Prognostic Relevance of the Lung Ultrasound Score: A Multioutcome Study in Infants with Respiratory Distress Syndrome.

OBJECTIVE: There is growing evidence for the usefulness of the lung ultrasound score (LUS) in neonatal intensive care. We evaluated whether the LUS is predictive of outcomes in infants with respiratory distress syndrome (RDS). STUDY DESIGN: Neonates less than 34 weeks of gestational age were eligible for this prospective, multicenter cohort study. The outcomes of interest were the need for mechanical ventilation (MV) at <72 hours of life, the need for surfactant (SF), successful weaning from continuous positive airway pressure (CPAP), extubation readiness, and bronchopulmonary dysplasia. Lung scans were taken at 0 to 6 hours of life (Day 1), on Days 2, 3, and 7, and before CPAP withdrawal or extubation. Sonograms were scored (range 0-16) by a blinded expert sonographer. The area under the receiver operating characteristic curve (AUC) was used to estimate the prediction accuracy of the LUS. RESULTS: A total of 647 scans were obtained from 155 newborns with a median gestational age of 32 weeks. On Day 1, a cutoff LUS of 6 had a sensitivity (Se) of 88% and a specificity (Sp) of 79% to predict the need for SF (AUC = 0.86), while a cutoff LUS of 7 predicted the need for MV at <72 hours of life (Se = 89%, Sp = 65%, AUC = 0.80). LUS acquired prior to weaning off CPAP was an excellent predictor of successful CPAP withdrawal, with a cutoff level of 1 (Se = 67%, Sp = 100%, AUC = 0.86). CONCLUSION: The LUS has significant predictive ability for important outcomes in neonatal RDS. KEY POINTS: · Lung ultrasound has significant prognostic abilities in neonatal RDS.. · Early sonograms (0-6 h of life) accurately predict the requirement for SF and ventilation.. · Weaning off CPAP is effective when the LUS (range 0-16) is less than or equal to 1..

Modified lung ultrasound score predicts ventilation requirements in neonatal respiratory distress syndrome.

BACKGROUND: We propose a modified lung ultrasound (LUS) score in neonates with respiratory distress syndrome (RDS), which includes posterior instead of lateral lung fields, and a 5-grade rating scale instead of a 4-grade rating scale. The purpose of this study was to evaluate the reproducibility of the rating scale and its correlation with blood oxygenation and to assess the ability of early post-birth scans to predict the mode of respiratory support on day of life 3 (DOL 3). As a secondary objective, the weight of posterior scans in the overall LUS score was assessed. METHODS: We analyzed 619 serial lung scans performed in 70 preterm infants < 32 weeks gestation and birth weight < 1500 g. Assessments were performed within 24 h of birth (LUS0) and on days 2, 3, 5, 7, 10, 14, 21 and 28. LUS scores were correlated with oxygen saturation over fraction of inspired oxygen (S/F) and mode of respiratory support. Interrater agreement was determined with the intraclass correlation coefficient (ICC) and Cronbach's alpha. Probabilities of the need for various respiratory support modes on DOL 3 were assessed with ordinal logistic regression. Least square (ls) means of the posterior and anterior pulmonary field scores were compared. RESULTS: The LUS score correlated significantly with S/F (Spearman rho = -0.635; p < 0.0001) and had excellent interrater agreement (ICC = 0.94, 95% CI 0.93-0.95; Cronbach's alpha = 0.99). Significant predictors of ventilation requirements on DOL 3 were LUS0 (p < 0.016) and birth weight (BW) (p < 0.001). In the ROC analysis, LUS0 had high reliability in prognosing invasive ventilation on DOL 3 (AUC = 0.845 (95% DeLong CI: 0.738-0.951; p < 0.001)). Invasive ventilation was the most likely mode of respiratory support for LUS0 scores: ≥7 (in infants with BW 900 g), ≥ 10 (in infants with BW 1050 g) and ≥ 15 (in infants with BW 1280 g). Posterior fields exhibited significantly higher average scores than anterior fields. Respective ls means (confidence levels) were 4.0 (3.8-4.1) vs. 2.2 (2.0-2.4); p < 0.001. CONCLUSIONS: Post-birth LUS predicts ventilation requirements on DOL 3. Scores of posterior pulmonary fields have a predominant weight in the overall LUS score.

