Kajsa Bohlin

Continuous Positive Airway Pressure and Surfactant

Nasal continuous positive airway pressure (nCPAP) is an effective treatment of respiratory distress syndrome. Due to long-standing experience of early nCPAP as the primary respiratory support option in preterm infants, this approach is sometimes labeled ‘the Scandinavian Model’. Mechanical ventilation is potentially harmful to the immature lungs and cohort studies have demonstrated that centers using more CPAP and less mechanical ventilation have reduced rates of bronchopulmonary dysplasia. However, there is a lack of evidence in the form of larger, randomized controlled trials to prove the superiority of either method. Surfactant is essential in the treatment of respiratory distress syndrome and has generally been reserved for infants on mechanical ventilation. With the development of INSURE (INtubation SURfactant Extubation), in which surfactant is administered during a brief intubation followed by immediate extubation, surfactant therapy can be given during nCPAP treatment further reducing need for mechanical ventilation. In this review the history, current knowledge and techniques of CPAP and surfactant are discussed.

Nasal CPAP and surfactant for treatment of respiratory distress syndrome and prevention of bronchopulmonary dysplasia

The Scandinavian approach is an effective combined treatment for respiratory distress syndrome (RDS) and prevention of bronchopulmonary dysplasia (BPD). It is composed of many individual parts. Of significant importance is the early treatment with nasal continuous positive airway pressure (nCPAP) and surfactant treatment. The approach may be supplemented with caffeine citrate and non‐invasive positive pressure ventilation for apnoea. The low incidence of BPD seen as a consequence of the treatment strategy is mainly due to a reduced need for mechanical ventilation (MV).

Long-Term Impact of Preterm Birth on Exercise Capacity in Healthy Young Men: A National Population-Based Cohort Study

Background Increasing numbers of survivors of preterm birth are growing into adulthood today. Long-term health-effects of prematurity are still poorly understood, but include increased risk for diabetes, obesity and cardiovascular diseases in adult life. To test if reduced physical fitness may be a link in the causal chain of preterm birth and diseases in later life, the association of preterm birth and adult exercise capacity was investigated. The hypothesis was that preterm birth contributes independently of other risk factors to lower physical fitness in adulthood. Methods and Findings Population-based national cohort study of all males conscripting for military service in 1993–2001 and born in Sweden 1973–1983, nu200a=u200a218,820. Data were retrieved from the Swedish Conscript Register, the Medical Birth Register and the Population and Housing Census 1990. Primary outcome was the results from maximal exercise test (Wmax in Watt) performed at conscription. Association to perinatal and socioeconomic risk factors, other co-variates and confounders were analysed. General linear modelling showed that preterm birth predicted low Wmax in a dose-response related pattern, with 25 Watt reduction in Wmax for the lowest gestational ages, those born ≤27 weeks. Low birth weight for gestational age also independently predicted low Wmax compared to normal and high birth weight (32 Watt reduction for those with a birth weight Standard Deviation Score <2). Low parental education was significantly associated with reduced Wmax (range 17 Watt), as well as both low and high current BMI, with severe obesity resulting in a 16 Watt deficit compared to Wmax top performance. Conclusion Being born preterm as well as being born small for gestational age predicts low exercise capacity in otherwise healthy young men. The effect size of being born preterm equal or exceed that of other known risk factors for unfitness in adults, such as low parental education and overweight.

Nasal high-frequency oscillation ventilation in neonates: a survey in five European countries

AbstractNasal high-frequency oscillation ventilation (nHFOV) is a non-invasive ventilation mode that applies an oscillatory pressure waveform to the airways using a nasal interface. nHFOV has been shown to facilitate carbon dioxide expiration, but little is known about its use in neonates. In a questionnaire-based survey, we assessed nHFOV use in neonatal intensive care units (NICUs) in Austria, Switzerland, Germany, the Netherlands, and Sweden. Questions included indications for nHFOV, equipment used, ventilator settings, and observed side effects. Of the clinical directors of 186 NICUs contacted, 172 (92xa0%) participated. Among those responding, 30/172 (17xa0%) used nHFOV, most frequently in premature infants <1500xa0g (27/30) for the indication nasal continuous positive airway pressure (nCPAP) failure (27/30). Binasal prongs (22/30) were the most common interfaces. The median (range) mean airway pressure when starting nHFOV was 8 (6–12) cm H2O, and the maximum mean airway pressure was 10 (7–18) cm H2O. The nHFOV frequency was 10 (6–13) Hz. Abdominal distension (11/30), upper airway obstruction due to secretions (8/30), and highly viscous secretions (7/30) were the most common nHFOV side effects.n Conclusion: In a number of European NICUs, clinicians use nHFOV. The present survey identified differences in nHFOV equipment, indications, and settings. Controlled clinical trials are needed to investigate the efficacy and side effects of nHFOV in neonates.

RDS - CPAP or surfactant or both

There is mounting evidence that early continuous positive airway pressure (CPAP) from birth is feasible and safe even in very preterm infants. However, many infants will develop respiratory distress syndrome (RDS) and require surfactant treatment. Combining a non‐invasive ventilation approach with a strategy for surfactant administration is important, but questions remain about the optimal timing, mode of delivery and the value of predictive tests for surfactant deficiency.

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

PurposeCongenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO).MethodsEleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The 13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4xa0days of the study.ResultsFractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4xa0±xa00.33 vs. 8.0xa0±xa02.4%/day, pxa0=xa00.04). The control group had a higher maximal enrichment (0.18xa0±xa00.03 vs. 0.09xa0±xa00.02 APE, pxa0=xa00.04) and reached this maximal enrichment earlier (46.7xa0±xa03.0 vs. 69.4xa0±xa06.6xa0h, pxa0=xa00.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups.ConclusionThese results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO.

