The knowledge about long-term consequences of preterm birth among health professionals, educational professionals, and parents in Slovenia.

AIM: To assess the knowledge about the long-term consequences of preterm birth and the need for training and information among various professionals working with preterm children and parents of preterm children. METHODS: In February and March 2018, physicians, psychologists, special education needs teachers, teachers, preschool teachers, and parents (N=488) filled in the Preterm Birth-Knowledge Scale and a survey regarding their perceptions and attitudes toward working with preterm children. RESULTS: Physicians and psychologists were most knowledgeable among the groups about the long-term consequences of preterm birth. Teachers, preschool teachers, and parents had significantly lower knowledge (F=23.18, P<0.001). The majority of professionals indicated that they did not feel adequately equipped to support the learning and development of preterm children and that they had not received sufficient training in this area. More than half indicated that they had received no formal training. In general, the participants tended to underestimate the long-term problems of preterm children. CONCLUSION: The findings underscore the importance of integrating the issue of the long-term outcomes of preterm birth and working with preterm children into formal education, and in other forms of educational activities.

Clinical Factors Influencing Endogenous Carbon Monoxide Production and Carboxyhemoglobin Levels in Neonates.

Carboxyhemoglobin (COHb) is an index of endogenous carbon monoxide formation during the hem degradation process and could be used to confirm hemolysis in neonates. The influence of other clinical factors on COHb values in neonates has not been fully investigated. We aimed to evaluate the influence of hemolysis, sepsis, respiratory distress, and postnatal age on COHb values. We retrospectively analyzed COHb measurements determined with a carbon monoxide-oximeter in 4 groups of term neonates: A-sepsis, B-respiratory distress, C-hemolysis, and D-healthy neonates. The mean COHb values were 1.41% (SD: 0.26), 1.32% (SD: 0.27), 2.5% (SD: 0.69), and 1.27% (SD: 0.19) (P<0.001) in groups A (n=8), B (n=37), C (n=16), and D (n=76), respectively. COHb in group C was significantly higher than in the other groups. There was a negative correlation between postnatal age and COHb in healthy neonates. A cut-off level of 1.7% had 93% (95% confidence interval [CI]: 89%-97%) sensitivity and 94% (95% CI: 90%-98%) specificity for diagnosis of hemolysis. COHb values were higher during the first days of life. We found that COHb levels in neonates with hemolysis were significantly higher and that the influence of sepsis and respiratory distress on COHb values was insignificant.

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.

Decreased tissue oxygenation in newborns with congenital heart defects: a case-control study.

AIM: To compare regional tissue oxygenation (rSO2) in the brain, intestine, and kidney between newborns with and without congenital heart defects (CHD). METHODS: This observational case-control study was conducted at the Neonatal Department of Children's Hospital Ljubljana between December 2012 and April 2014. It included 35 newborns with CHD and 30 healthy age- and sex-matched controls. CHD were assessed echocardiographically and divided into acyanotic and cyanotic group. RSO2 in the brain, intestine, and kidney was measured using near-infrared spectroscopy (NIRS). Simultaneously, heart rate (HR), breathing frequency (BF), mean arterial blood pressure (MAP), and arterial oxygen saturation (Sao2) were recorded. RESULTS: Newborns with CHD had significantly lower rSO2 in the left brain hemisphere (67±11% vs 76±8%, P=0.004), right brain hemisphere (68±11% vs 77±8%, P<0.001), and the kidney (68±13% vs 77±10%, P=0.015). RSO2 in the intestine did not significantly differ between the groups. HR, MAP, and Sao2 also did not differ between the groups, whereas BF was significantly higher in the CHD group (57±12 vs 39±10 breaths/min, P<0.001). Between cyanotic and acyanotic group, we found no significant differences in rSO2 of any tissue. CONCLUSIONS: Monitoring tissue oxygenation by NIRS could enable a timely detection of hemodynamically important CHD.

Neonatal Cyanosis Due to Hemoglobin Variant: Hb F-Sarajevo.

