Blood transferrin receptor expression in chromosomally abnormal fetuses

In a cross-sectional study of 13 chromosomally abnormal fetuses, umbilical venous blood was obtained by cordocentesis at 17–32 weeks' gestation. Fetal blood transferrin receptor (CD71) expression (mean=79·8 per cent, range=60–98 per cent) and nucleated red cell count (mean=10·4 × 10⁹ per 1, range=1·0–25·0 × 10⁹ per 1) were significantly higher than the appropriate normal mean for gestation (z=3·92, P<0·0001 and z=3·69, P<0·001, respectively). These haematological changes in chromosomally abnormal fetuses would facilitate their prenatal diagnosis by analysis of fetal nucleated red blood cells isolated from the maternal circulation on the basis of CD71 expression.     

Confined placental mosaicism in CVS and pregnancy outcome

The perinatal outcome of 26 patients with confined placental mosaicism (CPM) detected in chorionic villus sampling (CVS) who wished to continue their pregnancies was compared with that of two controls per patient matched for age and parity (n=52). There were no significant differences in birth weight or gestational age at delivery between patients with CPM and controls. There were no cases of intrauterine growth retardation (IUGR) in the CPM patients as compared with two (2/52, 3·8 per cent) in the control group (P>0·05). There was no significant increase in fetal loss between the study group (1/26, 3·6 per cent) and the controls (1/52, 1·9 per cent) (P>0·05).     

Hyperechoic fetal bowel: The perinatal consequences

A number of publications have reported an association between the finding of hyperechoic fetal bowel on prenatal sonogram and disorders such as aneuploidy and cystic fibrosis. To define more precisely the significance of this finding, we systematically reviewed the published material on the subject. Based on a total of 357 reported cases, we documented a high prevalence of cystic fibrosis (25·6 per cent) and chromosome abnormality (12·4 per cent) associated with increased bowel echogenicity in the fetus. High rates of intrauterine growth retardation (14·9 per cent), fetal demise (9·0 per cent), and prematurity (15·3 per cent) were also found. The data were obtained from a population at high a priori risk for aneuploidy and included fetuses at 1 in 4 risk for cystic fibrosis reported in two studies. This increased the bias towards an adverse outcome. The rate of complications when a hyperechoic abdomen is noted in a low-risk fetal population has so far not been delineated. Although the high frequency of complications found is of concern and warrants investigation, extrapolation of these risk figures to a fetal population at low a priori risk may not be appropriate.     

First trimester chorionic villus sampling versus mid-trimester genetic amniocentesis-preliminary results of a controlled prospective trial

This controlled prospective study assesses the relative risks of first trimester chorionic villus sampling (CVS) versus mid-trimester gentic amniocentesis (GA). CVS subjects and amnio-centesis controls were comparable with regard to several confounding variables which might influence the risk of pregnancy loss including maternal age, smoking, alcohol consumption, gestational age at study entry, and history of vaginal bleeding or poor prior reproductive outcome. The most common indication for prenatal diagnosis was advanced maternal age (n = 511). In this subgroup, spontaneous abortion (<24 weeks) occurred in 2·9 per cent of CVS subjects versus 4−3 per cent of amniocentesis controls. The sum of spontaneous and therapeutic abortions (<24 weeks) was identical (5·3 per cent) in both groups. Therefore, intervention in the CVS group (i.e., therapeutic abortion for cytogenetic abnormalities) did not influence the observed risk of pregnancy loss. Overall perinatal mortality rates were also similar in both groups. No significant differences were identified for a number of pregnancy outcome parameters including 5 min Apgar score, birth weight, body length, head circumference, gestational age at delivery, preterm delivery, fetal growth retardation, congenital malformations, and neonatal complications. Preliminary results of this controlled prospective study suggest that chorionic villus sampling carries a low and acceptable risk.     

