Prenatal diagnosis of the Rhesus D fetal blood type on amniotic fluid in daily practice.

OBJECTIVE: To retrospectively examine the diagnostic accuracy of prenatal RhD blood type genotyping on amniotic fluid, using a combination of two polymerase chain reaction (PCR) methods in daily practice. METHODS: Amniotic fluid was obtained from women undergoing amniocentesis. Two PCR protocols were carried out in two different laboratories. We obtained the postnatal serological RhD status. In cases with differing prenatal and postnatal test results, we investigated the possible error source by different methods. Sensitivity, specificity and the predictive values were calculated. RESULTS: Prenatal RhD genotyping was applied in 1,640 cases, of which the postnatal serologic RhD status was obtained in 927. No discordance between both PCR methods occurred. In nine out of 927 cases differing results between PCR and serologic status were encountered. The sensitivity was 99.5%, the specificity 98.6%, and both positive and negative predictive values 99.1%. CONCLUSION: Prenatal diagnosis of the fetal RhD blood type with PCR from amniotic fluid is highly accurate in daily practice and associated with a minimal sensitivity of 99.5% and a minimal specificity of 98.6%.

Screening for trisomy 21 with maternal age, fetal nuchal translucency and maternal serum biochemistry at 11-14 weeks: a regional experience from Germany.

OBJECTIVE: To examine the efficacy of first trimester screening for trisomy 21 using a combination of maternal age, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotropin (free beta-hCG) and pregnancy-associated plasma protein A (PAPP-A) in a regional setting [maternity unit of the Women's University Hospital, Hannover Medical School (study center); two regional private centers for prenatal diagnosis and human genetics; laboratory for prenatal diagnosis and human genetics]. METHODS: Fetal NT, crown-rump length, maternal serum free beta-hCG and PAPP-A were measured at 11-14 weeks of gestation. Risk calculation was carried out using the FMF computer algorithm. The patients were informed and counseled about possible invasive test options if the risk was 1 in 300 or greater. Fetal outcome was obtained by questionnaires given to the patients or sent to their gynecologists. The detection and false-positive rates for the different screening strategies were calculated. RESULTS: Pregnancy outcome was obtained in 2,497 cases, of which 2,196 cases had completed first trimester screening with NT and maternal serum biochemistry and 301 additional cases had NT measurement only. The median age was 32.5 years. In our population 11 affected fetuses were found. The estimated risk for trisomy 21 was 1 in 300 or greater in 64, 82, 88 and 88% of affected fetuses using maternal age alone, in combination with nuchal translucency, with maternal serum biochemical markers or with both NT and biochemical markers for a false-positive rate of 28.2, 5.1, 15.3 and 4.0%. CONCLUSIONS: First trimester screening using maternal age, NT, free beta-hCG and PAPP-A is highly effective for the detection of trisomy 21 and is associated with a sensitivity of about 90% for 5% false-positive patients.

[Small deletion--large effect]. / Kleine Deletion--grosse Auswirkung.

Velocardiofacial syndrome (VCFS) or Shprintzen's syndrome leads to cleft palate (69%), heart defects (74%), and characteristic facial dysmorphies as well as learning difficulties (70-90%). There is phenotypic overlap with DiGeorge syndrome (DGA). In 1992, it was shown that patients with VCFS had a partial 22q11 monosomy. The site and size of the deletion in many VCFS patients do not differ from patients with DGS. For the otolaryngologist, it is important to check for cardiac defects if the characteristic middle ear effects and possibly submucosal cleft palate are present. If a combination of these exist, it is advisable to carry out a genetic examination of the child in order to determine whether VCFS is present or not. This is the only way of providing an early diagnosis of this syndrome.

Screening for trisomy 21 by maternal age, fetal nuchal translucency and maternal serum biochemistry at 11-14 weeks: a German multicenter study.

OBJECTIVE: To examine the effectiveness of screening for trisomy 21 by a combination of maternal age, fetal nuchal translucency (NT) thickness and maternal serum biochemistry using free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks of gestation. METHODS: This was a multicenter study of screening for trisomy 21 by a combination of maternal age, fetal NT and maternal serum free beta-hCG and PAPP-A at 11-14 weeks of gestation, using the methodology developed by the Fetal Medicine Foundation. The distribution of estimated risks for trisomy 21 was determined and the sensitivity and false-positive rate for a risk cut-off of 1 in 300 were calculated. RESULTS: In total, 3864 singleton pregnancies with live fetuses at 11-14 weeks were examined and the fetal NT and maternal serum free beta-hCG and PAPP-A were successfully measured in all cases. The median maternal age was 33 (range 15-46) years and, in 1271 (35.8%), the age was 35 years or more, the median gestation at screening was 12 (11-14) weeks and the median fetal crown-rump length was 64 (range 45-84) mm. The fetal NT was above the 95th centile in 73.7% (14 of 19) of trisomy 21 and in 4.8% (169 of 3505) of normal pregnancies. The estimated risk for trisomy 21 based on maternal age, fetal NT and maternal serum free beta-hCG and PAPP-A was 1 in 300 or greater in 6.6% (233 of 3505) of normal pregnancies, in 84.2% (16 of 19) of those with trisomy 21 and 88.9% (24 of 27) of those with other chromosomal defects. CONCLUSIONS: In Germany, the results of screening for chromosomal defects by measurement of fetal NT and maternal serum biochemistry, in centers with appropriately qualified sonographers, are similar to those reported in the UK using the same methodology.

