Early N-Terminal Pro B-Type Natriuretic Peptide (NTproBNP) Plasma Values and Associations with Patent Ductus Arteriosus Closure and Treatment-An Echocardiography Study of Extremely Preterm Infants.

The aim was to investigate the association of gestational age (GA), echocardiographic markers and levels of plasma N-terminal pro-B-type natriuretic peptide (NTproBNP) with the closure rate of a haemodynamically significant patent ductus arteriosus (hsPDA). Ninety-eight Swedish extremely preterm infants, mean GA 25.7 weeks (standard deviation 1.3), born in 2012-2014, were assessed with echocardiography and for levels of NTproBNP. Thirty-three (34%) infants had spontaneous ductal closure within three weeks of age. Infants having spontaneous closure at seven days or less had significantly lower NTproBNP levels on day three, median 1810 ng/L (IQR 1760-6000 ng/L) compared with: infants closing spontaneously later, 10,900 ng/L (6120-19,200 ng/L); infants treated either with ibuprofen only, 14,600 ng/L (7740-28,100 ng/L); or surgery, 32,300 ng/L (29,100-35,000 ng/L). Infants receiving PDA surgery later had significantly higher NTproBNP values on day three than other infants. Day three NTproBNP cut-off values of 15,001-18,000 ng/L, predicted later PDA surgery, with an area under the curve in ROC analysis of 0.69 (0.54-0.83). In conclusion, the spontaneous PDA closure rate is relatively high in extremely preterm infants. Early NTproBNP levels can be used with GA in the management decisions of hsPDA.

A Novel Association between YKL-40, a Marker of Structural Lung Disease, and Short Telomere Length in 10-Year-Old Children with Bronchopulmonary Dysplasia.

Extremely preterm infants are born with immature lungs and are exposed to an inflammatory environment as a result of oxidative stress. This may lead to airway remodeling, cellular aging and the development of bronchopulmonary dysplasia (BPD). Reliable markers that predict the long-term consequences of BPD in infancy are still lacking. We analyzed two biomarkers of cellular aging and lung function, telomere length and YKL-40, respectively, at 10 years of age in children born preterm with a history of BPD (n = 29). For comparison, these markers were also evaluated in sex-and-age-matched children born at term with childhood asthma (n = 28). Relative telomere length (RTL) was measured in whole blood with qPCR and serum YKL-40 with ELISA, and both were studied in relation to gas exchange and the regional ventilation/perfusion ratio using three-dimensional V/Q-scintigraphy (single photon emission computer tomography, SPECT) in children with BPD. Higher levels of YKL-40 were associated with shorter leukocyte RTL (Pearson's correlation: -0.55, p = 0.002), but were not associated with a lower degree of matching between ventilation and perfusion within the lung. Serum YKL-40 levels were significantly higher in children with BPD compared to children with asthma (17.7 vs. 13.2 ng/mL, p < 0.01). High levels of YKL-40 and short RTLs were associated to the need for ventilatory support more than 1 month in the neonatal period (p < 0.01). The link between enhanced telomere shortening in childhood and structural remodeling of the lung, as observed in children with former BPD but not in children with asthma at the age of 10 years, suggests altered lung development related to prematurity and early life inflammatory exposure. In conclusion, relative telomere length and YKL-40 may serve as biomarkers of altered lung development as a result of early-life inflammation in children with a history of prematurity.

Cholestasis after very preterm birth was associated with adverse neonatal outcomes but no significant long-term liver disease: A population-based study.

