Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial.

Background: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation.

Methods: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants.

Diverging effects of premature birth and bronchopulmonary dysplasia on exercise capacity and physical activity - a case control study.

Background: Extreme prematurity has been associated with exercise intolerance and reduced physical activity. We hypothesized that children with bronchopulmonary dysplasia (BPD) would be especially affected based on long-term lung function impairments. Therefore, the objective of this study was to compare exercise capacity and habitual physical activity between children born very and extremely preterm with and without BPD and term-born children.

Short-term Pasteurization of Breast Milk to Prevent Postnatal Cytomegalovirus Transmission in Very Preterm Infants.

Background: Postnatally acquired cytomegalovirus (pCMV) infection through breast milk (BM) may cause severe illness and even death, yet BM is advantageous for preterm infants. Therefore, effective methods to prevent CMV transmission are needed.

Methods: To assess the effectiveness of short-term pasteurization (62°C for 5 seconds) in preventing CMV transmission via BM in preterm infants.

Secondary haemophagocytic lymphohistiocytosis triggered by postnatally acquired cytomegalovirus infection in a late preterm infant.

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition with impairment of cytotoxic T-cells and natural killer cells. Causes in infants are mostly hereditary immune defects as well as various infectious triggering factors, amongst these cytomegalovirus (CMV). Vertical CMV transmission may occur in utero, during birth, and by breast feeding.

A novel splicing mutation in the albumin gene (c.270+1G>T) causes analbuminaemia in a German infant.

Congenital analbuminaemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. The clinical diagnosis may be challenging because of the absence of unambiguous symptoms and because hypoalbuminemia may have many causes different from a genetic lack of the protein. We describe the clinical and molecular characterization of a new case of congenital analbuminaemia in an infant of apparently non-consanguineous parents from Treves, Germany.

Chorioamnionitis is essential in the evolution of bronchopulmonary dysplasia--the case in favour.

Bronchopulmonary dysplasia (BPD) is a major sequel of extremely premature birth. Multiple ante- and postnatal factors act in concert to injure the immature lung in the pathogenesis of the disease. Among them, chorioamnionitis--according to current evidence--plays a pivotal role.

Chorioamnionitis--the good or the evil for neonatal outcome?

Chorioamnionitis represents a major risk factor for preterm birth and contributes to prematurity-associated morbidity and mortality. Comparison of studies addressing neonatal outcome after exposure to either histological or clinical chorioamnionitis is hampered by the great heterogeneity regarding study cohorts and disease definitions which were applied. Moreover, the impact of exposure to inflammation in utero on neonatal outcome has become less evident with major advances in perinatal and neonatal care.

Airway angiopoietin-2 in ventilated very preterm infants: association with prenatal factors and neonatal outcome.

Objective: Pulmonary angiogenesis is a prerequisite for lung development. Angiopoietin-2 (Ang2) destabilizes endothelial cells through its endothelial receptor TIE-2, enabling vascular sprouting. Ang1 stabilizes new blood vessels.

Funisitis is associated with increased interleukin-10 gene expression in cord blood mononuclear cells in preterm infants ≤32 weeks of gestation.

Objectives: A systemic inflammatory response after intrauterine funisitis is assumed to be an important priming factor for acute and chronic pulmonary morbidity and neurological impairment in premature infants. Fetal lymphocytes and monocytes modulate the primary immune response. Genetic regulation of the cytokine-mediated process is partially known.

Chorioamnionitis: important risk factor or innocent bystander for neonatal outcome?

Chorioamnionitis as a major risk factor for spontaneous preterm birth, especially at earlier gestational ages, contributes to prematurity-associated mortality and morbidity. A gestation-independent effect of chorioamnionitis on neonatal outcome is much more difficult to assess. The influence of chorioamnionitis on neonatal outcome has become less evident with advances in neonatal care.

Soluble receptor for advanced glycation end products (sRAGE) in tracheobronchial aspirate fluid and cord blood of very low birth weight infants with chorioamnionitis and funisitis.

Background: A systemic fetal inflammatory response, reflected by histological funisitis is associated with pulmonary morbidity and increased mortality after premature birth. The receptor for advanced glycation end products (RAGE) is a membrane-bound multiligand receptor with a key role in inflammation. Soluble RAGE (sRAGE) is created by alternative mRNA splicing or shedding of the receptor's extracellular domain and can inhibit RAGE-activation.

