The objective of this study was to determined the influence of maternal wei
ght, maternal smoking habits, gravidity, parity and fetal gender on the lev
el of maternal serum marker used in first trimester screening for Down synd
rome. A total of 2449 singleton unaffected pregnancies from two centres wer
e studied. Maternal serum free beta-human chorionic gonadotrophin (hCG) and
alpha-fetoprotein (AFP) concentrations had been measured in all pregnancie
s, and pregnancy associated plasma protein (PAPP)-A levels had been measure
d in 924. All results were expressed as multiples of the gestation specific
median (MoM) values after regression, using each centre's own medians. Inf
ormation on maternal weight was available in 2259 pregnancies, on self-repo
rted current cigarette smoking in 1364 (of whom 117 (8.6%) were smokers), o
n gravidity in 1371, parity in 1303 and fetal gender in 253. All three mark
ers showed a statistically significant negative association with maternal w
eight (p < 0.0005) and in the subsequent analyses MoM values were weight ad
justed using standard methods. The median PAPP-A level in smokers was 0.81
MoM, a significant reduction (p < 0.005); free beta-hCG was also reduced (m
edian 0.89 MoM) but not significantly (p = 0.17), and AFP was unaltered. Th
e median AFP level in primagravidas was highly significantly greater than t
hat in gravid women (p < 0.0005). In PAPP-A the reverse effect was seen but
it did not reach statistical significance (p = 0.15) and there was no effe
ct for free beta-hCG. Results of a similar magnitude and direction were fou
nd for parity. The median level of free beta-hCG was higher ((I = 0.0005),
and the median AFP lower in female pregnancies. Maternal weight and, for PA
PP-A, maternal smoking are important first trimester screening co-variables
. Gravidity, parity and fetal gender also seem to influence one or moro fir
st trimester markers. Copyright (C) 2000 John Wiley & Sons, Ltd.