Safety Of Chorionic Villus Sampling Research Articles

Prenatal diagnosis of single gene disorders and role of multidisciplinary cooperative mode

Objective To evaluate the trend in prenatal diagnosis of single gene disorders (SGD) and role of multidisciplinary cooperative mode. Methods In January 1, 2012, a multidisciplinary cooperative mode for SGD diagnosis was established in the Peking University First Hospital, involving Departments of Obstetrics, Pediatrics, Neurology, Dermatology and Central Laboratory. For each pregnant woman with a family history of SGD for prenatal diagnosis, propositus should be diagnosed in the relevant departments, and then further diagnosed, managed and followed up by the Obstetrics Department. Up to December 31, 2014, of 6 681 women for prenatal diagnosis, 279 women had a family history of SGD: 76 of them received chorionic villus sampling (CVS) at 11 – 14 gestational weeks, and 203 received amniocentesis (AC) at 16 – 22 gestational weeks. The trend in SGD diagnosis and the safety of CVS and AC were analyzed using Chi–square test. Results The proportion of SGD family history in AC group was 3.2% (203/6 355), which stayed stable with 2.3% (47/2 054) in 2012, 3.9% (78/2 023) in 2013 and 3.4% (78/2 278) in 2014, and there was no significant difference between 2013 and 2014 (χ2=0.571, P=0.463). In CVS group, the proportion of SGD family history was 23.3% (76/326), showing an increasing trend with 18.2% (8/44) in 2012, 17.6% (19/108) in 2013 and 28.2% (49/174) in 2014, and there were significant differences between 2013 and 2014 (χ2=4.067, P=0.046). The proportion of SGD family history in CVS group was higher than in AC group in year 2012, 2013 and 2014 (χ2=42.626, 44.531 and 201.400, all P=0.000). Among the 279 cases of SGD family history, no complications and adverse outcome were observed except an intra–uterine fetal death occurring 6 months after CVS in one woman, but 3 fetuses were found to have chromosome anomalies with one trisomy 18, one 45, X, and one mosaicism of 45,X/46,XY which was determined to be normal by AC. Conclusions SGD family history is one of the important indicators in prenatal diagnosis, and CVS is feasible for prenatal diagnosis of SGD family history as early as in the first trimester. Multidisciplinary cooperative mode is helpful in SGD family history diagnosis. Key words: Genetic diseases, inborn; Prenatal diagnosis; Chorionic villi sampling; Pregnancy trimester, first

Safety of Chorionic Villus Sampling in the Presence of Asymptomatic Subchorionic Hematoma

Objective: According to our knowledge the safety of chorionic villus sampling (CVS) has not been studied in the presence of subchorionic hematoma (SCH). Our study aimed to evaluate the effects of CVS on the procedure-related fetal loss rate in patients with SCH. Method: Fifty-six patients with asymptomatic SCH (cases) and 986 controls in whom there was no hematoma underwent elective CVS for a prenatal diagnosis of β-thalassemia and were entered into a prospective study. Mean gestational age (±SD) at diagnosis for the case and control groups were 11.07 weeks (±0.95, range 10–13 weeks) and 11.51 weeks (±1.04, range 10–13 weeks), respectively. Procedural fetal loss rates were evaluated in these groups after follow-up until 28 weeks of gestation. Results: The average hematoma volume (±SD) was 1.83 ml (±1.57, range 0.3–10.0 ml). Post-CVS early fetal loss was seen in 3.57% (2/56) of patients in the case group and 1.62% (16/986) of patients in the control group. Late fetal loss (up to the 28th week) in the case and control groups was 8.16% (4/49) and 3.76% (29/771), respectively. Post-CVS early fetal loss was seen in 2.44% (1/41) of patients with small-sized SCH (<20% of gestational sac circumference) and in 6.67% (1/15) of patients with medium-sized SCH (20–50% of gestational sac circumference). Comparison of procedure-related early and late fetal loss in the case and control groups using Fisher’s exact test demonstrated no statistically significant difference (p value = 0.252, p value = 0.128). Difference in CVS-related early fetal loss in small- and medium-sized hematoma groups (6.67 vs. 2.44%) was not significant either (p value = 0.468). Conclusion: We were unable to detect any statistically significant difference in fetal loss rate after performing CVS in patients with SCH in comparison to the control group. However, it seems that fetal loss rate may be higher in the presence of medium-sized (20–50% of gestational sac circumference) SCH and further cases are necessary to evaluate the safety of doing CVS in this group.

Transcervical chorionic villus sampling in multiple pregnancies using a biopsy forceps

The aim of this study was to assess the effectiveness and safety of chorionic villus sampling (CVS) performed in multiple pregnancies by means of a transcervical biopsy forceps. The study included CVS performed from January 1990 to March 2000 in our Unit. The results were analysed in two consecutive periods, period A (1990-1994) and period B (1995-2000), in an attempt to assess the effect of increasing experience. Seventy-five samplings were performed in 39 multiple pregnancies, 38 twin sets and one triplet. A cytogenetic report was obtained in 73% of cases in period A and in 98% in period B. An abnormal karyotype was observed in 11 samples. The need for subsequent amniocentesis decreased from 38% in period A to 10% in period B. The spontaneous fetal loss rate in chromosomally and structurally normal fetuses before the 20th week decreased from 8.7% in period A to 3.3% in period B. The fetal loss rate after the 20th week was 3.3% in period B and none in period A. It must be noted that in three out of the four cases of fetal loss an amniocentesis was needed after CVS. Our results suggest that effectiveness and safety improved with increasing experience. Transcervical chorionic villus sampling allows an earlier prenatal genetic diagnosis in multiple pregnancies and this may be particularly relevant for a safer selective termination when chosen by parents if one of the fetuses has an abnormal karyotype.

