Richard Plavka

European Consensus Guidelines on the Management of Neonatal Respiratory Distress Syndrome in Preterm Infants – 2010 Update

Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RDS), controversies still exist. We report the updated recommendations of a European panel of expert neonatologists who had developed consensus guidelines after critical examination of the most up-to-date evidence in 2007. These updated guidelines are based upon published evidence up to the end of 2009. Strong evidence exists for the role of a single course of antenatal steroids in RDS prevention, but the potential benefit and long-term safety of repeated courses are unclear. Many practices involved in preterm neonatal stabilisation at birth are not evidence-based, including oxygen administration and positive pressure lung inflation, and they may at times be harmful. Surfactant replacement therapy is crucial in the management of RDS, but the best preparation, optimal dose and timing of administration at different gestations is not always clear. Respiratory support in the form of mechanical ventilation may also be lifesaving, but can cause lung injury, and protocols should be directed at avoiding mechanical ventilation where possible by using nasal continuous positive airways pressure or nasal ventilation. For babies with RDS to have best outcomes, it is essential that they have optimal supportive care, including maintenance of a normal body temperature, proper fluid management, good nutritional support, management of the ductus arteriosus and support of the circulation to maintain adequate tissue perfusion.

European consensus guidelines on the management of neonatal respiratory distress syndrome

Abstract Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RDS), controversies still exist. We report the recommendations of a European panel of expert neonatologists who developed consensus guidelines after critical examination of the most up-to-date evidence in 2007. Strong evidence exists for the role of antenatal steroids in RDS prevention, but it is not clear if repeated courses are safe. Many practices involved in preterm neonatal stabilization at birth are not evidence based, including oxygen administration and positive pressure lung inflation, and they may at times be harmful. Surfactant replacement therapy is crucial in management of RDS but the best preparation, optimal dose and timing of administration at different gestations is not always clear. Respiratory support in the form of mechanical ventilation may also be life saving but can cause lung injury, and protocols should be directed to avoiding mechanical ventilation where possible by using nasal continuous positive airways pressure. For babies with RDS to have the best outcome, it is essential that they have optimal supportive care, including maintenance of a normal body temperature, proper fluid management, good nutritional support, management of the ductus arteriosus and support of the circulation to maintain adequate blood pressure.

A prospective randomized comparison of conventional mechanical ventilation and very early high frequency oscillatory ventilation in extremely premature newborns with respiratory distress syndrome

Objective: To compare the effectiveness and safety of very early high-frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) in treatment of the respiratory distress syndrome (RDS) and to evaluate their impact on the incidence of chronic pulmonary disease and early and late morbidity of very low-birthweight neonates. Design: A prospective randomized clinical trial. Setting: Tertiary neonatal intensive care unit in the Perinatology Center in Prague. Patients: 43 premature newborns, delivered in the Department of Obstetrics in the Perinatology Center, were randomly divided into two groups (HFOV and CMV) immediately after delivery; 2 patients in each group died, 2 fulfilled crossover criteria from CMV to HFOV, and 2 were excluded because of congenital malformations. Nineteen patients treated with HFOV were therefore compared with 18 infants in the CMV group. Methods: The two contrasting modes of ventilation were introduced immediately after intubation. Maintenance of optimal lung volume in HFOV to optimize oxygenation and the therapeutic administration of surfactant after fulfilling defined criteria are important points of the strategy and design of the study. Measurements and main results: Except for a higher proportion of males in the HFOV group (p < 0.02), the basic clinical characteristics (gestational age, birthweight, Apgar score at 5 min, umbilical arterial pH), the two groups were similar. In the acute stage of RDS, infants treated with HFOV had higher proximal airway distending pressure with HFOV for 6 h after delivery (p < 0.05). For a period of 12 h after delivery lower values for the alveolar-arterial oxygen difference (p < 0.03) were noted. The number of patients who did not require surfactant treatment was higher in the HFOV group (11 vs 1, p < 0.001). In the HFOV group the authors found a lower roentgenographic score at 30 days of age (p < 0.03) and a lower clinical score in the 36th postconceptional week (p < 0.05), using these two scoring systems for assessing chronic lung disease according to Toce scale. The incidence of pneumothorax, pulmonary interstitial emphysema, intraventricular hemorrhage and retinopathy of prematurity in both groups was the same. Conclusions: HFOV, when applied early and when the clinical strategy of maintenance of optimal lung volume is used, improves oxygenation in the acute stage of RDS, reduces the need of surfactant administration, and can decrease the injury to lung tissue even in extremely immature newborns to whom surfactant is administered therapeutically.

