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 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.     

Mid-trimester amniocentesis and antibiotic prophylaxis

Objectives and Methods Assuming that the rate of fetal loss after amniocentesis may be reduced in patients receiving antibiotic prophylaxis, we conducted a retrospective study on untreated versus treated patients receiving prophylactic antibiotics (amoxicillin/clavulanic-acid or azithromycin) and evaluated the fetal loss rate within the 22nd week of gestation, also with respect to the risk of spontaneous abortion, both preexisting and related to mid-trimester amniocentesis. Results Spontaneous abortion occurred in 22 cases out of 1744 (1.26%). The incidence of spontaneous abortion was 1.3% among patients treated with antibiotic prophylaxis and 1.2% among untreated patients. Between patients with risk factors that predated amniocentesis, the spontaneous fetal loss rate was 9.2% in untreated patients versus 2.3% in patients treated (p = 0.10). In patients with procedure-related risk factors at amniocentesis, the spontaneous abortion rate was, respectively, 2.2 and 1.2% (p = 0.72). Conclusion Our data demonstrate that antibiotic prophylaxis does not reduce the risk of spontaneous abortion within the 22nd week of gestation. Compared with untreated patients, patients treated with amoxicillin showed the lower fetal loss rate (1.16 vs 0.31%), but the difference was not statistically significant (odds ratio (OR) = 3.68, p = 0.32). The same was true for patients with preexisting risks (OR = 4.25, p = 0.10). Copyright © 2007 John Wiley & Sons, Ltd.     

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).     

Clinical and pathological factors in spontaneous abortion following chorionic villus sampling

Twenty-nine cases of spontaneous abortion following first-trimester chorionic villus sampling (CVS) were reviewed out of a series of 722 patients. Of the 29 cases, there were only four abnormal CVS results. Pathological examination was performed in 79 per cent of cases, and this did not identify any characteristic pathological feature associated with spontaneous abortion after CVS. There was no obvious difference in the pathological features following the transabdominal (TA) or the transcervical (TC) methods. The majority of miscarriages occurred within 4 weeks of the procedure, but 38 per cent of cases aborted between 7 and 14 weeks after CVS. The TC method was used in 22 patients; the TA in 6; and both methods in 1 patient. The TA method was associated with a significantly lower fetal loss rate than the TC method (TA 2 per cent, TC 9 per cent, p < 0.001).     

The risks of early cordocentesis (12–21 weeks): Analysis of 500 procedures

Five hundred cordocenteses were performed between 12 and 21 weeks. The indications were thalassaemia (386), rapid karyotyping (97), feto-maternal allo-immunization (10), rubella (6), and toxoplasmosis (1). One hundred and ten pregnancies underwent termination on the basis of the result, while 20 of the 370 pregnancies intended to continue were lost to follow-up. Amongst these were 16 fetal losses (4·3 per cent) and 22 premature deliveries (5·9 per cent); no other complications were reported. Four adverse prognostic factors were identified: (a) cord bleeding; (b) fetal bradycardia; (c) prolonged procedure time; and (d) anterior insertion of the placenta. There was no‘obvious’ difference in fetal loss rate with advancing gestation until 19–21 weeks, when the risk of fetal loss decreased to 2·5 per cent.     

Complications of cordocentesis in high-risk pregnancies: Effects on fetal loss or preterm delivery

Between 1990 and 1993, 166 cases underwent cordocentesis and were followed for at least the following 4 weeks in the Prenatal Diagnosis and Therapy Centre of Vienna University. The indications for the procedure were structural malformations in 46·4 per cent of the cases, other high-risk diagnoses in 48·8 per cent, and maternal age over 35 years in only 4·8 per cent. We investigated retrospectively all cases of complications resulting in fetal loss or preterm labour. Abortion, intrauterine fetal death, chorioamnionitis, and preterm delivery occurred in 0·6, 5·4, 0·6 and 9·0 per cent of these cases, respectively, adding up to a total of 26 cases (15·7 per cent). Although this rate looks relatively high, 20 of the 26 cases had already displayed signs implying a complicated prognosis. Neither maternal age, gestational age, number of attempts, nor placental location correlated with fetal loss or preterm delivery. Significantly higher rates of fetal loss or preterm delivery were observed when cordocentesis was performed in cases diagnosed as duodenal/intestinal stenosis or hydrops–ascites–hydrothroax/hygroma colli (P=0·0488 and P=0·0005). The frequency of complications did not decrease as the experience of the operators increased.     

