Meeting the need for effective and standardized neonatology training: a pan-European Master's Curriculum.

Neonatology is a pediatric sub-discipline focused on providing care for newborn infants, including healthy newborns, those born prematurely, and those who present with illnesses or malformations requiring medical care. The European Training Requirements (ETR) in Neonatology provide a framework for standardized quality and recognition of equality of training throughout Europe. The latest ETR version was approved by the Union of European Medical Specialists (UEMS) in April 2021. Here, we present the curriculum of the European School of Neonatology Master of Advanced Studies (ESN MAS), which is based on the ETR in Neonatology and aims to provide a model for effective and standardized training and education in neonatal medicine. We review the history and theory that form the foundation of contemporary medical education and training, provide a literature review on best practices for medical training, pediatric training, and neonatology training specifically, including educational frameworks and evidence-based systems of evaluation. The ESN MAS Curriculum is then evaluated in light of these best practices to define its role in meeting the need for a standardized empirically supported neonatology training curriculum for physicians, and in the future for nurses, to improve the quality of neonatal care for all infants. IMPACT STATEMENT: A review of the neonatology training literature was conducted, which concluded that there is a need for standardized neonatology training across international contexts to keep pace with growth in the field and rapidly advancing technology. This article presents the European School of Neonatology Master of Advanced Studies in Neonatology, which is intended to provide a standardized training curriculum for pediatricians and nurses seeking sub-specialization in neonatology. The curriculum is evaluated in light of best practices in medical education, neonatology training, and adult learning theory.

Feasibility of Cerebellar Measurements with Phased Array Sonography through the Anterior Fontanelle in Comparison to MRI.

OBJECTIVE: Cerebral sonography (CS) through the anterior fontanelle is a neonatal brain imaging method that has become an integral part of modern neonatal bedside care for both screening and diagnostic purposes. Premature infants with cognitive delay have a reduction in cerebellar size at term corrected age on magnetic resonance imaging (MRI). We aimed to determine the level of agreement between postnatal MRI and CS for cerebellar biometry and to determine the level of agreement within one and between different examiners. STUDY DESIGN: Cerebellar sonography and MRI measurements of the cerebellum from 30 term infants was assessed by Bland-Altman plots. Measurements between both modalities were compared using Wilcoxon's signed rank test. A p-value < 0.01 was considered statistically significant. Intraclass correlation coefficients (ICC) for intra- and interrater reliabilities of CS measurements were calculated. RESULTS: There was no statistically significant difference between CS and MRI for linear measurements, but the measurements of perimeter and surface area differed significantly between the two techniques. There was a systematic bias between both modalities for most measurements except for anterior-posterior (AP) width and vermis height (VH). For measurements that were not statistically different from MRI, we found excellent intrarater ICC for the AP width, VH, and cerebellar width. The interrater ICC was excellent for the AP width and VH, but poor for the transverse cerebellar width. CONCLUSION: With a strict imaging protocol, cerebellar measurements of the AP width and the VH can be used as an alternative to MRI for diagnostic-screening purposes in a neonatal department where multiple clinicians perform bedside CS. KEY POINTS: · Abnormal cerebellar growth and injuries affect neurodevelopmental outcome.. · Cerebral sonography through the anterior fontanelle is used for bedside imaging.. · Postnatal sonographic cerebellar measurements are not validated against MRI.. · Measuring vermis height and anterior-posterior width are reliable.. · Measuring transverse cerebellar width through anterior fontanelle is unreliable..

What does the evidence tell us? Revisiting optimal cord management at the time of birth.