Sonographic findings in a neonate with Cobb syndrome.

Cobb syndrome (cutaneomeningospinal angiomatosis) is a rare phacomatosis characterized by vascular abnormality of the spinal cord associated with a vascular naevus at the same metamere. We report the case of a newborn with Cobb syndrome, diagnosed by sonography of the spine and later confirmed by MRI. In neonates and young infants with dermatomal cutaneous vascular abnormalities, sonography of the spine should be used as the first imaging modality.

FiO2 Before Surfactant, but Not Time to Surfactant, Affects Outcomes in Infants With Respiratory Distress Syndrome.

Aim: To establish the impact of oxygen requirement before surfactant (SF) and time from birth to SF administration on treatment outcomes in neonatal respiratory distress syndrome (RDS). Methods: We conducted a post-hoc analysis of data from a prospective cohort study of 500 premature infants treated with less invasive surfactant administration (LISA). LISA failure was defined as the need for early (<72 h of life) mechanical ventilation (MV). Baseline clinical characteristic parameters, time to SF, and fraction of inspired oxygen (FiO2) prior to SF were all included in the multifactorial logistic regression model that explained LISA failure. Results: LISA failed in 114 of 500 infants (22.8%). The median time to SF was 2.1 h (IQR: 0.8-6.7), and the median FiO2 prior to SF was 0.40 (IQR: 0.35-0.50). Factors significantly associated with LISA failure were FiO2 prior to SF (OR 1.03, 95% CI 1.01-1.04) and gestational age (OR 0.82, 95 CI 0.75-0.89); both p <0.001. Time to SF was not an independent risk factor for therapy failure (p = 0.528) or the need for MV at any time during hospitalization (p = 0.933). Conclusions: The FiO2 before SF, but not time to SF, influences the need for MV in infants with RDS. While our findings support the relevance of FiO2 in SF prescription, better adherence to the recommended FiO2 threshold for SF (0.30) is required in daily practice.

Ultrasound Monitoring of Umbilical Catheters in the Neonatal Intensive Care Unit-A Prospective Observational Study.

Introduction: Umbilical catheterization provides a quick yet demanding central line that can lead to complications seen nowhere else. The aim of our study was to determine whether the repeated ultrasound scanning can influence the catheterization time, prevent some of the catheter-related complications, support the decision-making process and allow prolonged catheterization in patients without an alternative central access route. Methods: A prospective observational study was performed in a tertiary neonatal intensive care unit. A total of 129 patients and 194 umbilical catheters (119 venous and 75 arterial) were analyzed with a total of 954 scans. Ultrasound screening consisted of 1) assessing the catheter tip, location, movability, and surface and 2) analyzing the catheter trajectory. The outcome variables were defined as 1) catheter dislocation and 2) associated thrombosis. Results: Dislocation of catheter throughout the whole catheterization period was observed in 68% (81/119) of UVCs and 23% (17/75) of UACs. Thrombotic complications were observed in 34.5% (41/119) of UVCs and 12% (9/75) of UACs. 1/3 of UAC-associated thrombi were visible only after catheter removal. 51% (61/119) of UVC patients and 8% (6/75) of UAC patients made a clinical decision regarding the obtained catheter image. Conclusion: Bedside ultrasound imaging of catheters supports the decision-making process related to the catheterization duration, shortening the time if abnormalities are detected and allowing a safer prolonged UC stay when an alternative central line cannot be inserted.

Serum very long-chain fatty acids (VLCFA) levels as predictive biomarkers of diseases severity and probability of survival in peroxisomal disorders.