Adverse outcome in pregnancy following amniotic fluid isolation of Ureaplasma urealyticum

Infections in pregnancy with Ureaplasma urealyticum have been associated with a wide range of adverse outcomes, such as early abortion, stillbirth, prematurity, and neonatal morbidity and mortality. Causality has been difficult to demonstrate secondary to the high prevalence of asymptomatic lower genital tract (LGT) colonization and culture data from inaccessible or potentially contaminated sites. Between 1985 and 1989, 2461 second-trimester genetic amniocenteses were evaluated at the cytogenetics section of the Children's Hospital Medical Center of Akron. All were cultured for the genital mycoplasmas: Mycoplasma hominis and Ureaplasma urealyticum. A total of nine patients were positive, all for Ureaplasma urealyticum, with one patient excluded because of subsequent therapeutic abortion. In addition, complete follow-up data, such as indication for amniocentesis, serum alpha-fetoprotein levels, gestational age at parturition, and out- come of pregnancy, were available on 86 Ureaplasma-negative (U –) patients during an approximate 2-year span within the time-frame of the study. This was in part due to physician response to a questionnaire sent after amniocentesis. Of the eight positive cultures, 100 per cent were associated with an adverse outcome, defined as fetal loss or premature delivery. This was significant compared with the U–group (p<0.001) with a more than eight times greater risk of adverse outcome. Six (75 per cent) resulted in spontaneous miscarriage within 4 weeks of amniocentesis and at less than 21 weeks' gestation. Two (25 per cent) delivered prematurely, with one (12.5 per cent) neonatal death at 24+ weeks. Histological examination of all eight placentae and the seven fetuses revealed a 100 per cent incidence of chorioamnionitis and pneumonia, respectively. In addition, in four of the five cases (80 per cent), cultures were positive for Ureaplasma urealyticum in pure culture from either placenta, fetal lung, or both tissues. The remaining case (20 per cent) was negative for aerobes, anaerobes, and mycoplasmas. The study demonstrates a significant association and supports a causal relationship between isolation of Ureaplasma from mid-trimester amniotic fluid with fetal wastage and premature birth.     

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.     

Transcervical (TC) and transabdominal (TA) CVS for prenatal diagnosis in rotterdam: Experience with 3611 cases

Data from 3611 consecutive CVS (TC, N= 1780; TA, N= 1831) were analysed with emphasis put on influence of maternal and gestational age at CVS on the fetal loss rate < 28 weeks. For TC-CVS the gestational age varied from 9.3–11.6 weeks, for TA-CVS from 9.3–20 weeks. Sampling efficacy at first attempt was 86.5 per cent and 95 per cent respectively. In 4.6 per cent an abnormal result was established. In older mothers (N=2362) the fetal loss rate was significantly higher (p = <0.05) when sampled before 12 weeks (TC-CVS 6.2 per cent, TA-CVS 5.8 per cent). When the CVS (TA) was performed after 12 weeks the fetal loss rate decreased to 2.4 per cent. In 1079 younger women the fetal loss rate remained low (TC 2.8 per cent; TA < 12 weeks 1.8 per cent; TA > 12 weeks 1.7 per cent) and was not influenced by gestational age at the time of sampling. We concluded both methods safe and reliable when the choice of application considers maternal age.     

