesizes scientific articles published between 2022 and 2026, including systematic reviews, meta-analyses, narrative reviews, and position statements from national and international scientific societies, addressing the epidemiology, clinical manifestations, diagnosis, mechanism of action, efficacy, safety, and public health impact of maternal RSV immunization. The bivalent prefusion F protein vaccine (RSVpreF; Abrysvo^®), administered as a single intramuscular dose between 32 and 36 weeks of gestation, induces maternal IgG that is transferred to the fetus and confers passive protection during the first six months of life. In the phase 3 MATISSE trial, vaccination demonstrated 81.8% efficacy against severe RSV lower respiratory tract infection within 90 days of birth and 69.4% within 180 days, alongside reductions in hospitalization. The safety profile was favorable, with predominantly mild and transient adverse events; a numerical imbalance in preterm birth remains under surveillance and underlies the precautionary gestational window. Maternal vaccination and long-acting monoclonal antibodies (nirsevimab) are best regarded as complementary rather than competing strategies. Current evidence supports maternal immunization as one of the most effective measures to reduce the burden of RSV disease in early infancy. Full article

Omega-3-fortified foods sit at the interface of lipid science, food technology, and prevention-oriented nutrition. The aim of this narrative review is to define practical criteria for evaluating whether fortified foods can deliver physiologically relevant eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) rather than merely declare omega-3 addition. This review focuses on fish oils, fish-processing by-product oils, single-cell oils, and encapsulated or emulsified delivery systems used in dairy products, bakery products, beverages, spreads, eggs, infant and maternal foods, nutrition bars, and related functional foods. It integrates evidence on raw material composition, refining, oxidative stability, food-matrix compatibility, retained dose during shelf life, bioavailability, biomarker response, health benefits, safety concerns, and regulatory communication. The proposed source-to-status quality-by-design framework emphasizes that applied value depends on traceable source selection, analytical quality control, matrix-specific protection, end-of-shelf-life verification, transparent dose labeling, and claims that remain proportional to evidence. Ordinary low-dose fortified foods should not be presented as equivalents of prescription omega-3 products or as general disease-prevention tools. Their defensible role is status-oriented dietary optimization in populations with low EPA/DHA intake. Full article

Cytomegalovirus (CMV) remains one of the most relevant congenital and early-life infections in pediatrics because of its high global seroprevalence, lifelong latency, and potential for reactivation or reinfection. Biologically, the virus poses a particular threat during pregnancy, when maternal primary infection carries a substantially higher risk of transplacental transmission than non-primary infection, with fetal and neonatal consequences that vary according to gestational timing and host vulnerability. In children, CMV infection is common in the first years of life and may contribute to a broad spectrum of outcomes, ranging from asymptomatic infection to severe multisystem disease, neurodevelopmental impairment, and sensorineural hearing loss. Clinically, the document highlights the importance of timely maternal diagnosis, differentiation between primary and recurrent infection, and integration of prenatal, neonatal, radiological, and audiological assessment. Attention is given to symptomatic and asymptomatic newborns, preterm infants, and infants exposed through breast milk. The availability of antiviral strategies in pregnancy and infancy strengthens the rationale for early identification and risk stratification. Universal newborn screening emerges as a potentially valuable approach to improve case detection, enable prompt follow-up, and reduce long-term disability. Overall, a multidisciplinary and early-intervention framework is essential to optimize prevention, diagnosis, treatment, and long-term outcomes in pediatric CMV infections. Full article

