Testing for fetal pulmonary maturity: ROC analysis involving covariates, verification bias, and combination testing

The lecithin/sphingomyelin ratio (L/S) and the measured value of saturated phosphatidylcholine (SPC), amniotic fluid determinations obtained to assess fetal pulmonary maturity, were evaluated with receiver operating characteristic (ROC) curve analysis. The effects of covariates on the ROC curves were analyzed with a regression methodology that took into account all the available data when constructing an ROC curve for each subgroup. To correct for verification bias the authors used a logistic regression analysis to model the probability of verification, thereby permitting correction for verification bias of a fully stratified data set in spite of small cell frequencies. They examined combination testing with prediction rules using prospective logistic modeling, including as variables test results and clinical features. The L/S was found to be significantly better than SPC for assessing fetal pulmonary maturity. For older gestational age the L/S and SPC performed better than for younger gestational age. Contamination of the specimen degraded the ROC curves. Correcting for verification bias did not influence the ROC curves significantly but changed the cutoff value of the test variable for any particular operating point. Prediction rules to evaluate combination testing showed that obtaining the SPC level in addition to the L/S ratio added no significant information compared with the L/S only. Including gestational age in the prediction rule of either test improved the prediction.