A novel echocardiography method to assess upper body systemic blood flow in preterm infants and comparison with superior vena cava flow measurement.

To evaluate feasibility, reproducibility, and prognostic value of a new echocardiographic method to assess systemic arterial blood flow directed to the upper part of the body (UBAF, upper body arterial flow) alternative to superior vena cava flow (SVCF) measurement. We performed echocardiographic evaluations in 106 infants in the first 2 days of life to obtain SVCF, left ventricle output (LVO), UBAF, and standard parameters of patent ductus arteriosus (PDA) significance. UBAF was calculated by subtracting from LVO the aortic arch blood flow measured immediately distally to the origin of the left subclavian artery. Main outcome measures: UBAF and SVCF agreement was assessed by Bland-Altman analysis in terms of bias, limits of agreement and repeatability index. The Intraclass Correlation Coefficient was used to measure the strength of inter-rater agreement. The agreement between UBAF and SVCF was high. The Concordance Correlation Coefficient (CCC) was 0.7434. (CCC 0.7434, 95% C.I. [0.656, 0.8111]). There was a good absolute agreement between the two raters ICC = 0.747; p value < 0.0001; 95%CI [0.601; 0.845]. Adjusting for confounding factors (BW, GA, PDA) included in the model, there was a statistically significant relationship between UBAF and SVCF. CONCLUSION: UBAF showed a strong agreement with the SCVF with a better reproducibility. Our data support UBAF as a potentially useful marker of cerebral perfusion in the evaluation of preterm infants. WHAT IS KNOWN: • Low SVC (superior vena cava) flow in the neonatal period has been associated with periventricular haemorrhage and unfavourable long-term neurodevelopmental outcome. • Ultrasound measurement of flow in SVC shows relatively high inter-operator variability. WHAT IS NEW: • Our study highlights how much overlap there is between upper-body arterial flow (UBAF) measurement and SCV flow measurement. UBAF is easier to perform and has a strong correlation with better reproducibility. • UBAF may replace measurement of cava flow as a method for haemodynamic monitoring of unstable preterm and asphyxiated infants.

Normal values for superior vena cava flow in preterm neonates using a new echocardiographic approach.

OBJECTIVE: Recently, a novel approach to imaging Superior Vena Cava (SVC) flow has been presented, showing better repeatability and better agreement with MRI-derived SVC flow measures. The objective was to establish normal values of SVC flow with the novel approach in the first 48 h of life. STUDY DESIGN: This was a prospective, observational study. All infants with gestational age (GA) less than 31 weeks were eligible. Echocardiographic evaluation was performed at 5, 12, 24, 48 h of postnatal life. A subgroup of uncomplicated infants was studied to define a normal range for SVC flow. RESULTS: Forty-five infants were enrolled. We estimated normative values in a subgroup of 31 uncomplicated infants. The median SVC flow significantly increases from 83 ml/kg/min at 5 h of life to 153 ml/kg/min at 48 h (p < .001). CONCLUSION: Using the novel approach we derived normal values of SVC flow in a cohort of uncomplicated preterm population at high risk for developing IVH.

Strict glycaemic control in very low birthweight infants using a continuous glucose monitoring system: a randomised controlled trial.

OBJECTIVE: To evaluate the efficacy of a strict glycaemic control protocol using a continuous glucose monitoring (CGM) in infants at high risk of dysglycaemia with the aim of reducing the number of dysglycaemic episodes. DESIGN: Randomised controlled trial. SETTING: Neonatal intensive care unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome. PATIENTS: All infants <1500 g fed on parental nutrition (PN) since birth were eligible. A total of 63 infants were eligible and 48 were randomised. INTERVENTION: All participants wore a CGM sensor and were randomised in two arms with alarms set at different cut-off values (2.61-10 mmol/L (47-180 mg/dL) vs 3.44-7.78 mmol/L (62-140 mg/dL)), representing the operative threshold requiring modulation of glucose infusion rate according to an innovative protocol. MAIN OUTCOME MEASURES: The primary outcome was the number of severe dysglycaemic episodes (<2.61 mmol/L (47 mg/dL) or >10 mmol/L (180 mg/dL)) in the intervention group versus the control group, during the monitoring time. RESULTS: We enrolled 47 infants, with similar characteristics between the two arms. The number of dysglycaemic episodes and of infants with at least one episode of dysglycaemia was significantly lower in the intervention group (strict group): respectively, 1 (IQR 0-2) vs 3 (IQR 1-7); (p=0.005) and 12 (52%) vs 20 (83%); p=0.047. Infants managed using the strict protocol had a higher probability of having normal glycaemic values: relative risk 2.87 (95% CI 1.1 to 7.3). They spent more time in euglycaemia: 100% (IQR 97-100) vs 98% (IQR 94-99), p=0.036. The number needed to treat to avoid dysglycaemia episodes is 3.2 (95% CI 1.8 to 16.6). CONCLUSION: We provide evidence that CGM, combined with a protocol for adjusting glucose infusion, can effectively reduce the episodes of dysglycaemia and increase the percentage of time spent in euglycaemia in very low birthweight infants receiving PN in the first week of life.