AIM: To describe outcome linked to neonatal cholestasis in a defined cohort of very preterm infants. METHODS: Population-based retrospective case-control study of preterm infants, gestational age <30 weeks, surviving for 28 days, in Stockholm County. Cholestasis was defined as conjugated bilirubin ≥30 µmol/L exceeding 20% of total level at least twice and graded as high if exceeding 100 µmol/L. Cholestatic cases were matched on gestational week with two non-cholestatic controls. RESULTS: The incidence rate of cholestasis was 37/250 (14.8%), with increasing rates in lower gestational weeks. Perinatal factors associated with cholestasis were pre-eclampsia and being born small for gestational age. Cholestatic infants had three times more bronchopulmonary dysplasia and eight times more retinopathy of prematurity. The mortality was 13.5% in cholestatic infants versus 2.7% in controls (P = .040). All deceased cholestatic infants had high-grade cholestasis. No surviving infants developed chronic liver disease by 10 years of age. CONCLUSION: Cholestasis was common in very preterm infants and linked to disease severity and adverse outcome. Cholestasis may be an independent risk factor for bronchopulmonary dysplasia and retinopathy of prematurity and more severe cholestasis associated with increased mortality. Cholestasis was not associated with chronic liver disease later in childhood.

Physical Activity in 6.5-Year-Old Children Born Extremely Preterm.

Physical activity (PA) can prevent cardiovascular diseases. Because of increased risks of impairments affecting motor activity, PA in children born preterm may differ from that in children born at term. In this prospective cohort study, we compared objectively measured PA in 71 children born extremely preterm (<27 weeks gestational age), to their 87 peers born at term, at 6.5 years of age. PA measured with accelerometer on the non-dominant wrist for 7 consecutive days was compared between index and control children and analyzed for associations to prenatal growth, major neonatal brain injury, bronchopulmonary dysplasia and neonatal septicemia, using ANOVA. Boys born extremely preterm spent on average 22 min less time per day in moderate to vigorous physical activity (MVPA) than control boys (95% CI: -8, -37). There was no difference in girls. Amongst children born extremely preterm, major neonatal brain injury was associated with 56 min less time in MVPA per day (95%CI: -88, -26). Subgroups of children born extremely preterm exhibit lower levels of physical activity which may be a contributory factor in the development of cardiovascular diseases as adults.

Hematopoietic cellular aging is not accelerated during the first 2 years of life in children born preterm.

BACKGROUND: Prematurity in itself and exposure to neonatal intensive care triggers inflammatory processes and oxidative stress, leading to risk for disease later in life. The effects on cellular aging processes are incompletely understood. METHODS: Relative telomere length (RTL) was measured by qPCR in this longitudinal cohort study with blood samples taken at birth and at 2 years of age from 60 children (16 preterm and 44 term). Viral respiratory infections the first year were evaluated. Epigenetic biological DNA methylation (DNAm) age was predicted based on methylation array data in 23 children (11 preterm and 12 term). RTL change/year and DNAm age change/year was compared in preterm and term during the 2 first years of life. RESULTS: Preterm infants had longer telomeres than term born at birth and at 2 years of age, but no difference in telomere attrition rate could be detected. Predicted epigenetic DNAm age was younger in preterm infants, but rate of DNAm aging was similar in both groups. CONCLUSIONS: Despite early exposure to risk factors for accelerated cellular aging, children born preterm exhibited preserved telomeres. Stress during the neonatal intensive care period did not reflect accelerated epigenetic DNAm aging. Early-life aging was not explained by preterm birth. IMPACT: Preterm birth is associated with elevated disease risk later in life. Preterm children often suffer from inflammation early in life. Stress-related telomere erosion during neonatal intensive care has been proposed. Inflammation-accelerated biological aging in preterm is unknown. We find no accelerated aging due to prematurity or infections during the first 2 years of life.

Key paediatric messages from Amsterdam.

The Paediatric Assembly of the European Respiratory Society (ERS) maintained its high profile at the 2015 ERS International Congress in Amsterdam. There were symposia on preschool wheeze, respiratory sounds and cystic fibrosis; an educational skills workshop on paediatric respiratory resuscitation; a hot topic session on risk factors and early origins of respiratory diseases; a meet the expert session on paediatric lung function test reference values; and the annual paediatric grand round. In this report the Chairs of the Paediatric Assembly's Groups highlight the key messages from the abstracts presented at the Congress.

