Serum measurements of pregnancy‐associated plasma protein A (PAPP‐A) and the free β‐human chorionic gonadotrophin (hCG) subunit were made in 13 women with Down syndrome (DS) pregnancies and six other women with fetal aneuploidy ascertained at chorionic villus sampling (CVS), as well as 89 women with contemporaneous normal control pregnancies. Median serum PAPP‐A measurements (0·31 MOM, 95 per cent confidence interval (CI) 0·22–0·65 vs. normal 1·06, 95 per cent CI 0·89–1·20) were lower and free β‐hCG subunit measurements (1·13 MOM, 95 per cent CI 0·93–2·63 vs. normal 0·91, 95 per cent CI 0·79–1·03) were higher at statistically significant levels. Receiver operator characteristic (ROC) curves showed that the highest sensitivity for detection, 71·2 per cent (95 per cent CI 54·7–87·6 per cent), was for depressed PAPP‐A levels; the combination of low serum PAPP‐A levels, maternal age, and elevated free β‐hCG levels yielded a detection rate of 78·9 per cent (95 per cent CI 64·9–92·8 per cent) of the affected pregnancies at 8–12 weeks' gestation.

Objective To assess the relation between maternal serum pregnancy associated plasma protein A (PAPP-A) in the first trimester and the outcome of pregnancy by karyotype.Design A retrospective study of PAPP-A levels in blood samples collected prior to chorionic villus sampling.Setting Milan, Italy.Subjects Five hundred twenty-two women, aged 20 to 47, at 7 to 11 weeks gestation, prior to undergoing chorionic villus sampling. Four hundred forty-five women had a pregnancy with a normal karyotype; in 30 pregnancies the karyotype was abnormal (including 14 cases of Down's syndrome and 7 of trisomy 18).Main outcome measures Normal or abnormal fetal karyotype. Serum PAPP-A at 6 to 11 weeks gestation measured by radioimmunoassay.Results The median value of PAPP-A in the abnormal group was 0.27 multiples of the normal median (MoM). This is significantly lower than the median value in the normal group (1.01 MoM) (95% CI for the difference 0.46-0.84 MoM; P<0.00001 Mann-Whitney test).Conclusions There is an association between low levels of PAPP-A in the first trimester with chromosome anomalies. Screening by measurement of PAPP-A might detect 60% of cases of Down's syndrome in the first trimester with a false positive rate of 5%.

Low maternal serum α-fetoprotein values during the second trimester of pregnancy are associated with an increased risk of Down syndrome in the fetus. In this study a sensitive, monoclonal-based radioimmunoassay for α-fetoprotein was used to determine whether such an association also applies to the first trimester and if maternal serum α-fetoprotein screening could successfully detect a significant number of pregnancies in which the fetus had a trisomy or other chromosome disorder. Sera were obtained prospectively from 540 women just before chorionic villus sampling for prenatal diagnosis of chromosome defects (largely because of advanced maternal age) at 8 to 12 weeks' fetal age and assayed for α-fetoprotein under code without knowledge of the cytogenetic results. Eight of 27 (29.6%) of all serious chromosome defects were associated with low maternal serum α-fetoprotein values (≤0.6 multiples of the median). Overall, 59 of 540 patients (10.9%) had maternal serum α-fetoprotein values ≤0.6 multiples of the median, eight of whom had a fetus with a serious chromosome defect. Women whose maternal serum α-fetoprotein value was ≤0.6 multiples of the median had one in eight odds of carrying a fetus with a trisomy and one in seven odds of the fetus having any serious chromsome defect. From this study of a group of women at higher risk, we conclude that first-trimester maternal serum α-fetoprotein screening for chromsome defects is feasible. A prospective study to determine detection efficiency is now required of a consecutive routine pregnancy population in whom gestational age is determined by menstrual dates as is usually the case in clinical practice

Feto-maternal transfusion following chorionic villus sampling (CVS) in the first trimester of pregnancy was evaluated by alpha-fetoprotein (AFP) level determination in maternal serum before and after sampling. Some fetal haemorrhage was suggested in 72% of 283 continuing pregnancies by a significant increase of maternal AFP level. Fetal bleeding appeared to stop a short time after CVS, and did not complicate detection of neural tube defects (NTDs) in the second trimester. The change in the maternal serum AFP level was correlated with the size of the chorionic tissue specimen, but no association was observed between fetal and neonatal outcome. The risk of maternal rhesus (Rh) iso-immunization must be taken into account, and anti-D immunoglobulin administrated after CVS. Maternal Rh immunization should be considered as a contraindication to CVS.