Am Weindling

The Relationship between Cardiac Output, Cerebral Electrical Activity, Cerebral Fractional Oxygen Extraction and Peripheral Blood Flow in Premature Newborn Infants

Cardiac output is a determinant of systemic blood flow and its measurement may therefore be a useful indicator of abnormal hemodynamics and tissue oxygen delivery. The purpose of this study was to investigate in very premature newborn infants the relationships between cardiac output (left and right ventricular outputs), systemic blood pressure, peripheral blood flow (PBF) and two indicators of cerebral oxygen delivery (cerebral electrical activity and cerebral fractional oxygen extraction (CFOE)). This was a prospective observational study performed on 40 infants of less than 30 wk gestation. Digital electroencephalograms (EEGs) were recorded for one hour every day during the first four days after birth and subjected to qualitative and quantitative analysis. Left and right ventricular outputs, mean blood pressure (MBP), CFOE, PBF and arterial blood gases were measured at the same time. Within the ranges studied, there was no apparent relationship between left or right ventricular output (RVO), PBF and indicators of cerebral perfusion (cerebral electrical activity and CFOE). The EEG was normal in infants with low left and right ventricular outputs (<150 mL/kg/min) and MBP > 30 mm Hg. Infants with low cardiac output and normal MBP seem able to maintain cerebral perfusion, possibly through vasodilatation of the cerebral microvasculature.

A randomized controlled trial of early physiotherapy for high-risk infants

The aim of this study was to investigate the hypothesis that infants at high risk of cerebral palsy would benefit from early physiotherapy. In total, 105 infants with abnormal cranial ultrasound scans were randomized at around term to early physiotherapy or standard treatment (delaying physiotherapy until abnormal physical signs became apparent). At 12 and 30 months there were clinical and objective assessments. Nine infants died and nine were lost to follow‐up by 12 months when 87 infants were assessed. One other child had died and three others were lost to follow‐up by 30 months when 83 children were assessed. Cerebral palsy was only accurately predicted in 45 (54%) infants. There was no difference in outcome. The difficulty of predicting cerebral palsy reliably and the heterogeneity of the condition should be borne in mind when planning treatment and assessing its efficacy.

An explanatory randomised placebo controlled trial of levothyroxine supplementation for babies born <28 weeks' gestation: results of the TIPIT trial.

AbstractBackgroundBabies born before 28 weeks’ gestation have lower plasma thyroid hormone concentrations than more mature infants. This may contribute to their risk of poor developmental outcome. Previous studies have suggested that thyroxine supplementation for extremely preterm neonates may be beneficial. The aim of this study was to investigate the effect of administration of supplemental thyroxine to very premature babies on brain size and somatic growth at 36 weeks’ corrected gestational age (CGA).MethodsIn this explanatory multicentre double blind randomised placebo controlled trial, 153 infants born below 28 weeks’ gestation were randomised to levothyroxine (LT4) supplementation or placebo until 32 weeks’ CGA. The primary outcome was brain size assessed by the width of the subarachnoid space measured by cranial ultrasound at 36 weeks’ CGA. Lower leg length was measured by knemometry.ResultsBabies in the LT4-supplemented and placebo groups had similar baseline characteristics. There were no significant differences between infants given LT4 (n=78) or placebo (n=75) for width of the subarachnoid space, head circumference at 36 weeks’ CGA, body weight at 36 weeks’ CGA or mortality. Infants who received LT4 had significantly shorter leg lengths at 36 weeks’ CGA although adjusted analysis for baseline length did not find a statistical difference. There was a significant correlation between low FT4 and wider subarachnoid space. No unexpected serious adverse events were noted and incidence of adverse events did not differ between the two groups.ConclusionThis is the only randomised controlled trial of thyroxine supplementation targeting extremely premature infants. Supplementing all babies below 28 weeks’ gestation with LT4 had no apparent effect on brain size. These results do not support routine supplementation with LT4 for all babies born below 28 weeks’ gestation.Trial registrationCurrent Controlled Trials ISRCTN89493983 EUDRACT number: 2005-003-09939