CONCLUSION: VLCFA levels correlate with the severity of the clinical course of ZS, DBP and mild ZSD. The best predictive value for estimating the projected disease severity and survival time is a concentration of C26:0.

[Respiratory syncytial virus prophylaxis among preterm infants--four seasons' experience]. / Profilaktyka zakazen wirusem RS u noworodków urodzonych przedwczesnie--4 letnie doswiadczenia wlasne.

BACKGROUND: Respiratory syncitial virus (RSV) is the main reason of hospitalizations due to respiratory tract infection in children within the first year of life. The course of infection is more severe in children from a risk group, which includes children who were born preterm, these with bronchopulmonary dysplasia (BPD), children with heart defects significantly influencing their hemodynamics, and immunocompromised children. Palivizumab is a humanized monoclonal antibody class IgG-1 used to prevent RSV infection. AIM: To assess the results of treatment and to evaluate factors influencing the efficacy of RSV infection prophylaxis in preterm newborns. METHODS: The study included 55 preterm newborns (mean birth weight-970g, mean gestational age-27 weeks), who were given a dose of palmivizumab of 15mg per kg body weight every four weeks in autumn and winter from season 2004/ 2005 to season 2007/2008. RESULTS: Ten children (18%) required hospitalization between the doses and within 28 days after the last dose of palmivizumab. Among these, 2 children (3.6%) were hospitalized because of very severe RSV infection. Eight children (16%) were hospitalized due to respiratory tract infection within 12 months after completing the prophylaxis; none of them was infected with RSV. The episodes of respiratory tract infection between the doses and within 28 days after the last dose occurred in 19 children (31%), and in 26 patients included in the follow-up (51%) within 12 months after completing the prophylaxis. The effect of treatment was most beneficial in preterm neonates with extremely low birth weight and in children who did not require respiratory medications at the moment of discharge from the neonatal unit. CONCLUSION: RSV infection prophylaxis is of most benefit in children born with extremely low birth weight. In this group of children the prophylaxis should be considered both for children suffering from BPD and in children free of this disease.

Umbilical catheters as vectors for generalized bacterial infection in premature infants regardless of antibiotic use.

Introduction. Umbilical catheterization offers unique vascular access that is only possible in the neonatal setting due to unobstructed umbilical vessels from foetal circulation. With the cut of the umbilical cord, two arteries and a vein are dissected, allowing quick and painless catheterization of the neonate. Unfortunately, keeping the umbilical access sterile is challenging due to its mobility and necrosis of the umbilical stump, which makes it a perfect model for vessel catheter colonization analysis.Aim. The aim of this study was to evaluate bacterial colonization of the umbilical catheter, with a focus on the difference between various sections of the catheter, the duration of catheterization, patient status and gestational age.Methodology. We performed bacterial cultures for 44 umbilical catheters, analysing the superficial and deep parts of the catheter separately, and revealed colonization in one-third of cases.Results. One hundred per cent of the colonization occurred in preterm infants, with a shift towards extreme prematurity. The catheters were mainly colonized by coagulase-negative staphylococci. The majority of catheters presented with superficial colonization dominance, and there were no cases of deep colonization. The bacterial strains and their resistance were consistent between the catheter's proximal and distal parts, as well as positive blood cultures. The patients with the most intense bacterial catheter colonization presented with sepsis around removal time or a couple of days later, especially if they were extremely premature and exhibited very low birth weight. Catheterization time did not play a major role.Conclusion. Umbilical catheters are vectors for skin microflora transmission to the bloodstream via biofilm formation, regardless of antibiotic use and the duration of catheterization, especially in preterm neonates.

Association between X-linked lissencephaly with ambiguous genitalia syndrome and lenticulostriate vasculopathy in neonate.

