Ductal flow ratio as a measure of transition in preterm infants after birth: a pilot study

Background: Cardiovascular changes during the transition from intra- to extrauterine life, alters the pressure gradient across the ductus arteriosus (DA). DA flow ratio (R-L/L-R) has been suggested to reflect the infant's transitional status and could potentially predict neonatal outcomes after preterm birth.Aim: Determine whether DA flow ratio correlates with oxygenation parameters in preterm infants at 1 h after birth.Methods: Echocardiography was performed in preterm infants born < 32 weeks gestational age (GA), as part of an ancillary study. DA flow was measured at 1 h after birth. DA flow ratio was correlated with FiO(2), SpO(2), and SpO(2)/FiO(2) (SF) ratio. The DA flow ratio of infants receiving physiological-based cord clamping (PBCC) or time-based cord clamping (TBCC) were compared.Results: Measurements from 16 infants were analysed (median [IQR] GA 29 [27-30] weeks; birthweight 1,176 [951-1,409] grams). R-L DA shunting was 16 [17-27] ml/kg/min and L-R was 110 [81-124] ml/kg/min. The DA flow ratio was 0.18 [0.11-0.28], SpO(2) 94 [93-96]%, FiO(2) was 23 [21-28]% and SF ratio 4.1 [3.3-4.5]. There was a moderate correlation between DA flow ratio and SpO(2) [correlation coefficient (CC) -0.415; p = 0.110], FiO(2) (CC 0.384; p = 0.142) and SF ratio (CC -0.356; p = 0.175). There were no differences in DA flow measurements between infants where PBBC or TBCC was performed.Conclusion: In this pilot study we observed a non-significant positive correlation between DA flow ratio at 1 h after birth and oxygenation parameters in preterm infants.Developmen

Clinical aspects of incorporating cord clamping into stabilisation of preterm infants

Fetal to neonatal transition is characterised by major pulmonary and haemodynamic changes occurring in a short period of time. In the international neonatal resuscitation guidelines, comprehensive recommendations are available on supporting pulmonary transition and delaying clamping of the cord in preterm infants. Recent experimental studies demonstrated that the pulmonary and haemodynamic transition are intimately linked, could influence each other and that the timing of umbilical cord clamping should be incorporated into the respiratory stabilisation. We reviewed the current knowledge on how to incorporate cord clamping into stabilisation of preterm infants and the physiological-based cord clamping (PBCC) approach, with the infant's transitional status as key determinant of timing of cord clamping. This approach could result in optimal timing of cord clamping and has the potential to reduce major morbidities and mortality in preterm infants

Effect of breathing on venous return during delayed cord clamping: an observational study

Real-time echocardiographic monitoring of blood flow in the ductus venosus and hepatic vein was undertaken during perinatal transition with intact umbilical cord of term born infants. Antegrade flow increased during inspiration, preferentially directing blood flow from the ductus venosus into the right atrium.Objective To investigate the effect of spontaneous breathing on venous return in term infants during delayed cord clamping at birth. Methods Echocardiographic ultrasound recordings were obtained directly after birth in healthy term-born infants. A subcostal view was used to obtain an optimal view of the inferior vena cava (IVC) entering the right atrium, including both the ductus venosus (DV) and the hepatic vein (HV). Colour Doppler was used to assess flow direction and flow velocity. Recordings continued until the umbilical cord was clamped and were stored in digital format for offline analyses. Results Ultrasound recordings were obtained in 15 infants, with a median (IQR) gestational age of 39.6 (39.0-40.9) weeks and a birth weight of 3560 (3195-4205) g. Flow was observed to be antegrade in the DV and HV in 98% and 82% of inspirations, respectively, with flow velocity increasing in 74% of inspirations. Retrograde flow in the DV was observed sporadically and only occurred during expiration. Collapse of the IVC occurred during 58% of inspirations and all occurred caudal to the DV inlet (100%). Conclusion Spontaneous breathing was associated with collapse of the IVC and increased antegrade DV and HV flow velocity during inspiration. Therefore, inspiration appears to preferentially direct blood flow from the DV into the right atrium. This indicates that inspiration could be a factor driving placental transfusion in infants.Research into fetal development and medicin

Perinatal stabilisation of infants born with congenital diaphragmatic hernia: A review of current concepts

Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidity, mainly due to disrupted lung development related to herniation of abdominal organs into the chest. Pulmonary hypertension is a major contributor to both mortality and morbidity, however, treatment modalities are limited. Novel prenatal and postnatal interventions, such as fetal surgery and medical treatments, are currently under investigation. Until now, the perinatal stabilisation period immediately after birth has been relatively overlooked, although optimising support in these early stages may be vital in improving outcomes. Moreover, physiological parameters obtained from the perinatal stabilisation period could serve as early predictors of adverse outcomes, thereby facilitating both prevention and early treatment of these conditions. In this review, we focus on the perinatal stabilisation period by discussing the current delivery room guidelines in infants born with CDH, th

Physiological-based cord clamping in very preterm infants — Randomised controlled trial on effectiveness of stabilisation

Aim: To test whether stabilising very preterm infants while performing physiological-based cord clamping (PBCC) is at least as effective as the standard approach of time-based delayed cord clamping (DCC). Methods: A randomised contr

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Health and the environment : assessing the impacts, addressing the uncertainties

Environmental health problems have become increasingly complex. Climate change, increased urbanization or exposure to electromagnetic fields are highly divergent examples of issues about which no scientific consensus exists, for which no straightforward solutions are available and which are embedded in a wide societal context. It is challenging to assess the health impacts of such so-called “systemic risks”. Integrated Environmental Health Impact Assessment (IEHIA) has been proposed as a set of methods to deal with systemic risks in environmental health. IEHIA includes, amongst others, methods to take account of complexities and uncertainties, potential indirect effects, effects in the far future, and stakeholder perspectives. This thesis presents some methods that can be applied in IEHIA, illustrated with example applications. As such, it makes insights from other disciplines relevant and practicable for environmental health researchers. The methods that are being described include (1) the use of conceptual frameworks, (2) the selection and presentation of indicators, (3) dealing with uncertainties and (4) methods for expert elicitation. (1) Conceptual frameworks are –often graphical- representations of the issues that are being assessed and the relationships between the various elements in IEHIA. These frameworks may for example show the links between the driving forces of environmental problems, the exposure in the population and the subsequent health or economical effects. We distinguish different types of conceptual frameworks and illustrate their potential uses in IEHIA. (2) Indicators are used to communicate the results of IEHIA. They present the relevant outcomes of an assessment in a clear and effective way. This thesis provides guidelines for the selection and presentation of indicators. (3) Uncertainty is an important and often partly ignored element in assessments. Uncertainties can be expressed quantitative of qualitative, derive from natural variation or lack of knowledge, involve the boundaries of the assessment or a specific model parameter, etc. A typology of uncertainty is presented which can be used to characterize different types of uncertainties. It points into directions for dealing with these uncertainties and is illustrated using examples from environmental burden of disease studies. (4) Expert elicitation can be a tool to deal with uncertainties, in case no further empirical evidence can easily be derived. We describe a structured stepwise approach towards organizing a formal expert elicitation. Customization of these steps for specific applications is necessary, based on the types of uncertainties considered, the intended use of the elicited information, and the available resources. The expert elicitation procedure is applied in the context of impact assessment of ultrafine particles (UFP), the smallest fraction of air pollution. Opinions of twelve leading European scientists have been elicited about (1) the health effects considered to be causally related to exposure to UFP; (2) the potential causal mechanisms that underlie UFP-related cardiovascular effects and (3) the concentration-response functions that quantitatively describe the effect of UFP on a variety of health endpoints. Finally, all the methods outlined above are discussed in the context of the need for further development of IEHIA methods and the limitations and potential benefits of the methodology

Assessment of complex environmental health problems: framing the structures and structuring the frameworks.

Many environmental risks are multi-faceted and their health consequences can be far-ranging in both time and space. It can be a challenging task to develop informed policies for such risks. Integrated environmental health impact assessment aims to support policy by assessing environmental health effects in ways that take into account the complexities and uncertainties involved. For such assessment to be successful, a clear and agreed conceptual framework is needed, which defines the issue under consideration and sets out the principles on which the assessment is based. Conceptual frameworks facilitate involvement of stakeholders, support harmonized discussions, help to make assumptions explicit, and provide a framework for data analysis and interpretation. Various conceptual frameworks have been developed for different purposes, but as yet no clear taxonomy exists. We propose a three-level taxonomy of conceptual frameworks for use in environmental health impact assessment. At the first level of the taxonomy, structural frameworks show the wide context of the issues at hand. At the second level, relational frameworks describe how the assessment variables are causally related. At the third level, this causal structure is translated into an operational model, which serves as a basis for analysis. The different types of frameworks are complementary and all play a role in the assessment process. The taxonomy is illustrated using a hypothetical assessment of urban brownfield development for residential uses. We suggest that a better understanding of types of conceptual frameworks and their potential roles in the different phases of assessment will contribute to more informed assessments and policies