Maternal urine and serum steroid measurements to identify steroid sulfatase deficiency (STSD) in second trimester pregnancies

Objective To document the performance of second trimester maternal urine and serum steroid measurements for detecting fetal steroid sulfatase deficiency (STSD). Methods We studied detection rate and false positive rate (DR, FPR) of analytes in maternal urine [combinations of 16 alpha-OH-dehydroepiandrosterone sulfate (16 alpha-OH-DHEAS), 11 beta-hydroxyandrosterone, total estriol] and serum [combinations of 16 alpha-OH-DHEAS, 11 beta-hydroxyandrosterone, total estriol, unconjugated estriol (uE3)]. Samples were obtained from pregnancies which were screen positive for Smith-Lemli-Opitz syndrome (SLOS). Results Among 1079 301 pregnancies, 3083 (0.29%) were screen positive for SLOS. Urine and/or serum samples were available from 917 viable pregnancies with known gender. We assigned likelihood ratios (LRs) to steroid measurements from male fetuses with known STSD and unaffected female fetuses. An LR >= 100 was present in urine from 84 of 86 STSD pregnancies (98% DR, 95% CI 92-99), along with 0 of 198 pregnancies with normal female fetuses (0.0% FPR, CI 0-1.9). LRs were >= 100 in 4 of 129 female fetuses with major abnormalities (3% FPR). In maternal serum, steroid measurements performed less effectively, achieving a 71% DR for STSD at a 1.6% FPR. Conclusion Maternal urine steroid measurements are effective for detecting STSD, including those with point mutations and those with full deletions. Copyright (C) 2009 John Wiley & Sons, Ltd.