A newborn who receives a placental transfusion at birth from delayed cord clamping (DCC) obtains about 30% more blood volume than those with immediate cord clamping (ICC). Benefits for term neonates include higher hemoglobin levels, less iron deficiency in infancy, improved myelination out to 12 months, and better motor and social development at 4 years of age especially in boys. For preterm infants, benefits include less intraventricular hemorrhage, fewer gastrointestinal issues, lower transfusion requirements, and less mortality in the neonatal intensive care unit by 30%. Ventilation before clamping the umbilical cord can reduce large swings in cardiovascular function and help to stabilize the neonate. Hypovolemia, often associated with nuchal cord or shoulder dystocia, may lead to an inflammatory cascade and subsequent ischemic injury. A sudden unexpected neonatal asystole at birth may occur from severe hypovolemia. The restoration of blood volume is an important action to protect the hearts and brains of neonates. Currently, protocols for resuscitation call for ICC. However, receiving an adequate blood volume via placental transfusion may be protective for distressed neonates as it prevents hypovolemia and supports optimal perfusion to all organs. Bringing the resuscitation to the mother's bedside is a novel concept and supports an intact umbilical cord. When one cannot wait, cord milking several times can be done quickly within the resuscitation guidelines. Cord blood gases can be collected with optimal cord management.   Conclusion: Adopting a policy for resuscitation with an intact cord in a hospital setting takes a coordinated effort and requires teamwork by obstetrics, pediatrics, midwifery, and nursing.

Assessing patent ductus arteriosus in preterm infants from standard neonatal intensive care monitoring.

Monitoring patent ductus arteriosus (PDA) in premature infants is currently performed intermittently using echocardiography which requires considerable expertise. The aim of this pilot study was to investigate whether PDA status could be assessed from standard neonatal intensive care monitoring. Electrocardiography (ECG) and blood pressure (BP) waveforms were acquired from extremely preterm infants using standard neonatal monitors. We developed software using MATLAB to analyse ECG and BP waveforms and their interrelationships in terms of pulse transit time (PTT) and pulse wave velocity (PWV). The times from peak systolic BP to diastolic trough (BPFt) and from the diastolic trough to peak systolic BP (BPRt) were also calculated. PTT, BPFt and BPRt were normalised for heart rate (HR) termed NPTT, NBPFt and NBPRt, respectively. ECG, invasive aortic BP monitoring and echocardiography were performed in 14 preterm infants < 29 weeks' gestation in the first 3 days after birth. The median (range) birth weight of the infants was 0.90 (0.48-1.31) kg, gestation 26.6 (24.0-28.7) weeks, PDA diameter 1.6 (0.8-3.6) mm and mean BP 32 (16-40) mmHg. We found a significant positive correlation between PDA diameter and NPTT (r = 0.69, P = 0.007) as well as NBPFt (r = 0.65, P = 0.012) and NBPRt (r = 0.71, P = 0.005). No relationship was found between PDA diameter and pulse pressure.Conclusions: Interrelationships between ECG and BP traces as well as BP waveform time analysis are straightforward to measure and associated with PDA diameter. The results of this pilot study suggest that this approach may help provide biomarkers for continuous monitoring PDA diameter and function. What is Known: • Patent ductus arteriosus (PDA) in premature infants is associated with increased risk of developing chronic lung disease, necrotising enterocolitis and cerebral injury. • Currently PDA is assessed intermittently using echocardiography which requires considerable expertise and sometimes is not well tolerated by critically ill preterm infants. What is New: • Blood pressure (BP) and ECG waveform interrelation and BP trace time analysis, taking account of heart rate, relate to PDA diameter. • ECG and BP waveform phase difference as well as BP waveform time analysis may be useful in the continuous assessment of PDA function.

A hybrid type I, multi-center randomized controlled trial to study the implementation of a method for Sustained cord circulation And VEntilation (the SAVE-method) of late preterm and term neonates: a study protocol.

