Assigning risk for Smith-Lemli-Opitz syndrome as part of 2nd trimester screening for Down's syndrome.

OBJECTIVES: To design a reliable model in the context of prenatal screening for assigning the risk in an individual pregnancy of Smith-Lemli-Opitz syndrome (SLOS) and assess its performance.

SETTING: A 2nd trimester screening programme for Down's syndrome that measures unconjugated estriol (uE3) along with other serum markers.

METHODS: Development of individual risk estimates with a trivariate model incorporating measurements of maternal serum uE3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) in both SLOS and unaffected pregnancies.

RESULTS: Population parameters were computed for the three analytes, as were pairwise correlation coefficients and truncation limits, based on an unbiased collection of 29 affected pregnancies. Published parameters were used for unaffected pregnancies. With a cut off level of risk of 1:50, 62% of SLOS pregnancies can be detected by initially identifying 0.34% of unaffected pregnancies as screen positive. About 1 in 90 screen positive pregnancies will be affected.

CONCLUSIONS: It is possible to screen for SLOS as an add on to existing 2nd trimester maternal serum screening, if uE3 is already being measured. A large, prospective trial is necessary to determine whether diagnostic testing can be performed in maternal urine or serum rather than amniotic fluid.