title: 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.
authors.affiliation: Duncan Guthrie Institute of Medical Genetics, Yorkhill Hospital, Glasgow, U.K.
authors.forename: E
authors.initials: E
authors.lastname: Berry
authors.forename: D A
authors.initials: DA
authors.lastname: Aitken
authors.forename: J A
authors.initials: JA
authors.lastname: Crossley
authors.forename: J N
authors.initials: JN
authors.lastname: Macri
authors.forename: J M
authors.initials: JM
authors.lastname: Connor
mesh_terms: D000033:Abortion, Threatened / Q000097:blood; D000328:Adult; D001835:Body Weight; D006063:Chorionic Gonadotropin / Q000097:blood*; D018997:Chorionic Gonadotropin, beta Subunit, Human; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D005865:Gestational Age; D006801:Humans; D010446:Peptide Fragments / Q000097:blood*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012044:Regression Analysis; D014427:Twins; D016216:Ultrasonography, Prenatal; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D010446:Peptide Fragments; D000509:alpha-Fetoproteins