Analysis of maternal serum alpha‐fetoprotein and free beta human chorionic gonadotrophin in the first trimester: Implications for down's syndrome screening

Abstract

The aim of this study was to determine the maternal population, pregnancy, serum alpha-fetoprotein (AFP) and free beta subunit of human chorionic gonadotrophin (F beta hCG) parameters in a large series of women attending prenatal clinics before 15 weeks' gestation and to assess the practical problems of population screening for Down's syndrome in the first trimester using these markers. Serum samples were collected from 8600 women attending prenatal clinic booking visits. Maternal serum AFP and F beta hCG medians were calculated for each day of gestation (49-104 days), using both dates and ultrasound estimates of gestation. The effects of maternal weight, twin pregnancies, and threatened abortion on AFP and F beta hCG levels were analysed. The median age of the population was 27.1 years and the median weight 62.1 kg. Twenty-six per cent of samples were collected before 70 days and 50 per cent before 78 days' gestation. Eighty-nine per cent of all samples had gestational estimates by dates, 60 per cent by ultrasound and 52 per cent by both dates and ultrasound. The AFP median was 5 kU/l at 49 days, 5.9 kU/l at 70 days, and 17.9 kU/l at 100 days. The peak median F beta hCG level was 66.4 ng/ml at 64 days, falling to 20.6 ng/ml at 100 days' gestation. Both AFP and F beta hCG levels showed log Gaussian distributions but the standard deviation for AFP was 20 per cent greater than that found in the second trimester. AFP and F beta hCG levels showed an inverse relationship with maternal weight and were increased in twin pregnancies (1.68 and 1.97 multiples of the median, respectively). AFP and F beta hCG can be readily measured in a large screening population in the first trimester. Down's syndrome screening protocols based on these markers could be refined by the use of gestations in individual days but AFP is likely to be a less effective marker and detection rates are likely to be lower than in the second trimester. To realize the potential of first-trimester screening, more women should be encouraged to attend the prenatal clinic in early pregnancy and ultrasound dating should be carried out for all pregnancies at this stage.

Screening for trisomy 21 in twin pregnancies in the first trimester using free ?-hCG and PAPP-A, combined with fetal nuchal translucency thickness

“…What data there are suggests that free b-hCG may be elevated to about twice normal. Berry et al (1995) showed median levels of 1.97 MoM in 50 sets of twins and Noble et al (1997) similarly found median levels of 1.94 MoM in 136 sets of twins. Brambati et al (1997) also showed a median of 1.94 in 35 dichorionic and 4 monochorionic twin pregnancies.…”

FIRST-TRIMESTER URINE FREE BETA hCG, BETA CORE, AND TOTAL OESTRIOL IN PREGNANCIES AFFECTED BY DOWN'S SYNDROME: IMPLICATIONS FOR FIRST-TRIMESTER SCREENING WITH NUCHAL TRANSLUCENCY AND SERUM FREE BETA hCG

“…We used the measured population parameters for the urine markers, published normal parameters for serum free beta hCG (Berry et al, 1995) with data for Down's pregnancies ascertained from a meta analysis (Cuckle, 1996) of 340 cases from the world's literature (unpublished data, Spencer, 1996), and data on nuchal translucency from the combined King's College studies (unpublished data, Nicolaides et al, 1996). Using these population parameters, a series of random MOM values or delta nuchal translucency values (Pandya et al, 1995) were selected from within the distributions of the affected and unaffected populations for each analyte.…”

Simultaneous Determination of α-Fetoprotein and Free β-Human Chorionic Gonadotropin by Element-Tagged Immunoassay with Detection by Inductively Coupled Plasma Mass Spectrometry

“…␣-Fetoprotein (AFP) and ␤-human chorionic gonadotropin (hCG␤) are important tumor markers and also serve as aids in prenatal detection of fetal malformations (25)(26)(27)(28). Numerous immunologic methods for determining AFP and hCG␤ concentrations have been described (29 -35 ), but few methods other than time-resolved immunofluorometric assays and enzyme immunoassays can measure them simultaneously (28,36,37 The coating buffer was 100 mmol/L sodium carbonate buffer (pH 9.5) containing 9 g/L NaCl and 0.…”