Complete karyotype discrepancy between placental and fetal cells in a case of ring chromosome 18.

A case of complete karyotype discrepancy between cultured chorionic villi and amniotic in addition to fetal cells is reported. Ring chromosome 18 and monosomy 18 mosaicism was detected after amniocentesis. The pregnancy was terminated in the 23rd gestational week. Cytogenetic analysis of cultured umbilical cord tissue after termination confirmed the finding of ring chromosome 18/monosomy 18 mosaicism. In cultured umbilical blood lymphocytes monosomic cells 45,-18 were not detected and the karyotype was 46,XY,r(18). In contrast, short-term and long-term cultured chorionic villi showed a normal male karyotype of 46,XY. Ultrasonographic examination revealed amniotic band syndrome and scoliosis in the caudal region of the spine.

Screening for trisomy 21 by fetal nuchal translucency and maternal age: a multicenter project in Germany, Austria and Switzerland.

OBJECTIVE: To examine the effectiveness of screening for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation in Germany, Austria and Switzerland. METHODS: This was a multicenter study of screening for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation. All the sonographers involved in the study had received The Fetal Medicine Foundation Certificate of Competence in the 10-14-week scan. Fetal nuchal translucency thickness and crown-rump length were measured in 23 805 singleton pregnancies with live fetuses. In each case the risk for trisomy 21 was estimated on the basis of maternal age and fetal nuchal translucency thickness for crown-rump length with the use of The Fetal Medicine Foundation's software. The distribution of estimated risk was determined and the sensitivity and false-positive rate for a risk cut-off of 1 in 300 was calculated. RESULTS: Fetal nuchal translucency thickness was successfully measured in all 23 805 pregnancies and outcome was available in 21 959. The median maternal age was 33 (range 15-49) years and in 7935 (36.1%) the age was 35 years or greater. The median gestation at screening was 12 (10-14) weeks and the median fetal crown-rump length was 61 (range 38-84) mm. The estimated risk for trisomy 21 based on maternal age and fetal nuchal translucency thickness for crown-rump length was 1 in 300 or greater in 13.0% (2800 of 21 475) normal pregnancies, in 87.6% (184 of 210) of those with trisomy 21 and in 87.2% (239 of 274) with other chromosomal defects. CONCLUSIONS: In Germany, Austria and Switzerland the results of screening for chromosomal defects by measurement of fetal nuchal translucency thickness, in centers with appropriately qualified sonographers and using The Fetal Medicine Foundation's software, are similar to those reported in the UK using the same methodology.

Rapid prenatal diagnosis of aneuploidies in uncultured amniocytes by fluorescence in situ hybridization. Evaluation of >3,000 cases.

OBJECTIVE: A new method in prenatal diagnostics allows to demonstrate certain numeric chromosomal aneuploidies in amniotic cells within 24 h in contrast to conventional methods which take 1-3 weeks. MATERIALS: The experience with this rapid fluorescence in situ hybridization (FISH) method is compared to standard karyotyping and its clinical relevance is described in a large clinical pilot study. FISH on uncultured amniocytes has been performed from 12 weeks of gestation to the third trimester using commercially available chromosome-specific DNA probes for chromosomes 13, 18, 21, X and Y. RESULTS: FISH was performed successfully in 3,150 prenatal cases. All trisomies 13, 18 and 21 and all cases with gonosomal aberrations were detected by FISH analysis. Neither false-positive nor false-negative results were obtained using FISH. For all analyzable disorders the FISH results were in complete agreement with standard cytogenetics. CONCLUSIONS: In our experience, FISH is a valuable and reliable method for rapid diagnosis of numeric chromosomal aneuploidies.

Trisomy 13 (Patau syndrome) with an 11-year survival.

Trisomy 13 is very rare in live-born children. Only a small number of these children survive the first year and very few cases are reported to live longer. Survival time depends partly on the cytogenetic findings--full trisomy 13 or trisomy 13 mosaicism--and partly on the existence of serious somatic malformations. We report on a 11-year-old girl with full trisomy 13. In this case, missing cerebral and cardiovascular malformations probably allowed the long survival.

Factor XII (Hageman) deficiency in women with habitual abortion: new subpopulation of recurrent aborters?