European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update.

Advances in the management of respiratory distress syndrome (RDS) ensure that clinicians must continue to revise current practice. We report the third update of the European Guidelines for the Management of RDS by a European panel of expert neonatologists including input from an expert perinatal obstetrician based on available literature up to the beginning of 2016. Optimizing the outcome for babies with RDS includes consideration of when to use antenatal steroids, and good obstetric practice includes methods of predicting the risk of preterm delivery and also consideration of whether transfer to a perinatal centre is necessary and safe. Methods for optimal delivery room management have become more evidence based, and protocols for lung protection, including initiation of continuous positive airway pressure and titration of oxygen, should be implemented from soon after birth. Surfactant replacement therapy is a crucial part of the management of RDS, and newer protocols for surfactant administration are aimed at avoiding exposure to mechanical ventilation, and there is more evidence of differences among various surfactants in clinical use. Newer methods of maintaining babies on non-invasive respiratory support have been developed and offer potential for greater comfort and less chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease although minimizing the time spent on mechanical ventilation using caffeine and if necessary postnatal steroids are also important considerations. Protocols for optimizing the general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.

Tissue Metabolism and Plasma Levels of Thyroid Hormones in Critically Ill Very Premature Infants

Thyroid status was characterized in very preterm infants (gestational age≤32 wk; n = 61) from birth through d 14, and in infants who died within 16 d after delivery (n = 10), where it was also correlated with metabolism of iodothyronines in peripheral tissues (brain, liver, kidney, skeletal muscle, and adipose tissue). At 3 d of life, mean plasma levels of thyroxine, triiodothyronine, and TSH started to decrease, being lower in the critically ill compared with healthy premature neonates. Activities of the three iodothyronine deiodinases enzymes (type I, II, and III, respectively) were detected in all postmortem tissue samples, except for absence of the type II activity in kidney. All activities were the highest in liver and differed in other tissues. Lack of correlation between the type I activity in liver(and kidney), and plasma levels of thyroid hormones suggested that the thyroid was the primary source of circulating triiodothyronine. On the other hand, namely in brain, correlations between activity of the deiodinases and plasma hormone levels were found which suggested a complex control by thyroid hormones of their own metabolism. High activity of type III in liver, adipose tissue, and skeletal muscle demonstrated a role of these tissues in thyroid hormones degradation. Results support the view that peripheral tissues of very preterm infants are engaged in local generation of triiodothyronine, and inactivation of thyroid hormones, but do not represent a major source of circulating triiodothyronine.

The Neonatal European Study of Inhaled Steroids (NEUROSIS): An EU-Funded International Randomised Controlled Trial in Preterm Infants

a Department of Neonatology, University Children’s Hospital, Tubingen , Germany; b Royal Maternity Hospital, and Department of Child Health, Queen’s University, Belfast , UK; c General Faculty Hospital in Prague, Prague , Czech Republic; d Department of Pediatrics and Adolescence and Neonatal Research Laboratory, Oulu University Hospital, University of Oulu, Oulu , Finland; e Department of Neonatology, Kaplan Medical Center, Rehovot, and f Hebrew University, Jerusalem , Israel; g Assistance Publique-Hopitaux de Paris, Service de Medecine Neonatale de Port-Royal and Universite Paris Descartes, Paris , France; h Department of Paediatrics, Children’s Hospital, Azienda Ospedaliero-Universitaria, Ancona , Italy; i Children’s National Medical Center, Washington, D.C. , USA; j Department of Paediatrics, Erasmus MC Sophia Children’s Hospital, Rotterdam , The Netherlands; k Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart , and l Department of Clinical Pharmacology, University Hospital Tubingen, Tubingen , Germany

The CURPAP Study: An International Randomized Controlled Trial to Evaluate the Efficacy of Combining Prophylactic Surfactant and Early Nasal Continuous Positive Airway Pressure in Very Preterm Infants

Moreover, these data have been obtained in the early 1990s when prenatal steroids were used less than currently and the respiratory assistance with noninvasive nasal continuous positive airway pressure (CPAP) was poorly adopted in very preterm infants. These assumptions introduced the need for better understanding the role of prophylactic/early surfactant administration in the light of a modern perspective.