X-linked lissencephaly with ambiguous genitalia syndrome (XLAG) (OMIM #3000215) is a rare, severe malformation of the brain cortex with abnormal neuronal migration caused by mutations of the ARX gene. All the reported patients with lissencephaly are males who presented with a posterior-to-anterior gradient, moderately increased thickness of the brain cortex, agenesis of corpus callosum, micropenis, and cryptorchidism. We describe the neurosonographic findings associated with the XLAG syndrome. To our knowledge, the association between XLAG and lenticulostriate vasculopathy has not been reported before.

Novel mutation-deletion in the PHOX2B gene of the patient diagnosed with Neuroblastoma, Hirschsprung's Disease, and Congenital Central Hypoventilation Syndrome (NB-HSCR-CCHS) Cluster.

INTRODUCTION: Neuroblastoma (NB), Hirschsprung disease (HSCR), Congenital Central Hypoventilation Syndrome (CCHS), clinically referred as the NB-HSCR-CCHS cluster, are genetic disorders linked to mutations in the PHOX2B gene on chromosome 4p12. SPECIFIC AIM: The specific aim of this project is to define the PHOX2B gene mutations as the genomic basis for the clinical manifestations of the NB-HSCR-CCHS cluster. PATIENT: A one day old male patient presented to the Jagiellonian University Medical College (JUMC), American Children Hospital, neonatal Intensive Care Unit (ICU) due to abdominal distention, vomiting, and severe apneic episodes. With the preliminary diagnosis of the NB-HSCR-CCHS, the blood and tissue samples were acquired from the child, as well as from the child's parents. All procedures were pursued in accordance with the Declaration of Helsinki, with the patient's Guardian Informed Consent and the approval from the Institutional Review Board. GENETIC/GENOMIC METHODS: Karyotyping was analyzed based upon Giemsa banding. The patient's genomic DNA was extracted from peripheral blood and amplified by polymerase chain reaction. Direct microfluidic Sanger sequencing was performed on the genomic DNA amplicons. These procedures were pursued in addition to the routine clinical examinations and tests. RESULTS: G-banding showed the normal 46 XY karyotype. However, genomic sequencing revealed a novel, heterozygous deletion (8 nucleotides: c.699-706, del8) in exon 3 of the PHOX2B gene on chromosome 4. This led to the frame-shift mutation and malfunctioning gene expression product. CONCLUSION: Herein, we report a novel PHOX2B gene mutation in the patient diagnosed with the NB-HSCR-CCHS cluster. The resulting gene expression product may be a contributor to the clinical manifestations of these genetic disorders. It adds to the library of the mutations linked to this syndrome. Consequently, we suggest that screening for the PHOX2B mutations becomes an integral part of genetic counseling, genomic sequencing of fetal circulating nucleic acids and / or genomes of circulating fetal cells prenatally, while preparing supportive therapy upon delivery, as well as on neonates' genomes of intubated infants, when breathing difficulties occur upon extubation. Further, we hypothesize that PHOX2B may be considered as a potential target for gene therapy.

[Thanatophoric dysplasia: three patients hospitalized in PAIP in 1994-2000]. / Karlowatosc tanatoforyczna--prezentacja trzech pacjentów hospitalizowanych w PAIP w latach 1994-2000.