Background: Low-birth-weight (LBW, <2500 g) infants are at increased risk of suboptimal hepatitis B vaccine responses; yet, data on their immunogenicity patterns and modifiable determinants remain limited. This study aimed to assess hepatitis B vaccine immunogenicity in LBW infants and to examine whether postnatal catch-up growth and maternal–neonatal characteristics are independently associated with antibody levels. Methods: We enrolled 511 LBW infants who completed the recommended 3-dose hepatitis B vaccination series at 0, 1, and 6 months. Blood samples were collected 4–6 weeks after completion of the full vaccination series. Geometric mean concentration (GMC) and seroprotection rate (SPR, anti-HBs ≥ 10 mIU/mL) were evaluated. Catch-up growth was quantified as the change in weight-for-age Z-score between 6 and 8 months of age (ΔWAZ). Multivariable linear regression was used to identify independent predictors of log-transformed antibody titers, adjusting for gestational age, maternal hepatitis B surface antigen (HBsAg) positivity, maternal body mass index (BMI), maternal fasting glucose, maternal thyroid disease, infant hemoglobin at 6 months, and ΔWAZ. Results: The overall SPR was 99.41% (508/511), with a GMC of 1045.37 mIU/mL (95% CI: 916.24–1192.70). SPR remained consistently high across all subgroups. In multivariable analysis, ΔWAZ was not significantly associated with antibody levels (β = −0.063, p = 0.571). Maternal HBsAg positivity showed no significant association (β = −0.104, p = 0.792). Maternal thyroid disease was independently associated with higher antibody levels (β = 0.793, 95% CI: 0.213–1.373, p = 0.007). None of the other covariates reached statistical significance. Conclusions: Hepatitis B vaccination demonstrated high immunogenicity in LBW infants, with very high seroprotection rates. Postnatal catch-up growth did not independently influence antibody levels. The significant positive association between maternal thyroid disease and infant antibody response warrants further prospective investigation. Full article

Every year, respiratory syncytial virus (RSV) causes an estimated 33 million lower respiratory tract infections in children under five years of age, driving millions of hospitalizations worldwide and substantial mortality in developing countries. For 28 years, the monoclonal antibody (mAb) palivizumab has been the principal agent for RSV immunoprophylaxis, reducing hospitalization in defined high-risk groups through monthly intramuscular dosing. The recent approval of two second-generation long-acting mAbs, nirsevimab and clesrovimab, and maternal preF vaccine has fundamentally changed the RSV prevention landscape. In contrast to palivizumab, the long-acting mAbs offer single-dose seasonal protection across a broader infant population, enabling universal immunization programmes for the first time. In this review, we conjointly examine nirsevimab and clesrovimab across their mechanisms of action, pharmacokinetics, efficacy, safety and cost-effectiveness, using palivizumab as the reference standard. Cross-trial efficacy comparisons are complicated by differences in study populations and endpoint definitions; however, when these factors are considered, the available evidence suggests that all three agents offer broadly comparable protection against severe RSV disease. All three agents also demonstrate favourable and comparable tolerability profiles. Nirsevimab is now supported by a substantial body of real-world evidence confirming effectiveness in routine immunization programmes that closely align with registrational studies. Clesrovimab, as the newest agent, currently lacks real-world effectiveness, and both long-acting monoclonals require further confirmatory evidence in high-risk groups. Overall, existing data support that both monoclonals have equivalent efficacy and safety profiles as palivizumab, and choice should be based on cost-effectiveness and local availability, with consideration given to optimal integration of infant immunoprophylaxis alongside maternal RSV vaccination programmes. Full article

L-citrulline is a non-protein amino acid with critical roles in perinatal and neonatal physiology through the intestinal–renal arginine–citrulline axis and nitric oxide (NO) production. During pregnancy, L-citrulline supports placental angiogenesis, vascular adaptation, and fetal growth through augmentation of arginine availability and endothelial NO production. In neonates, particularly preterm infants, developmental immaturity of citrulline and arginine synthesis contributes to hypoargininemia and may increase susceptibility to necrotizing enterocolitis, bronchopulmonary dysplasia with pulmonary hypertension, sepsis, and impaired intestinal function. Although L-citrulline has emerged as a promising modulator of NO bioavailability, prior reviews have largely focused on either adult cardiovascular disease or isolated neonatal applications, with limited integration of its mechanistic and translational relevance across the perinatal and neonatal continuum. Collectively, current evidence supports L-citrulline as a promising translational target in maternal–fetal and neonatal medicine because of its central role in vascular, inflammatory, and metabolic regulation. However, adequately powered clinical trials are needed to define optimal dosing, timing, patient selection, and long-term outcomes before routine clinical implementation can be recommended. This review provides a comprehensive evaluation of L-citrulline metabolism and its therapeutic potential from pregnancy through neonatal life, with emphasis on the intestinal–renal arginine–citrulline axis, endothelial function, and NO-mediated vascular regulation. We specifically examine the role of citrulline in key pathophysiologic mechanisms underlying maternal and neonatal disease, including endothelial dysfunction, impaired NO bioavailability, inflammation, oxidative stress, and abnormal placental vascular remodeling. Full article