BACKGROUND: An intact umbilical cord allows the physiological transfusion of blood from the placenta to the neonate, which reduces infant iron deficiency and is associated with improved development during early childhood. The implementation of delayed cord clamping practice varies depending on mode of delivery, as well as gestational age and neonatal compromise. Emerging evidence shows that infants requiring resuscitation would benefit if respiratory support were provided with the umbilical cord intact. Common barriers to providing intact cord resuscitation is the availability of neonatal resuscitation equipment close to the mother, organizational readiness for change as well as attitudes and beliefs about placental transfusion within the multidisciplinary team. Hence, clinical evaluations of cord clamping practice should include implementation outcomes in order to develop strategies for optimal cord management practice. METHODS: The Sustained cord circulation And Ventilation (SAVE) study is a hybrid type I randomized controlled study combining the evaluation of clinical outcomes with implementation and health service outcomes. In phase I of the study, a method for providing in-bed intact cord resuscitation was developed, in phase II of the study the intervention was adapted to be used in multiple settings. In phase III of the study, a full-scale multicenter study will be initiated with concurrent evaluation of clinical, implementation and health service outcomes. Clinical data on neonatal outcomes will be recorded at the labor and neonatal units. Implementation outcomes will be collected from electronic surveys sent to parents as well as staff and managers within the birth and neonatal units. Descriptive and comparative statistics and regression modelling will be used for analysis. Quantitative data will be supplemented by qualitative methods using a thematic analysis with an inductive approach. DISCUSSION: The SAVE study enables the safe development and evaluation of a method for intact cord resuscitation in a multicenter trial. The study identifies barriers and facilitators for intact cord resuscitation. The knowledge provided from the study will be of benefit for the development of cord clamping practice in different challenging clinical settings and provide evidence for development of clinical guidelines regarding optimal cord clamping. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04070560 . Registered 28 August 2019.

Prevention of iron deficiency anemia in infants and toddlers.

Anemia, defined as a low blood hemoglobin concentration, is a major global public health problem. Identification of anemia is crucial to public health interventions. It is estimated globally that 273 million children under 5 years of age were anemic in 2011, and about ~50% of those cases were attributable to iron deficiency (Lancet Global Health 1:e16-e25, 2013). Iron-deficiency anemia (IDA) in infants adversely impacts short-term hematological indices and long-term neuro-cognitive functions of learning and memory that result in both fatigue and low economic productivity. IDA contributes to death and disability and is an important risk factor for maternal and perinatal mortality, including the risks for stillbirths, prematurity, and low birth weight (Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors. Ch. 3 (World Health Organization, Geneva, 2004)). Reduction in early infantile anemia and newborn mortality rates is possible with easily implemented, low- to no-cost intervention such as delayed cord clamping (DCC). DCC until 1-3 min after birth facilitates placental transfusion and iron-rich blood flow to the newborn. DCC, an effective anemia prevention strategy, requires cooperation among health providers involved in childbirth, and a participatory culture change in public health. Public intervention strategies must consider multiple factors associated with anemia listed in this review before designing intervention studies that aim to reduce anemia prevalence in infants and toddlers. IMPACT: Anemia, defined as a low blood hemoglobin concentration, is a major global public health problem and identification of anemia is crucial to public health interventions. Delayed cord clamping (DCC) until 1-3 min after birth facilitates placental transfusion and iron-rich blood flow to the newborn. Reduction in early infantile anemia and newborn mortality rates is possible with easily implemented, low- to no-cost intervention such as DCC.

Pharmacokinetic study (phase I-II) of a new dobutamine formulation in preterm infants immediately after birth.