Neonatal cyanosis is rarely due to hemoglobin variants with low oxygen affinity. We describe the clinical course and results of molecular genetic analysis of a boy who presented after birth with severe cyanosis. Arterial blood-gas analysis demonstrated a pronounced shift of the oxygen-hemoglobin dissociation curve to the right and molecular genetic analysis revealed a γ-globin variant, Hb F-Sarajevo. The patient presented is the second reported case of neonatal cyanosis due to this mutation, which was first described in 2012 by Zimmermann-Baer and coauthors. With the introduction of universal screening for congenital heart disease, the finding of low oxygen saturation will uncover more neonates with hemoglobinopathies with low oxygen affinity.

Clinical presentation and spectrum of neuroimaging findings in newborn infants with incontinentia pigmenti.

AIM: To report on the neurological presentation and neuroimaging findings in newborn infants with incontinentia pigmenti. METHOD: The clinical and neurological course including neuroimaging and follow-up data of eight newborn infants with the neurological phenotype of incontinentia pigmenti were retrospectively reviewed. RESULTS: While the clinical picture was polymorphic, the neurological manifestations were defined as encephalopathic and comprised lethargy and seizures in all but one of the infants. Magnetic resonance imaging (MRI) abnormalities were predominantly in the white matter. Diffusion-weighted imaging (DWI) was obtained during the acute phase in seven of the eight infants, showing restricted diffusion in the deep and subcortical white matter but also in the corpus callosum, basal ganglia, thalami, cerebellum, and cerebral peduncles. Susceptibility-weighted imaging (SWI), performed in five infants, showed a variable amount of signal loss, mainly in the white matter, within areas of restricted diffusion. Extensive MRI abnormalities in newborn infants were followed by abnormal neurodevelopment, with significant motor, cognitive, and/or visual problems. INTERPRETATION: To assess the extent of central nervous system involvement, MRI is recommended in the clinical evaluation of infants with incontinentia pigmenti. They have a characteristic pattern of brain lesions seen on MRI, best recognized using DWI and SWI in the acute neonatal phase, which allow the identification of and distinction between ischaemic and haemorrhagic lesions.

Vitamin D Status and Its Determinants in Healthy Slovenian Pregnant Women.

BACKGROUND/AIMS: Vitamin D deficiency is a common underdiagnosed condition. The aim of this was to analyze the status of vitamin D and its determinants in healthy Slovenian pregnant women. METHODS: A total of 132 volunteer pregnant women completed a questionnaire including baseline demographics, food frequency, physical activities; anthropometrical measurements, body mass index and levels of 25-(OH)D in serum were performed during the third trimester, and dietary intakes were assessed during the 27-28th week of gestation. RESULTS: Vitamin D deficiency was present in 14% while insufficiency was present in 41% of women. The risk for inadequacy was higher in women older than 30 years (p = 0.01), in those with less frequent outdoor physical activity (p = 0.01) and in pregnancies during the low sun exposure season (p = 0.04). Insufficiency was not significantly more frequent in less educated women, unemployed and in those living in urban area. The median value of vitamin D from habitual dietary intake was 1.5 µg/day (range 0.1-13.4) and did not influence 25-hydroxyvitamin D level (p = 0.91). CONCLUSIONS: The prevalence of vitamin D inadequacy was 55% and was dependent on age, season and outdoor physical activities. The results suggest a discrepancy between vitamin D intake through habitual diet and the reference needs.

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.

Treatment of Symptomatic Focal Hepatic Hemangioma with Propranolol in Neonates: Is It Efficient?

Hepatic hemangiomas (HH) - classified into congenital hepatic hemangiomas (CHH) or infantile hepatic hemangiomas (IHH) - are benign vascular tumors that are mainly asymptomatic, but may cause clinical problems that require treatment. While focal, multifocal, and diffuse IHH are responsive to propranolol treatment, CHH is mainly focal and thought to be resistant to treatment with propranolol. The clinical and imaging distinctions between CHH and IHH in cases of focal lesions can be challenging, while histopathological distinction is mostly lacking in the clinical setting. We report 4 neonatal symptomatic cases of focal HH treated with propranolol, with partial or complete resolution of the tumor, and the positive hemodynamic effect of propranolol in one case. We believe that although clear differentiation cannot be achieved between CHH and IHH without histopathological examination in cases of focal HH in neonates, propranolol treatment should be attempted in symptomatic cases since its benefits outweigh the possible small risk of side effects of propranolol.

