[Quick prenatal diagnosis using FISH in the analysis of non-cultured amniotic fluid cells]. / Recours au diagnostic prénatal rapide par l'analyse FISH des cellules du liquide amniotique non cultivées.

We report our experience with fluorescence in situ hybridization (FISH) on uncultured amniocytes and standard cytogenetic analysis. The method have been suggested to 259 patients and performed for 199 amniotic fluid samples. Commercially available chromosome-specific DNA probes (Aneurysm) for chromosomes 13, 18, 21, X and Y were used. All full trisomy 18, 21 and monosomy X were detected by FISH analysis with exception of one case of mosaic monosomy X. No false-positive result was observed. The efficiency, practicability and acceptability of the FISH diagnosis are discussed.

Second-trimester maternal serum screening for Down's syndrome: free beta-human chorionic gonadotrophin (HCG) and alpha-fetoprotein, with or without unconjugated oestriol, compared with total HCG, alpha-fetoprotein and unconjugated oestriol.

The aim of our study was to compare three protocols for second-trimester maternal serum screening for Down's syndrome in the same serum samples, using two triple tests [total human chorionic gonadotrophin (HCG), alpha-fetoprotein, unconjugated oestriol; and free beta-HCG, alpha-fetoprotein, unconjugated oestriol] and a double test (free beta-HCG and alpha-fetoprotein). The three protocols were compared in a series of 23 serum samples from Down's syndrome pregnancies and in a cohort of 2516 pregnant women receiving routine antenatal care between June 1992 and June 1993. Among the 23 affected cases, at a cut-off risk of 1:380, the detection rate of Down's syndrome was comparable with the double test (74%; 17/23) and the triple tests (65%; 15/23) (not significantly different). At the same cut-off risk, in the cohort of 2516 pregnant women screened between 15 and 18 weeks gestation, both protocols using free beta-HCG achieved a significant reduction of the number of false positive cases (P = 0.013 and 0.004 for double and triple tests respectively). We conclude that, compared to total HCG, alpha-fetoprotein and unconjugated oestriol, use of free beta-HCG and alpha-fetoprotein represents a better second-trimester screening test for Down's syndrome, because it significantly decreases the false positive rate at a lower running cost. The addition of unconjugated oestriol to the double test adds no further advantage.

Pregnancy-associated plasma protein A (PAPP-A): measurement by highly sensitive and specific enzyme immunoassay, importance of first-trimester serum determinations, and stability studies.

It has recently been established that maternal serum pregnancy-associated plasma protein A (PAPP-A) was reduced in pregnancies with fetal Down syndrome in the first but not in the second trimester of gestation. In comparison with two other placental proteins, human chorionic gonadotrophin and pregnancy-specific beta 1-glycoprotein, an explanation for this can be formulated based on the large molecular weight of PAPP-A. With the increasing clinical demand for fetal abnormalities to be diagnosed in the first rather than in the second trimester of pregnancy, maternal serum PAPP-A is a strong potential candidate for being used in routine trisomy screening. We have developed a sensitive enzyme immunoassay (ELISA) intended at smaller laboratories due to its long shelf life. Here we show that repeated freezing and thawing, or the addition of iodoacetate (5 mM) did not affect the results, at both high or low concentration of PAPP-A. It is also possible to introduce the serum into the test as a dry sample on blotting paper, easily posted in an envelope. A decrease of 21% was observed after such dry storage for three weeks at room temperature, which can be compensated for by the inclusion of a dried control serum, mailed with the sample(s).

[Thoracopagus fetus. Ultrasonic diagnosis at 16 weeks]. / Foetus thoracopages. Diagnostic échographique à 16 semaines.

This paper reports the ultrasound diagnosis at 16 weeks' gestation of thoracopagus conjoined twins. Ultrasound examination showed the two fetuses conjoined at the sternum, with a single heart and a single liver. After informing the couple of the extremely poor prognosis, medical termination of pregnancy was requested. Pathologic examination of the conjoined female fetuses revealed a single, non-duplicated heart, two livers connected at the right lobe, completely separate bile ducts and digestive tract, and a single placenta and umbilical cord containing two arteries and six veins. The karyotype was normal. Diagnostic ultrasound criteria for thoracopagus conjoined twins include: the relative position of the two fetuses facing each other, hyperextension of the cervical spine, continuity of the skin and mirror image body parts with limbs close together. The presence of a single heart, liver and umbilical cord, all of increased size, confirms the diagnosis. Various degrees of fetal fusion result from incomplete division of the inner cell mass 13 to 15 days after fertilization. Although the precise causes are unknown, many workers believe that the factors responsible for monozygosity may also play a role in conjoined twins. In Switzerland, 1% of all live births are twins with approximately 1/4 of these monozygotic. If incomplete division of the inner cell mass occurs in 1% of these cases, the estimated incidence of conjoined twins is 1/40000 births. Although thoracopagus twins are more frequent, omphalopagus twins are more commonly encountered at birth, due to lower fetal mortality. The overall prognosis depends on the degree of organ sharing between fetuses. Very few surgically separated thoracopagus conjoined twins have lived and those who did survive had separate hearts. Also, conjoined twins can cause dystocia with the risk of rupture of the uterus, and often require cesarean section which may have negative consequences for the obstetrical future of the mother. However, an early ultrasound diagnostic can modify prognosis and allow medical termination of pregnancy in the case of seriously malformed thoracopagus conjoined twins. The risk that the condition recurs in a subsequent pregnancy may be considered negligible.

Cytogenetic analysis of 570 first trimester chorionic villi samplings: technique and results.

In this report we present our experience based on 570 chorionic villi samplings performed by the transcervical method at 8 to 12 weeks gestation. Cytogenetic results were obtained for 551 samples, hence a failure rate of 3.33%. The previously described technique was modified by prolonging the incubation period to 48 hours. The total number of abnormalities was 26, which represents 4.71% of our sample. Of 24 chromosomal abnormalities, 21 were unbalanced and 3 were balanced of parental origin. Five discordant cases are thoroughly discussed.

[Interlaboratory variation in the prenatal screening test for neural tube closing defects]. / Etude de la variation interlaboratoire du test de dépistage prénatal des défauts de fermeture du tube neural.

Early detection of neural-tude defects is possible by determining Alpha-fetoprotein (AFP) in maternal serum. 16'685 pregnant women were observed. Three methods for the determination of the "normal" range are compared. The first one, already used in similar studies, makes use of a constant multiple of the median. The other two ones make use of robust estimates of location and scale. Their comparison shows the interest of the robust methods to reduce the interlaboratory variability.