Jens Bang

Randomised controlled trial of genetic amniocentesis in 4606 low-risk women.

Outcome of pregnancy after amniocentesis was studied in a randomised controlled trial of 4606 women, age-range 25-34 years, without known risk of genetic disease. Spontaneous abortion rate was 1.7% in the study group after amniocentesis and 0.7% in the control group after ultrasound (relative risk 2.3). In the study group, increased levels of maternal serum alpha-fetoprotein before amniocentesis, perforation of the placenta during amniocentesis, and withdrawal of discoloured amniotic fluid were associated with an increased risk of spontaneous abortion. In the first six weeks after amniocentesis/ultrasound scan, amniotic fluid leakage occurred more often in the study group but there was no difference in the rate of vaginal bleeding. Frequency of postural malformations in the infants in the two groups was the same. In the study group, respiratory distress syndrome was diagnosed more often (relative risk 2.1) and more babies were treated for pneumonia (relative risk 2.5).

Feto-maternal haemorrhage associated with genetic amniocentesis: results of a randomized trial

Maternal serum alpha‐fetoprotein (AFP) levels were determined before and after genetic amniocentesis (n=283) or ultrasound scan (n=268) in a group of women participating in a randomized trial of genetic amniocentesis. Increases in AFP levels were seen significantly more often after amniocentesis than after ultrasound scan (P<0·001) and 48 women in the amniocentesis group had increases in AFP (ΔAFP) that were larger than the maximum ΔAFP (±25 μg/1) seen in the ultrasound group. If a ΔAFP of <25 μg/1 represents a feto‐maternal haemorrhage (FMH) attributable to amniocentesis, the rate of amniocentesis‐induced FMH was 17%. Such FMH was seen significantly more often after transplacental amniocentesis or after amniocentesis performed by less experienced operators. No association was detected between birthweight and FMH attributable to amniocentesis.

Naturally conceived twins with monochorionic placentation have the highest risk of fetal loss

The aim of this study was to estimate the rate of fetal loss in dichorionic (DC) and monochorionic (MC) twin pregnancies stratified according to zygosity and method of conception.

Prenatal karyotyping of twins by ultrasonically guided amniocentesis

Twins were diagnosed with ultrasound in two women who had been referred because of a higher than normal risk of having malformed children. Amniocentesis was carried out under the guidance of ultrasound and amniotic fluid from both fetuses was removed for diagnostic procedures. Injection of Congo red proved that the amniocentesis needle was not re-entering the same amniotic cavity at repeated puncture. In both mothers the fetuses were found to be of different sexes. Mixture of maternal cells was excluded by means of quinacrine staining, allowing evaluation of chromosome markers.

MULTISCAN ‐ A Scandinavian multicenter second trimester obstetric ultrasound and serum screening study

AIM To study the detection rates of second trimester ultrasound screening for neural tube defects (NTD), abdominal wall defects (AWD) and Downs syndrome (DS) in low risk populations at tertiary centers, and to compare the ultrasound screening detection rates with those that were obtainable by biochemical serum screening (double test: alpha-fetoprotein/human chorion gonadotrophin/age test). STUDY DESIGN Prospective multicenter study with a three year inclusion period: 1/1/1989-31/12/1991. SUBJECTS 27,844 low-risk women at 18-34 years of age who had a second trimester ultrasound screening examination. Of these, 10,264 also had a serum test. METHODS An ultrasound malformation scan and a serum test were carried out at 17-19 weeks of gestation. Risk calculations regarding DS were based on alpha-fetoprotein, human chorion gonadotrophin and maternal age; performed retrospectively for the first two years. RESULTS In total 73 cases were identified in the study population: NTD (n=34), AWD (n=7) and DS (n=32). The detection rates, (%, with 95% confidence interval) for ultrasound screening were: NTD: 79.4 (62.1-91.3); AWD: 85.7 (42.1-99.6); DS: 6.3 (0.8-20.8). In the subgroup of women who had both tests, the detection rates for ultrasound screening vs double test were: NTD: 62.5 (24.5-91.5) vs 75.0 (34.9-96.8); AWD: 66.7 (9.4-99.2) vs 100 (29.2-100.0); DS: 7.7 (0.2-36.0) vs 46.2 (19.2-74.9). The false positive rates (%) for ultrasound screening vs double test were: NTD: 0.01/3.3; AWD: 0.01/3.3; DS: 0.1/4.0. CONCLUSION Second trimester ultrasound screening in a low risk population gave a low detection rate for fetal DS (6.3%) and an acceptable detection rate for NTD (79.4%) and AWD (85.7%). In the subgroup of women who had both tests, serum screening performed better than ultrasound as applied in the present study, especially regarding DS.

