Neuregulins play a critical role in the developing heart, nervous, and mammary systems. Neuregulin-1-induced cardiac, neuronal, and mammary differentiation is based on a cell-cell communication model, where the ligand neuregulin-1 is produced and secreted by one cell type, which does not express its receptors erbB3 and erbB4 and acts on neighboring cell types that do express these receptors. We proposed that neuregulin-1 affects fetal lung maturation through a similar mechanism. Immunostaining showed neuregulin-1 in fetal lung that increased in fibroblasts at the onset of surfactant synthesis. Neuregulin-1 beta was found to be secreted by the fetal lung fibroblast and stimulated type II cell surfactant synthesis. Both fetal lung fibroblast-conditioned media and neuregulin-1 stimulated erbB2 receptor phosphorylation in type II cells. The effects of neuregulin-1 and of fibroblast-conditioned media on both surfactant synthesis and type II cell erbB2 phosphorylation were specifically blocked by antibody to neuregulin-1. Thus, neuregulin-1 beta may control fetal lung maturation through mesenchymal-epithelial interactions in a paracrine mechanism similar to that described for the developing heart, brain, and mammary systems.
CONTEXT Low oxygen saturation appears to decrease the risk of severe retinopathy of prematurity (ROP) in preterm newborns when administered during the first few weeks after birth. High oxygen saturation seems to reduce the risk at later postmenstrual ages (PMAs). However, previous clinical studies are not conclusive individually. OBJECTIVE To perform a systematic review and meta-analysis to report the association between severe ROP incidence of premature infants with high or low target oxygen saturation measured by pulse oximetry. METHODS Studies were identified through PubMed and Embase literature searches through May 2009 by using the terms “retinopathy of prematurity and oxygen” or “retinopathy of prematurity and oxygen therapy.” We selected 10 publications addressing the association between severe ROP and target oxygen saturation measured by pulse oximetry. Using a random-effects model we calculated the summary-effect estimate. We visually inspected funnel plots to examine possible publication bias. RESULTS Low oxygen saturation (70%–96%) in the first several postnatal weeks was associated with a reduced risk of severe ROP (risk ratio [RR]: 0.48 [95% confidence interval (CI): 0.31–0.75]). High oxygen saturation (94%–99%) at ≥32 weeks’ PMA was associated with a decreased risk for progression to severe ROP (RR: 0.54 [95% CI: 0.35–0.82]). CONCLUSIONS Among preterm infants with a gestational age of ≤32 weeks, early low and late high oxygen saturation were associated with a reduced risk for severe ROP. We feel that a large randomized clinical trial with long-term developmental follow-up is warranted to confirm this meta-analytic result.
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