Detection of pregnancies with trisomy 18 in screening programmes for Down's syndrome.

Abstract

It is possible to identify pregnancies with trisomy 18 as part of screening programmes for Down's syndrome that use maternal age, IX fetoprotein (AFP), unconjugated oestriol (uE3), and either total human chorionic gonadotrophin (total hCG) or its subunit, free ~-hCG. While the detection rates and false positive rates using risk as the test variable have been published for maternal age with (a) AFP, uE3, and hCG 2 and with (b) AFP and free ~-hCG3 this has not been done for maternal age with AFP, uE3,and free ~-hCG. Here we summarise the parameters of the distributions of the markers in affected and unaffected pregnancies, and in affected pregnancies we calculate the' standard deviation for the free ~-hCG and the correlation between free i3-hCG and AFP and between free ~-hCG and uE3.We then estimate the detection rates and false positive rates. The parameters of the distribution of all four markers in unaffected pregnancies have been published. In trisomy 18 pregnancies: (a) the parameters for AFP, uE3, and total hCG were taken from reference 2; (b) the median free ~-hCG was taken from reference 3; (c) the standard deviation for free ~-hCG was calculated by taking the difference in variance between trisomy 18 and unaffected pregnancies from reference 3 and adding this to the unaffected variance from reference 4; (d) the correlation between AFP and free ~-hCG was calculated by taking the difference in covariance between trisomy 18 and unaffected pregnancies obtained from reference 3, adding this to the unaffected covariance from reference 4 and then dividing by the standard deviations in (a) and (c); (e) there is no available correlation between uE3 and free ~-hCG and so it is assumed to be the same as in unaffected pregnancies. The truncation limits (that is, the range over which the distributions are Gaussian) for AFP, uE3, and total hCG were taken from reference 2. The limits for free i3-hCG are not yet known and are therefore assumed to be the same as for total hCG because of the high correlation between these two markers. Table 1 shows the parameters for the serum markers in the detection of trisomy 18. As in Down's syndrome pregnancies, trisomy 18 pregnancies tend to have low values for AFP and uE3, but unlike Down's pregnancies they have low levels of total hCG and free ~-hCG. Table 2 shows the detection rates, false positive rates, and odds of being affected given a positive result (OAPR) when using maternal age (England and Wales, 1984-88), AFP, uE3, and either total hCG or free ~-hCG. The birth prevalence of trisomy 18 is taken as one tenth that of Down's syndrome' with a spontaneous fetal loss rate of 70% between 16 weeks and term. A mid-trimester risk cut off of 1 in 100 with AFP, uE3, and total hCG in combination with maternal age yields a detection rate of 59% and a false positive rate of 0·19%. The OAPR at term is 1:23. With a 1% fetal loss rate due to amniocentesis there would be 0·23 unaffected fetal losses for every term pregnancy