Contrast-Enhanced Ultrasound (CEUS) and Ultra-Microangiography (UMA) in Critically Ill Children with Acute Kidney Injury.

Acute kidney injury (AKI) is an acute condition of impaired kidney function with decreased glomerular filtration rate, which results in dysregulation in volume, electrolyte, and acid-base equilibrium. AKI can be a life-threatening condition and can also lead to chronic kidney disease. It is important to diagnose AKI early in the course of the disease or to predict its development, as this can influence therapeutic decisions, outcome, and, consequently, the prognosis. In clinical practice, an elevated serum creatinine concentration remains the most common laboratory indicator for diagnosing AKI. However, due to the delay in its rise, creatinine levels are often insensitive and inaccurate for early diagnosis. Novel biomarkers of kidney tubular injury and the renal angina index have shown promise in predicting AKI earlier and more accurately. Contrast-enhanced ultrasonography (CEUS) and ultra-microangiography (UMA) are radiological methods that can quantify renal microperfusion and may be able to predict the development of AKI. They have not yet been used for quantifying renal perfusion in children with risk factors for developing AKI. Further research is needed to compare these sonographic techniques with the renal angina index and emerging kidney injury biomarkers for predicting acute kidney injury (AKI) in both children and adults.

Longitudinal Strain vs. Conventional Echocardiographic Parameters in the First Week of Life in Healthy Term Newborns.

The first week of life is characterized by substantial alterations in hemodynamic conditions. Changes in myocardial contractility will reflect these changes. We aimed to assess right and left ventricular function on the third and seventh days of life in 50 healthy term newborns. To assess myocardial function, we used speckle tracking echocardiography. Pulsed-wave tissue Doppler imaging, M-mode, Doppler and pulsed-wave Doppler were also used to assess ventricular function. We found a significant increase in both right and left longitudinal strain and an increase in systolic and diastolic tissue Doppler velocities, whereas most other parameters remained unchanged. At both time points, the measured parameters were significantly greater for the right ventricle, but the changes with time were similar for both ventricles. We also found an increase in right ventricular outflow tract acceleration time as an indirect sign of decreasing pulmonary vascular resistance and an increase in systolic blood pressure, pointing to increasing systemic vascular resistance. Together with a decreasing proportion of patients with patent ductus arteriosus, the estimated left ventricular cardiac output decreased and right ventricular cardiac output increased but not to a statistically significant degree. In conclusion, the results of our study show how different echocardiographic techniques capture hemodynamic changes and changes in myocardial contractility and compliance. Both longitudinal strain and tissue Doppler imaging parameters seem to offer greater sensitivity in comparison with conventional echocardiographic parameters.

The Effect of Caffeine on Heart Rate Variability in Newborns: A Pilot Study.

Neonatal apnoea can be treated with caffeine, which affects the central nervous and cardiovascular systems. Heart rate variability (HRV) reflects the activity of the autonomic nervous system (ANS) and might be used as a measure of ANS maturation in newborns. We aimed to establish the effect of caffeine on HRV in newborns and investigated the potential correlation between HRV and postmenstrual age (PMA). In 25 haemodynamically stable newborns hospitalized due to apnoea and treated with caffeine (2.5 mg/kg), we assessed breathing frequency, arterial oxygen saturation, body temperature, and the heart rate while they were sleeping. We assessed HRV by spectral analysis using fast Fourier transformation. The same protocol was reapplied 100 h after caffeine withdrawal to assess the control parameters. Caffeine increased breathing frequency (p = 0.023) but did not affect any other parameter assessed including HRV. We established a positive correlation between postmenstrual age and HRV during treatment with caffeine as well as after caffeine had been withdrawn (total power: p = 0.044; low-frequency band: p = 0.039). Apparently, the maintenance dose of caffeine is too low to affect the heart rate and HRV. A positive correlation between PMA and HRV might reflect maturation of the ANS, irrespective of caffeine treatment.

Tackling Neonatal Sepsis-Can It Be Predicted?