Corrigendum: Prognostic value of various diagnostic methods for long-term outcome of newborns after hypoxic-ischemic encephalopathy treated with hypothermia.

[This corrects the article DOI: 10.3389/fped.2022.856615.].

Prevalence of congenital cytomegalovirus infection in Slovenia: a study on 2,841 newborns.

Human cytomegalovirus (CMV) is the most frequent cause of congenital infection in humans. In the first prevalence study of congenital CMV infection in Eastern and Central Europe, all neonates born in a 22-month period in two Slovenian maternity units (total of 2,841 newborns) were screened prospectively for congenital CMV infection by a real-time polymerase chain reaction (PCR) in urine. In all newborns with positive screening results, plasma and dried blood spots (DBS) collected at birth were tested additionally for CMV DNA. Congenital CMV infection was confirmed by virus isolation from a urine sample collected within the first 2 weeks of life. Congenital CMV infection was identified in four out of 2,841 newborns tested (incidence 0.14%; 95% CI, 0.05-0.39%). In four newborns with confirmed congenital infection, the concentration of CMV DNA in urine ranged from 4.68 to 8.18 log(10) copies/ml, all four newborns had detectable CMV DNA in plasma taken at birth (1.26-3.34 log(10) copies/ml) and two out of four had detectable CMV DNA in DBS collected during newborn metabolic screening. None of the four newborns with confirmed congenital CMV infection was symptomatic. The study showed that the prevalence of congenital CMV infection at birth in Slovenia is among the lowest in the world and that CMV DNA PCR testing of urine is a suitable and affordable real-time screening strategy for congenital CMV infection. If it is performed in 24 mini-pools, the cost of screening is 1.4 €/newborn and the cost of detecting a single newborn with congenital CMV infection 1,000 €.

The influence of maternal levels of vitamin D and adiponectin on offspring's health.

BACKGROUND: From the very beginning of life, biological events in the intrauterine environment influence the developing child, its growth, maturation and adaptation. The aim of this study was to assess the impact of maternal vitamin D and adiponectin status on offspring growth, general and bone health. METHODS: 162 healthy pregnant women were included in the study, with their vitaminD and adiponectin levels measured in the 32 nd week of pregnancy. Body weight and bone mineral density measurements of their offspring were performed at birth and at the age of three, six, nine and twelve months. Information on children's infectious, allergic and chronic disease was collected from their medical records. RESULTS: Vitamin D insufficiency/deficiency was present in 44% of pregnant women. There was no significant association between maternal vitamin D during pregnancy and offspring body weight at birth or later, as well as between maternal vitamin D and newborn bone mineral density. Additionally, there was no significant association between maternal vitamin D and infectious, allergic or other chronic diseases in offspring. A negative correlation between maternal adiponectin and offspring's body weight at birth was observed (r = - 0.37, p = 0.002), while association with bone mineral density in newborns was not significant. CONCLUSION: Despite the significant prevalence of vitamin D insufficiency among pregnant women, it did not influence growth or health of their offspring in this study. Maternal adiponectin levels showed an inverse relationship with birth weight of the infants, which may highlight the important link between maternal health and the offspring's growth.

Prognostic Value of Various Diagnostic Methods for Long-Term Outcome of Newborns After Hypoxic-Ischemic Encephalopathy Treated With Hypothermia.

