No abstract

The German Neonatal Network (GNN) is a prospective cohort study with the focus on long term development of very-low-birth-weight infants. It was the aim of this study to determine detailed information on causes of mortality in the GNN birth cohort 2010.Major contributors to hospital mortality were recorded by the attending neonatologists for the cohort of very-low-birth-weight (VLBW) infants born in centres of the German Neonatal Network (GNN) in 2010. The data quality was approved by on-site monitoring.2 221 VLBW infants were born in GNN centres in 2010, and death occurred in 221 infants. Male infants carried a higher risk than females (58.8% males among non-survivors vs. 51.7% among survivors, p=0.047). In 11 infants, the major contributor to death was not determined by the attending neonatologist. In 25 infants born at the limit of viability, comfort palliative care was primarily initiated and 14 infants had lethal malformations. The majority of non-survivors suffered from inflammatory diseases including sepsis- or necrotizing enterocolitis (NEC)-associated death (n=56). Respiratory pathology was a major contributor to death in 65 infants including 11 infants who died from pulmonary haemorrhage.Potentially preventable complications of preterm birth such as sepsis, NEC and pulmonary haemorrhage predominate the major contributors to mortality in the GNN 2010 cohort. In order to decrease the rate of these associated deaths, future trials should focus on prophylaxis and therapy optimization strategies for these outcomes.

Congenital heart defects (CHDs) are the most common birth defect with 30%‐40% being explained by genetic aberrations. With next generation sequencing becoming widely available, we sought to evaluate the clinical utility of exome sequencing (ES) in prenatally diagnosed CHD. We retrospectively analyzed the diagnostic yield as well as non‐conclusive and incidental findings in 30 cases with prenatally diagnosed CHDs using ES, mostly as parent‐child trios. A genetic diagnosis was established in 20% (6/30). Non‐conclusive results were found in 13% (4/30) and incidental findings in 10% (3/30). There was a phenotypic discrepancy between reported prenatal and postnatal extracardiac findings in 40% (8/20). However, none of these additional, postnatal findings altered the genetic diagnosis. Herein, ES in prenatally diagnosed CHDs results in a comparably high diagnostic yield. There was a significant proportion of incidental findings and variants of unknown significance as well as potentially pathogenic variants in novel disease genes. Such findings can bedevil genetic counseling and decision making for pregnancy termination. Despite the small cohort size, our data serve as a first basis to evaluate the value of prenatal ES in CHD for further studies emerging in the near future.

Of all resuscitated infants with a birthweight <501 g, 56% survived to school age. Of these, composite outcome score showed normal development or mild disability in one-half, and moderate or severe disability in the other half of them. Investigators should include such infants in studies and their reports should give specific information about them.

ABSTRACT:In the present study, we tested the hypothesis that exposure of newborn mice to sublethal hyperoxia would alter lung development and expressions of fibroblast growth factor receptors (FGFRs)-3 and FGFR-4. Newborn FVB mice were exposed to 85% O 2 or maintained in room air for up to 14 d. No animal mortality was observed, and body weight gains were not affected by hyperoxia. At postnatal d 7 and 14 (P7, P14), lungs of mice exposed to 85% O 2 showed fewer alveolar secondary crests and larger alveoli or terminal air spaces than did mice in room air. In pups kept in room air, lung levels of FGFR-3 and FGFR-4 mRNA were greater at P3 than at P1, but similar increases were not observed in hyperoxic mice. Immunoreactivity of FGFR-3 and FGFR-4 was lower in lungs of hyperoxic mice than in controls at P14. In pups kept in room air, lung fibroblast growth factor (FGF)-7 mRNA levels were greater at P14 than at P1, but similar changes were not observed in hyperoxic mice. The temporally and spatially specific alterations in the expressions of FGFR-3, FGFR-4, and FGF-7 in the mice exposed to hyperoxia may contribute to aberrant lung development. B ronchopulmonary dysplasia (BPD) was described initially as lung injury-and repair-related effects that were associated with radiologic findings of streaky, fibrous densities, alternating with hyperlucent areas (1,2). The primary risk factors were premature birth, respiratory distress, mechanical ventilation, and administration of supplemental oxygen (FIO 2 Ͼ0.21). Inflammation, problems in nutritional support, and comorbid conditions also contribute to the development of BPD. Modifications of therapeutic strategies have decreased the incidence of BPD, as the disease was described originally, but the overall incidence of BPD has not declined. The "new BPD" of recent years shows little acute injury and repair described by Northway et al. (1,2), but is characterized by fewer and larger alveoli and less organized alveolar vascularization, suggesting arrested or disordered lung development. The events occurring during secondary septation of terminal gas exchange units and maturation of alveolar microvasculature are therefore of particular interest in research on mechanisms responsible for the new BPD (3-8).Lung development in humans normally progresses through sequential structural changes that are observed similarly in rats and mice, which, at term, exhibit lungs that structurally resemble human lungs at 26 -30 wk of gestation (9). Infants born at this age frequently encounter respiratory problems, arising from immature pulmonary surfactant metabolism, respiratory drive and coordination, or other deficiencies. Prematurely delivered nonhuman primate models of BPD may mimic human development more closely than do rodent models, but practical constraints limit the investigations that can be explored with primate models (4,5,10).The lungs of newborn rodents are sufficient for extrauterine life and are adequate for maturation into normal adult lungs. Studies in rats and mice indicate th...