Neonatal resuscitation and respiratory support in prevention of bronchopulmonary dysplasia

Educational aims To understand the physiology of respiratory support immediately after birth To learn the current guidelines for neonatal resuscitation To discuss noninvasive ventilation strategies in relation to development of bronchopulmonary dysplasia Summary Bronchopulmonary dysplasia (BPD) remains the most common severe adverse pulmonary outcome of preterm birth. Low gestational age and birth weight are the strongest risk factors for the development of BPD, but the pathogenesis is complex. The strategy for respiratory support immediately after birth and during the initial neonatal period may have a critical impact on the development of BPD. The preterm lung is highly susceptible to injury. An understanding the physiology of the first breath, the initiation of breathing and respiratory adaptation after birth is essential for adequate resuscitation measures and a lung protective ventilation strategy. Excessive oxygen use in preterm infants can increase the risk of BPD. The recently developed nomograms for oxygen saturation levels during the neonatal transition phase have become part of the newly revised resuscitation guidelines. For term neonates, starting resuscitation with air, rather than 100% oxygen, is now advised. Preterm infants may require a higher initial inspiratory oxygen fraction than term infants; however, the ideal level remains to be defined. Primary intubation is no longer a prerequisite for preterm survival. Recent trials have demonstrated that even very preterm infants can be safely stabilised after delivery with continuous positive airway pressure and later be selectively treated with surfactant for respiratory distress syndrome. This initially less invasive strategy has the advantage of reducing the need for mechanical ventilation and, thereby, the risk of lung injury; however, to date, it has not been clearly shown to reduce the incidence of BPD. Combining an approach of noninvasive ventilator support with a strategy of minimally invasive surfactant administration is important, but questions remain about the optimal timing, mode of delivery and value of predictive tests for surfactant deficiency.

Low Exercise Capacity Increases the Risk of Low Cognitive Function in Healthy Young Men Born Preterm: A Population-Based Cohort Study

Background Preterm birth is a risk factor for decreased exercise capacity and impaired cognitive functions in later life. The objective of this study was to disentangle the associations between preterm birth, physical fitness and cognitive performance in young adulthood. Methods This population-based cohort study included 218,802 young men born in Sweden 1973–1983. Data on birth characteristics was obtained from the Medical Birth Register and linked to exercise capacity assessed by ergometer cycling and cognitive tests performed at conscription for military service in 1993–2001. Cognitive performance was assessed using stanine (STAndard NINE) scores. The results were adjusted for socioeconomic factors. Results Exercise capacity was positively associated with cognitive performance across all gestational ages. The sub-group of men who were born extremely preterm (gestational age <28 weeks) and had low exercise capacity exhibited the lowest odds ratio (OR = 0.26, 95%CI:0.09–0.82) of having a cognitive function above the mean stanine score (2.9) for men born at term with normal birth weight. Men born extremely preterm with a high exercise capacity had similar or even higher ORs for cognitive function (OR = 0.59; 95% CI:0.35–0.99) than men born at term with low Wmax (OR = 0.57; 95% CI:0.55–0.59). Conclusions Physical fitness is associated with higher cognitive function at all gestational ages, also in young men born extremely preterm. Targeting early physical exercise may be a possible intervention to enhance cognitive performance and educational achievements in populations at risk, such as childhood and adult survivors of preterm birth.

Prematurity and Lung Function in Relation to Telomere Length and Inflammation in 10-Year Old Children

Background and aims: Oxidative stress, as a result of inflammation and oxygen toxicity, may affect lung growth and contribute to the development of bronchopulmonary dysplasia (BPD) in preterm infants. Preterm infants have longer telomeres than term infants at birth. In adults, chronic obstructive lung disease has been related to shorter telomeres. Telomere length in relation to prematurity and lung function therefore was studied.Methods: Relative telomere length (RTL) was measured using real-time PCR on extracted DNA in children born preterm with a history of BPD at the age of 10 years and a control group of children born healthy at term with a history of asthma. Lung function as dynamic spirometry and inflammation examined as fractional exhaled nitric oxygen (NO) was performed.Results: Children with BPD (n= 23) compared to children with asthma (n=19) had shorter telomeres (RTL 1,43 vs 1,61, p< 0,05) and reduced lung function (Forced Expiratory Fraction (FEF 25-75%), 1,55 vs 1,88, p< 0,05) but lower levels of exhaled NO (NO 12,6 ppb vs 22,3 ppb, p< 0,05). Lung function and levels of NO were not independently correlated to RTL.Conclusions: Preterm birth and lung disease in infancy resulted in shorter telomere length and reduced lung function at 10 years of age compared to controls with asthma. This may indicate faster telomere attrition in preterm infants with BPD. The influence of oxidative stress and inflammation in the neonatal period and beyond needs to be further studied in relation to intra-individual telomere shortening rate and long term outcome.

Education, training, and accreditation of Neonatologist Performed Echocardiography in Europe—framework for practice

There is a growing interest worldwide in using echocardiography in the neonatal unit to act as a complement to the clinical assessment of the hemodynamic status of premature and term infants. However, there is a wide variation in how this tool is implemented across many jurisdictions, the level of expertise, including the oversight of this practice. Over the last 5 years, three major expert consensus statements have been published to provide guidance to neonatologists performing echocardiography, with all recommending a structured training program and clinical governance system for quality assurance. Neonatal practice in Europe is very heterogeneous and the proximity of neonatal units to pediatric cardiology centers varies significantly. Currently, there is no overarching governance structure for training and accreditation in Europe. In this paper, we provide a brief description of the current training recommendations across several jurisdictions including Europe, North America, and Australia and describe the steps required to achieve a sustainable governance structure with the responsibility to provide accreditation to neonatologist performed echocardiography in Europe.