Introduction: Prediction of outcome in newborns with hypoxic-ischemic encephalopathy (HIE) has been modulated by hypothermia treatment (HT). We assessed the predictive value of diagnostic methods commonly used in neonates with HIE for short-term neurodevelopmental outcome and long-term neurological outcome. Materials and Methods: This longitudinal cohort study followed up 50 term newborns who underwent HT after HIE between July 2006 and August 2015, until preschool age. We estimated sensitivity and specificity for short-term neurodevelopmental outcome at 18 months and long-term neurological outcome at five years based on Amiel-Tison Neurological Assessment (ATNA), electroencephalography (EEG), and magnetic resonance imaging (MRI) performed in the neonatal period. Results: The accuracy of all neonatal methods tested was higher for long-term neurological outcome compared to the predictive accuracy for short-term neurodevelopmental outcome at 18-24 months. Sensitivity and specificity in predicting unfavorable long-term neurological outcome were: MRI (sensitivity 1.0 [95%CI 0.96-1.0]; specificity 0.91 [95%CI 0.86-1.0]), EEG (sensitivity 0.94 [95%CI 0.71-1.0]; specificity 1.0 [95% CI 0.89-1.0]), and ATNA (sensitivity 0.94 [95%CI 0.71-1.0]; specificity 0.91 [95%CI 0.76-0.98]). Conclusion: MRI is a powerful predictor of long-term neurological outcome when performed in the first week after HIE in HT treated infants, as are EEG and ATNA performed in the second or third week postnatally.

Neonatal Group B Streptococcal Meningitis: Predictors for Poor Neurologic Outcome at 18 Months.

AIM: To find early predictors for poor neurodevelopmental outcome after neonatal group B streptococcal meningitis. METHODS: We retrospectively analyzed clinical characteristics of 23 patients with neonatal group B streptococcal meningitis and their neurodevelopmental outcome at 18 months. Available group B Streptococcus strains were serotyped and their genomes characterized. RESULTS: We found several differences between patients with early- (n = 5) and late-onset (n = 18) disease. Nine children had neurologic abnormalities at 18 months and 4 had epilepsy, all of them after late-onset disease. Most important risk factors for poor outcome were impaired consciousness at admission, hemodynamic instability, seizures, or abnormal electroencephalogram during the acute illness and abnormal neurologic and ophthalmologic examination at the end of treatment, whereas abnormalities in laboratory and imaging studies were not predictive. Hypervirulent serotype III, multilocus sequence type 17 group B Streptococcus was the predominant pathogen. CONCLUSIONS: Neurodevelopmental impairment after neonatal group B streptococcal meningitis is likelier in those with clinical and neurophysiological features indicating worse disease severity.

Genetic-cellular epilepsy: Clues to diagnosing newborns with neonatal seizures.

OBJECTIVE: The aim of this study was to analyse clinical characteristics of newborns with genetic-cellular epilepsy (GCE) to compare them to those of newborns with seizures with other aetiologies and elucidate clues to the diagnosis of GCE. METHODS: This retrospective single-centre study analysed data from an 8-year cohort of newborns with seizures from 2010-2017. Clinical, neurophysiological, laboratory, and imaging data and outcomes of children with GCE were compared to those of newborns with seizures with other aetiologies. RESULTS: A total of 112 newborns (N = 68; 61% boys) were included. Hypoxic-ischaemic encephalopathy (N = 42; 29%) was the most common seizure aetiology; GCE (with pathogenic variants KCNQ2, KCNQ3, SCN2A, TBC1D24, CHD2, and STXBP) was diagnosed in 9 (6%). The group of newborns with GCE significantly differed from the group with seizures with other aetiologies in terms of family history of epilepsy (p = 0.000), neonatal epileptic status (NES) (p = 0.007), normal imaging studies (p = 0.000), and outcomes (p = 0.034), but did not differ regarding the type and age of seizure onset, number of antiepileptic drugs administered, and EEG results. Positive family history of epilepsy (p = 0.027), presence of NES (p = 0.041), and normal imaging studies (p = 0.002) were most indicative of the diagnosis of GCE. Probability of GCE with this combination was 0.92. CONCLUSION: In a heterogenous group of newborns with seizures, a positive family history of epilepsy, presence of NES, and normal imaging studies were most indicative of the diagnosis of GCE.