BACKGROUND: Dobutamine is particularly suited to treatment of haemodynamic insufficiency caused by increased peripheral vascular resistance and myocardial dysfunction in the preterm infant. Knowledge of the elimination half-life is essential to estimate the steady state when its efficacy/safety can be evaluated. METHODS: Analysis of pharmacokinetic data in ten preterm newborns treated with a new neonatal formulation of dobutamine (IMP) after screening for haemodynamic insufficiency within the first 72 h from birth. Blood samples were withdrawn at the end of IMP infusion and at a random time after the end of infusion (5 min, 15 min, 45 min, 2 h and 6 h). IMP concentration in each sample was measured by ultra-high performance liquid chromatography with electrochemical detection. RESULTS: Median duration of IMP infusion was 37.7 h (IQR 21.2). Calculated IMP half-life ranged between 3.06 and 36.1 min (median 10.6 min), leading to a time to reach the steady-state concentration between 15 min and >2 h. Adverse events were not related to IMP. CONCLUSIONS: The wide variability in dobutamine metabolism in preterm infants requires awareness about the risk of under- or overtreatment. A delay of up to 3 h might be required before drawing blood samples to evaluate the effective dose. IMPACT: Small trials suggest dobutamine as the optimal drug in the preterm infant with haemodynamic insufficiency after birth. Age-related differences in drug pharmacokinetics may result in suboptimal treatments. The lack of formal studies in preterms results in inadequate data on efficacy and safety. This study provides data on the variability of the elimination half-life of dobutamine in the very preterm infant during transitional circulation. There is a wide variation in the time to reach the plasma concentration corresponding to steady state, the moment when its efficacy/safety can be reliably evaluated. This information is crucial for planning future trials on cardiovascular support.

Characterisation of Textile Embedded Electrodes for Use in a Neonatal Smart Mattress Electrocardiography System.

Heart rate monitoring is the predominant quantitative health indicator of a newborn in the delivery room. A rapid and accurate heart rate measurement is vital during the first minutes after birth. Clinical recommendations suggest that electrocardiogram (ECG) monitoring should be widely adopted in the neonatal intensive care unit to reduce infant mortality and improve long term health outcomes in births that require intervention. Novel non-contact electrocardiogram sensors can reduce the time from birth to heart rate reading as well as providing unobtrusive and continuous monitoring during intervention. In this work we report the design and development of a solution to provide high resolution, real time electrocardiogram data to the clinicians within the delivery room using non-contact electric potential sensors embedded in a neonatal intensive care unit mattress. A real-time high-resolution electrocardiogram acquisition solution based on a low power embedded system was developed and textile embedded electrodes were fabricated and characterised. Proof of concept tests were carried out on simulated and human cardiac signals, producing electrocardiograms suitable for the calculation of heart rate having an accuracy within ±1 beat per minute using a test ECG signal, ECG recordings from a human volunteer with a correlation coefficient of ~ 87% proved accurate beat to beat morphology reproduction of the waveform without morphological alterations and a time from application to heart rate display below 6 s. This provides evidence that flexible non-contact textile-based electrodes can be embedded in wearable devices for assisting births through heart rate monitoring and serves as a proof of concept for a complete neonate electrocardiogram monitoring system.

Method of Blood Pressure Measurement in Neonates and Infants: A Systematic Review and Analysis.

OBJECTIVES: To determine the recommended blood pressure (BP) measurement methods in neonates after systematically analyzing the literature regarding proper BP cuff size and measurement location and method. STUDY DESIGN: A literature search was conducted in MEDLINE, PubMed, Embase, Cochrane Library, and CINAHL from 1946 to 2017 on BP in neonates <3 months of age (PROSPERO ID CRD42018092886). Study data were extracted and analyzed with separate analysis of Bland-Altman studies comparing measurement methods. RESULTS: Of 3587 nonduplicate publications identified, 34 were appropriate for inclusion in the analysis. Four studies evaluating BP cuff size support a recommendation for a cuff width to arm circumference ratio of approximately 0.5. Studies investigating measurement location identified the upper arm as the most accurate and least variable location for oscillometric BP measurement. Analysis of studies using Bland-Altman methods for comparison of intra-arterial to oscillometric BP measurement show that the 2 methods correlate best for mean arterial pressure, whereas systolic BP by the oscillometric method tends to overestimate intra-arterial systolic BP. Compared with intra-arterial methods, systolic BP, diastolic BP, and mean arterial pressure by oscillometric methods are less accurate and precise, especially in neonates with a mean arterial pressure <30 mm Hg. CONCLUSIONS: Proper BP measurement is critical in neonates with naturally lower BP and attention to BP cuff size, location, and method of measurement are essential. With decreasing use of intra-arterial catheters for long-term BP monitoring in neonates, further studies are urgently needed to validate and develop oscillometric methodology with enhanced accuracy.