The Safety of Chorionic Villus Sampling A Synthesis of the Literature

Altogether 10 reports on the safety of chorionic villus sampling, either by the transcervical (TC) or the transabdominal (TA) approach, were reviewed and combined with our own data. After discussion of how unintended fetal loss rates are best estimated, the excess total fetal loss after TC and TA compared with amniocentesis were estimated to be 1.70% (+/- 0.65%) and practically zero (+/- 1.0%), respectively (standard errors in parentheses). The absolute risk of unintended loss after TC is +2.7% (+/- 0.7%) and after TA 1.0% (+/- 1.0%). These estimates are still too uncertain to allow precise weighting of benefits and human costs. A uniform style of reporting studies in this area is proposed.

Low Fetal Loss Rates after Ultrasound-Proved Viability in Early Pregnancy

Once pregnancy is recognized clinically, it is accepted that 12% to 15% undergo spontaneous abortion. However, the actual time of fetal demise has not yet been determined. To address this question, the outcomes of pregnancies identified before 21 days of conception by serum β-human chorionic gonadotropin assays were studied. All subjects underwent ultrasound examinations at eight and 12 weeks' gestation. Among 220 women who had a viable pregnancy at eight weeks, only seven (3.2%) experienced a fetal loss thereafter. The results of this study suggest that most clinically recognized spontaneous abortions manifested after eight weeks actually represent pregnancies in which fetal demise occurred before eight weeks. These findings have important implications with respect to the safety of chorionic villi sampling and to the identification of exogenous agents that cause fetal wastage. ( JAMA 1987;258:2555-2557)

Spontaneous Fetal Loss after Demonstration of a Live Fetus in the First Trimester

Chorionic villus sampling is being considered as an alternative to amniocentesis for genetic evaluation. The risk of subsequent spontaneous abortion from this invasive procedure, however, remains unclear. A prospective analysis of pregnancy outcome after ultrasound documentation of fetal viability at eight to 12 weeks' gestation was carried out in an uninstrumented population of patients to establish a background loss rate against which to evaluate the safety of chorionic villus sampling. All patients presenting to the authors' private practice from December 1983 to January 1986 were enrolled in the study. An ultrasound examination was performed at the first visit to confirm intrauterine pregnancy and assess gestational age; in gestations less than eight weeks, the sonogram was repeated four weeks later. Four hundred eighty-nine delivered patients are the subject of this study. We evaluated the differences between this group and those patients presenting either with a blighted ovum or beyond the first trimester, as well as the outcome of those patients with spotting early in gestation. This study suggests that if a live fetus is documented by ultrasonography at eight to 12 weeks' gestation, the risk of spontaneous abortion before 20 weeks' gestation in an uninstrumented population is 2.0%.

Low Fetal Loss Rates After Ultrasound-Proved Viability in Early Pregnancy

Once pregnancy is recognized clinically, it is accepted that 12% to 15% undergo spontaneous abortion. However, the actual time of fetal demise has not yet been determined. To address this question, the outcomes of pregnancies identified before 21 days of conception by serum beta-human chorionic gonadotropin assays were studied. All subjects underwent ultrasound examinations at eight and 12 weeks' gestation. Among 220 women who had a viable pregnancy at eight weeks, only seven (3.2%) experienced a fetal loss thereafter. The results of this study suggest that most clinically recognized spontaneous abortions manifested after eight weeks actually represent pregnancies in which fetal demise occurred before eight weeks. These findings have important implications with respect to the safety of chorionic villi sampling and to the identification of exogenous agents that cause fetal wastage.

1 Techniques of chorion villus sampling

Whilst randomized studies into the safety of chorionic villus sampling (CVS) are already under way the technique is now offered as an acceptable alternative to amniocentesis in many diagnostic centres. In counselling, the obstetrician can now quote a risk to the pregnancy of 2-4% which, even if the inevitable losses before 16 weeks are excluded, represents probably at least twice the risk of amniocentesis. The evolution of the obstetric procedures has meant that the transcervical approach to CVS has been the most popular to date but there is now increasing interest in transabdominal aspiration as it minimizes the possibility of infection. The two best known transcervical methods are aspiration with a plastic or metal cannula and biopsy with rigid forceps. The majority of aspirations have been performed using the Portex cannula technique. Using this, three centres (Milan, Chicago and Philadelphia) have had experience of over 5000 cases with a failure rate of less than 1% and a minimal fetal loss of 2.2%. However, the proportion of fetal losses may be between 4 and 7% by the time complete obstetric follow-up is available (Brambati et al, 1985). A similar technique has been used with a variety of cannulae. The experience of the first 1000 cases from San Francisco (Hogge et al, 1986) led them to conclude that CVS by this technique was acceptably safe but that continuing investigation was needed before CVS was offered routinely as an alternative to amniocentesis. The only other transcervical technique that is practical for routine use is biopsy with rigid forceps. The failure and fetal loss rates associated with this method are comparable to the aspiration technique. The pioneering work of Hahnemann and his colleague Smidt-Jensen has established transabdominal aspiration as a reliable alternative approach. Its main advantage should be to minimize the risk of infection which is inherent in all transcervical techniques. In addition, it does not need to be confined to 9-11 weeks gestation and thus offers couples the possibility of diagnosis between 12 and 14 weeks rather than waiting for amniocentesis at 16 weeks. The quality and quantity of the sample depends on the size of the needle used and the technique is said to have high patient acceptability. Nevertheless, fetal losses occur following the procedure (1.8-3.2%) and it may not always be successful (failure rate 1.9-4.2%).