MATERNAL‐SERUM‐ALPHAFETOPROTEIN SCREENING FOR FETAL MALFORMATIONS IN 28062 PREGNANCIES

Abstract. From 1st March, 1980 and up to 29th February 1984 a multicenter serum α‐fetoprotein (S‐AFP) screening project was carried out for the detection of severe fetal malformations. S‐AFP was determined by a radio‐immunoas‐say in 28062 pregnant women between the 16th and 20th week of gestation. Patients with elevated S‐AFP values, e.g. above 95 percentile, were examined further with a second S‐AFP and by ultrasound scan. 244 amniocenteses (0.9%) were carried out to detect 62 malformations (21 anen‐cephalies, 14 spina bifidas, 2 encephaloceles, 7 omphaloceles, 5 gastroschises, 4 chromosome abnormalities and 9 other malformations). Fifteen of the 16 cases of spina bifida could not be verified by ultrasound scan, whereas all other malformations except chromosome abnormalities were confirmed by ultrasonography. Two cases of spina bifida and one case of skin‐covered encephalocele had normal S‐AFP concentrations and were therefore not detected. There were no definitive false‐positives, e.g. therapeutic abortion of a normal fetus. Our conclusion is that a nationwide S‐AFP screening should be recommended.

Routine Examination by Ultrasound for the Detection of Fetal Malformations in a Low Risk Population

A low risk population was offered screening for malformations in the second and third trimesters of pregnancy. Of 16,763 scans of pregnancies in the second trimester, 61 malformations were identified (0.36%). In the third trimester, scanning of 10,752 pregnancies revealed 24 malformations (0.22%): in all, in a low risk population 0.58% major malformations were found. The sensitivity for noncardiac malformations of the second trimester scanning was 54.3 with a specificity of 99.9%. The malformations overlooked was a more benign spectrum than the cases diagnosed. The sensitivity for cardiac malformations was less than 20%.

Fetal Cells in Maternal Blood: A Comparison of Methods for Cell Isolation and Identification

Objective: A variety of methods have been used to select and identify fetal cells from maternal blood. In this study, a commonly used 3-step selection method is compared with selection directly from whole blood. Identification of fetal origin by XY FISH of male cells was also evaluated. Methods: Maternal blood was drawn either before invasive chorion villus sampling (pre-CVS) or after (post-CVS) from women carrying a male fetus. Fetal cells were isolated either by density gradient centrifugation succeeded by CD45/CD14 depletion and CD71-positive selection from CD45/CD14-negative cells, or by CD71-positive selection directly from whole blood. The true origin of fetal cells recovered by the two methods was established by two rounds of XY chromosome FISH in reverse colors, in some instances combined with anti-zeta (ζ) or anti-ζ/anti-gamma (γ) antibody staining. Results: In blood samples taken post-CVS and enriched by CD71 selection directly from whole blood, fetal cells were identified with a frequency that was almost four orders of magnitude higher than in post-CVS samples enriched by the 3-step method. In blood samples taken pre-CVS and enriched by the 3-step procedure, no fetal cells were identified by reverse color FISH in 371 ml of blood. In similar samples enriched by CD71 selection on whole blood, two fetal cells were identified in 27 ml of blood. Rehybridization with X and Y chromosome probes with reverse colors was necessary to exclude false Y chromosome signals. Not all fetal cells identified by the presence of a true Y chromosome signal stained with anti-ζ antibody. Conclusions: Selection of fetal NRBCs from maternal blood by CD71-positive selection directly from whole blood is superior to density gradient centrifugation succeeded by CD45/CD14 depletion and CD71 selection of CD45/CD14-negative cells. Combining two markers for fetal origin is recommended for unambiguously identifying a cell as fetal.

Chromosome Analysis of Fetuses in Risk Pregnancies

Abstract. In three centers in Copenhagen prenatal chromosome analysis has been carried out on 93 fetuses. Forty patients had earlier born a child with Downs syndrome. One had a 47, XY,+D trisomy fetus. Twenty were 40 years of age or more. Two fetuses in this group had 47, XY,+21 trisomy and one patient had a spontaneous abortion, which was found to have the same constitution. in four of five pregnancies with familial translocations the fetus was a translocation heterozygote. in five cases with relatives affected with Downs syndrome, in seven where the mother had earlier born a child with a chromosome anomaly not being +21 trisomy and in seven at risk of various inborn errors of metabolism, the fetuses were normal with regard to the chromosome constitution. Seven of nine cases, which were at risk of having an X‐linked disease, were males. Five of these were therepeutic aborted, one denied abortion and had an affected male child. One male fetus had a haemophilic father and the family did not want another carrier female.

Haemophilia A and B--two years experience of genetic counselling and prenatal diagnosis

Haemophilia A. Thirty‐one pregnant women, obligate or probable carriers of haemophilia A, requested prenatal diagnosis if sex determination showed the foetus to be a male. In 11 of the 31 cases the foetuses were females; in two, the genetic variant of the disease rendered prenatal diagnosis impossible; and in two, the mother aborted spontaneously. From the remaining 16 male foetuses, blood samples were obtained in uteri in the 17th to 20th week of gestation. Examination of the samples showed that 11 of the foetuses were unaffected and five affected. Haemophilia B. Three carriers of haemophilia B had male foetuses. Examination of foetal blood obtained in utero showed that these three foetuses were affected. Confirmation. All women with an affected foetus requested termination of pregnancy. In one of thecdses of abortion, no blood was obtained for confirmative examination. In the remaining cases, the prenatal prediction was confirmed in the abortus or in the child after birth; three women are still pregnant.