Survival at 24 weeks was only 43% despite treatment with antenatal steroids and exogenous surfactant. The cost per survivor for infants born at 24 weeks was higher than the cost for those born after 1 more week in utero. Outcome improved markedly between 24 and 26 weeks, and small differences in gestational age lead to large economic differences. All efforts should be attempted to prolong pregnancy, and if prolongation is unsuccessful, treatment options including nonintervention should be available to parents of 24-week gestations.
Although the incidence of cerebral palsy was low in these three groups, the high percentage of infants born at 24 and 25 weeks' gestation with cognitive deficits is concerning.
We report the activity of recombinant human surfactant apoprotein-C (rSP-C[Cys]2) and various phospholipids in a preterm rabbit model of respiratory distress syndrome (RDS). Mixtures of rSP-C(Cys)2 and certain phospholipids had similar activity (lung compliance and lung pressure-volume behavior) to rabbit surfactant in this model. The activity of rSP-C(Cys)2 was maximal at 1 mol% protein and varied significantly with the phospholipid composition. Chemically synthesized SP-C had similar activity to rSP-C(Cys)2. Deletion of six amino-terminal residues did not affect function. Substitution of cysteines and cysteine6 with adjacent serines (rSP-C[Ser]2) by site-specific mutagenesis minimized aggregation of rSP-C but did not affect activity. Palmitoylation of cysteine5 and cysteine6 in rSP-C (rSP-C[C16]2) did not enhance the activity of rSP-C(Cys)2. We conclude that bacterial expression is a practical source of functional SP-C, and that nonacylated forms of SP-C may be useful adjuvants to phospholipids in the treatment of RDS and possibly other forms of acute lung injury.
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