(1) Background: Early signs of sepsis in a neonate are often subtle and non-specific, the clinical course rapid and fulminant. The aim of our research was to analyse diagnostic markers for neonatal sepsis and build an application which could calculate its probability. (2) Methods: A retrospective clinical study was conducted on 497 neonates treated at the Clinical Department of Neonatology of the University Children's Hospital in Ljubljana from 2007 to 2021. The neonates with a diagnosis of sepsis were separated based on their blood cultures, clinical and laboratory markers. The influence of perinatal factors was also observed. We trained several machine-learning models for prognosticating neonatal sepsis and used the best-performing model in our application. (3) Results: Thirteen features showed highest diagnostic importance: serum concentrations of C-reactive protein and procalcitonin, age of onset, immature neutrophil and lymphocyte percentages, leukocyte and thrombocyte counts, birth weight, gestational age, 5-min Apgar score, gender, toxic changes in neutrophils, and childbirth delivery. The created online application predicts the probability of sepsis by combining the data values of these features. (4) Conclusions: Our application combines thirteen most significant features for neonatal sepsis development and predicts the probability of sepsis in a neonate.

Right Ventricular Function in Neonates During Early Postnatal Period: A Prospective Observational Study.

Previous echocardiographic studies were mainly focused on preterm infants and early fetal-to-neonatal transition period, whereas little is known about changes in the parameters of the right ventricular (RV) function after 72 h of life. Our aim was to quantitatively characterize potential changes in RV function by echocardiography in healthy term newborns between the third and the seventh day of life. We conducted a prospective observational study in 35 full-term newborns, in whom we performed echocardiographic examinations on the third and the seventh day of life. We assessed RV function, output and afterload and found a significant increase in all tissue Doppler velocities as well as in RV longitudinal strain, a higher mean RV outflow tract velocity time integral and lower myocardial performance index (MPI'), whereas the tricuspid annular plane systolic excursion, RV filling pattern, and RV outflow tract acceleration time were not significantly different between the third and the seventh day of life. Conclusions: Increased RV systolic and diastolic myocardial velocities, cardiac output and longitudinal deformation and decreased RV MPI' between the third and the seventh day of life point to a reduction of RV afterload and adaptive myocardial maturation in term newborns during this period. Moreover, PW-TDI and 2D speckle-tracking echocardiography seem to be more sensitive for evaluating RV function in comparison with M-mode echocardiography and pulsed-wave Doppler analysis of RV filling.

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.

Genomic and phenotypic characterisation of invasive neonatal and colonising group B Streptococcus isolates from Slovenia, 2001-2018.

BACKGROUND: Group B Streptococcus (GBS) is the leading cause of invasive neonatal disease in the industrialized world. We aimed to genomically and phenotypically characterise invasive GBS isolates in Slovenia from 2001 to 2018 and contemporary colonising GBS isolates from screening cultures in 2018. METHODS: GBS isolates from 101 patients (invasive isolates) and 70 pregnant women (colonising isolates) were analysed. Basic clinical characteristics of the patients were collected from medical records. Antimicrobial susceptibility and phenotypic capsular serotype were determined. Whole-genome sequencing was performed to assign multilocus sequence types (STs), clonal complexes (CCs), pathogenicity/virulence factors, including capsular genotypes, and genome-based phylogeny. RESULTS: Among invasive neonatal disease patients, 42.6% (n = 43) were females, 41.5% (n = 39/94) were from preterm deliveries (< 37 weeks gestation), and 41.6% (n = 42) had early-onset disease (EOD). All isolates were susceptible to benzylpenicillin with low minimum inhibitory concentrations (MICs; ≤0.125 mg/L). Overall, 7 serotypes were identified (Ia, Ib, II-V and VIII); serotype III being the most prevalent (59.6%). Twenty-eight MLST STs were detected that clustered into 6 CCs. CC-17 was the most common CC overall (53.2%), as well as among invasive (67.3%) and non-invasive (32.9%) isolates (p < 0.001). CC-17 was more common among patients with late-onset disease (LOD) (81.4%) compared to EOD (47.6%) (p < 0.001). The prevalence of other CCs was 12.9% (CC-23), 11.1% (CC-12), 10.5% (CC-1), 8.2% (CC-19), and 1.8% (CC-498). Of all isolates, 2.3% were singletons. CONCLUSIONS: A high prevalence of hypervirulent CC-17 isolates, with low genomic diversity and characteristic profile of pathogenicity/virulence factors, was detected among invasive neonatal and colonising GBS isolates from pregnant women in Slovenia. This is the first genomic characterisation of GBS isolates in Slovenia and provides valuable microbiological and genomic baseline data regarding the invasive and colonising GBS population nationally. Continuous genomic surveillance of GBS infections is crucial to analyse the impact of IND prevention strategies on the population structure of GBS locally, nationally, and internationally.