Cell-based strategies to reconstitute vital functions in preterm infants with organ failure.

Infants born preterm face a number of challenges. Depending on the degree of prematurity, they are at a risk of developing several specific conditions and diseases related to organ immaturity and complications of long-term neonatal intensive care. Various organ systems are affected, such as the lung, resulting in bronchopulmonary dysplasia (BPD); the vascular system, resulting in pulmonary hypertension; the brain, with the risk of intracranial hemorrhage; the eye with retinopathy of prematurity; and the gut, manifesting in the severe complication of necrotizing enterocolitis. A common hallmark for all these prematurity-related conditions is that inflammation seems to be a major driving force in the pathogenesis, and that injury repair is essential for recovery and long-term health. In addition, the available treatment options are often only supportive, not curative. This chapter reviews the recent advances of stem cell therapy that have opened up new possibilities to restore organ function following prematurity.

Paediatrics: messages from Munich.

The aim of this article is to describe paediatric highlights from the 2014 European Respiratory Society (ERS) International Congress in Munich, Germany. Abstracts from the seven groups of the ERS Paediatric Assembly (Respiratory Physiology and Sleep, Asthma and Allergy, Cystic Fibrosis, Respiratory Infection and Immunology, Neonatology and Paediatric Intensive Care, Respiratory Epidemiology, and Bronchology) are presented in the context of the current literature.

Paediatrics in Barcelona.

This update will describe the paediatric highlights from the 2013 European Respiratory Society (ERS) annual congress in Barcelona, Spain. Abstracts from the seven groups of the ERS Paediatric Assembly (Respiratory Physiology and Sleep, Asthma and Allergy, Cystic Fibrosis, Respiratory Infection and Immunology, Neonatology and Paediatric Intensive Care, Respiratory Epidemiology, and Bronchology) have been chosen by group officers and are presented in the context of current literature.

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

UNLABELLED: 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). CONCLUSION: Early-postnatal treatment with nCPAP and surfactant decreases the severity and mortality of RDS and BPD. This is mainly due to a diminished use of MV in the first days of life.

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.

Surfactant phosphatidylcholine metabolism in neonates with meconium aspiration syndrome.

OBJECTIVE: Because meconium directly inhibits surfactant function, we sought to determine the effect of meconium on endogenous surfactant synthesis and clearance. STUDY DESIGN: We studied surfactant phosphatidylcholine kinetics with the use of stable isotopes in 11 newborn infants with meconium aspiration syndrome (MAS) who required extracorporeal membrane oxygenation (ECMO). For comparison we studied 6 neonates with persistent pulmonary hypertension (PPHN) on ECMO and 10 term neonates ventilated for non-pulmonary indications and not on ECMO. All patients received a 24-hour [U- 13C]glucose infusion as precursor for the palmitic acid in surfactant phosphatidylcholine. RESULTS: In the meconium group, the maximal 13C-incorporation in phosphatidylcholine (PC) was half of that in controls (0.09 +/- 0.01 vs 0.18 +/- 0.03 atom percent excess [APE], P = .027). There was a trend toward lower surfactant synthesis in the MAS group (3.3 +/- 0.7%/day) and PPHN group (2.6 +/- 0.3%/day) compared with controls 8.0 +/- 2.4%/day, P = .058). Significantly lower PC concentrations in tracheal aspirates were found in the MAS group (4.4 +/- 2.6 mg/mL) and PPHN group (3.6 +/- 2.0 mg/mL) compared with controls (12.8 +/- 2.6 mg/mL, P = .01). Endogenously synthesized surfactant had a similar half-life in all groups, ranging from 63 to 98 hours. CONCLUSION: We conclude that surfactant synthesis is disturbed and that surfactant PC concentrations are low in infants with MAS on ECMO.