Risk assessment of amniocentesis between 11 and 15 weeks: Comparison to later amniocentesis controls

We studied 693 consecutive early amniocenteses (prior to 15 weeks) and found a spontaneous abortion rate to 28 weeks' gestation of 1·5 per cent. A control group of women having standard amniocentesis (15–20 weeks) experienced a 0·6 per cent fetal loss in the same period. There were no other apparent differences between the two groups. Early amniocentesis results are generally available 4–6 weeks before standard amniocentesis and 1–3 weeks after chorionic villus sampling (CVS). Alpha-fetoprotein (AFP) can be accurately assayed in 11- to 15-week amniotic fluid samples but additional studies are necessary to determine the accuracy of neural tube defect (NTD) detection. Including the present study, over 5800 early amniocenteses have been reported and the results suggest that this is a relatively safe prenatal diagnostic test and an alternative to CVS and later amniocentesis.     

Risks of transabdominal chorionic villus sampling before the 12th week of amenorrhea

The authors report on a series of 210 chorion villus sampling diagnoses made with a needle by the transabdominal route. The rate of fetal loss was 4·2 per cent. Placental localization was important: fetal losses were 8 per cent when the placenta was strictly posterior (transamniotic route), whereas it was only 1·6 per cent when it was not posterior. Moreover, all fetal losses occurred (apart from one at 12·5 weeks of amenorrhea) before the 12th week of amenorrhea. The authors suggest that choriocentesis by the transabdominal route should not be performed before the 12th week of amenorrhea, and that the amniotic membrane should not be disturbed before the 13th week of amenorrhea.     

A comparison of amniotic fluid alpha-fetoprotein and acetylcholinesterase in the prenatal diagnosis of open neural tube defects and anterior abdominal wall defects

Amniotic fluid samples received for routine prenatal diagnosis of open neural tube defects were used for a study to compare amniotic fluid acetylcholinesterase (AChE) determination using a monoclonal antibody (4F19) enzyme antigen immunoassay and amniotic fluid alpha-fetoprotein (AFP) measurement as diagnostic tests for open neural tube defects. The study was based on 9964 women with singleton pregnancies and known outcome (including 6 with anencephaly and 18 with open spina bifida) having an amniocentesis at 14–23 weeks of gestation. The AChE immunoassay yielded detection rates for anencephaly of 100 per cent (95 per cent confidence interval (CI) 54·07–100 per cent), for open spina bifida of 100 per cent (95 per cent CI 81·47–100 per cent), for anterior abdominal wall defects of 20 per cent (95 per cent CI 0-51-71-64 per cent), and a false-positive rate of 0·22 percent (95 per cent CI 0·14–0·34 per cent) excluding anencephaly, open spina bifida, and anterior abdominal wall defects. For similar detection rates the false-positive rate of the AFP test was significantly higher, 0·74 per cent (95 per cent CI 0·58–0·94 per cent). On the basis of these findings, it is recommended that the technically simple AChE immunoassay should be used on all samples; the AFP test should only be used on the 0·5 per cent of the samples with concentrations of AChE activity ⩾ 8·5 nkat/1 for clear samples and blood-stained samples becoming clear after centrifugation, and ⩾ 25·0 nkat/1 for blood-stained samples that are discoloured after centrifugation; an AFP cut-off level of 2·0 MOM is recommended for this policy. Thereby, the detection rates for anencephaly, open spina bifida, and anterior abdominal wall defects would be 100, 100, and 20 per cent, respectively (95 per cent CIs 54·07–100, 81·47–100, and 0·51–71·64 per cent, respectively), and the false-positive rate would be 0·08 per cent (95 per cent CI 0·03–0·16 per cent) (excluding anencephaly, open spina bifida, and anterior abdominal wall defects).     

Justification of maternal serum alphafetoprotein screening in a population with low incidence of neural tube defects