Transabdominal villus sampling in early second trimester: A safe sampling method for women of advanced age

Transabdominal chorionic villus sampling (TA-CVS) was performed in 707 viable singleton pregnancies to exclude chromosomal abnormalities. Maternal age ranged between 36 and 49 years (mean 37·9 years); gestational age varied between 10·2 and 18·3 weeks (mean 13·3 weeks). In 639 women (90·4 per cent), a sufficient amount of chorionic tissue (⩾ 10 mg) was obtained after one needle insertion; in 66 women (9·3 per cent) two insertions were needed. An abnormal chromosome pattern was established in 19 cases (2·9 per cent). Vaginal bleeding or spotting within 28 days after TA-CVS occurred in 11 cases (1·5 per cent). The completed follow-up of 678 chromosomally normal pregnancies showed an overall fetal loss rate of 2·6 per cent before 28 weeks. The overall perinatal mortality was 0·9 per cent. When relating fetal loss to gestational age at TA-CVS, this was 6·6 per cent in women sampled before 12 weeks against only 1·8 per cent after 12 weeks. At the same time, the percentage of fetal loss occurring within 2 weeks following the procedure was 75 and 30 per cent, respectively. It is suggested that these data reflect the decline in spontaneous abortion rate during this particular period of pregnancy. It is concluded that TA-CVS is an effective procedure which, when performed after the natural decrease of fetal loss, appears to be a safe option for women of advanced maternal age.     

Transabdominal chorionic villus sampling and amniocentesis for prenatal diagnosis: 5 years' experience at a University Centre

The fetal loss rates and fetal congenital birth defects in 821 transabdominal (TA) chorionic villus sampling (CVS) and 771 amniocentesis (AC) cases were evaluated from a 5-year period (1987–1991) at the University Central Hospital of Turku. The parents were given the option of choosing between the two sampling procedures. CVS was performed, in most cases, at 11 weeks of gestation; and AC, at 15 weeks. The rate of total post-procedure loss was 6·7 per cent in the CVS group and 4·4 per cent in the AC group (p=0·08). The rate of spontaneous abortions was 1·9 per cent in the CVS group and 1·0 per cent in the AC group (p=0·10). The number of birth defects was low in both study groups. No limb reduction cases were observed. Mosaicism was noted in 14 CVS cases and in five AC cases. We conclude that TA-CVS is a safe and practical alternative to AC in prenatal fetal karyotyping.     

Transabdominal chorionic villus sampling. Clinical experience of 1159 cases

The efficacy and risks of transabdominal free-hand ultrasound-guided fine needle aspiration technique were evaluated in 1159 pregnancies submitted to chorionic villus sampling (CVS) in the first trimester and early in the second trimester. An adequate amount of chorionic tissue was obtained by two needle insertions in 99·7 per cent of cases, and a second tapping was needed in 3·5 per cent of cases. A local peritoneal reaction was the only early complication clearly related to the procedure, and it occurred in 0·3 per pent of cases without any adverse effect on the maternal and fetal outcome. The correct abortion rate in 716 consecutive concluded pregnancies was 2·4 per cent, while the rate of late obstetrical complications and perinatal mortality and morbidity compares favourably with the rates in the general population. Because of its simplicity and practicability, transabdominal aspiration is the procedure of choice and is especially recommended fonintensive CVS routine conditions.     

First-trimester maternal serum alpha-fetoprotein as a marker for fetal chromosomal disorders

We evaluated first-trimester maternal serum alpha-fetoprotein (MS-AFP) as a marker for fetal chromosomal disorders. The multicentre study was performed under the auspices of the Dutch Working Party on Prenatal Diagnosis. MS-AFP was measured in 2404 normal pregnancies and 72 chromosomally abnormal pregnancies. The median multiple of the normal median (MOM) in 32 Down's syndrome pregnancies was 0·83 with a 95 per cent confidence interval ranging from 0·60 to 1·04. The difference between the distributions of first-trimester MS-AFP in normal and Down's syndrome pregnancies was statistically significant (t-test: t = 2·34, P<0·05). Thirty-one per cent of the Down's syndrome pregnancies were found below the tenth percentile. We found no difference between normal pregnancies and pregnancies with other chromosomal disorders (eight cases with trisomy 18, MOM = 1·26; seven cases with sex chromosome abnormalities, MOM = 1·07; 22 cases with a chromosomal mosaic pattern in chorionic villi, MOM = 1·08). We conclude that first-trimester MS-AFP can discriminate between normal and Down's syndrome pregnancies, but is not an effective marker. First-trimester MS-AFP has no value as a marker for other fetal chromosomal disorders.     