BACKGROUND: Thanatophoric dwarfism is a lethal bone dysplasia causing severe disturbance in body proportions, shortening and deformation of the long bones and maldevelopment of the chest leading to severe respiratory failure and early death. The disease is caused usually by de novo mutation in the gene of fibroblast growth factor receptor 3 (FGFR3). Inheritance is autosomal dominant. The most common mutation C742T leads to substitution of arginine by cysteine in 248 position of polypeptide (R248C). GOAL: Presentation of clinical picture, radiological findings and molecular diagnostics in three patients with TD hospitalized in PAIP in 1994-2000. PATIENTS: Three patients with TD were hospitalized in PAIP between 1994 and 2000. They were admitted in the 1st, 2nd, 19th day of life. Two patients were referred with diagnosis of achondroplasia. One newborn was born after uncomplicated pregnancy with cesarean section due to large head circumference found on prenatal USG. Two other newborns were born preterm (34 week of gestation), vaginally. One pregnancy was complicated by polyhydramnios. All patients required oxygen therapy, two were artificially ventilated (21 and 16 days). Three newborns died due to respiratory failure, average length of life--29 days. METHODS AND RESULTS: The diagnosis was established based on clinical presentation (abnormal proportions, shortening and deformation of the extremities, maldevelopment of the chest, large cranium) and radiological presentation (typical vertebral bodies, long bones shaped as telephone receiver). In two cases molecular analysis was performed, which excluded achondroplasia, in one of those patients molecular studies directly confirmed presence of the most common mutation leading to TD (R248C).

[Blood gases values forecasting by artificial neural network in prematurely born infants with respiratory distress]. / Zastosowanie sztucznej sieci neuronowej w prognozowaniu wartosci gazometrii krwi u wczesniaków z zaburzeniami oddychania.

Artificial Neural Networks (ANN) are modern tools for data analysis. They can compete with commonly used statistical methods. Till the date they were not used for modeling continuous parameters in medicine. The aim of this paper is to assess accuracy of ANN in forecasting blood gases values in preterm infants with respiratory distress. The study was conducted with the use of the data from Neonatal Information System (NIS) describing first 30 days of the hospital stay of 19 newborns with birthweight < or = 1500 g admitted to the unit before second day of life in 1997. Separate ANN was created for prognosis of 4 parameters of arterial blood gases (pH, pCO2, pO2, HCO3) and oxygenation index (pO2/FiO2) for 1 hour in advance. For each forecasted parameter input set of parameters was established. The ANN was taught with back propagation algorithm using data of 18 patients, the accuracy of prognosis was tested on the data of the remaining patient. This procedure was repeated 19 times. The error of prognosis was assessed in comparison to predefined curves of the maximal error. The accuracy of achieved prognoses was respectively for pH, pCO2, pO2, HCO3, pO2/FiO2 98.9, 99.7, 97.1, 98.3, 95%.

[Diagnostic and prognostic reliability of interleukin-10 measurements in very low birth weight infants with late-onset sepsis]. / Wartosc diagnostyczna i prognostyczna oznaczania stezenia interleukiny-10 u noworodków z bardzo niska urodzeniowa masa ciala.

BACKGROUND: There exists little data on releasing Interleukin-10 (IL-10) and on the clinical usefulness of its measurements in very low birth weight (VLBW) infants. AIM: The evaluation of diagnostic and prognostic reliability of IL-10 measurement in VLBW infants with sepsis. METHODS: 87 newborns with the median birth weight (BW) 1060 g and median gestational age (GA) 28 wks were divided into 3 groups: A) with no clinical signs of sepsis in the first month of life-control group (n = 28), B) with clinical signs of sepsis but with negative blood cultures (n = 13), and C) with clinically and microbiologically confirmed sepsis (n = 46). In the control group IL-10 was measured on admission and in the 10th, 20th and 30th day of life. The remaining newborns had IL-10 measured when sepsis was suspected. RESULTS: IL-10 levels did not correlate with GA (R = -0.01) or BW (R = -0.04). In the control group there was no correlation between IL-10 levels and the calendar age. IL-10 levels were statistically higher in the group C than in the remaining ones (Me: 0 vs 1.32 vs 99.8 pg/ml). IL-10 level > 20 pg/ml allowed to distinguish between the group B and C with 79% sensitivity and 82% specificity. The highest levels of IL-10 were detected in the newborns who died of sepsis (Me = 889 pg/ml). IL-10 level > 680 pg/ml predicted the death of a newborn with 80% sensitivity and 100% specificity. CONCLUSIONS: IL-10 measurements possess a great diagnostic and prognostic reliability and allow the detection of newborns with poor outcome, thus the measurement of IL-10 may be useful in clinical practice.

