Antenatal reflex DNA screening for Down’s syndrome using total instead of free B-hCG in the Combined test

Our recently reported estimates of the performance of antenatal reflex DNA screening for Down’s syndrome ¹ were based on reflexing a proportion of women to DNA screening according to their risk of having an affected pregnancy using a first trimester Combined test (free β-human chorionic gonatrophin [hCG], pregnancy associated plasma protein-A, and nuchal translucency with maternal age). We have been asked (private communication) for corresponding estimates using total instead of free β-hCG in the Combined test. Table 1 shows detection and false-positive rates according to the proportion of women reflexed, together with the first trimester risk cut-off required to achieve the specified reflexing proportions according to the week of pregnancy (11, 12, or 13 completed weeks). Table 2 shows, for measurements at 11, 12, and 13 weeks of pregnancy, the reflexing proportion according to the Combined test risk cut-off. The results are similar to those using free β-hCG in the Combined test. ¹ At a 10% reflexing proportion and with Combined test markers measured at 11 completed weeks’ gestation, the detection rate is 89.9% instead of 90.8%, and the false-positive rate unchanged (0.025%).

Table 1.

Reflex DNA screening linked to the Combined test using total instead of free β-hCG: Detection rate and false-positive rate and first trimester test risk cut-off according to proportion of women reflexed to DNA testing (with risk cut-off specified) and completed week of gestation (DNA test failures have Integrated test using a risk cut-off 1 in 25).

Women	11 completed weeks			12 completed weeks			13 completed weeks
reflexed (%)	Risk cut-off 1 in:	DR (%)	FPR (%)	Risk cut-off 1 in:	DR (%)	FPR (%)	Risk cut-off 1 in:	DR (%)	FPR (%)
1	62	72.8	0.005	65	72.7	0.005	60	70.4	0.006
2	123	78.5	0.009	127	78.0	0.009	118	76.4	0.009
3	188	81.6	0.011	194	81.0	0.012	180	79.9	0.012
4	256	83.7	0.013	262	83.1	0.014	244	82.3	0.014
5	327	85.3	0.015	335	84.8	0.015	312	84.0	0.015
6	402	86.6	0.018	409	86.0	0.019	383	85.4	0.018
7	482	87.6	0.019	488	87.1	0.019	459	86.6	0.021
8	566	88.5	0.023	571	88.0	0.022	539	87.6	0.023
9	653	89.3	0.024	657	88.7	0.024	621	88.5	0.025
10	744	89.9	0.025	747	89.4	0.026	708	89.2	0.027
15	1257	92.2	0.036	1250	91.8	0.036	1205	91.8	0.036
20	1868	93.7	0.046	1851	93.4	0.046	1812	93.4	0.046
25	2602	94.7	0.056	2568	94.4	0.056	2547	94.6	0.057
30	3470	95.4	0.065	3411	95.2	0.065	3438	95.4	0.065
35	4487	96.0	0.075	4407	95.8	0.076	4520	96.0	0.076
40	5692	96.5	0.085	5587	96.3	0.085	5816	96.4	0.085
45	7105	96.8	0.095	6973	96.7	0.095	7378	96.8	0.094
50	8790	97.1	0.103	8629	97.0	0.105	9291	97.1	0.105
60	13237	97.5	0.123	13018	97.5	0.123	14532	97.5	0.125
70	19862	97.8	0.144	19686	97.8	0.144	22953	97.8	0.144
80	30685	98.0	0.164	30835	98.0	0.162	38180	98.0	0.163
90	52462	98.1	0.182	54109	98.1	0.182	73610	98.0	0.183
99	136890	98.1	0.200	160169	98.1	0.201	284511	98.1	0.201

Table 2.

Reflexing proportion according to first trimester risk cut-off using the Combined test with total instead of free β-hCG and according to week of pregnancy.

Risk cut-	Women reflexed (%)
off 1 in:	11 weeks	12 weeks	13 weeks
100	1.6	1.6	1.7
200	3.2	3.1	3.3
300	4.6	4.5	4.8
400	6.0	5.9	6.2
500	7.2	7.1	7.5
600	8.4	8.3	8.7
700	9.5	9.5	9.9
800	10.6	10.6	11.0
900	11.6	11.6	12.1
1000	12.6	12.6	13.1
1100	13.6	13.6	14.0
1200	14.5	14.5	15.0
1300	15.4	15.4	15.9
1400	16.3	16.3	16.7
1500	17.1	17.2	17.6
1600	17.9	18.0	18.4
1700	18.7	18.8	19.2
1800	19.5	19.6	19.9
1900	20.2	20.4	20.7
2000	21.0	21.1	21.4