The burden of viral lower respiratory tract infections during the neonatal period: six-year experience at a tertiary referral hospital.

AIM: To identify the epidemiological and clinical features of acute viral lower respiratory tract infections (LRTI) caused by respiratory syncytial virus and other respiratory viruses, and to determine the risk factors for the severe disease among neonates. METHODS: We retrospectively reviewed the records of neonates aged up to 44 postconceptional weeks who were hospitalized at a tertiary referral hospital due to confirmed viral LRTI between January 2015 and December 2020. RESULTS: Of 228 neonates with viral LRTI, one-third were born prematurely. A seasonal distribution of LRTIs from December to March was noticed, peaking in February. Forty-two percent of neonates were treated in the neonatal intensive care unit. One third of these presented with complications and needed mechanical ventilation. The most detected viruses were respiratory syncytial virus and rhinovirus. Prematurity was identified as a risk factor for worse clinical course and more complications, while rhinovirus infection was associated with an increased risk of apnea. CONCLUSIONS: The burden of respiratory syncytial virus LRTI in the neonatal period is high, although other respiratory viruses can also cause a severe respiratory disease. In preterm infants, rhinovirus infection presents an important risk factor for a severe course of LRTI with complications. Infection with two respiratory viruses leads to a more severe clinical course.

A novel mutation of congenital nephrotic syndrome in a Slovenian child eventually receiving a renal transplant.

Congenital nephrotic syndrome (CNS) is a rare disease defined as heavy proteinuria, hypoalbuminemia, hyperlipidemia, and edema presenting in the first three months of life. It is most commonly caused by mutations in the NPHS1 gene associated with nephrotic syndrome type 1, also known as Finnish-type CNS, which is inherited in an autosomal recessive manner. Symptomatic treatment with intravenous albumins, vitamins, minerals, nutritional, and hormonal supplementation and treatment of complications are mandatory. Children refractory to the symptomatic treatment are recommended to undergo nephrectomy and renal replacement therapy, preferably renal transplantation. We report on a child with Finnish type CNS with a NPHS1 mutation, which is the first case confirmed by genetic study in Slovenia. We showed for the first time that homozygous mutation c.2928-3del in the NPHS1 gene caused exon 22 skipping, leading to a truncated protein and Fin-minor phenotype.

The Genetic Architecture of Congenital Heart Disease in Neonatal Intensive Care Unit Patients-The Experience of University Medical Centre, Ljubljana.

Congenital heart disease (CHD) is the most commonly detected congenital anomaly and affects up to 1% of all live-born neonates. Current guidelines support the use of chromosomal microarray analysis (CMA) and next-generation sequencing (NGS) as diagnostic approaches to identify genetic causes. The aim of our study was to evaluate the diagnostic yield of CMA and NGS in a cohort of neonates with both isolated and syndromic CHD. The present study included 188 infants under 28 days of age with abnormal echocardiography findings hospitalized at the Department of Neonatology, UMC Ljubljana, between January 2014 and December 2023. Phenotypic data were obtained for each infant via retrospective medical chart review. We established the genetic diagnosis of 22 distinct syndromes in 17% (32/188) of neonates. The most frequent genetic diagnoses in diagnosed cases were 22q11.2 microdeletion and CHARGE syndromes, followed by Noonan syndrome and Williams syndrome. In addition, we detected variants of uncertain significance in 4.8% (9/188) of neonates. Timely genetic diagnosis is important for the detection of syndrome-related comorbidities, prognosis, reproductive genetic risks and, when appropriate, genetic testing of other family members.

A lethal course of hypertrophic cardiomyopathy in Noonan syndrome due to a novel germline mutation in the KRAS gene: case study.

Noonan syndrome is a relatively common and heterogeneous genetic disorder, including congenital heart defect in more than half of the cases. If the defect is not large, life expectancy is normal. Here we report on a case of an infant with Noonan syndrome and rapidly progressive hypertrophic cardiomyopathy with lethal outcome, in whom we identified a novel mutation in the KRAS gene. This heterozygous unclassified missense variant in exon 3: c.179G> T (p.Gly60Val) might be associated with a lethal form of Noonan syndrome. The malignant clinical course of the disease and the lethal outcome in an infant only a few months old might be connected to RAS-mitogen-activated protein kinase pathway hyperactivation, consequently promoting cell growth and proliferation, leading to rapidly progressive hypertrophic cardiomyopathy. Further biochemical and functional studies are needed to confirm this hypothesis.

Neonatal Toxic Shock Syndrome-like Exanthematous Disease: A Report of Two Cases.

Neonatal toxic shock syndrome (TSS)-like exanthematous disease is characterized by exanthema, thrombocytopenia and fever in neonates infected with TSS toxin-1 producing Staphylococcus aureus . Although the disease is rare, it should be known to neonatologists as it represents a differential diagnosis in neonates with exanthema and thrombocytopenia. Two presented neonates with Neonatal TSS-like exanthematous disease are rare European cases of this specific neonatal disease.