Abernethy syndrome in Slovenian children: Five case reports and review of literature.

BACKGROUND: Abernethy syndrome is a congenital vascular anomaly in which the portal blood completely or partially bypasses the liver through a congenital portosystemic shunt. Although the number of recognized and reported cases is gradually increasing, Abernethy syndrome is still a rare disease entity, with an estimated prevalence between 1 per 30000 to 1 per 50000 cases. With this case series, we aimed to contribute to the growing knowledge of potential clinical presentations, course and complications of congenital portosystemic shunts (CPSS) in children. CASE SUMMARY: Five children are presented in this case series: One female and four males, two with an intrahepatic CPSS and three with an extrahepatic CPSS. The first patient, who was diagnosed with an intrahepatic CPSS, presented with gastrointestinal bleeding, abdominal pain and hyperammonaemia at six years of age. He underwent a percutaneous embolization of his shunt and has remained asymptomatic ever since. The second patient presented with direct hyperbilirubinemia in the neonatal period and his intrahepatic CPSS later spontaneously regressed. The third patient had pulmonary hypertension and hyperammonaemia due to complete portal vein agenesis and underwent liver transplantation at five years of age. The fourth patient was diagnosed immediately after birth, when evaluated due to another congenital vascular anomaly, and the last patient presented as a teenager with recurrent bone fractures associated with severe osteoporosis. In addition, the last two patients are characterised by benign liver nodules; however, they are clinically stable on symptomatic therapy. CONCLUSION: Abernethy syndrome is a rare anomaly with diverse clinical features, affecting almost all organ systems and presenting at any age.

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.

The effect of sleeping position on heart rate variability in newborns.

BACKGROUND: Lower heart rate variability (HRV) in a newborn might represent a risk factor for unfavourable outcome, a longer recovery after illness, and a sudden infant death. Our aim was to determine whether the newborn's sleeping position is associated with HRV. METHODS: We performed a prospective clinical study in 46 hospitalized cardiorespiratory stable term newborns. During sleeping, we measured the parameters of HRV in four body positions (supine, supine with tilt, prone, prone with tilt). RESULTS: The TP (total power spectral density) was significantly higher when lying supine in comparison to prone (p = 0,048) and to prone with tilt (p = 0,046). The HF (high frequency of power spectral density) in the supine position without tilt tended to be higher compared to prone without tilt (p > 0,05). The LF (low frequency power) was significantly higher when lying supine compared to prone, both without tilt (p = 0,018). TP and HF showed a positive correlation with gestational but not postmenstrual age (p = 0.044 and p = 0.036, respectively). CONCLUSIONS: In term newborns, sleeping position is associated with HRV. Higher TP and HF were found in the supine position, which might reflect better ANS stability. Gestational age positively correlated with TP and HF power, but only in supine position. TRIAL REGISTRATION: ISRCTN11702082, date of registration: March, 13th, 2020; retrospectively registered.

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.

A case report of short-chain acyl-CoA dehydrogenase deficiency (SCADD).

