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.

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.].

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.

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.

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.

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.

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.

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.

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.

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.

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.

The Influence of Maternal Levels of Vitamin D and Adiponectin on Anthropometrical Measures and Bone Health in Offspring.

BACKGROUND: From the conception onward, certain parameters associated with maternal health may affect foetal body composition, growth and bone mineral content. The objective of the study was to determine the association between maternal vitamin D and adiponectin status with the anthropometrical measures of newborns, and bone health status measured by Quantitative Ultrasound (QUS) at birth. METHODS: Circulating 25OHD and adiponectin concentration were measured in 73 pregnant women. Correlations with the anthropometrical measures and bone health status in their infants were studied. Bone health was evaluated using QUS with the measurements of speed of sound (SOS, in m/s) and Z score on the right tibia. RESULTS: There was no significant association between maternal 25OHD and newborn's anthropometrical measures at birth (weight p=0.35, length p=0.59 and head circumference p=0.47). There was a significant negative correlation between a maternal serum adiponectin and a) weight of infants at birth (R= -0.37, p=0.002); b) birth length (R= -0.31, p=0.008) and c) head circumference (R= -0.29, p=0.014). There was no significant correlation between maternal 25OHD blood levels during pregnancy and SOS in newborns (p=0.48). Additionally, a correlation between maternal adiponectin concentration during pregnancy and SOS in newborns was not significant (p=0.82). CONCLUSION: Although a high prevalence of low 25OHD level among pregnant women was found, maternal vitamin D status did not influence growth and bone health of their offspring at birth. Maternal adiponectin levels in plasma showed an inverse relationship with anthropometrical measures of infants at birth, while no correlation with the newborn's bone health was found.

Developmental outcome in a group of twins: Relation to perinatal factors and general movements.

BACKGROUND: The quality of general movements (GMs) has proven to have predictive value for the developmental outcome, but this has not yet been studied in twins. AIMS: Our aim was to analyse the quality of GMs and neurological and developmental outcome in relation to the gestational age (GA), mode of conception and other perinatal risk factors in a group of twins. STUDY DESIGN: The documentation of twins referred for follow-up in the period from 1998 to 2016 was studied retrospectively. Data concerning the quality of GMs, perinatal risk factors and developmental outcome were analysed. SUBJECTS: Eighty-nine twin pairs, GA from 24 to 38 weeks (median 35.0; IQR 3), birth weight 670 g-3820 g (median 2323; IQR 645) were included. OUTCOME MEASURES: Results of neurological, psychological and speech/language development and school outcome were analysed. RESULTS: GMs at term age and at three to four months postterm age did not differ with regard to the mode of conception. Preterm birth was significantly related to GMs at three to four months postterm age. At term age, GMs were significantly related to neurological outcome, while at three to four months postterm age, GMs were related to both the neurological and psychological outcome. Difficulties in speech/language development were diagnosed in almost half of the children, more frequently in boys and children with lower Apgar scores. CONCLUSION: The study highlights the value of GMs for predicting the developmental outcome in twins and indicates the importance of developmental, especially speech/language, follow-up in twins.

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.

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.

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.