Vaccine immune response, autoimmunity and morbidity after neonatal blood exchange transfusion.

INTRODUCTION: A blood exchange transfusion (BET) is most commonly performed to treat severe neonatal haemolytic disease. A distinct form of blood transfusion adverse reaction is transfusion-related immunomodulation. The purpose of our retrospective single-centre case-control cohort study was to investigate whether a blood exchange transfusion in the neonatal period provokes immunomodulation and affects humoral immune response to vaccination, morbidity and occurrence of autoantibodies. METHODS: Study subjects were 74 apparently healthy children, who were born at term as appropriate for gestational age and received four doses of diphtheria and tetanus toxoid vaccine. Forty-one received BET due to neonatal hemolytic disease and no other blood product afterwards, while 33 did not receive any blood products. Analysis of diphtheria, tetanus and autoimmune antibodies was performed and their medical records were analyzed for infectious, allergic, cancerous and autoimmune diseases. RESULTS: A clearly exaggerated immune response to diphtheria (1.016 IU/mL, 95% confidence interval (CI) 0.662-1.369 IU/mL vs. 0.515 IU/mL, 95% CI 0.363 to 0.626 IU/mL, P = 0.011) and slightly exaggerated immune response to tetanus vaccine (1.798 IU/mL, 95% CI 1.180-2.416 IU/mL vs. 1.036 IU/mL, 95% CI 0.398-1.673 IU/mL, P = non-specific) were observed in BET subjects. A propensity towards autoimmunity (25.8% vs. 12.5%, P = non-specific) was observed in BET subjects. However, BET in the neonatal period did not influence the occurrence of bacterial, childhood viral diseases with exception of varicella (43.9% vs. 21.2%, P = 0.040), autoimmune and cancer diseases. CONCLUSION: BET impacted humoral immune response to diphtheria and tetanus vaccine and occurrence of autoimmune antibodies, but did not affect morbidity and the occurrence of autoimmune diseases. These effects could be related to massive antigenic load of BET and an accelerated priming of immune cells and consequent immunomodulation.

Umbilical cord care: national survey, literature review and recommendations.

BACKGROUND: The basic principle of umbilical cord (UC) care is to keep it clean and dry, as this provides the fastest and safest UC healing. OBJECTIVE: To evaluate Slovenian UC care practice and compare its consistency with current international recommendations. METHODS: A questionnaire covering UC care from birth to complete healing of the umbilical wound was sent to all Slovenian primary-, secondary- and tertiary-level pediatric centers. Three different clinical conditions of the newborn's umbilicus were defined: healthy umbilicus (HU), umbilicus at risk (UR) and unhealthy umbilicus (UU). RESULTS: The study revealed a correlation between the clinical condition of the umbilicus, the frequency of UC care and the antiseptic usage in both the outpatient and inpatient UC care groups. HU was treated less frequently than UR and significantly less than UU. In both groups, these two conditions were also indications for UC care with antiseptic. The frequency of antiseptic usage for HU care was significantly lower in the outpatient care group. CONCLUSIONS: Slovenian UC care follows the general international recommendations. Based on these and our experience, we formulated recommendations for adjustments to UC care, depending on the clinical condition of the umbilicus, in order to prevent important complications.

Prognostic accuracy of clinical signs and diagnostic tests in cow's milk allergy in newborns.

BACKGROUND: The aim of the study was to explore the correlation between clinical signs and confirmatory tests for cow's milk allergy (CMA) in the neonatal period and their relation to family history and the occurrence of food allergies in the postneonatal period. METHODS: The medical documentation of 361 newborns with suspected CMA and exclusion of other comorbidities was analyzed. The correlations between clinical signs and methods to confirm CMA [elevated levels of total immunoglobulin E (IgE) and/or specific IgE for cow's milk, improvement after the introduction of a cow's milk-free diet and positive challenge procedure] were studied. In 90 children, the data were additionally analyzed in relation to outcome (at the age of 1-11 years), evaluated by questionnaires, which inquired about signs and symptoms of food allergy, methods of CMA confirmation, and the presence of other food allergies. RESULTS: There was a positive correlation between exanthema and confirmed CMA in the neonatal period (R = 0.184; p = <0.001; n = 361), and hematochezia and confirmed CMA in the neonatal (R = 0.203; p < 0.001; n = 361) and postneonatal period (R = 0.215; p = 0.042; n = 90). Additional food allergies in the postneonatal period were positively correlated with neonatal CMA (R = 0.275; p = 0.009; n = 90). No correlation was found between a positive family history of food allergies and CMA in the neonatal (R = -0.66; p = 0.398; n = 165) and postneonatal periods (R = 0.00; p = 1.000; n = 116). CONCLUSION: Neonatal exanthema and hematochezia were the predominant clinical signs in neonates with CMA. Allergies to other food allergens appeared more frequently in children with CMA in the neonatal period. Neonatal CMA did not occur more frequently in families with food allergies.