Severe herpes virus 6 interstitial pneumonia in an infant with three variants in genes predisposing to lung disease.

Infections due to human herpesvirus 6 (HHV-6) are frequent during early childhood. Usually, they have a favorable clinical course. Conversely, HHV-6 congenital infections occur in about 1% of neonates and may present with more severe clinical pictures. HHV-6 can be found in lung tissues and bronchoalveolar lavage (BAL) samples from patients with pneumonia and in immunocompromised patients can cause mild to severe pneumonia. In neonates, the role of HHV-6 in the genesis of severe pneumonia is poorly defined still now. We describe a healthy infant with a late-onset (15 days of life) severe interstitial pneumonia and heavy HHV-6 genome load, persistently detected in its BAL fluid. The baby underwent high-frequency oscillatory ventilation, hydroxychloroquine, steroids, and ganciclovir for 6 weeks and at 9 months she died. Next-generation sequencing of genes known to cause neonatal respiratory insufficiency revealed the presence of a "probably pathogenetic" heterozygous variant in the autosomal recessive DRC1 gene, a heterozygous variant of unknown significance (VUS) in the autosomal recessive RSPH9 gene, and a heterozygous VUS in the autosomal recessive MUC5B gene. HHV-6 infection should be considered in the differential diagnosis of late-onset severe respiratory distress in neonates and the co-occurrence of genetic predisposing factors or modifiers should be tested by specific molecular techniques. The intensity of HHV-6 genome load in BAL fluid could be an indicator of the response to antiviral therapy.

Neonatal lung ultrasonography score after surfactant in preterm infants: A prospective observational study.

OBJECTIVE: To assess changes in neonatal lung ultrasonography score (nLUS) after surfactant administration in preterm infants with respiratory distress syndrome (RDS). WORKING HYPOTHESIS: The reduction of nLUS score before (nLUSpre), 2 hours (nLUS2h), and 12 hours (nLUS12h) after surfactant administration to identify patients who will not need a second treatment. STUDY DESIGN AND SETTING: Prospective observational study in the tertiary neonatal intensive care unit. PATIENTS SELECTION: Forty-six preterm neonates with RDS of 32 weeks median gestational age (IQR 30-33) and mean birth weight of 1650 ± 715 g. METHODOLOGY: Lung ultrasonography was performed before, 2 hours, and 12 hours after surfactant administration in preterm infants with RDS needing surfactant treatment. Resulting nLUS was analyzed. RESULTS: The Wilcoxon signed-rank test demonstrated an nLUS lowering after 2 hours (P < .001) and 12 hours (P < .001) from surfactant administration. Sixteen newborns required surfactant retreatment with median gestational age of 32 weeks (IQR 29-33) and mean birth weight of 1519 ± 506 g.The receiver operating characteristic analysis for the nLUS2h yielded an area under the curve of 0.80 (95% confidence interval, 0.76-0.85; P < .001). A nLUS2h ≥7 showed a sensitivity of 94% and a specificity of 60% for needing a second treatment with surfactant. CONCLUSIONS: In preterm infants with RDS requiring surfactant treatment, nLUS evaluated 2 hours after surfactant administration can be used to identify patients who will not need a second treatment.

Short therapy in a septic arthritis of the neonatal hip.

Septic arthritis (SA) is a serious joint infection associated with significant morbidity that can cause permanent damage with articular cartilage destruction, osteonecrosis and lifelong deformities if not diagnosed and treated promptly. In neonates, because of the paucity of signs and symptoms, SA is difficult to diagnose. The treatment for SA in children is empirical antibiotic for weeks, initially intravenously, and surgical (arthrotomy) in particular for the hip and shoulder because of the high risk of sequelae in these joints. Actually, there isn't a consensus about the duration of antibiotic treatment, because of the lack of powered studies, and a variable period from 2 weeks to 4 months has been suggested in the literature. Data in the neonatal population are very limited. We describe a case of neonatal hip arthritis with a good outcome treated with a short antibiotic course of 2 weeks.

Fish oil-based lipid emulsion in the treatment of parenteral nutrition-associated cholestasis.