[Influence of the lactose free and lactose containing diet on prevalence of gram-negative sepsis and feeding intolerance in very low birth weight infants: double-blind randomized trial]. / Wplyw rodzaju stosowanej diety na tolerancje karmienia i czestosc posocznicy Gram ujemnej u noworodków z bardzo niska urodzeniowa masa ciala.

OBJECTIVE: VLBW infants have a developmental lactase deficiency in the gut. The aim of the study was to evaluate the influence of lactose containing and lactose free diets on prevalence of feeding intolerance and Gram negative sepsis in VLBW infants. METHODS: 80 newborns with mean (+/- SEM) birth weight 1091 +/- 25 g and gestational age 28.5 +/- 0.24 wks were randomized into 2 groups fed during 1st month of life with 1) formula containing lactose (Bebilon Nenatal--BN group; n = 40) or 2) lactose free formula (Pregestimil--PG group; n = 40). The end points of the study were: feeding intolerance episodes, Gram negative sepsis, weight gain and the length of parenteral nutrition. RESULTS: The birthweight (1112 vs 1114 g), gestational age (28.8 vs 28.3 wks), 5th min. Apgar score (5 vs 6 pts), sex (52% vs 55% male), type of delivery (65 vs 58% vaginal delivery) did not differ between the groups. Thirty (75%) newborns of the BN group and 31 (77.5%) newborns of the PG group completed the study (RR = 1.11; 95% CI: 0.54-2.44). The prevalence of Gram negative sepsis were similar in both groups (2/40 vs. 3/40; RR = 0.67; 95% CI: 0.12-3.78). Also a comparable number of children had at least one episode of feeding intolerance (14/40 vs. 12/40; RR = 1.17; 95% CI: 0.69-2.20) The weight gain (11.7 vs 10.9 g/day) and the length of parenteral nutrition did not differ between the groups (16 vs 15 days). CONCLUSION: The inclusion of lactose into feeding formula does not influence feeding tolerance in VLBW infants.

Can early echocardiographic findings predict patent ductus arteriosus?

BACKGROUND: Prophylactic treatment with prostaglandin synthetase inhibitors (PSI) is potentially harmful. Moreover, long-term benefits of prophylactic use of indomethacin or ibuprofen are not proven. Early treatment of a high-risk population is alternative to the routine prophylactic use of PSI, but it remains unclear which newborn is at greatest risk for patent ductus arteriosus (PDA). OBJECTIVE: Evaluation of the prognostic value of early echocardiographic studies with respect to PDA in later life. METHODS: Sixty preterm infants with a mean birth weight of 1,087 g and mean gestational age of 28.5 weeks were included in a prospective study. Cardiac scans were performed in all newborns on entry into the study (within 12-48 h after birth) and further in case of clinical suspicion of PDA or obligatorily on the 7th and 28th days of life. There was no prophylactic or treatment use of any PSI during the study period. Newborns were divided into 2 cohorts: with significant left to right shunt requiring surgical ligation of PDA (n = 16) or without significant PDA during follow-up (control group, n = 44). RESULTS: On entry, the mean internal diameter of the ductus arteriosus (2.6 vs. 0.91 mm/kg; p < 0.01), mean cardiac index across aortic valve (2.96 vs. 2.37 l/min/m(2); p < 0.01) and early filling peak velocity (43.1 vs. 33.7; p = 0.01) were significantly higher in babies who later needed surgical ligation of PDA. There was no difference in the mean values of the other echocardiographic parameters studied. An early ductal diameter of >1.5 mm/kg predicted symptomatic PDA with a sensitivity of 94% and a specificity of 73%, and its positive predictive value equaled 57% and negative predictive value amounted to 97%. CONCLUSIONS: Early echocardiographic studies possess negative predictive value and may decrease unnecessary surgical ligation of PDA in very low birth weight infants.