Glucocorticoids potentiate IL-6-induced SP-B expression in H441 cells by enhancing the JAK-STAT signaling pathway.

The respiratory distress syndrome (RDS) contributes to perinatal morbidity and mortality associated with preterm birth. Surfactant protein B (SP-B) is decreased in RDS. Both maternal antenatal steroid administration and chorioamnionitis reduce the incidence and severity of RDS.

Response of leukocytes and nucleated red blood cells in very low-birth weight preterm infants after exposure to intrauterine inflammation.

Objectives: To test the hypothesis if very immature preterm infants exposed to chorioamnionitis would exhibit increased numbers of leukocytes, neutrophils, and nucleated red blood cells (NRBC) in peripheral blood.

Study Design: Preterm infants with birth weight <1500 g were prospectively evaluated. Blood cells were counted within the first hour of life in infants exposed to histological chorioamnionitis and controls.

Treatment modalities of infants with upper airway obstruction--review of the literature and presentation of novel orthopedic appliances.

Objective: To present a new orthopedic method for treatment of infants with Pierre Robin sequence (PRS) and upper airway obstruction (UAO) as an alternative to other established nonsurgical and surgical techniques such as positioning, nasopharyngeal or endotracheal intubation, tongue-lip adhesion, extension, distraction, or tracheostomy.

Design: Review of the literature and presentation of novel orthopedic appliances.

Setting: Department of Orthodontics, Dental Clinic, Medical Faculty of the University of Wuerzburg, Germany, Department and Clinic of Pediatrics, Medical Faculty of the University of Wuerzburg, Germany, 2005 to 2008.

Intrauterine growth retardation in preterm infants ≤32 weeks of gestation is associated with low white blood cell counts.

It is unclear if very immature preterm infants who are born small for gestational age (SGA) have similar leukocyte counts as infants who are born appropriate for gestational age (AGA). Our study included 49 preterm infants with a gestational age ≤32 weeks and without exposure to chorioamnionitis and funisitis. Blood cells were counted in the first 2 hours of life.

Clara cell secretory protein in tracheobronchial aspirates and umbilical cord serum of extremely premature infants with systemic inflammation.

Background: A systemic fetal inflammatory response, reflected by chorioamnionitis with funisitis, is a risk factor for bronchopulmonary dysplasia. Clara cell secretory protein (CC10), a product of pulmonary Clara cells, has anti-inflammatory properties. Local down-regulation of CC10 has been associated with inflammatory lung disease.

Airway concentrations of angiopoietin-1 and endostatin in ventilated extremely premature infants are decreased after funisitis and unbalanced with bronchopulmonary dysplasia/death.

A systemic inflammatory response of the fetus, reflected by histologic funisitis, is a risk factor for bronchopulmonary dysplasia (BPD). Impaired pulmonary angiogenesis accompanied by simplification and rarification of alveoli is a histologic hallmark of BPD. Angiopoietin-1 mediates vascular development, maturation, and stabilization.

Systemic fetal inflammation and reduced concentrations of macrophage migration inhibitory factor in tracheobronchial aspirate fluid of extremely premature infants.

Objective: Macrophage migration inhibitory factor is a proinflammatory mediator of innate immunity, enhances cell growth, and plays a role in preterm delivery. We speculated that funisitis, reflecting fetal systemic inflammation, would be associated with higher concentrations of macrophage migration inhibitory factor in airways of extremely premature infants.

Study Design: We measured macrophage migration inhibitory factor by enzyme linked immunosorbent assay in tracheobronchial aspirate fluid of 35 ventilated infants less than 30 weeks' gestational age, throughout the first week of life.

Prevention and therapy of bronchopulmonary dysplasia - evidence and clinical practice.

The knowledge on the pathogenetic mechanisms of bronchopulmonary dysplasia (BPD) has increased considerably over recent years. However, the incidence of the disease has not substantially been changed by our therapeutic approaches. This review summarizes the existing evidence for a number of respiratory and medical strategies to prevent or ameliorate the disease and gives recommendations for clinical practice.

Management of infants with bronchopulmonary dysplasia in Germany.

Although official guidelines for diagnosis and treatment of bronchopulmonary dysplasia (BPD) exist in Germany the practice in tertiary care neonatology centres differs considerably. There is no consensus about the appropriate level of oxygen saturation for infants at risk for BPD or infants with established BPD. Targeting oxygen saturation just below 90% in the first weeks and in the lower nineties thereafter seems to be a reasonable approach.