Simultaneous placentacentesis and amniocentesis for prenatal karyotyping: Report on 250 cases

The efficacy and risks of simultaneous transabdominal chorionic villus biopsy (placentacentesis) and amniocentesis in the second and third trimesters were evaluated in 250 singleton pregnancies. The major indications were advanced maternal age (36·0 per cent), abnormal ultrasound findings (23·2 per cent), and low maternal AFP value (17·6 per cent). Nine abnormal karyotypes were found in placental tissue (3·6 per cent). The karyotypes of placental and amniotic cells were different in three cases, including two cases of false-positive mosaicism (08 per cent) and one case of a false-negative result (0·4 per cent) obtained by placental karyotyping. The problem of discrepant karyotypes in embryonic and extra-embryonic tissue does not seem to be restricted to the first trimester. The post-procedure fetal loss rate was estimated as approximately 1·8 per cent. We conclude that the procedure presented here combines the advantages of rapid karyotyping (placentacentesis) and high diagnostic reliability (amniocentesis). It does not seem to be necessary to restrict its use to late presentations and suspicious ultrasound findings.     

Chromosomal prenatal diagnosis: Study of 936 cases of intrauterine abnormalities after ultrasound assessment

Nine hundred and thirty-six prenatal chromosomal analyses were performed by four cytogenetic centres after ultrasound diagnosis of fetal abnormalities, amniotic fluid disorders, fetal growth retardation, and fetal or placental abnormalities. During the same period, 6515 fetal karyotypes were analysed because of maternal age. Frequencies of chromosomal aberrations in each case were respectively 4·4, 6·7 and 15·8 per cent, compared with 3·18 per cent when the fetal karyotype was performed because of maternal age. High rates of chromosomal aberrations are observed in cases of cervical hygroma, limb abnormalities, omphaloceles, duodenal stenosis, hydrocephalus, and facial abnormalities. In the case of polymalformations, this rate was 29·2 per cent. When malformations were seen together with an amniotic fluid disorder or growth retardation, 21·5 per cent chromosomal aberrations were observed. This frequency was 10·4 per cent when growth retardation was associated with an amniotic fluid disorder. Trisomy 13, 18, 21 and monosomy X accounted for 4/5 of all abnormalities in which we observed a high rate of triploidies (4·9 per cent) and balanced (3·3 per cent) or unbalanced (9·8 per cent) non-Robertsonian structural abnormalities. Sonographic ascertainment of these aberrations and prenatal characteristics of major anomalies are discussed.     

Comparison of first-trimester transvaginal amniocentesis with chorionic villus sampling and mid-trimester amniocentesis

Between August 1989 and December 1991, 356 patients underwent first-trimester transvaginal amniocentesis (10–12 weeks). The same number of patients referred in the same period for mid-trimester amniocentesis (14–21 weeks) was matched also for maternal age and indication. A third group consisted of the first 356 cases in which chorionic villus sampling (CVS) was attempted. The overall success rate was 99·7 and 100 per cent for early and mid-trimester amniocentesis, respectively, and 97·2 per cent for CVS. The mean harvesting time was 12·8, 11, and 7·9 days, respectively. The percentage of patients rescheduled was 3·4 per cent in first-trimester amniocentesis, 1·7 per cent in mid-trimester amniocentesis, and 6·2 per cent in the CVS group. The early (less than 2 weeks) pregnancy loss was 1·7 and 0·6 per cent in early and mid-trimester amniocentesis, respectively, and 1·7 per cent in CVS. The total pregnancy loss was 3·2, 0·9, and 2·9 per cent, respectively. The rate of preterm birth was 6·0, 5·2 and 6·9 per cent, respectively. The results indicate that CVS has the shortest procedure-result interval, but the highest rescheduling rate. First-trimester amniocentesis has a higher procedure and laboratory success rate but, until otherwise proved, mid-trimester amniocentesis is the most efficient and safest procedure.     

