Chorionic villi were obtained by an aspiration technique which proved to be the best of four alternative procedures. We report in detail the series of experiments which led to (1) successful, rapidly growing cell cultures practically free of maternal cell contamination (the use of hormone-supplemented Chang medium greatly increased the growth rate); (2) an efficient direct method to obtain high quality metaphases from the Langhans cells of the cytotrophoblast tissue and with which the fetal karyotype is defined within a few hours of chorionic villi sampling; and (3) successful testing for the activity of eight enzymes directly from the villi samples, thus showing that this material is suitable for a rapid, direct diagnosis of the related metabolic diseases.

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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%.

The value of the measurement of nuchal translucency thickness for predicting fetal Down's syndrome and other aneuploidies was prospectively evaluated at 8-15 weeks of gestation in 1819 consecutive pregnancies scheduled for karyotyping by chorionic villus sampling. In 43 cases, a chromosomal unbalanced aberration was found. Two teams of ultrasonologists who examined patients attending either National Health Service (Series 1) or private practice clinics (Series 2) were involved in the study. The same type of ultrasound machine and standardized approach were used in both study groups. In those cases in which the maximum subcutaneous thickness of the translucency was 3 mm or greater, the incidence of chromosomal aberration was 18.6% compared to 1.7% in the cases in which this was below 3 mm. The sensitivity, specificity and relative risk for all aneuploidies were 30%, 96% and 10.83, respectively, and no difference was found between trisomy 21 and other types of aneuploidy. The sensitivity and specificity and relative risk were significantly higher at 9-10 weeks than between 11 and 15 weeks. The results were concordant in the two series; however, the overall values for sensitivity (20% vs. 39%), specificity (94% vs. 98%) and relative risk (4.13 vs. 24.20) were clearly higher in the group of private patients. The results obtained confirm the potential application of the measurement of nuchal translucency thickness for fetal aneuploidy screening before the end of the first trimester and suggest that a multiplicity of individual, structural and organizational factors may interact and play a crucial role in determining the actual efficiency of ultrasound screening programs.