Host defense against early-life infections such as chorioamnionitis, neonatal sepsis, or necrotizing enterocolitis (NEC) relies primarily on innate immunity, in which antimicrobial peptides (AMPs) play a major role. AMPs that are important for the fetus and neonate include α and β defensins, cathelicidin LL-37, antiproteases (elafin, SLPI), and hepcidin. They can be produced by the fetus or neonate, the placenta, chorioamniotic membranes, recruited neutrophils, and milk-protein ingestion or proteolysis. They possess antimicrobial, immunomodulating, inflammation-regulating, and tissue-repairing properties. AMPs are expressed as early as the 13th week and increase progressively through gestation. Limited studies are available on AMP expression and levels in the fetus and neonate. Nevertheless, existing evidence supports the role of AMPs in pathogenesis of chorioamnionitis, neonatal sepsis, and NEC, and their association with disease severity. This suggests a potential role of AMPs in diagnosis, prevention, prognosis, and treatment of sepsis and NEC. Herein, we present an overview of the antimicrobial and immunomodulating properties of human AMPs, their sources in the intrauterine environment, fetus, and neonate, and their changes during pre- and post-natal infections and NEC. We also discuss emerging data regarding the potential utility of AMPs in early-life infections, as diagnostic or predictive biomarkers and as therapeutic alternatives or adjuncts to antibiotic therapy considering the increase of antibiotic resistance in neonatal intensive care units.

Necrotizing enterocolitis (NEC) is the most prevalent and potentially fatal intestinal injury mainly affecting premature infants, with significant long-term consequences for those who survive. This review explores the scale of the problem, highlighting advancements in epidemiology, the understanding of pathophysiology, and improvements in the prediction and diagnosis of this complex, multifactorial, and multifaced disease. Additionally, we focus on the potential role of metabolomics in distinguishing NEC from other conditions, which could allow for an earlier and more accurate classification of intestinal injuries in infants. By integrating metabolomic data with other diagnostic approaches, it is hoped to enhance our ability to predict outcomes and tailor treatments, ultimately improving care for affected infants.

Background/Objectives: This is the first systematic review and meta-analysis investigating early myocardial dysfunction in children/adolescents with celiac disease and the effect of a gluten-free diet by comparing early echocardiographic markers between patients and healthy individuals and between compliant and non-compliant celiac disease patients (based on serum antibody titers). Methods: A systematic literature search was conducted across major electronic databases, with data collection extending up to 3 March 2024. Results: In total, 15 studies with 916 children/adolescent patients with celiac disease and 569 healthy individuals were included. Our results showed a trend toward reduced myocardial function in all echocardiographic parameters (conventional and advanced), with statistical significance in fractional shortening and the myocardial performance index. However, these parameters did not differ significantly after adherence to a gluten-free diet. Conclusions: Therefore, we recommend that an examination of the cardiovascular system should be incorporated into the routine investigations of children with celiac disease in order to detect early subclinical myocardial dysfunction based on echocardiography. Although the results of our meta-analysis indicate that the myocardial performance index may serve as a useful, non-invasive marker for assessing myocardial function in children and adolescents with celiac disease, further research is needed in order to confirm its reliability and clinical applicability in this population. The improvement of echocardiographic parameters after long-term compliance to a gluten-free diet is yet to be evaluated.

Background/Objectives: Cow’s milk allergy (CMA) manifests with various clinical syndromes and has a wide range of symptoms in infants. This study aims to investigate the prevalence, clinical presentation, and outcome of clinical types and subtypes of CMA diagnosed in children within the first 12 months of life. Methods: Children with a CMA diagnosis were included in this mixed retrospective and prospective cohort study and were followed up for four years. Data recorded included clinical manifestations, feeding modes, and outcomes. Follow-up included oral cow’s milk (CM) challenge and/or elimination—reintroduction of CM, provided there was parental consent. Also, skin prick test and serum CM-specific IgE were assessed when needed. Results: A total of 93 infants (age: 3 days to 24 months) diagnosed with CMA were included. Prevalence was 28% for IgE-mediated CMA and 72%, 49.5%, 18.3%, and 3.7% for non-IgE-mediated CMA and its subtypes, Allergic Proctocolitis (AP), Food Protein induced Enteropathy (FPE), and Food Protein Induced Enterocolitis Syndrome (FPIES), respectively. Main manifestations were gastrointestinal (74%), skin rash (31%), failure to thrive (11.8%), feeding aversion (15.1%), respiratory symptoms (5.4%), and irritability/restlessness (9.7%). Follow-up revealed a high rate of AP and FPE tolerance within the first year, while FPIES and IgE-mediated CMA achieved tolerance at an older age. Conclusions: Our study demonstrated the predominance of AP and increased incidence of gastrointestinal involvement. Outcome was good for AP and FPE but less favorable for FPIES and IgE-mediated CMA. Our results, combined with published data, could increase our understanding of CMA-associated syndromes in infants and contribute to the guidance of effective management.

Background/Objectives: Opportunistic infections remain clinically important after kidney transplantation and may contribute to morbidity and graft dysfunction in pediatric recipients. Data regarding their timing, spectrum and clinical course in children remain limited. Methods: We retrospectively reviewed pediatric kidney transplant recipients followed at a single tertiary center between 2014 and 2024. Demographic and clinical characteristics, infection type, timing after transplantation, management and outcomes were recorded. Infection incidence was assessed at the patient level, whereas pathogen distribution and timing were analyzed per infection episode. Results: Twenty-seven pediatric kidney transplant recipients were included, with a mean follow-up of 5.6 years. Ten patients (37.0%) developed at least one clinically significant opportunistic infection, and one patient experienced two distinct episodes, resulting in 11 infection events. BK virus was the most frequent pathogen, followed by fungal infections and cytomegalovirus (CMV). Five episodes (45.5%) occurred within the first post-transplant year, whereas six (54.5%) occurred later during follow-up. Late infections included CMV, fungal infections, BK virus and West Nile virus. Most infections resolved after targeted management without persistent graft impairment; however, one patient developed biopsy-confirmed BK virus-associated nephropathy with sustained graft dysfunction. No infection-related mortality was observed. Conclusions: Clinically significant opportunistic infections occurred both early and late after pediatric kidney transplantation, with more than half of all infectious episodes developing beyond the first post-transplant year. Although overall outcomes were favorable, BK virus-associated nephropathy remained clinically relevant because of its impact on graft function.