Evaluating the thresholds of abnormal second trimester multiple marker screening tests associated with intra-uterine growth restriction

Abstract

Our objective was to evaluate the optimal thresholds for unexplained abnormal multiple marker screening (MMS) results that are associated with intrauterine growth restriction (IUGR). This was a case-control study from our perinatal database. MMS analyte levels (multiples of median [MoM]) of cases with IUGR (birthweight < 5th percentile for gestational age) were compared with a control group without IUGR. Pregnancies with fetal anomalies were excluded. Biochemical markers evaluated include alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3). Using receiver operating characteristic curves, the optimal thresholds of MMS (OTMs) associated with IUGR were determined. We identified 255 (12.3%) cases with IUGR and complete MMS records from the database. These were compared with 1785 controls without IUGR randomly selected from our perinatal database in a 1:7 ratio. The OTMs associated with IUGR were AFP > 2.0 MoM (odds ratio [OR] = 2.3; 95% confidence interval [CI], 1.4 to 3.7), hCG > 2.5 MoM (OR = 1.8; 95% CI, 1.1 to 3.2) and uE3 < 0.9 MoM (OR = 2.7; 95% CI, 2.0 to 3.7). The sensitivity, specificity, and positive and negative predictive values for predicting IUGR in the presence of at least one abnormal MMS were 46, 66, 11, and 90%, respectively. Elevated AFP > 2.0 MoM and hCG > 2.5 MoM were the most specific markers for MMS, with specificity of 94 and 95%, respectively. When all three analytes were abnormal, the specificity for predicting IUGR increased to 99%. Abnormal MMS results are associated with IUGR. As a screening tool for IUGR, the biochemical markers were associated with poor sensitivity. Elevated AFP and hCG, however, were highly specific in predicting IUGR. The provided thresholds could be useful in designing policies regarding women who would benefit most from sonographic screening for IUGR.