Comparison of MRI and neurosonogram 1- and 2-dimensional morphological measurements of the newborn corpus callosum.

BACKGROUND: Developmental abnormalities of the corpus callosum (CC) are linked to multiple neuro-developmental disorders, for which neonatal neuroimaging may allow earlier diagnosis and intervention. MRI is often considered the most sensitive imaging modality to white matter changes, while neurosonogram (NS) remains the clinical staple. This study assesses the correlation between MRI and US measurements of the neonatal CC using a protocol derived from established methodologies. METHODS: MR and NS images from an existing cohort of term infants (≥37 weeks gestational age) were studied. Length and area measurements of the CC made with linear (LUS) and phased array US (PUS) data were compared to those from MRI. Intra-observer reliabilities were estimated. RESULTS: Moderate-to-strong correlation strengths were observed for length measurements and the total area of the CC. Sectional area measurements showed poorer correlations. Bland-Altman plots support improved correspondence of length and total area measurements. LUS data appeared to correspond closer to MRI. All three modalities showed comparable repeatability. CONCLUSION: NS correlates well with some MRI measurements of the CC and shows similar levels of repeatability, making them possibly interchangeable. Use of LUS, a technique rarely used for NS, may be preferable to the standard approach for morphological studies.

Recommendations for the design of therapeutic trials for neonatal seizures.

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population.

Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes.