Background/Objectives: In the first months of their life, infants rely on maternal antibodies for immune protection. Breastmilk is a major source of these defenses, supplying secretory IgA, IgG, and IgM that help guard mucosal surfaces against pathogens such as SARS-CoV-2. Most studies on breastmilk immunity in the context of COVID-19 have emphasized circulating monomeric IgA, rather than the multimeric secretory IgA (sIgA) that is active at mucosal barriers. This study assessed in-depth the contribution of breastmilk antibody subtypes to SARS-CoV-2 neutralization capacity and how these profiles differ following maternal COVID-19 infection versus vaccination during pregnancy or postpartum. Methods: In this prospective cohort study, breastmilk samples were collected longitudinally from individuals who had COVID-19 during pregnancy or received COVID-19 mRNA vaccination during pregnancy or postpartum. Serological assays measured IgG, IgM, systemic IgA, and secretory IgA against SARS-CoV-2 spike and nucleocapsid antigens. Results: COVID-19 infection during pregnancy resulted in significantly higher systemic and secretory IgA levels compared to vaccination. Secretory IgA demonstrated a strong correlation with neutralization capacity. Principal component analysis revealed distinct antibody profiles in COVID-19-exposed individuals versus vaccinated cohorts, with significant overlap between pregnancy and postpartum vaccination groups. Conclusions: Although both COVID-19 vaccination and disease elicit sustained COVID-19-related antibodies in breastmilk, COVID-19 infection elicits a broader and more diverse antibody response in breastmilk, specifically with a greater secretory IgA generation. These findings support the value of maternal vaccination to safely confer mucosal immunity to neonates and the need for optimized vaccine formulations for mucosal immunity. Full article

Background and Objectives: Despite global commitment to the World Health Organization triple elimination initiative, evidence on integrated antenatal service delivery models that simultaneously address human immunodeficiency virus (HIV), syphilis, and hepatitis B virus (HBV) remains fragmented, particularly across diverse health-system contexts. Eliminating vertical transmission of HIV, syphilis, and HBV is a global priority. Pregnant women are disproportionately affected by these infections, and untreated maternal disease leads to significant infant morbidity. Integrating antenatal screening and treatment provides an opportunity to address all three conditions simultaneously. Purpose: This systematic review and meta-analysis aimed to identify and synthesise evidence on integrated antenatal service delivery models addressing HIV, syphilis, and HBV simultaneously within maternal health services. It specifically examined model characteristics, screening uptake, treatment and follow-up outcomes, implementation barriers and facilitators, and evidence on cost-effectiveness. Methods: This systematic review and meta-analysis followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420261342186). We searched Scopus, PubMed, Web of Science, and Dimensions for studies published between January 2007 and January 2026. Of 423 records identified, 11 met the inclusion criteria after excluding two studies that did not provide empirical results for an integrated service model addressing all three target infections simultaneously. Data on study characteristics, service delivery, diagnostics, outcomes, and implementation factors were extracted. A random-effects meta-analysis of proportions was conducted using the DerSimonian–Laird estimator with logit transformation. Results: Eleven studies covered Asia, Africa, Europe, and Latin America, mostly in low- and lower-middle-income countries. Integration ranged from rapid test packages in community clinics to comprehensive programmes including STI treatment, malaria testing, and HBV birth-dose vaccination. Pooled triple testing uptake was 97% (95% CI 92 to 100%). Large programmes achieved over 99% coverage and reduced HIV vertical transmission to below 3%. Pilot studies showed feasibility but noted stockouts, data gaps, and weak treatment linkage. Economic analyses supported cost-effectiveness. Conclusions: Integrated antenatal services appear feasible and can achieve high testing uptake, particularly in well-supported programmes. However, evidence remains uneven regarding treatment completion, infant follow-up, HBV prophylaxis, long-term transmission outcomes, and sustainability in resource-constrained settings. Key challenges include supply constraints, workforce limitations, and follow-up gaps. Future research should evaluate the full care cascade, not screening uptake alone. Full article