Mitochondrial Energy Metabolism in Very Premature Neonates

The activity, amount and protein composition of pyruvate dehydrogenase (PDH) and respiratory chain complexes were studied in muscle mitochondria obtained postmortally from 6 neonates with a gestational age of 23–29 weeks. The activities of PDH and respiratory chain complex III and IV and citrate synthase were significantly lower in comparison with control children aged 0.5–2 and 2–20 years. Protein analyses revealed a parallel decrease in the content of PDH, respiratory chain complexes and their subunits in the cases analyzed. The observed immaturity of the mitochondrial energy-providing system suggests that significant development of mitochondrial energy metabolism occurs during the last 3 months of prenatal development. The metabolic disturbances of mitochondrial energy conversion associated with the low functional capacity and content of PDH and respiratory chain complexes may play an important role in the morbidity of very premature neonates.

Fast Decline of Hematopoiesis and Uncoupling Protein 2 Content in Human Liver after Birth: Location of the Protein in Kupffer Cells

Hepatic hematopoiesis is prominent during fetal life and ceases around birth. In rodent liver, the decline of the hepatic hematopoiesis starts abruptly at birth being accompanied by a decrease of mitochondrial uncoupling protein 2 (UCP2) expression in monocytes/macrophages, whereas hepatocytes may express UCP2 only under pathologic situations. The goals of this study were to characterize hepatic hematopoiesis in humans around birth, and to identify cells expressing UCP2. Hematopoiesis was evaluated histologically in the liver of 22 newborns (mostly very premature neonates), who died between 45 min and 140 d after birth, and one fetus. UCP2 expression was characterized by Northern blots, immunoblotting, immunohistochemistry, and by in situ hybridization. The number of hematopoietic cells started to decrease rapidly at birth, irrespectively of the gestational age (23–40 wk) of neonates. A similar decline was observed for UCP2 expression, which was relatively high in fetal liver. UCP2 was detected only in myeloid cells (mainly in Kupffer cells), but not in hepatocytes, although sepsis or other pathologies occurred in the critically ill newborns. Kupffer cells represent the major site of mitochondrial UCP2 expression in the human newborn. UCP2 may be essential for the differentiation and function of macrophages and serve as a marker for these cells in human liver during the perinatal period.

Newborn Boys and Girls Differ in the Lipid Composition of Vernix Caseosa

Vernix caseosa protects the skin of a human fetus during the last trimester of pregnancy and of a newborn after the delivery. Besides its cellular and proteinaceous components, an important constituent and functional agent is a complex lipid fraction, implicated in a multitude of salubrious effects of vernix caseosa. Little is known about how the chemical composition of vernix caseosa lipids is affected by various biological characteristics of the baby, such as the gestational age, birth weight, and, last but not least, the gender of the newborn. This study reports on the chemical variability of lipids contained in the vernix caseosa of twenty newborn girls and boys and shows that the quantitative patterns of the lipids are sex-specific. The specificity of lipids was investigated at the level of fatty acids in the total lipid extracts and intact lipids of several neutral lipid classes. Hydrocarbons, wax esters, cholesteryl esters, diol diesters and triacylglycerols were isolated using optimized semipreparative thin-layer chromatography, and the molecular species within each class were characterized using matrix-assisted laser desorption/ionization mass spectrometry. Statistical evaluation revealed significant quantitative sex-related differences in the lipid composition of vernix caseosa among the newborns, pronounced in the two lipid classes associated with the activity of sebaceous glands. Higher proportions of wax esters and triacylglycerols with longer hydrocarbon chains were observed in newborn girls.