OBJECTIVE: To examine the possible association between factor XII (FXII) deficiency and an elevated number of abortions. DESIGN: Factor XII activity, FXII antigen concentration, other blood clotting parameters, and phospholipid antibodies were examined in venous blood from 43 women with repeated (3 to 7) abortions before the 28th week of gestation but without gynecological and chromosomal abnormalities. The data were compared with those obtained from 49 age-matched women without fetal loss. RESULTS: Eight cases with moderately reduced FXII activity (35% to 68% of normal) could be identified in the abortion group, whereas among controls no abnormalities in FXII activity and antigen concentration were found. The relative occurrence of reduced FXII level was higher among patients with more than three abortions as compared with those with three abortions. CONCLUSION: Repeated abortions may be associated with reduced level of FXII activity of unknown origin.

Genetic amniocentesis in twin pregnancies: results of a multicenter study of 529 cases.

To evaluate the risk of abortion after genetic amniocentesis in twin pregnancies, a retrospective study of 15 centers was performed. The spontaneous abortion rate up to 20 completed weeks of gestation was 2.3%; the abortion rate up to 28 completed weeks, as defined by WHO, was 3.7%. The abortion rate could not be correlated either with the number of needle insertions or with the type of marker dye used. There was also no correlation between the abortion rate and the gestational age at which amniocentesis was performed. A significant association was shown between congenital intestinal obstructions and the application of methylene blue intra-amniotically as a marker dye. Considering the increased natural loss rate in multiple gestations, amniocentesis in twin pregnancies seems to be a safe and reliable technique.

Incidence of abortion after genetic amniocentesis in twin pregnancies.

Fetal outcome after genetic amniocentesis (AC) in viable twin pregnancies was analysed in a retrospective study at three centres in order to estimate the rate of fetal loss after AC. The maternal age ranged from 33 to 45 years (mean 36.7 years). The gestational age varied between 15 and 20 weeks of gestation (mean 17.1). In 98 viable twin pregnancies with complete follow-up, spontaneous abortion of both fetuses occurred within 28 completed weeks of gestation in eight pregnancies and six women aborted within 20 completed weeks of gestation after AC, corresponding to a rate of fetal loss of 8.1 and 6.1 per cent, respectively (excluding the loss of five twins with viable outcome of the co-twin in five pregnancies).

[Risk of abortion following genetic amniocentesis in the 2d trimester in twin pregnancies]. / Abortrisiko nach genetischer Amniozentese im II. Trimenon bei Zwillingsschwangerschaften.

Though the risk of abortion after amniocentesis in singleton pregnancies is well known, that for twin pregnancies is still unclear. A retrospective study was performed during December 1985 to May 1989 on all twin pregnancies that had undergone an amniocentesis, because of advanced maternal age. Out of the 33 patients aged greater than or equal to 35 years with viable and sonographically normal foetuses at the time of amniocentesis, three aborted spontaneously within 28 weeks of gestation, representing a risk of abortion after amniocentesis of 9.1%; using a cut-off at 20 weeks of gestation, only two patients aborted, giving a risk figure of 6.1%. This is 3.6 times higher than in singleton pregnancies (1.7%). However, to evaluate the procedure-related risk of amniocentesis, the age-dependent spontaneous abortion risk in twin pregnancies has to be considered. Accepting a spontaneous abortion risk of 4.5% after 16 weeks of gestation we have to calculate an amniocentesis-dependent risk of 1.6% up to the 20th week of gestation. It is essential, that the obviously higher genetic risk in twin pregnancies and the risk of procedure should be discussed carefully, before a patient with a twin pregnancy is advised to undergo genetic amniocentesis.

Prenatal diagnosis and postnatal follow-up of a child with two de novo unrelated balanced reciprocal translocations.

Two unrelated, apparently balanced, reciprocal translocations involving chromosomes 3 and 17, and 10 and 15 were found in cultured amniotic fluid cells from a 41-year-old 10-gravida. Chromosome analysis of peripheral blood lymphocytes of both parents revealed normal karyotypes. Post-partum examination of lymphocyte cultures from the proband confirmed the chromosome rearrangements. The child showed normal development during follow-up examinations up to the age of 4 years.

[Fetal kidney screening: growth curves and indices]. / Fetales Nieren-Screening: Wachstumskurven und Indizes.

Kidney size was measured ultrasonographically in a cross-sectional study of 612 foetuses. Values of the length (Nlgs), width (Nqu), thickness (Nap) as well as cross-sectional area (Nqu-Fl) of the kidney were calculated by statistical means and correlated to gestational age. Because of the great biological variance, the ratio of kidney length and width to the thorax width and the ratio of kidney area to the thorax area, was calculated and the standard deviation was found to be very small. The ratios for growth-retarded and macrosomic foetuses from diabetic mothers were examined. The results are discussed and the syndromes, which is often associated with renal abnormality are tabulated.