BACKGROUND: Infants born preterm (before 37 weeks' gestation) have poorer outcomes than infants at term, particularly if born before 32 weeks. Early cord clamping has been standard practice over many years, and enables quick transfer of the infant to neonatal care. Delayed clamping allows blood flow between the placenta, umbilical cord and baby to continue, and may aid transition. Keeping baby at the mother's side enables neonatal care with the cord intact and this, along with delayed clamping, may improve outcomes. Umbilical cord milking (UCM) is proposed for increasing placental transfusion when immediate care for the preterm baby is needed. This Cochrane Review is a further update of a review first published in 2004 and updated in 2012. OBJECTIVES: To assess the effects on infants born at less than 37 weeks' gestation, and their mothers of: 1) delayed cord clamping (DCC) compared with early cord clamping (ECC) both with immediate neonatal care after cord clamping; 2) DCC with immediate neonatal care with cord intact compared with ECC with immediate neonatal care after cord clamping; 3) DCC with immediate neonatal care after cord clamping compared with UCM; 4) UCM compared with ECC with immediate neonatal care after cord clamping. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 November 2017), and reference lists of retrieved studies. We updated the search in November 2018 and added nine new trial reports to the awaiting classification section to be assessed at the next update. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing delayed with early clamping of the umbilical cord (with immediate neonatal care after cord clamping or with cord intact) and UCM for births before 37 weeks' gestation. Quasi-RCTs were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Random-effects are used in all meta-analyses. Review authors assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: This update includes forty-eight studies, involving 5721 babies and their mothers, with data available from 40 studies involving 4884 babies and their mothers. Babies were between 24 and 36+6 weeks' gestation at birth and multiple births were included. The data are mostly from high-income countries. Delayed clamping ranged between 30 to 180 seconds, with most studies delaying for 30 to 60 seconds. Early clamping was less than 30 seconds and often immediate. UCM was mostly before cord clamping but some were milked after cord clamping. We undertook subgroup analysis by gestation and type of intervention, and sensitivity analyses by low risk of selection and attrition bias.All studies were high risk for performance bias and many were unclear for other aspects of risk of bias. Certainty of the evidence using GRADE was mostly low, mainly due to imprecision and unclear risk of bias.Delayed cord clamping (DCC) versus early cord clamping (ECC) both with immediate neonatal care after cord clamping (25 studies, 3100 babies and their mothers)DCC probably reduces the number of babies who die before discharge compared with ECC (average risk ratio (aRR) 0.73, 95% confidence interval (CI) 0.54 to 0.98, 20 studies, 2680 babies (moderate certainty)).No studies reported on 'Death or neurodevelopmental impairment' in the early years'.DCC may make little or no difference to the number of babies with severe intraventricular haemorrhage (IVH grades 3 and 4) (aRR 0.94, 95% CI 0.63 to 1.39, 10 studies, 2058 babies, low certainty) but slightly reduces the number of babies with any grade IVH (aRR 0.83, 95% CI 0.70 to 0.99, 15 studies, 2333 babies, high certainty).DCC has little or no effect on chronic lung disease (CLD) (aRR 1.04, 95% CI 0.94 to 1.14, 6 studies, 1644 babies, high certainty).Due to insufficient data, we were unable to form conclusions regarding periventricular leukomalacia (PVL) (aRR 0.58, 95% CI 0.26 to 1.30, 4 studies, 1544 babies, low certainty) or maternal blood loss of 500 mL or greater (aRR 1.14, 95% CI 0.07 to 17.63, 2 studies, 180 women, very low certainty).We identified no important heterogeneity in subgroup or sensitivity analyses.Delayed cord clamping (DCC) with immediate neonatal care with cord intact versus early cord clamping (ECC) (one study, 276 babies and their mothers)There are insufficient data to be confident in our findings, but DCC with immediate neonatal care with cord intact may reduce the number of babies who die before discharge, although the data are also compatible with a slight increase in mortality, compared with ECC (aRR 0.47, 95% CI 0.20 to 1.11, 1 study, 270 babies, low certainty). DCC may also reduce the number of babies who die or have neurodevelopmental impairment in early years (aRR 0.61, 95% CI 0.39 to 0.96, 1 study, 218 babies, low certainty). There may be little or no difference in: severe IVH; all grades IVH; PVL; CLD; maternal blood loss ≥ 500 mL, assessed as low certainty mainly due to serious imprecision.Delayed cord clamping (DCC) with immediate neonatal care after cord clamping versus umbilical cord milking (UCM) (three studies, 322 babies and their mothers) and UCM versus early cord clamping (ECC) (11 studies, 1183 babies and their mothers)There are insufficient data for reliable conclusions about the comparative effects of UCM compared with delayed or early clamping (mostly low or very low certainty). AUTHORS' CONCLUSIONS: Delayed, rather than early, cord clamping may reduce the risk of death before discharge for babies born preterm. There is insufficient evidence to show what duration of delay is best, one or several minutes, and therefore the optimum time to clamp the umbilical cord remains unclear. Whilst the current evidence supports not clamping the cord before 30 seconds at preterm births, future trials could compare different lengths of delay. Immediate neonatal care with the cord intact requires further study, and there are insufficient data on UCM.The nine new reports awaiting further classification may alter the conclusions of the review once assessed.

Strategies for implementing placental transfusion at birth: A systematic review.