Fetal choroid plexus cysts and trisomy 18: Assessment of risk based on ultrasound findings and maternal age

This paper examines the association between fetal choroid plexus cysts (CPCs) and trisomy 18 and proposes a method by which risks can be derived taking into account both sonographic findings and maternal age. Data from our centre on the sonographic findings of 58 fetuses with trisomy 18 and 387 fetuses with CPCs as well as data from published series were used. It was calculated that the prevalence of CPCs in the general population is approximately 1 per cent and at mid-gestation the incidence of CPCs in fetuses with trisomy 18 is approximately 50 per cent. In the 387 fetuses with CPCs, the incidence of trisomy 18 increased with maternal age and the likelihood ratio for trisomy 18 increased with the number of additional abnormalities, from 0·03 for those with isolated CPCs to 0·4 if there was one additional abnormality and 20·5 if there were two or more additional abnormalities. It was concluded that if the cysts are apparently isolated, the risk for trisomy 18 is only marginally increased and maternal age should be the main factor in deciding whether or not to offer fetal karyotyping. If one additional abnormality is found, the maternal age-related risk is increased, so that even for a 20-year-old the risk for trisomy 18 is at least as high as the risk for trisomy 21 in a 35-year-old. In this respect, it may be considered desirable to offer such patients the option of karyotyping.     

Maternal serum inhibin levels in second-trimester down's syndrome pregnancies

Maternal serum inhibin levels were measured in 19 second-trimester pregnancies affected by fetal Down's syndrome and 95 unaffected control pregnancies matched for gestational age. A statistically significant elevation was found in the affected pregnancies compared with the controls (Wilcoxon rank sum test: one-tail P=0·02). The median level in the cases was 1·3 times that in the controls, with 95 per cent confidence limits of 0·9–1·9. Although the inhibin levels were unrelated to those of alpha-fetoprotein and unconjugated oestriol in the same samples, there was a statistically significant correlation with human chorionic gonadotropin. This together with the relatively small elevation in cases suggests that inhibin would be of limited value in maternal serum screening for Down's syndrome.     

Normal fetal growth in women with antiphospholipid syndrome treated with high-dose intravenous immunoglobulin (IVIG)

Antiphospholid antibodies are associated with fetal distress and fetal death. Although different therapeutic regimens have been used, the incidence of fetal growth retardation varies between 30 and 60 per cent of reported cases. We report the evolution of fetal growth in patients with antiphospholipid antibody syndrome treated with high-dose intravenous immunoglobulins (IVIG). Fourteen patients with a history of recurrent spontaneous abortion and immunological diagnosis of antiphospholipid syndrome were followed longitudinally. Intravenous immunoglobulin at a dose of 0.5 g/kg body weight for two consecutive days was started from the fifth week of pregnancy and repeated every 4 weeks until the 33rd week of gestation. Fetal biometry was evaluated longitudinally from the appearance of the gestational sac at 4 weekly intervals. In the period between 26 and 34 weeks, the frequency of evaluation was increased to every 14 days. Data obtained were compared with a control group of 70 fetuses with uneventful pregnancies matched for gestational age. Neonatal weight is shown in relation to the centiles for the normal population. One patient out of 14 (7.1 per cent) developed gestational hypertension and abruptio placentae. No other pregnancy complications were seen. No proteinuria was found. The mean maternal age was 31.2±3.8 years. Median birth weight was 3433 g±287. The median centile of the birth weight was 65.3±18.6. Mean gestational age at delivery was 1.3 weeks. No fetal or neonatal growth retardation was seen. No significant differences were found in the biometrical parameters investigated in the various gestational ages vs. the control group (Student's t-test not significant); a significant increase in head circumference (P< 0.001) and abdominal circumference (P< 0.05) was found at 36–37 weeks gestational age in the IVIG-treated fetuses. The presence of antiphospholipid antibodies is considered detrimental for pregnancy outcome because of their negative effects on placental vascular perfusion and fetal transfer of metabolites. The use of IVIG seems to avoid or inhibit the reduced availability of nutrients for the fetal anabolic functions, as the expected reduction in fetal growth was not seen in our series.     

Abnormal immunological development in fetuses with trisomy 18

Flow cytometry was used to enumerate the lymphocyte subpopulations in fetal blood obtained by cordocentesis from eight trisomy 18 fetuses at 20–36 weeks' gestation. Compared with values in chromosomally normal fetuses, in trisomy 18 the mean T- and natural killer (NK) cell counts were significantly lower (t= − 7·63, P<0·001 and t= − 3·58, P<0·01, respectively); the mean B-cell count was not significantly different (t= − 1·32). These findings demonstrate that in trisomy 18 there is abnormal intrauterine development of the immune system.     

