Background: Physicians and parents face significant uncertainties when making care decisions for extremely low birth weight (ELBW) infants. Many published estimates of death and developmental outcome are from well-funded university programs and may not reflect outcomes of infants from a variety of settings. The best estimates of the probabilities of death and severe disability combine local experience and published data. Objective: To describe the neurodevelopmental outcome of ELBW infants from centers of the ELBW Infant Follow-Up Group of the Vermont Oxford Network (VON) and to identify characteristics associated with severe disability. Methods: Predefined measures of living situation, health and developmental outcome were collected at 18–24 months’ corrected age for infants born from July 1, 1998 to December 31, 2003 with birth weights of 401–1,000 g at 33 North American VON centers. Logistic regression was used to identify characteristics associated with severe disability. Results: 6,198 ELBW infants were born and survived until hospital discharge; by the time of follow-up, 88 infants (1.4%) had died. Of the remaining 6,110 infants, 3,567 (58.4%) were evaluated. Severe disability occurred in 34% of the assessed infants. Multivariate logistic regression suggested cystic periventricular leukomalacia, congenital malformation and severe intraventricular hemorrhage were the characteristics most highly associated with severe disability. There were marked variations among the follow-up clinics in the attrition rate. Conclusion: ELBW infants completing evaluation were at a high risk for severe disability. There are considerable differences among participating centers in attrition at follow-up. Further resources will be needed to study the effect of follow-up care for this group of infants.

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Hyperoxic lung injury is an unfortunate consequence of ventilatory oxygen therapy that is necessary to sustain life in certain clinical situations. The biochemical events that accompany hyperoxia of the lung, and the molecular mechanisms underlying these events, are incompletely understood. To better understand hyperoxic lung injury, our laboratory has cloned a set of genes corresponding to mRNAs that increase in abundance in the lungs of hyperoxic rabbits. In this report, we focus on three hyperoxia-induced cDNA clones, which encode surfactant apoprotein A (SP-A), the tissue inhibitor of metalloproteinases (TIMP), and metallothionein. In situ hybridizations and RNA dot blots of isolated lung cell populations indicate that the abundance of mRNA encoding all three proteins is increased by hyperoxia in specific cell types. SP-A mRNA increases in type II alveolar epithelial cells and in bronchiolar epithelial cells. TIMP mRNA increases in interstitial fibroblasts, in chondrocytes of the cartilage surrounding airways, and in endothelial cells of a specific subset of vessels, probably venules. Metallothionein transcripts also increase in chondrocytes and pulmonary fibroblasts. A comparison of the increase in these mRNAs during hyperoxic exposure in adults and newborns indicates that adults respond faster and to a greater extent than newborns and suggests that the rate and extent of these increases is correlated with the time course and severity of the injury.

The physiologic response of the lung to oxygen toxicity is complex, and similar among all mammals studied. Acute exposure to 100% O2 results in severe decreases in respiratory function and is accompanied by alterations in pulmonary surfactant metabolism, including the regulation of surfactant proteins A, B, and C (SP-A, SP-B, SP-C). Because surfactant proteins and their mRNAs can be expressed in alveolar epithelial type II cells, and nonciliated bronchial epithelial (Clara) cells, we were interested in determining if alterations in the abundance of SP-A, SP-B, and SP-C mRNAs occurred differentially in these two cell types during hyperoxic lung injury. Using quantitative in situ hybridization, we found that hyperoxic lung injury resulted in nearly 20-fold increases in SP-A and SP-B mRNAs in Clara cells, with relatively small (2-fold or less) increases in type II cells. Immunohistochemical analysis suggested a commensurate increase in SP-A protein in Clara cells. SP-C mRNA was only detected in type II cells, and changed little in hyperoxic lung. Because Clara cells are not known to produce surfactant, and appear to lack SP-C mRNA, these observations suggest that increased SP-A and SP-B may serve nonsurfactant functions in hyperoxic lung.

A statewide, hospital-based quality-improvement project targeting hospital staff members and community physicians was effective in improving documented newborn preventive services during the birth hospitalization.