A prospective study of maternal serum alphafetoprotein (α-FP) screening of 9838 women in an area with low prevalence of neural tube defects and predominance of anencephalics revealed that an intervention point of single serum α-FP level above 2·8 times the median was appropriate for this population. Ninety per cent of anencephalics and all fetuses with anterior abdominal wall defects were detected. There was no spina bifida among the population screened. Two per cent of the population screened had serum α-FP level above this cut-off level. Thirty-two per cent of twin pregnancies, 7 per cent of small-for-gestational age infants and 9 per cent of pregnancies which ended in either abortion or perinatal death in the population screened also had one serum α-FP level above this intervention point. The false positive rate was 66 per cent. This false positive rate was only reduced to 63 per cent if instead of one, two serum α-FP level above this intervention point was considered abnormal. Using this strategy there was no significant reduction in the detection rate of fetal anomalies and other pregnancy complications. Because of the predominance of anencephalics in this population the diagnosis of fetal anomaly in women with abnormal serum a-FP level was made by ultrasound examination alone. The reason amniocentesis was not performed in these patients was to avoid unnecessary loss of normal pregnancies which may result from this procedure.     

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.     

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.     

The value of sonographic diagnosis of fetal malformations: Different results between indication-based and screening-based investigations

The advantages of a routine screening or indication-based ultrasound investigation during pregnancy are still under debate. This is the first study where both methods are compared in two different time periods. More malformations were diagnosed before the 24th week of gestation by means of screening-based than indication-based investigation (18 per cent vs. 5 per cent, P<0·005), and before 28 weeks in 26 per cent compared with 15 per cent respectively (P<0·01). Twenty-six per cent of all malformations were detected by means of screening-based investigations as opposed to 15 per cent by means of indication-based scans. Primary fetal malformations were also diagnosed much earlier (25 weeks vs. 30 weeks). Except for the fetal head, the detection rate of malformations was higher in nearly all other body regions of the fetus in the screening-based investigation. The most important advantage of a screening-based ultrasound investigation during pregnancy is to detect the malformations early enough in pregnancy for possible intrauterine treatment or to offer safe termination of pregnancy for the woman, at least for those anomalies that are lethal or significantly handicapping.     

Transplacental amniocentesis: Is it really a higher-risk procedure?

The aim of this study was to compare transplacental with non-transplacental amniocentesis in terms of related complications. Between January 1991 and December 1992, 4564 genetic amniocenteses were performed in 4527 patients (4491 singleton, 35 twin, and one triplet pregnancy) at 15–16 weeks of gestation. All the procedures were ultrasound-guided and performed by the same operator. In 1487 cases, an anterior placenta was traversed with the needle, whereas in 3077 cases, the needle was inserted directly into the amniotic cavity without traversing the placenta. After the exclusion of patients in whom amniotic cell culture failed or in whom an abnormal karyotype was obtained, and of patients lost to follow-up, a total of 4454 patients (98 per cent) were followed for 30 days after amniocentesis. Two spontaneous abortions occurred after a transplacental procedure, and five after a non-transplacental procedure (P = not significant). There were no episodes of amniotic fluid leakage in the first group, whereas 16 ruptures of the membranes that resolved spontaneously occurred in the second group (P<0·01). Our data suggest that transplacental amniocentesis carries a similar abortive risk to and a lower risk of transient rupture of the membranes than non-transplacental amniocentesis and may therefore be preferred at the gestational period examined (15–16 weeks). However, the risk of feto-maternal haemorrhage, which is reported to be higher for a transplacental procedure, must be considered in the case of an anterior placenta.     

Four years' experience of maternal alpha-fetoprotein screening and its effect on the pattern of antenatal care

Estimation of alpha-fetoprotein (A.F.P.) in maternal serum was used as a screening method for the detection of fetal neural tube defect (N.T.D.) in 7315 women over a four year period. Of these, 5668 pregnancies were tested between 15 and 21 weeks. Action was advised in 129 patients (2·3 per cent). In 74 patients, the only action required was reviewing the notes, including the report of any ultrasound examination, and repeating the blood A.F.P. Detailed ultrasound including scanning the fetal spine was requested in 47 patients and amniocentesis was advised in 19 of these (0·33 per cent). In practice the incidence of amniocentesis was 0·28 per cent as three patients declined our advice. The programme gave detection rates between 15 and 21 weeks of 100 per cent and 75 per cent respectively for anencephaly and open spina bifida. A high fetal mortality was associated with persistently elevated blood A.F.P. levels whether amniocentesis was performed or not.     

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.