Second‐trimester maternal serum screening using alpha‐fetoprotein, human chorionic gonadotrophin, and unconjugated oestriol: Experience of a regional programme

Abstract

Over a 2-year period from January 1991 to December 1992, second-trimester maternal serum screening for Down's syndrome using alpha-fetoprotein (alpha FP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) was made available to five health districts in East Anglia, with a total population of 1.2 million. Amniocentesis was offered when the risk of Down's syndrome at term was 1:200 or greater. 25,359 singleton pregnancies were screened, representing an uptake of 77 per cent. The recall rate for the 24 per cent of women who had not had a dating scan prior to the test was 9.4 per cent compared with 3.9 per cent for those who had been scanned (P < 0.0005). Seventy-five per cent (36/48) of Down's syndrome pregnancies were detected for a false-positive rate of 4.0 per cent. Twenty-five out of 36 of detected Down's syndrome pregnancies were dated by scan prior to sampling, and in the 11 remaining cases, the dates were confirmed by scan after a high-risk result was obtained. The exclusion of uE3 from the screening protocol would have reduced the detection rate to 52 per cent (25/48) for the same false-positive rate. Eighty-five per cent of women identified at high risk accepted the offer of an amniocentesis. Other fetal abnormalities detected were trisomy 18 (3), trisomy 13 (2), 45,X (6), 69,XXX (5), other chromosome abnormalities (9), open neural tube defects (26), hydrocephalus (7), abdominal wall defects (4), and steroid sulphatase deficiency (6).

Utilization of Amniocentesis by Women Screening Positive for Down Syndrome on the Second-Trimester Triple Test

“…The widespread incorporation of screening for Down syndrome in prenatal care has been documented in a 1995 United States survey that showed that approximately 63% of pregnant women receive this screening [2]. Initial prospective studies that evaluated the performance of the triple test showed that 62–85% of women with screen-positive results underwent amniocentesis [7, 8, 9, 10, 11, 12]. The amniocentesis procedure carries an approximately 0.5% risk of fetal loss [13], which may be unacceptable to some women.…”

Unconjugated Estriol as Maternal Serum Marker for the Detection of Down Syndrome Pregnancies

“…We believe that the high median level of uE 3 obtained in our Down syndrome popula tion cannot be attributed to the use of frozen sera in our sample, as was commented by Goodburn et al [10], since estriol conjugates are very stable [17,18] and since their sponta neous hydrolysis in frozen sera is highly un likely.…”

“…Varying results have been reported. Wald et al [1] and Goodburn et al [10] showed a small improvement in the DR of Down syn drome with a corresponding decrease in the FP rate. MacDonald et al [3] showed an increase in the DR at the expense of an increase in the FP.…”

Age-Independent Indices in Second-Trimester Serum Screening for Down's Syndrome Are Useless

“…Risk calculation for Down's syndrome, based on maternal age in combination with the determination of alpha-fetoprotein (AFP), oestriol (uE3), and human chorionic gonadotropin (hCG), allows the detection of 65 per cent of all cases with trisomy 21 (Wald e t al., 1992; Haddow e t Phillips et al, 1992;Cheng et al, 1993;Goodburn et al, 1994). For given multiples of the median (MOM) for the three markers, however, the calculated risk is exclusively dependent on the maternal age.…”