Maternal serum screening for fetal trisomy 18: benefits of patient-specific risk protocol

Our goal was to evaluate the effectiveness of two approaches to screen pregnancies for trisomy 18.

We analyzed the outcome of all pregnancies that were screen positive for trisomy 18 by multiple marker screening (alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin) from May 1993 to June 1998. We compared the results of a fixed cutoff protocol to a protocol that incorporates maternal age to generate a patient-specific risk figure.

A total of 45,145 patients were screened. By using the fixed cutoff protocol, 113 patients (0.25%) were screen positive. The risk-based approach was associated with a 0.55% screen-positive rate (250 patients). Eight of 12 cases (67% detection rate) of trisomy 18 were identified by using the risk method, and only 5 cases (42% detection rate) were detected by using the fixed cutoff method. By using the risk-based protocol, 21 pregnancies with chromosomal abnormalities (8, trisomy 18; 7, triploidy; 5, trisomy 21; and 1, mosaic 45X/46XX) were detected. Subsequent fetal death occurred for 42 patients whose fetuses were chromosomally normal and without structural malformations.

The patient-specific risk protocol to screen for trisomy 18 is a beneficial adjunct to screening programs already in place for Down syndrome and neural tube defects. Patients found to be screen positive for trisomy 18 are at significant risk for adverse pregnancy outcome.