Fetoscopy and fetal blood sampling in the management of a twin pregnancy with 45,X/46,XX amniotic fluid cell mosaicism and a suspected fluid sampling error

A 37 year-old woman with a twin pregnancy underwent amniocentesis to exclude fetal chromosome abnormality. The results indicated that both fetuses were mosaics, with 45,X and 46,XX, cell lines. Since it was suspected from the ultrasound scan that the twins were dizygotic, the result was questioned. Fetoscopy and fetal blood sampling were performed and karyotyping the fetal lymphocytes confirmed that one twin was indeed a mosaic, 45,X/ 46,XX, but the other had a normal male chromosome complement. The pregnancy resulted in the birth of a phenotypically normal girl, in whom the 45,X/46,XX mosaicism was confirmed, and a normal boy.     

Invasive assessment of fetal renal abnormalities: urinalysis,fetal blood sampling and biopsy

There are a number of potential biochemcial markers that may have some role in predicting renal function postnatally. These include urinary sodium, calcium and β2‒microglobulin. The latter may also be measured in fetal serum. However, the accuracy of these parameters at a point in time is far from perfect as urinary tract obstruction is a progressive disease which may be best defined by repeated observations throughout pregnancy. Copyright © 2001 John Wiley & Sons, Ltd.     

Fetal cystic hygromata: Insights gained from fetal blood sampling

Twelve second-trimester fetuses with cystic hygroma underwent fetal blood sampling for rapid karyotyping, haematologic evaluation, and blood gas analysis. An abnormal karyotype was found in seven cases: monosomy X in five, trisomy 21 in one, and trisomy 13 in the other. Eight often fetuses undergoing blood gas analysis showed hypoxaemia, five of which were growth-retarded. Nine pregnancies were terminated. Of the remaining three, only one fetus survived the perinatal period.     

Chorionic villus sampling for fetal karyotyping in missed abortions

Chorionic villus sampling (CVS) was performed in 12 pregnant women (9–25 gestational weeks) with ultrasonographic evidence of missed abortion. An ultrasonographically guided transabdominal (eight cases) or transcervical (four cases) approach was used. Fetal karyo-typing was successful in all cases; in five, chromosomal aberrations were found and in seven, chromosome analyses revealed normal karyotypes. Tissue culture for fetal karyotyping was successful in only 72.5 per cent of 40 live pregnancies which were electively interrupted because of abnormal ultrasonographic findings or an abnormal fetal karyotype, and in 57 per cent of seven missed abortions. CVS is suggested as a feasible and effective method for fetal karyotyping in missed abortions and it seems to be superior to post-abortion tissue culture.     

Short communication the natural history of fetal cytomegalovirus infection as assessed by serial ultrasound and fetal blood sampling: A case report

A patient in whom intrauterine fetal cytomegalovirus (CMV) infection was diagnosed at approximately 25 weeks' gestation is presented. The fetus was evaluated by serial fetal blood samplings and ultrasound examinations. The fetus manifested evidence of severe thrombocytopenia and hepatic inflammation, with recovery over a period of approximately 8 weeks. The initial sonographic findings of marked fetal ascites and cardiomegaly gradually resolved; ventriculomegaly developed during the third trimester. At delivery, the baby was morphologically normal with the exception of mild ventriculomegaly. Cord blood was negative for CMV IgM but urine was culture-positive for CMV. At age 3, the child has a severe but stable unilateral hearing deficit and is otherwise developmentally normal. This case demonstrates the utility of serial ultrasound and fetal blood sampling in the prenatal diagnosis and management of fetal CMV infection.     

Does chorionic villus sampling compromise fetal umbilical blood flow?