The impact of networks on clinical trials in the United Kingdom

The conduct of clinical trials in the UK has been affected by the recent introduction of managed clinical networks, clinical research networks and rigorous governance regulations. This commentary considers the challenges that these changes have posed for clinical triallists in the UK, based on experiences derived in the conduct of a multicentre neonatal clinical trial under the conditions that now prevail. We conclude that the considerable skills and knowledge that are now required to be an effective Principal Investigator should be recognised and that application processes, including issuing honorary contracts, should be simplified and centralised.

[Editorial] The future of paediatric education

The paediatric virology subspecialty proposal (1) is a good paradigm of innovation in paediatric education and its further evaluation will be really helpful (2). To date, research in medical education in neonatology and paediatrics has been focused on fundamental changes to its structure and content aiming to improve outcomes of medical knowledge, skills, and behaviours and promote neonatal and paediatric health (3). In future, best practice in undergraduate and postgraduate medical training in paediatrics as well as the process of continuing professional development is expected to be dramatically different from current practice (3,4). Technology-enhanced simulation (TES) as an educational modality in neonatology and paediatrics is an example (5,6). Modern technologies have resulted in a great revolution in this direction and they should be effectively used in future education. This is a key principle, but not fundamental. What should be the fundamental principles that should be kept clearly in mind when we are talking about the future of paediatric education? Our interview (2) highlights seven principles: i) Humility; ii) a holistic approach to medicine; iii) awareness of cost effectiveness; iv) teaching an understanding of the evidence base of medicine; v) encouraging paediatric trainees to ask the question ‘Why?’; vi) quality improvement; and vii) teamwork. Neonatal and paediatric health professionals are frequently required to manage ethically complex and challenging cases (7). Neonatologists, in particular, regularly encounter situations where crucial life or death decisions need to be made in the best interest of an infant and its family. While physicians and their professional societies seem often consider these best interest standards by weighing the risk of mortality and morbidities, parents are likely to have other considerations. For these reasons, humility is the most fundamental principle. This helps you to realise that ‘it is just not possible to know everything, and that continuing learning is important’ (2). Moreover, a holistic approach (2) is required for teaching and training that combines a traditional understanding of ethical theory and reasoning, advanced skills in communication and counseling, a disposition to engage in self‐reflection and to an awareness of the emotional and spiritual dimensions of neonatal medicine and paediatrics. Over the past two decades, rising and burdensome health care costs have driven interest in the neonatal and paediatric practice of high-value care (HVC) and this has already inspired relevant training across all levels of medical education (8). Although paediatricians may find it difficult to integrate the concept of cost-effectiveness into their clinical practice, this principle is really essential, especially during the current era of limited resources and financial crisis. Medical schools should continue to teach the principles of evidence-based medicine (EBM) as part of their undergraduate curriculum. Paediatric trainees should be encouraged to include EBM into their clinical practice and learn how to overcome barriers that they may experience when attempting to apply its principles (9). Their priority should also be to ask the question ‘Why?’ trying to use their acquired knowledge ‘to answer practical clinical questions’ (2). Neonatal and paediatric training should also address quality improvement (QI) (10). As highlighted in our interview, it is very important to minimise ‘the stress to families of having a child in an intensive care unit, which is tremendously upsetting and stressful’ (2); this should be one of the targets for research into the neonatal care of the future. An appreciation of this is something that has to be taught to future paediatricians at both undergraduate and postgraduate levels. Paediatric care, especially for children with special/complex needs, requires the collaboration of different professionals and scientists. Hospital-, as well as community-based Correspondence to: Professor Demetrios A. Spandidos, Department of Clinical Virology, School of Medicine, University of Crete, Heraklion 71003, Greece E-mail: spandidos@spandidos.gr