BACKGROUND: Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare inherited mitochondrial fatty acid oxidation disorder associated with variations in the ACADS (Acyl-CoA dehydrogenase, C-2 to C-3 short chain) gene. SCADD has highly variable biochemical, genetic and clinical characteristics. Phenotypes vary from fatal metabolic decompensation to asymptomatic individuals. SUBJECT AND METHODS: A Romani boy presented at 3 days after birth with hypoglycaemia, hypotonia and respiratory pauses with brief generalized seizures. Afterwards the failure to thrive and developmental delay were present. Organic acids analysis with gas chromatography-mass spectrometry (GS/MS) in urine and acylcarnitines analysis with liquid chromatography-tandem mass spectrometry (LC-MS/MS) in dried blood spot were measured. Deoxyribonucleic acid (DNA) was isolated from blood and polymerase chain reactions (PCRs) were performed for all exons. Sequence analysis of all exons and flanking intron sequences of ACADS gene was performed. RESULTS: Organic acids analysis revealed increased concentration of ethylmalonic acid. Acylcarnitines analysis showed increase of butyrylcarnitine, C4-carnitine. C4-carnitine was 3.5 times above the reference range (<0.68 µmol/L). Confirmation analysis for organic acids and acylcarnitine profile was performed on the second independent sample and showed the same pattern of increased metabolites. Sequence analysis revealed 3-bp deletion at position 310-312 in homozygous state (c.310_312delGAG). Mutation was previously described as pathogenic in heterozygous state, while it is in homozygous state in our patient. CONCLUSIONS: In our case clinical features of a patient, biochemical parameters and genetic data were consistent and showed definitely SCAD deficiency.

The prevalence and pattern of pharmaceutical and excipient exposure in a neonatal unit in Slovenia.

OBJECTIVE: Because of the restraints on conducting studies on pharmaceutical use in sick newborns, many drugs are used off-label in this population. Moreover, industrially manufactured pharmaceuticals may contain different excipients, which may be either untested or not licensed for use in neonates. The aim of our study was to determine the prevalence and pattern of pharmaceutical and excipient exposure in newborns hospitalized at the Department of Neonatology, Ljubljana, Slovenia. METHODS: A longitudinal prospective cross-sectional study was performed during a one-month period and included all hospitalized neonates. Route of administration, site of action, type of manufacture, licensing status, type and concentrations of excipients for all pharmaceuticals given to the neonates were determined. RESULTS: Twenty seven different pharmaceutical preparations were prescribed to a total of 48 hospitalized newborns. In most cases, newborns were prescribed various pharmaceuticals that were not approved for use in this population. Newborns were exposed to 60 different excipients in industrially manufactured pharmaceutical preparations. More than half of the received pharmaceuticals contained potentially harmful and harmful excipients. CONCLUSIONS: Two-thirds of pharmaceutical preparations for neonates were used off-label. Newborns receive more auxiliary substances, which may be unsuitable for this age group and may even be toxic to them, via industrially manufactured pharmaceuticals.

Benign familial neonatal convulsions caused by mutation in KCNQ3, exon 6: a European case.

Benign familial neonatal convulsions (BFNC) is a rare, clinically and genetically heterogenous epileptic disorder. Two voltage gated potassium genes, KCNQ2 and KCNQ3, have been identified as genes responsible for BFNC1 and BFNC2 respectively. While as many as 73 mutations of KCNQ2 have been described up to date, only 4 mutations in KCNQ3, 3 of them appearing in exon 5, have been identified. Mutation in exon 6 was found for the first time in a Chinese family, and here we report the same missense mutation of KCNQ3 within exon 6 in a Caucasian family, whose history and clinical picture were in accordance with BFNC.

Thyroid function in the third trimester of pregnancy and after delivery in an area of adequate iodine intake.