BACKGROUND: Enhanced placental transfusion reduces adverse neonatal outcomes, including death. Despite being endorsed by the World Health Organization in 2012, the method has not been adopted widely in practice. METHODS: We performed a systematic literature search and included quality improvement projects on placental transfusion at birth and studies on barriers to implementation. We extracted information on population, methods of implementation, obstacles to implementation, and strategies to overcome them. RESULTS: We screened 99 studies out of which 18 were included in the review. The preferred methods of implementation were protocol development (86% of studies) reinforced by targeted education (64% of studies) and multidisciplinary team involvement (43% of studies). Barriers to implementation were mentioned in 12 studies and divided into four categories: general factors such as lack of staff awareness (5 studies) and professional resistance to change (5 studies); obstetrician-specific concerns, including the impact during cesarean (3 studies) and the risk of postpartum hemorrhage (3 studies); pediatrician-specific concerns, including the need for resuscitation (5 studies), risk of jaundice (3 studies), and polycythemia (2 studies); and logistical difficulties. The main strategies to facilitate placental transfusion at birth included effective multidisciplinary team collaboration, protocol development, targeted education, and constructive feedback sessions. CONCLUSIONS: Placental transfusion implementation requires a multidisciplinary approach, with obstetricians, midwives, nurses, and pediatricians central to adoption of the practice. Understanding the obstacles to implementation informs strategies to increase placental transfusion adoption of practice worldwide. We suggest a stepwise approach to implementation and enhancement of placental transfusion into practice.

Intra- and Inter-rater Agreement of Superior Vena Cava Flow and Right Ventricular Outflow Measurements in Late Preterm and Term Neonates.

OBJECTIVES: To explore the intra- and inter-rater agreement of superior vena cava (SVC) flow and right ventricular (RV) outflow in healthy and unwell late preterm neonates (33-37 weeks' gestational age), term neonates (≥37 weeks' gestational age), and neonates receiving total-body cooling. METHODS: The intra- and inter-rater agreement (n = 25 and 41 neonates, respectively) rates for SVC flow and RV outflow were determined by echocardiography in healthy and unwell late preterm and term neonates with the use of Bland-Altman plots, the repeatability coefficient, the repeatability index, and intraclass correlation coefficients. RESULTS: The intra-rater repeatability index values were 41% for SVC flow and 31% for RV outflow, with intraclass correlation coefficients indicating good agreement for both measures. The inter-rater repeatability index values for SVC flow and RV outflow were 63% and 51%, respectively, with intraclass correlation coefficients indicating moderate agreement for both measures. CONCLUSIONS: If SVC flow or RV outflow is used in the hemodynamic treatment of neonates, sequential measurements should ideally be performed by the same clinician to reduce potential variability.

Hemodynamic and metabolic effects of a new pediatric dobutamine formulation in hypoxic newborn pigs.

BACKGROUND: The aim of our study was to measure drug-related changes in hemodynamics and oxygen metabolism in response to different doses of an age-appropriate dobutamine formulation in hypoxic pigs. A secondary aim was to validate superior vena cava flow (SVCF) as a marker of cardiac index (CI) for subsequent clinical trials of this formulation in humans. METHODS: Newborn pigs (n = 18) were exposed to 2-h hypoxia (10-15% oxygen) followed by reoxygenation (21-30% oxygen 4 h). After 1-h reoxygenation, pigs were randomized to: control group (no treatment), dobutamine infusion at a rate of 10-15 or 15-20 µg/kg/min. Dobutamine groups received two dobutamine doses during 30 min with a 60 min washout period between doses. Cardiovascular profile and oxygen metabolism were monitored. In four animals, an ultrasonic perivascular flow probe was placed around superior vena cava to measure SVCF. RESULTS: Hypoxia significantly decreased CI, systemic vascular resistance and mean arterial blood pressure (MABP). Dobutamine doses significantly increased heart-rate, CI, and oxygen-delivery without changes in stroke-volume and MABP. Only 10-15 µg/kg/min increased oxygen consumption and peripheral tissue oxygenation measured by Near-infrared spectroscopy. A positive correlation was observed between SVCF and CI. CONCLUSION: The new pediatric dobutamine formulation improved hemodynamic status, with dose-specific differences in metabolic response. SVCF may be a useful surrogate for CI in subsequent clinical trials.

A Literature Review of the Pharmacokinetics and Pharmacodynamics of Dobutamine in Neonates.

