Amniocentesis results: investigation of anxiety. The ARIA trial. The effect of fast reporting by amnio-PCR on anxiety levels in women with positive biochemical screening for Down syndrome--a randomized controlled trial. Comparison of chorionic villus sampling and amniocentesis for fetal karyotyping at 10-13 weeks' gestation. Reducing the need for amniocentesis in women 35 years of age or older with serum markers for screening. Second trimester maternal serum screening using alpha fetoprotein, free beta human chorionic gonadotropin and maternal age specific risk: result of chromosomal abnormalities detected in screen positive for Down syndrome in an Asian population. Randomised study of risk of fetal loss related to early amniocentesis versus chorionic villus sampling. Implementation of an antenatal serum screening programme for Down's syndrome in two districts (Brighton and Eastbourne). The Brighton and Eastbourne Down's Syndrome Screening Group. Anxiety levels in women undergoing prenatal maternal serum screening for Down syndrome: the effect of a fast reporting system by mobile phone short-message service. Randomized trial comparing first-trimester transcervical chorionic villus sampling and second-trimester amniocentesis.
The Amniocentesis Results: Investigation of Anxiety (ARIA) trial tested two hypotheses: first, that giving amniocentesis results out on a fixed date alters maternal anxiety during the waiting period, compared with a policy of telling parents that the result will be issued 'when available' (i.e. a variable date), and secondly, that issuing early results from a rapid molecular test alters maternal anxiety during the waiting period, compared with not receiving any results prior to the karyotype. The effects of the two interventions on anxiety 1 month after receiving karyotype results were also examined.
                A multi-centre, randomised, controlled, open fixed sample, 2 x 2 factorial design trial, with equal randomisation.
                Twelve hospitals in England offering amniocentesis as a diagnostic test for Down's syndrome.
                A total of 226 women who had had an amniocentesis were randomised between June 2002 and July 2004. Eight women with abnormal results or test failure were excluded post-randomisation.
                Issuing karyotype results on a prespecified fixed date, rather than issuing them as soon as they became available and issuing karyotype results alone, or subsequent to issuing results from a rapid molecular test for the most common chromosomal abnormalities.
                Average anxiety during the waiting period, calculated using daily scores from the short version of the Spielberger State-Trait Anxiety Inventory (STAI). Recalled anxiety, measured 1 month after receiving karyotype results, using a rating scale. Anxiety at the 1-month follow-up, measured using the short-form STAI.
                There was no evidence that giving out karyotype results on a fixed or on a variable date altered maternal anxiety during the waiting period. However, the analysis only had sufficient power to detect a moderate to large effect. Issuing early results from a partial, but rapid, test reduced maternal anxiety during the waiting period, compared with receiving only the full karyotype results. This was a moderate to large effect. In addition, group differences in recalled anxiety reflected fairly closely the differences in anxiety women had experienced while waiting for results. One month after receiving normal karyotype results, anxiety was low in all groups, but women who had been given rapid test results were more anxious than those who had not. This was a small to moderate effect.
                Since there are no clear advantages in anxiety terms of issuing karyotype results as soon as they become available, or on a fixed date, women could be given a choice between them. Rapid testing was a beneficial addition to karyotyping, at least in the short term. This does not necessarily imply that early results would be preferred to comprehensive ones if women had to choose between them. There should be further research, including more qualitative studies, into the causes, characteristics and consequences of anxiety associated with prenatal testing. The effects of different testing regimes on short- and long-term anxiety, on the preferences of women and on the relationship between anxiety and preference should be investigated. More research is needed on the ways in which information might be used to minimise anxiety in different testing regimes. Further research is also required into the policy implications of incorporating individual preferences for different testing regimes into prenatal testing programmes. To study the effect of fast reporting by polymerase chain reaction on amniotic fluid cells (amnio-PCR) on anxiety levels in women with positive biochemical screening for Down syndrome.
                Between May 2000 and April 2001, 60 screen-positive women were randomized before amniocentesis into either having (group A) or not having (group B) fast-reporting by amnio-PCR. Anxiety levels were measured by the Spielberger State-Trait Anxiety Inventory just prior to amniocentesis, three days (when PCR results were known to group A) and three weeks (when standard karyotype results were known to both groups) afterwards.
                Two women were excluded because in one woman amnio-PCR showed trisomy 21 and the other miscarried shortly after amniocentesis. The state-anxiety scores increased over the three-week period after being informed of the positive-screen result in both groups. The trait- and state-anxiety scores at all points did not differ between the two groups.
                In contrast to the general belief, fast reporting by amnio-PCR did not alleviate anxiety in women who are screen-positive for Down syndrome.