OBJECTIVE: To establish whether the higher thyroid stimulating hormone (TSH) levels and lower levels of the 2 free thyroid hormones noted toward the end of pregnancy are in relation with iodine supply. METHODS: We compared these hormones' levels in the third trimester of pregnancy and 4 months after delivery in 116 consecutive women without thyroid disease and otherwise healthy. The study was conducted in Slovenia, an iodine-sufficient area. The Mann-Whitney test, the Kruskal-Wallis rank test, and Spearman analysis were used for statistical analysis. RESULTS: In the third trimester TSH was significantly higher and both free thyroid hormones were significantly lower than after delivery (P=0.003 and P<0.001), but the free thyroxine to free triiodothyronine ratios in the third trimester and 4 months after delivery did not significantly differ. Urinary iodine concentration (UIC) was significantly higher during pregnancy than after delivery (P=0.044). We found no significant correlations between UIC and TSH or between UIC and both free thyroid hormones during pregnancy or after delivery. CONCLUSION: The decrease of both free thyroid hormones in the third trimester of pregnancy is most likely due to reasons that are not related to iodine supply.

Thyroid volume changes during pregnancy and after delivery in an iodine-sufficient Republic of Slovenia.

OBJECTIVE: Literature data concerning thyroid enlargement during pregnancy are not conclusive. Our aim was to systematically follow the thyroid volume changes during pregnancy and after delivery in an iodine-sufficient area. STUDY DESIGN: Prospective study of healthy pregnant women living in an iodine-sufficient area. We followed 118 pregnant women with the mean age 30.9+/-4.1 years in the first trimester (mean 11.2+/-2.5 weeks of pregnancy), in the third trimester (mean 31.6+/-1.7 weeks of pregnancy), and 4 months after delivery (mean 15.9+/-3.9 weeks). Additionally, 71 women were also evaluated 14 months after delivery (mean 13.3+/-1.1 months). All women were negative for thyroid autoantibodies. We measured urinary iodine concentration (UIC), thyroid volume, serum TSH, and body mass index (BMI). After delivery, in a subgroup of women we also estimated the colour flow Doppler sonography (CFDS) patterns 0, I, II and III, where thyroid vascularity increased from pattern 0 to III, and the peak systolic velocity (PSV) using a 7.5 mHz linear transducer. RESULTS: Median UIC in the third trimester (176 microg/g creatinine) was significantly higher than 4 and 14 months after delivery (P=0.030, P<0.001, respectively). Thyroid volume in the third trimester (11.3+/-3.1 mL) was significantly greater (P<0.001) than in the first trimester (8.7+/-2.5 mL), 4 months after delivery (8.6+/-2.5) and 14 months after delivery (7.8+/-2.4 mL). TSH concentration was significantly higher in the third trimester than in the first trimester and 4 months after delivery (P=0.007, P=0.006, respectively). As expected, BMI was the highest in the third trimester. CFDS pattern I was more frequent 4 months after delivery than 14 months after delivery (P<0.001). Similarly, PSV was significantly higher 4 months after delivery than 14 months after delivery (P<0.001). Linear regression analysis revealed TSH and BMI as significant independent predictors for thyroid volume. CONCLUSION: In an iodine-sufficient area, thyroid volume increases during pregnancy and decreases after delivery, and the changes in volume are associated with changes in TSH and BMI. They may be viewed as indicators for metabolic and haemodynamic changes during pregnancy.

Menkes kinky hair disease (Menkes syndrome). A case report.

Menkes disease (MD) is a rare genetic neurodegenerative disorder. It is caused by a mutation in the ATP7A gene, which codes for the copper-transporting ATPase in the cell organelles. Dysfunction of many copper-dependent enzymes results in low concentrations of copper in some tissues and accumulation of copper in others. We report on a boy that at the age of 2 months presented with encephalopathy with epileptic seizures and later had a progressive developmental disorder. Despite treatment with various antiepileptic drugs, some seizures still persisted. Our diagnosis was made on the basis of clinical and laboratory findings. We also plan to confirm the diagnosis genetically. To the best of our knowledge, this is the first reported case of MD in Slovenia. Treatment of MD is usually not successful, especially in sporadic cases, because it usually begins too late. Early neonatal treatment may be successful in half of the cases.