Cardiorespiratory parameters in newborns during sedation with chloral hydrate.

We commonly use chloral hydrate sedation in newborns, though its cardiorespiratory side effects have not yet been fully investigated. Our study aimed to analyze the impact of chloral hydrate on cardiorespiratory parameters in term newborns. We performed a prospective, pre-post single-arm interventional study in 42 term, respiratorily and hemodynamically stable newborns. Oxygen saturation (SpO2), end-tidal CO2 (ETCO2), the apnea-hypopnea index and the respiratory and heart rates were recorded by polygraphy, starting 0.5-1 hour before oral administration of chloral hydrate at a dose of 40 mg/kg and ceasing 4 hours post-administration. After administration of chloral hydrate, the mean basal SpO2 dropped by 2.0% (from 97.1% to 95.1%; p < 0.001) and the mean basal ETCO2 increased by 3.9 mmHg (25.6 to 29.5 mmHg; p < 0.001). We found a significant decrease in the minimal SpO2 values (p < 0.001) and an increase in the percentage of time spent with SpO2 < 95% and < 90% (p < 0.001). The mean increase in the estimated apnea-hypopnea index was 3.5 events per hour (p < 0.001). The mean respiratory and heart rates were significantly lower 150 min after the administration of chloral hydrate when compared with pre-sedation values (51/min and 127/min versus 61/min and 138/min respectively; p < 0.001). A considerable number of patients exhibited changes in cardiorespiratory parameters that differed considerably from the normal ranges. In conclusion, SpO2, ETCO2, the estimated apnea-hypopnea index and the respiratory and heart rates changed after the administration of chloral hydrate. They remained within normal limits in most newborns, but the inter-individual variability was high in the studied population.

Association between neurological signs and developmental outcome: pilot results in preterm group.

AIM: To study the correlations between neurological signs and developmental performance, and to analyze the value of neurological signs in identification of developmental disabilities. METHODS: A group of 26 preterm infants (gestational age from 23 weeks to 36 weeks) was studied. The neurological assessment described by Amiel-Tison and Gosselin was performed at term age and repeated every 3 months up to the age of 2, when the sum of all adverse findings was categorized. According to the nature and associations of neurological and cranial signs, patients were divided into 5 categories: 1) cerebral palsy; 2) minimal cerebral palsy; 3) Amiel-Tison triad; 4) intermediate; and 5) normal. Developmental assessment using the Bayley Scales of Infant Development, second edition, was performed between the age of 2 and 3, and the Mental and Psychomotor Developmental Index was determined. RESULTS: The developmental performance was highest in the group of children without neurological signs and lowest in the group with cerebral palsy. There was a strong correlation between neurological signs and mental developmental performance (Spearman rho=0.71), while the correlation between neurological signs and psychomotor developmental performance was weaker (Spearman rho=0.54). CONCLUSION: Categorization of neurological assessment and identification of 3 minor neurological signs may be a valuable tool for early detection of children with developmental disabilities.

Psychosocial functioning in adolescents: results according to Amiel-Tison neurological assessment in a group of preterm infants.

OBJECTIVE: This prospective study investigated the relationship between Amiel-Tison neurological assessment (ATNA) in preterm children and their psychosocial functioning in adolescence. METHODS: From the initial group of 45 children regularly assessed by the ATNA from term until the age of 2 years, 27 participated in the follow-up at 13 years. RESULTS: Of the three groups categorized by neurological signs as normal, intermediate or abnormal, parents of adolescents with normal ATNA reported the lowest number of executive function problems (p = 0.019) and behavioral symptoms (p = 0.011), while the adolescents themselves reported the lowest number of behavioral symptoms (p = 0.005) and the highest quality of life (p = 0.012). The number of problems reported increased with the number of abnormal neurological signs. CONCLUSION: Standardized neurological assessment may be a helpful clinical tool for the identification of children at risk for later psychosocial problems who could benefit from prevention and early intervention programs.

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.