                Copyright 2002 John Wiley & Sons, Ltd. We did a prospective study of women with singleton viable pregnancies at 10-13 weeks' gestation who requested first-trimester fetal karyotyping because of advanced maternal age, parental anxiety, or family history of chromosomal abnormality. Women were counselled as to the available options of non-invasive screening or invasive testing by mid-trimester amniocentesis, early amniocentesis (EA), or chorionic villus sampling (CVS), or randomisation to EA or CVS at 10-13 weeks. EA was done in 731 patients (493 by choice and 238 by randomisation) and CVS in 570 (320 by choice and 250 by randomisation). Both procedures were done by transabdominal ultrasound-guided insertion of a 20-gauge needle. The rate of successful sampling was the same for both procedures (97.5%). Spontaneous loss (intrauterine or neonatal death) was significantly higher after EA (total group mean = 5.3%, 95% CI 3.8-7.2; randomised subgroup mean = 5.9%, 3.3-9.7) than after CVS (total group: mean = 2.3%, 1.2-3.9; randomised subgroup: mean = 1.2%, 0.3-3.5). The gestation at delivery and birthweight of the infants after EA and CVS were similar. In the EA group the incidence of talipes equinovarus (1.63%), was higher than in the CVS group (0.56%), but this difference was not significant. As maternal age advances, the risk of fetal Down's syndrome increases. Pregnant women 35 years of age or older are routinely offered amniocentesis because of this risk. Recently, maternal serum markers have been reported to be useful in screening for Down's syndrome, primarily in younger women. We therefore investigated whether offering amniocentesis only to selected women 35 years of age or older who were identified by screening measurements in serum might prove a useful alternative to the current practice.
                We studied 5385 women with singleton pregnancies who were 35 years of age or older and were undergoing routine amniocentesis. Along with information about the pregnancy, we obtained a serum sample for measurement of alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin. Individual estimates of the risk of Down's syndrome in the fetus were calculated for each pregnancy before the karyotype was known.
                If amniocentesis had been reserved for the women calculated to have a risk greater than 1 in 200 of having a fetus with Down's syndrome, 48 of the 54 cases of Down's syndrome (89 percent) would have been identified, 25 percent of the unaffected pregnancies would also have been identified as being at high risk for Down's syndrome (false positives). Seven of 15 fetuses (47 percent) with other trisomies, 11 of 25 (44 percent) with sex aneuploidy, and 1 of 9 (11 percent) with miscellaneous chromosomal abnormalities would also have been detected. In practice, such screening would have made 75 percent of the amniocentesis unnecessary, along with a proportion of the amniocentesis-associated fetal losses. If the cutoff for the risk of Down's syndrome were set higher than 1 in 200, both the rate of detection and the false positive rate would be lower. Conversely, these rates would be higher if the cutoff were set lower.
                Prenatal screening of serum to generate individual estimates of the risk of Down's syndrome in the fetus can provide a basis for decision making in the cases of women 35 years of age or older, as it does in younger pregnant women, and is an alternative to current testing practices. This study was to determine the incidence of chromosome abnormalities in Taiwanese women undergoing prenatal chromosome analysis after a second trimester Down syndrome screening by using maternal age and serum dual-marker testing (alpha-fetoprotein and free-beta unit human chorionic gonadotropin).
                A total of 10,098 Taiwanese women with pregnancy between 15 and 23 weeks' gestation received second-trimester Down syndrome risk evaluation by dual-marker and maternal age specific risk testing in a single medical center. The study took 22 months. Ninety-seven percent of this study population was less than 34 years old. Ninety-six percent of our cases were screened between 15-20 weeks of gestation. This population was included only after a routine ultrasonography scan for correction of gestational age and exclusion of major structural anomalies. By using an algorithm to detect Down's syndrome, with a risk of 1:270 as a cut-off value, 816 patients were screen-positive for Down syndrome (screen-positive rate 8.0%). Karyotypes were reviewed for 670 (82.1%) mothers who received prenatal karyotype analysis.
                Twelve cases of Down syndrome were identified in the screen positive group with an estimated detection rate of 67% (false positive rate 8%). Three cases of Down syndrome were detected in late trimester among the screen-negative group. Seven other fetal chromosome abnormalities were also found among the screen-positive pregnancy. In addition, seven cases were screen-positive for trisomy 18; all of these patients received amniocentesis and only one case was confirmed.
                These findings indicate that this screening program combining alpha-fetoprotein (AFP), free beta human chorionic gonadotropin (free-hCG) and maternal age-specific would achieve a screening efficiency in Taiwanese populations as comparable to those obtained in Caucasian populations. Our results also suggest that approximately 3% of pregnancies with a positive dual marker and maternal age-specific screen results will have a chromosome abnormality despite having a normal routine ultrasound scan. Mothers with positive screening results should be made aware of the implications of a positive result. Several cohort studies have shown the feasibility of early amniocentesis (between 11 and 13 weeks of gestation) as an alternative to chorionic villus sampling (CVS) for karyotyping, but the only completed randomised study of fetal safety showed a significant fetal-loss risk related to first-trimester amniocentesis. We assessed fetal safety in early amniocentesis and CVS.
                We assessed early amniocentesis at 11-13 weeks gestational age compared with the fetal risk associated with CVS at 10-12 weeks. 1160 pregnant women were randomly assigned one procedure (581 early amniocentesis, 579 CVS) after a baseline ultrasound examination at 10 weeks' gestation and were followed up until birth. Total fetal loss and neonatal morbidity were the primary outcome measures. Sampling success and pregnancy complications were secondary outcomes. We used a filter to increase the cell yield in the early amniotic-fluid samples. CVS was transabdominal.