Ultrasonic placental localization in relation to spontaneous abortion after mid-trimester amniocentesis

This paper summarizes our experience with a series of 562 women referred for mid-trimester amniocentesis for prenatal diagnosis. Ultrasonography was utilized for placental localization. Follow-up revealed a fetal loss rate of 3.03 per cent with 1.96 per cent being spontaneous abortions. Patients with an anterior placenta had a fetal loss and spontaneous abortion rate of 4.06 per cent and 3·05 per cent, respectively. No significant difference in the incidence of fetal loss (p > 0·1) or spontaneous abortion (p > 0·5) was found in patients having an anterior versus a posterior placenta. Neither multiple insertions through an anterior placenta nor blood contaminated amniotic fluid from patients with an anterior placenta were associated with an increased incidence of fetal loss or spontaneous abortion.     

Pure fetal blood samples obtained by cordocentesis: Technical aspects of 322 cases

Three hundred and twenty-two percutaneous umbilical blood samplings were performed over 4 years in our prenatal diagnostic centre. A 3·5 MHz sector ultrasound transducer was used to guide a 22·5-gauge needle under local anaesthesia. Sampling was performed fcir rapid fetal karyotyping (within 72 h) in 120 cases, for diagnosis of fetal toxoplasmosis in 133 cases, for determination of the severity of Rh immunization in 15 cases, and for diagnosis of congenital rubella in 4 cases. Pure fetal blood was obtained in 98·7 per cent of the cases after two attempts. The approach to the cord was either transamniotic or trans-piacental. Puncturing was preferentially done at the placental insertion of the cord (72·2 per cent of the cases) and the mean blood sample volume was 3·5 ml. The rate of fetal death in utero was 1 9 per cent, including two cases of amnionitis, one trisomy 18, and one severe bradycardia. The failures were due to sampling at an early stage of pregnancy (before gestation week 18), to maternal obesity, oligohydramnios, and the inexperience of the operator.     

Second-trimester maternal serum screening using alpha-fetoprotein,human chorionic gonadotrophin,and unconjugated oestriol: Experience of a regional programme

Over a 2-year period from January 1991 to December 1992, second-trimester maternal serum screening for Down's syndrome using alpha-fetoprotein (aFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE₃) was made available to five health districts in East Anglia, with a total population of 1·2 million. Amniocentesis was offered when the risk of Down's syndrome at term was 1:200 or greater. 25359 singleton pregnancies were screened, representing an uptake of 77 per cent. The recall rate for the 24 per cent of women who had not had a dating scan prior to the test was 9·4 per cent compared with 3·9 per cent for those who had been scanned (P<0·0005). Seventy-five per cent (36/48) of Down's syndrome pregnancies were detected for a false-positive rate of 4·0 per cent. Twenty-five out of 36 of detected Down's syndrome pregnancies were dated by scan prior to sampling, and in the 11 remaining cases, the dates were confirmed by scan after a high-risk result was obtained. The exclusion of uE₃ from the screening protocol would have reduced the detection rate to 52 per cent (25/48) for the same false-positive rate. Eighty-five per cent of women identified at high risk accepted the offer of an amniocentesis. Other fetal abnormalities detected were trisomy 18 (3), trisomy 13 (2), 45,X (6), 69,XXX (5), other chromosome abnormalities (9), open neural tube defects (26), hydrocephalus (7), abdominal wall defects (4), and steroid sulphatase deficiency (6).     

Maternal serum free beta hCG screening: Results of studies including 480 cases of down syndrome

The median maternal serum free beta human chorionic gonadotropin (hCG) multiple of the median (MOM) of 480 Down syndrome cases in the second trimester was 2·64, significantly greater than the reported median MOM of intact hCG (p<0·0001). In 234 of these cases from retrospective and prospective studies, the effectiveness of maternal serum free beta hCG was evaluated in combination with alpha-fetoprotein (AFP) and maternal age in second-trimester Down syndrome screening. Down syndrome detection in the gestational age range of 14–16 weeks was 82 per cent. In all gestational weeks (14–22), a 77·7 per cent Down syndrome detection rate was achieved. In prospective screening of 44 272 patients under the age of 35 years, 69 per cent of Down syndrome cases were detected (73 per cent in gestational weeks 14–16). The false-positive rate for the prospective study was 3·8 per cent. The use of free beta hCG combined with maternal serum AFP and maternal age-related risk for Down syndrome in a screening population (i.e., women under 35 years) yields an improved detection efficiency over other protocols.