A possible association of limb reduction defects with chorionic villus sampling (CVS) may be related to compromised umbilical blood flow from the trauma of the procedure. We hypothesized that because CVS may disrupt or compromise umbilical blood flow to the fetus, either by vasoconstriction, bradycardia, or emboli, we would detect these changes using Doppler velocimetry. A cohort of 21 consecutive consenting patients undergoing first-trimester elective CVS for prenatal diagnosis were entered into a prospective longitudinal study. Colour flow Doppler velocimetry was performed on fetal umbilical arterial blood flow immediately before and after CVS to measure the pulsatility index, fetal heart rate, per cent flow time, and maximum flow velocity. Measurements were obtained from three consecutive cardiac cycles in three different umbilical segments and averaged. Potentially confounding variables also recorded included gestational age, method of CVS, number of passes, number of aspirations, placental location, tissue sample size, and operator. Umbilical velocimetry values before and after CVS were compared using the paired t-test and showed no statistically significant differences. No differences were found when data were analysed by gestational age, sample size, method, number of aspirations, placental location, or operator. We were unable to detect any significant change in fetal umbilical arterial blood flow velocimetry or heart rate after performing CVS. Umbilical blood flow does not appear to be routinely compromised by CVS.     

Prenatal testing for inherited immune deficiencies by fetal blood sampling

We attempted to develop a prenatal diagnosis in fetuses at risk for immunodeficiency by fetal blood sampling performed under fetoscopy at 18–22 weeks of gestation. In order to obtain normal values, we first investigated thirty-five control fetuses whose blood punctures were undertaken for the diagnosis of haemoglobinopathies. Surface markers and in vitro mitogen-induced proliferation of the fetal lymphocytes were studied using micromethods. We then examined two fetuses at risk for two different types of severe combined immunodeficiency and established their immunological integrity, hence avoiding an unjustified termination of pregnancy. This immunological integrity was confirmed after birth.     

Cardiac flow after fetal blood sampling in normally grown and growth-retarded fetuses

The objective of this study was to evaluate the effect of fetal blood sampling on cardiac flow velocity waveforms. Flow velocity waveforms were measured from the ascending aorta and pulmonary artery immediately before and after fetal blood sampling in 29 normally grown and 12 growth-retarded fetuses. The latter group was characterized by abnormal Doppler indices in the umbilical artery and middle cerebral artery suggestive of uteroplacental insufficiency as the causative factor of the impaired growth. The flow velocity parameters studied were the peak velocity, the time to peak velocity, and the left and right cardiac output and their ratio. In normally grown fetuses, the peak velocity and right and left cardiac output values increased significantly after fetal blood sampling, while no significant changes were observed in the other indices considered. The gestational age at the time of the procedure was positively related to the amplitude of these changes. In growth-retarded fetuses, fetal blood sampling did not induce any significant increase in cardiac output or peak velocities, while in more than 50 per cent of the fetuses these Doppler indices decreased. The amplitude of the decrease was significantly related to the severity of acidosis in the umbilical vein. In conclusion, the cardiac haemodynamic response to fetal blood sampling differs between normally grown and growth-retarded fetuses. This difference may explain the higher rate of complications occurring in the latter group of fetuses after blood sampling.     

Chorionic villus sampling: Analysis of fetal losses to delivery,placental pathology,and cervical microbiology

A population of 1639 patients were seen for chorionic villus sampling (CVS). Embryonic death was identified at ultrasound in 5.3 per cent of patients. The number of patients undergoing CVS was 1551, with 1416 transcervical procedures and 135 transabdominal procedures. The most common indication for CVS was advanced maternal age. Spontaneous pregnancy losses identified by increased risk of pregnancy loss with increasing aspiration attempts. The total fetal loss for this population was 5.4 per cent with the pregnancy loss estimated due to procedure being 1.2 per cent. Analysis of placentae from patients having CVS and amniocen-tesis showed no differences. Microbiological assessment prior to CVS was similar to previous publications.     

Extra embryonic/fetal karyotypic discordance during diagnostic chorionic villus sampling

From a total of 1312 diagnostic chorionic villus samplings (CVS) there were 22 which showed discordance between the karyotype of the chorionic villi and that of the fetus. This frequency was some 20-fold higher than that reported at amniocentesis. In the majority of discordant cases, the fetal karyotype was normal while the placenta! karyotype was mosaic. In four cases, the placenta! karyotype was non-mosaic (a trisomy 16, a monosomy X, and two tetraploids) while the fetal karyotype was normal. In one case, the placenta was trisomy 18 while the fetus was mosaic. There were two ‘false-negative’ results where short-term methods showed only normal cells while both long-term cultures of chorionic villi and fetal cells were mosaic, in one 46,XY/47.XXY and in the other 46,X Y/47.X Y, + 21.     

