Tim Schindler

The 'Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low Birth-Weight Infants (ETTNO)' Study: Background Aims, and Study Protocol

Background: Infants with extremely low birth weight uniformly develop anemia of prematurity and frequently require red blood cell transfusions (RBCTs). Although RBCT is widely practiced, the indications remain controversial in the absence of conclusive data on the long-term effects of RBCT. Objectives: To summarize the current equipoise and to outline the study protocol of the ‘Effects of Transfusion Thresholds on Neurocognitive Outcome of extremely low birth-weight infants (ETTNO)’ study. Methods: Review of the literature and design of a large pragmatic randomized controlled trial of restrictive versus liberal RBCT guidelines enrolling 920 infants with birth weights of 400–999 g with long-term neurodevelopmental follow-up. Results and Conclusions: The results of ETTNO will provide definite data about the efficacy and safety of restrictive versus liberal RBCT guidelines in very preterm infants.

Evaluation of Neonatal Regional Cerebral Perfusion Using Power Doppler and the Index Fractional Moving Blood Volume

Background: The high cerebral morbidity of premature neonates is thought to be related to changes in tissue perfusion in vulnerable areas of the brain. Quantification of power Doppler (PD) images using the index fractional moving blood volume (FMBV) may allow measurement of regional cerebral perfusion. Objective: To evaluate the reproducibility of calculating FMBV using PD ultrasound images to estimate cerebral perfusion. Methods: Two experienced clinicians performed head ultrasounds on 24 normally-grown neonates at less than 33 weeks’ gestation. Both clinicians independently acquired and stored three PD images in two different coronal planes. FMBV was calculated offline after selecting two predefined regions of interest within these planes (basal ganglia and subependymal regions). Reproducibility was evaluated by calculating the intraclass correlation coefficient (intraCC) and the interclass correlation coefficient (interCC). Results: FMBV was successfully evaluated in 24/24 neonates by both clinicians. The intraCC for repeatability for observer A was 1.00 (95% CI 1.00–1.00) for the basal ganglia and 0.99 (95% CI 0.99–1.00) for the subependymal region, and for observer B was 0.99 (95% CI 0.99–1.00) for the basal ganglia and 0.96 (95% CI 0.92–0.98) for the subependymal region. The interCC was 0.86 (95% CI 0.68–0.94) for the basal ganglia and 0.93 (95% CI 0.86–0.97) for the subependymal region. Conclusion: Using standardised settings and a well-defined region of interest, the calculation of FMBV using PD images is a reproducible method of estimating neonatal regional cerebral perfusion.

False-positive MIBG uptake in pneumonia in a patient with stage IV neuroblastoma.

A 32-month-old female child with a history of stage IV favorable biology neuroblastoma with a 123-I MIBG (metaiodobenzylguanidine scan) avid adrenal mass, with retroperitoneal nodal extension and bony metastasis, was in complete remission after intense multimodal therapy. Seventeen months after diagnosis a surveillance 123-I MIBG scan showed abnormal tracer uptake in the midzone of the right thorax. Chest x-ray and CT scan confirmed right upper lobe consolidation corresponding to the tracer uptake. Chest x-ray after antibiotics showed resolution of the abnormality. 123-I MIBG scan 3 months later showed no abnormal uptake. False-positive MIBG uptake in pneumonia has not been previously reported.

Magnetic Non-Invasive Acupuncture for Infant Comfort (MAGNIFIC) – A single-blinded randomized controlled pilot trial

To determine the safety and feasibility of auricular noninvasive magnetic acupuncture (MA) to decrease infant pain during heel pricks.

Cerebral oxygenation as measured by near-infrared spectroscopy in neonatal intensive care: correlation with arterial oxygenation

To assess correlation between cerebral oxygenation (rScO2), as measured by near‐infrared spectroscopy (NIRS), and arterial oxygenation (PaO2), as measured by arterial blood gases, in preterm neonates.

Congenital central hypoventilation syndrome: A pictorial demonstration of absent electrical diaphragmatic activity using non-invasive neurally adjusted ventilatory assist

Congenital central hypoventilation syndrome: A pictorial demonstration of absent electrical diaphragmatic activity using non-invasive neurally adjusted ventilatory assist Ruth Sinclair, Arthur Teng, Catherine Jonas and Tim Schindler Department of Newborn Care, Royal Hospital for Women, Faculty of Medicine, University of New South Wales and Department of Sleep Medicine, Sydney Children’s Hospital, Sydney, New South Wales, Australia

Basal ganglia perfusion in the preterm infant during transition

Background:The preterm brain is susceptible to changes in blood flow. Using power Doppler images, digital imaging techniques have been developed to measure the total amount of blood flow in a defined area, giving the index: fractional moving blood volume (FMBV). The aim of this study was to investigate temporal changes in basal ganglia perfusion during the transitional period after birth.Methods:Twenty-four preterm infants were examined with serial cranial ultrasounds at four time points during the first 48 h of life. FMBV was calculated using power Doppler images at each time point.Results:All infants had analyzable data and FMBV was successfully calculated at all time points. Twenty-three of the 24 infants had an increasing trend in FMBV over time. The median FMBV increased from 17% at 6 h to 25% at 48 h. One-way repeated measures ANOVA showed a significant increase in values at P < 0.001 at each of the four time points.Conclusion:We have demonstrated changes in basal ganglia blood flow as the cerebral circulation adapts to extrauterine life. With further investigation, this technique may be useful in the assessment of preterm circulatory adaptation, either alone or in conjunction with other modes of evaluating cerebral blood flow.