Since its discovery in 1975 dobutamine has been used off-label for treating hemodynamic insufficiency in newborns and children. We present a structured literature review of pharmacokinetic and pharmacodynamic data for dobutamine in the pediatric population. Structured searches were conducted to identify relevant articles according to pre-defined inclusion criteria. Where possible, results for the pharmacodynamic and pharmacokinetic effect of dobutamine were reported as pooled data. Forty-six papers met the inclusion criteria. With regard to pharmacodynamic data a number of studies reported significant increases in a number of clinical parameters such as heart rate, blood pressure, cardiac output across a wide range of pediatric populations. With regard to pharmacokinetic data studies reported that the infusion rate was positively correlated to plasma dobutamine concentration. There was great variability with regard to dobutamine clearance between individuals and as to whether it followed first- or zero-order elimination kinetics. While the pharmacodynamic effects of dobutamine appear to reflect the pharmacological profile of the drug, the pharmacokinetic data are difficult to interpret due to inhomogeneity between study populations ages, comorbidities, dobutamine dosages and methodologies. High-quality prospective pharmacokinetic and pharmacodynamic data especially in newborns are urgently required prior to a large randomized study.

Parents report positive experiences about enrolling babies in a cord-related clinical trial before birth.

AIM: The aim of this study was to evaluate parents' perceptions when they were asked to enrol their unborn preterm infant in a randomised trial involving delayed cord clamping or cord milking. METHODS: The parents of 58 infants were asked to take part in a qualitative study using semi-structured interviews to provide feedback about how they felt about their infants being included in the research project. A total of 37 parents - 15 fathers and 22 mothers - agreed to take part. RESULTS: Parents were generally positive about their experiences of their baby taking part in the trial, but the findings raised some concerns about the validity of the consent obtained before delivery, as it was given in a hurry, and some participants had difficulty remembering that they had agreed to take part. Four themes were identified from the interviews: implications of taking part, reasons for enrolling infants, experiences of recruitment and suggestions for improvement. CONCLUSION: Overall, the parents were positive about their baby taking part in the trial, but the consent process could be improved, by providing information about relevant trials earlier in the pregnancy or implementing continuous consent at key points in the trial.

Effects of placental transfusion in extremely low birthweight infants: meta-analysis of long- and short-term outcomes.

BACKGROUND: Risks and benefits of increasing placental transfusion in extremely preterm infants (extremely low birthweight [ELBW], <1000 g) are ill defined. We performed a meta-analysis to compare long- and short-term outcomes of ELBW infants in trials of enhanced placental transfusion regimens. STUDY DESIGN AND METHODS: We conducted a meta-analysis of randomized controlled trials (RCTs) of delayed umbilical cord clamping or umbilical cord milking in compliance with PRISMA and Cochrane Collaborative guidelines for systematic reviews. We searched multiple databases for medical literature up to December 2012. Inclusion criteria were preterm infants less than 30 weeks and less than 1000 g birthweight, randomly assigned to enhanced placental transfusion (either delayed cord clamping or cord milking) versus immediate cord clamping. The primary outcome was standardized neurodevelopmental outcome at 18 to 24 months corrected age using a standardized scale. Several short-term outcomes were also evaluated as secondary variables. RESULTS: We found 19 studies of which 10 studies could be included (n = 199). Three reported neurodevelopmental outcomes, none of which showed significant rates of disability. Two reported these at 18 to 24 months (n = 42) but used different scales preventing pooling. Short-term benefits of enhanced placental strategies included better blood pressure and hemoglobin on admission, along with reduced blood transfusions, a trend to reduced intraventricular hemorrhage, and episodes of late-onset sepsis. CONCLUSIONS: Strategies to enhance placental transfusion may improve short-term outcomes of ELBW infants. However, paucity of data on neurodevelopmental outcomes and safety concerns tempers enthusiasm for these interventions. Appropriately designed RCTs to assess short-term and longterm outcomes are needed in ELBW infants.