Prenatal diagnosis of alpha-1-antitrypsin deficiency by fetal blood sampling

Fetal blood sampling for the diagnosis of alpha-1-antitrypsin deficiency using protein isoelectric focusing was carried out in the period 1980–1985. The results of 25 cases from 18 mothers are reported. All had a previous history of a PiZ child affected by liver disease. The method was found to be technically satisfactory and the fetal results were subsequently confirmed in all 18 cases where follow-up was possible. The fetus was found to be PiZ in nine cases and all these pregnancies were terminated. Of the remaining pregnancies three cases aborted or were delivered prematurely and 13 proceeded to term without complications.     

In vitro characteristics of human fetal cells obtained from chorionic villus sampling and amniocentesis

In vitro characteristics of human fetal cells have been investigated after chorionic villus sampling at the first trimester and amniocentesis at the second trimester of pregnancy. Light microscopy revealed heterogeneous morphology of cell types in both the chorionic villus culture and the amniotic fluid cultures. Based on the experiments performed, chorionic villus cells are more sensitive to pronase, trypsin, and versene during subculture and have a higher DNA content per single cell and release more [¹²⁵I]-Beta-human chorionic gonadotropin into culture medium than those found in amniotic fluid cells. The practical applications of this study are discussed.     

Easurements of placental,decidual, and fetal proteins before and after chorionic villus sampling

Circulating placental [human chorionic gonadotrophin (hCG), Schwangerschafts protein 1 (SP1), pregnancy-associated plasma protein A (PAPP-A), decidual (pregnancy protein) 12 (PP12), and fetal alphafetoprotein (AFP)] proteins were measured immediately before and within 1 h in 18 women undergoing diagnostic chorionic villus sampling (CVS) in the first trimester. An elevation of serum AFP levels was consistently seen, while fluctuations in excess of 10 per cent of the pre-CVS levels of SP1 and PP12 were seen in the majority of patients. Fluctuations in hCG and PAPP-A were consistently less than 10 per cent of pre-CVS values. Post-CVS changes in levels were not apparently associated with any feature of the technique, the pregnancy, or its outcome (one missed abortion). As feto-maternal haemorrhage is a common event, anti-D should be offered to rhesus-negative women undergoing CVS. In the prediction of subsequent miscarriage, only hCG and PAPP-A measurements should be considered.     

A rare case of cytogenetic discrepancy between extraembryonic and fetal tissue

We present a case of false-negative discrepancy between extraembryonic and fetal tissue sampled at 14 weeks of amenorrhoea when ultrasound examination showed morphological anomalies of the fetus. The same cytogenetic characteristic was confirmed on tissue samples after abortion.     

Transabdominal chorionic villus sampling for fetal genetic diagnosis. Technical and obstetrical evaluation of 100 cases

First trimester fetal diagnosis was established in 100 pregnancies at risk by transabdominal chorionic villus sampling (TA-CVS). Forty-eight per cent of the women were 35 years or more at the time of sampling. Using the double needle technique, both the aspiration and the diagnostic success rate were 100 per cent. The mean amount of villi aspirated was 28·2 mg (10–50 mg). The mean needle time was 3 min. Vaginal spotting appeared in 2 per cent of the women. Four women had therapeutic abortion due to abnormal findings and one for social reasons. Three fetuses with normal karyotypes were lost. Excluding the therapeutic abortions, the fetal loss rate was 3±2 per cent. The fetal loss rate in the amniocentesis control group (n = 200) was 3±6 per cent. The cytogenetic diagnosis was carried out by the direct preparation technique as well as by chorion villus cultivation. All karyotypes were confirmed by lymphocyte cultures from umbilical cord blood or heel blood from the newborn or from aborted fetal tissue. Transabdominal CVS is deemed a safe and easy tool for achieving chorionic villi in the first trimester.