BACKGROUND: Parenteral nutrition-associated cholestasis (PNAC) is a serious complication in preterm infants receiving prolonged parenteral nutrition. Soybean lipid emulsion (SLE) seems to have a role in its pathogenesis, whereas fish oil-based emulsion (FOLE) seems to be able to reverse cholestasis. This study aimed to evaluate the effectiveness of a FOLE in reversing PNAC. METHODS: The effectiveness in reversing PNAC was evaluated in prospective cohort study of very preterm infants when compared to historical controls: twenty-six infants (27.0 ± 2.6 weeks GA; 724 ± 204 g) who developed cholestasis while receiving SLE were shifted to receive FOLE and were compared with 30 infants (27.3 ± 2.5 weeks GA¸ 838 ± 277 g) who continued to receive SLE at diagnosis of cholestasis. RESULTS: Time to reversal of cholestasis was the same in the two study groups (45 ± 21 vs 43 ± 32 days). CONCLUSIONS: FOLE does not seem to be superior to SLE in reversing cholestasis. Considering that definitive data on the actual efficacy of FOLE to reverse PNAC are lacking, larger randomized trials are required, mainly to asses if FOLE may have a role in PNAC prevention rather than PNAC treatment.

Lung ultrasonography score versus chest X-ray score to predict surfactant administration in newborns with respiratory distress syndrome.

OBJECTIVES: We aim to verify the diagnostic accuracy of a lung ultrasonography (LUS) score to early predict the need for surfactant therapy in newborns with respiratory distress syndrome (RDS), and to compare it with a chest X-ray score. METHODS: In this prospective diagnostic accuracy study we included all newborns admitted for respiratory distress and initially treated with nasal CPAP. LUS was performed within 2 h from nasal CPAP positioning and in any case before surfactant administration. A chest X-ray was also performed. A LUS score and an X-ray score were used and compared. Ability of the scores to predict surfactant administration was evaluated through ROC analysis. RESULTS: In our population of 56 newborns with mean gestational age of 31 weeks (SD 3) and mean birth weight of 1442 g (SD 520), LUS score showed higher AUC than X-ray score in early recognition of infants with respiratory distress syndrome requiring surfactant treatment (0.94; 95%CI, 0.89-0.98; P < 0.001 vs 0.80; 95%CI, 0.74-0.86; P < 0.001). It showed also higher sensitivity (86% vs 82%), higher specificity (88% vs 76%), better positive (83% vs 69%), and negative (91% vs 87%) predictive values. CONCLUSIONS: LUS is a non-invasive, bedside and reproducible method that could improve the management of neonatal respiratory distress. It is accurate and reliable to early identify patients who will need treatment with surfactant allowing both an early treatment and a reduction of radiation exposure.

Continuous glucose monitoring in preterm infants: evaluation by a modified Clarke error grid.

BACKGROUND: Continuous glucose monitoring using subcutaneous sensors has been validated in adults and children with diabetes, and was found to be useful in the management of glucose control. We aimed to assess feasibility and reliability of a new continuous glucose monitoring system (CGMS) in a population of preterm neonates using a Clarke error grid (CEG) specifically modified for preterm infants. METHODS: Preterm infants were recruited within 24 h from delivery. A subcutaneous sensor connected to a CGMS was inserted and maintained for 6 days. Data collected from CGMS were compared with data obtained using a glucometer. Management of the infants followed standard protocols and was not influenced by CGMS readings. RESULTS: Twenty patients (9 males) were included. Median (range) gestational age was 32 weeks (27-36) and median (range) birth weight was 1350 g (860-3360). Average CGMS recording time was 137 h, for a total of 449 paired glucose levels. CEG and modified CEG criteria for clinical significance were met. CONCLUSION: CGMS is a safe and clinically adequate method to estimate glucose levels in preterm infants. As the glucose level can be evaluated in real time, this CGMS could be useful to reduce the number of heel sticks, to observe glycaemic trends and to promptly detect episodes of both hypo- and hyper-glycaemia.

Endothelial and platelet function in children with previous Kawasaki disease.

We investigated whether children with a previous Kawasaki disease (KD) have evidence of abnormal vascular and/or platelet function. We included 14 patients with previous KD and 14 matched controls. We assessed endothelial function by flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), coronary microvascular function by coronary blood flow response (CBFR) to cold pressor test, and platelet reactivity by measuring monocyte-platelet aggregates (MPAs) and CD41-platelet expression by flow cytometry. No differences were found between the groups in FMD, cIMT, or CBFR to cold pressor test. The MPAs were similar in patients with KD and controls. CD41-platelet expression, however, was significantly increased in patients with KD compared with controls, both at rest (14.3 ± 1.9 vs 12.4 ± 1.9 mean fluorescence intensity [mfi], P = .01) and after adenosine diphosphate stimulation (19.3 ± 1.3 vs 17 ± 1.7 mfi, P < .001). In conclusion, children with a previous episode of KD showed increased platelet activation, compared with healthy participants despite no apparent vascular abnormality at follow-up.