                We found a significantly increased occurrence of talipes equinovarus in the early amniocentesis group (p < 0.01), the risk of which was associated with sampling at the earliest gestational ages and with temporary leakage of amniotic fluid after sampling. Therefore, the trial was stopped early, which reduced the power of the safety study. 4.8% (27) of fetuses in the CVS group and 5.4% (30) in the early amniocentesis group were lost after randomisation (p = 0.66). More detailed survival analysis did not show any significant differences in fetal loss rates. Leakage of amniotic fluid after sampling occurred significantly more frequently after early amniocentesis than after CVS (p < 0.001), but we found no other major differences in pregnancy complications. Significantly more CVS than early amniocentesis procedures were repeated or failed to produce a karyotype (p < 0.01).
                Even though the numbers were small, we found an association between early amniocentesis and talipes equinovarus. We believe this association to be true, since it supports a trend in a similar randomised study. Our results show that early amniocentesis, when done with the filter technique, is associated with an abortion risk similar to CVS, although the limited size of our study population reduced the strength of this conclusion. To evaluate the introduction to two health districts of an antenatal serum screening programme for Down's syndrome using the triple test-measurement of alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin concentrations in second trimester serum samples.
                All women delivering at the main maternity units in both districts were eligible for the screening programme. A serum sample was taken between 15 and 22 weeks' gestation, confirmed by ultrasound scan. An estimated risk of 1 in 250 or greater was considered to be a screen positive result and further diagnostic tests were offered. As far as possible the outcome of all screened pregnancies was recorded, and babies with Down's syndrome born to women who declined serum screening were also identified.
                6990 singleton pregnancies were screened over a two year period, representing an estimated uptake of 67% (6990/ 10,443). After a screen positive result 80% of women (168/211; 95% confidence interval 74.2 to 85.1%) opted for amniocentesis. The false positive rate was 2.9% (203/6979; 95% confidence interval 2.5 to 3.3%). The detection rate in the screened population was 73% (8/11). The estimated cost of identifying one Down's syndrome affected pregnancy was about 31,000 pounds.
                Successful introduction of the triple test to health districts where there is no established serum screening programme for neural tube defects is possible. The programme seems to be acceptable to most of those screened. Uptake of the programme is sufficient to make it more effective than a policy for Down's syndrome screening dependent on age only. To study the effect of fast reporting by mobile phone short-message service (SMS) on anxiety levels in women undergoing prenatal biochemical screening for Down syndrome.
                From January 2005 to December 2006, 2782 women undergoing prenatal biochemical serum screening were randomized into fast reporting by SMS (group A) or without mobile phone reporting (group B). Anxiety levels were measured with the Spielberger State-Trait Anxiety Inventory (STAI) before prenatal screen testing, before the appointed clinic (when the SMS report had already been given to group A), and 3 days after the appointed clinic (when the full screening report had been given to groups A and B).
                For screen-negative women, anxiety scores did not differ between groups before prenatal screen testing and 3 days after the appointed clinic. The state-anxiety scores measured on the second occasion had declined significantly in group A. The state-anxiety scores in both groups increased over the 3-week period after being informed of positive screen results. The trait- and state-anxiety scores at all points did not differ between the two groups of screen-positive women.
                The provision of a routine reporting system plus additional SMS report revealed some overall benefits in reducing anxiety among women with screen-negative result.
                2008 John Wiley & Sons, Ltd A total of 800 patients were randomized at the 9th to 11th week of pregnancy either for transcervical chorionic villus sampling (CVS) on the day of trial entry or for amniocentesis (AC) at the 16th week. The indication for fetal karyotyping was maternal age in 94 per cent of the cases; the mean maternal age was 39.2 years. An adequate sample was obtained in 98.3 per cent of the cases in the CVS group and in all cases in the AC group. Retesting was indicated in 3.3 per cent of the CVS cases. An abnormal karyotype was found in 6.1 per cent of the CV samples and in 4.5 per cent of the amniotic fluid samples. There was one false-positive chromosome result in both groups. Twelve (3.1 per cent) miscarriages occurred by the 22nd week of pregnancy in the CVS group in pregnancies intended to continue. No difference was seen between the groups for total fetal loss rates. The number of surviving infants in the CVS group was 92.2 per cent and in the AC group 91.7 per cent (rate difference 0.5 per cent (95 per cent confidence interval -3.3 to 4.3)). In our study, both the diagnostic accuracy and the risk of fetal loss were equal in the CVS and AC groups.
We found no conclusive evidence that, while waiting for the full karyotype following amniocentesis, issuing results from a rapid analysis reduces maternal anxiety. The limited evidence from the two trials included in this review does not help resolve the dilemma about whether full karyotyping should be abandoned in favour of limited rapid testing for women undergoing Down's syndrome screening. This choice will rest on clinical arguments and cost-effectiveness rather than impact on anxiety.
There is also no evidence to support the view that issuing amniocentesis results as soon as they are available is more user friendly than using a pre-defined fixed date. Studies evaluating the effect of different strategies for disclosing results on women anxiety for CVS are needed.