Spatiotemporal Image Correlation and Volumetric Impedance Indices in the Neonatal Brain Proof of Concept and Preliminary Reproducibility

Changes in tissue perfusion can be critically important in the vulnerable neonate, but they are very difficult to assess at the bedside. Spatiotemporal image correlation (STIC) sonography is an exciting concept that allows assessment of blood flow by rearranging and merging multiple 2‐dimensional color images to create serial 3‐dimensional images showing regional blood flow throughout the cardiac cycle. Variations in tissue blood flow may reflect tissue impedance and perfusion. The aim of this study was to demonstrate that it is possible to use STIC images to evaluate tissue impedance in the neonatal brain.

In premature infants born at borderline viability, do days matter?

Decisions regarding active resuscitation of preterm neonates can be extremely difficult at the limits of viability as clinicians and families weigh up individualised risks and estimate the chance of a favourable outcome. Knowledge of current mortality and morbidity rates based on prenatally known prognostic factors such as gestational age form the basis for decision making. We recently published hospital outcomes from a regional cohort of live born extreme preterm infants admitted to tertiary neonatal intensive care units within New South Wales and the Australian Capital Territory between 2007 and 2011 using the prospectively collected Neonatal Intensive Care Units’ Data Collection. We reported gestational age in completed weeks as per convention; however, because gestational age is a continuous variable, it is highly likely that there would be a difference in survival within weeks. If this hypothesis is proved, it challenges many regional and national resuscitation guidelines that currently direct clinicians to change resuscitation decisions based on gestational age week cut-off points. In this retrospective study, we tested the hypothesis that infants born late in a gestational week have better outcomes than those born earlier in the same week. We extended the cohort period to 6 years from 2007 to 2012 and analysed data from all live born infants 23–25weeks gestation admitted to a tertiary neonatal unit for provision of intensive care.We sought to determine differences in hospital mortality according to early days (week +0–3 days) and late days (week +4–6 days) at birth for each gestational week. The estimated gestation in weeks and days was determined by the clinical team, using a combination of last menstrual period and clinical assessment. Of 618 extremely preterm infants included, 401 babies survived to hospital discharge (65%). We determined the survival rates with 95% confidence intervals within each gestational age week. Infants born in the early days of each gestational age week had lower survival rates although these differences were not statistically significant (early 23 weeks, 25% (11–47%) vs. late 23 weeks, 30% (17-48%); early 24 weeks, 55% (46–63%) vs. late 24 weeks, 62% (52–71%); early 25 weeks, 74% (67–80%) vs. late 25 weeks, 75% (68–81%)). Differences in survival rates between infants born in the late days of each gestational week and infants born in the early days of the next week were statistically significant (late 23 weeks vs. early 24 weeks (P = 0.01); late 24 weeks vs. early 25 3 weeks [P = 0.03]) (Fig. 1). Only infants admitted to tertiary neonatal units were included in this analysis, which is a significant limitation to the prognostic value of these statistics for counselling purposes. In addition, these data include some infants where there was a decision to redirect care after admission to the neonatal unit. As these infants are not differentiated, we cannot assess how this might have affected survival rates. Like the decision to initiate resuscitation, the decision to discontinue intensive care is multifactorial and is likely to be influenced by individual attitudes to active management at this gestation. It is important to acknowledge that there are many factors other than gestation that need to be considered at borderline viability; however, when considering active resuscitation during this period, gestational age is a critically important prognostic factor. If additional days in utero mean an important gain for infant survival, this should be factored in when individualising prognosis. This study shows that there are potentially clinically important differences in survival within gestational age weeks; however, the size of this cohort meant that these differences did not reach statistical significance. Further investigation is warranted on a larger cohort of extreme preterm infants to answer this important question.

Survey on Clinical Practice of Parenteral Nutrition in Neonates in Australasia: Letters to the Editor

observed. Bilateral mildly enlarged exudative tonsils were noted. He had mild submandibular lymphadenopathy (<1 cm). No other skin or mucous membrane changes were appreciated on examination. Cardiorespiratory and abdominal exam was unremarkable. Investigations included – full blood count, electrolytes and liver enzymes, C-reactive protein, viral serology (Cytomegalovirus, Ebstein-Barr virus (EBV), mycoplasma), lactate dehydrogenase, urine microscopy culture sensitivities, blood culture and oral swabs for Herpes simplex virus and enterovirus. The full blood count was unremarkable, C-reactive protein was <2, while there was a very mild transaminitis noted on liver function tests. Swabs for HSV and enterovirus were negative. Urine MCS was normal and the blood culture remained negative. EBV serology was positive for IgG and IgM suggestive of acute infection. The patient was managed with supportive measures receiving analgaesia and intravenous fluids. He was also given a total of three doses of oral dexamethasone with a resultant clinical improvement in the mucosal swelling 4 days after presentation to hospital. Manifestations of EBV infection in children can be heterogeneous. Mucocutaneous presentations are thought to occur in 3–15% of patients with primary infection, with this most commonly manifesting as a morbilliform rash or as a hypersensitivity reaction to antibiotics such as penicillins. Other mucocutaneous manifestations may include transient urticaria, erythema nodosum or Gianotti-Crosti syndrome/papular acrodermatitis of childhood. Mucous membrane involvement has been known to occur in the form of non-sexually related acute genital ulcers, generally occurring in adolescent females. No cases of prominent lip or tongue swelling could be found in the literature as a presentation of primary EBV infection. We therefore suggest this case as a unique presentation of EBV infection in childhood currently not represented in the medical literature.