Maternal serum unconjugated estriol as a predictor for Smith-Lemli-Opitz syndrome and other fetal conditions.
OBJECTIVE
To assess the clinical value of low maternal serum unconjugated estriol (E3) level for diagnosing Smith-Lemli-Opitz syndrome and other fetal clinical conditions in pregnant members of a large health maintenance organization.


METHODS
We studied serum unconjugated E3 levels in 120,071 gravidas having California Expanded Alpha-Fetoprotein prenatal screening at 15-20 weeks' gestation during a 5-year period.


RESULTS
Of the 120,071 women, 323 (0.27%) had low unconjugated E3 levels (less than or equal to 0.2 ng/mL, or 0.15 multiples of the median). Excluding women who were screened too early or who had indeterminate screening results, 103 (0.08%) women with unexplained low unconjugated E3 level remained; of these 103 women, 33 had negative screening results and 68 had positive screening results, and two were tested too late for interpretation. Intrauterine fetal death occurred in 39 (57%) of the 68 women with low unconjugated E3 and positive screening results and occurred in two (6%) of the 33 women with low unconjugated E3 levels and negative screening results, a significant difference (P <.001). Two cases of Smith-Lemli-Opitz syndrome were identified and the patients did not survive the neonatal period; one was a therapeutic abortion for severe oligohydramnios, and the other died at age 48 hours. Low unconjugated E3 level also predicted presence of steroid sulfatase deficiency, a much more common X-linked skin disorder characterized by ichthyosis.


CONCLUSIONS
Low maternal serum unconjugated E3 diagnosed more cases of steroid sulfatase deficiency and undetected intrauterine fetal death than Smith-Lemli-Opitz syndrome (1:60,000 prevalence), although the clinical importance of having this information prenatally is uncertain.
Schoen
Edgar
E
Regional Perinatal Screening Program, Department of Genetics and Perinatology, Kaiser Permanente Medical Center, Oakland, California 94611-5693, USA. edgar.schoen@kp.org
Norem
Carol
C
O'Keefe
Jennifer
J
Krieger
Robyn
R
Walton
David
D
To
Trinh T
TT
D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004964:Estriol / Q000097:blood*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis; D005328:Fetal Viability; D005865:Gestational Age; D006801:Humans; D011237:Predictive Value of Tests; D011247:Pregnancy / Q000097:blood*; D011296:Prenatal Diagnosis; D015995:Prevalence; D011336:Probability; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D019082:Smith-Lemli-Opitz Syndrome / Q000175:diagnosis* / Q000453:epidemiology
D015415:Biomarkers; D004964:Estriol