Prenatal diagnosis and psychological distress: Amniocentesis or chorionic villus biopsy?

The psychological reactions of 211 women undergoing prenatal diagnosis (PND) with amniocentesis (group A, n = 122) or chorionic villus biopsy (group V, n = 90) were exmained by questionnaires and interviews. The distress experienced while waiting for the test, during the test procedure, and while waiting for the result was reported by the women, both in questionnaires and in interviews. In the questionnaires, no difference between the two diagnostic methods was observed. In the interviews, however, the women undergoing amniocentesis appeared significantly more distressed by the procedure. In group A 97 per cent and in group V 100 per cent wished a method which, like chorionic villus biopsy, could be used in the first weeks of pregnancy. The risk of miscarriage was, as described in other studies, regarded as a serious threat by the pregnant women.     

Psychological reactions to fetoscopy: A controlled study

Twenty woman at risk of carrying a fetus with homozygous beta-thalassemia who underwent fetoscopy and a matched control group of pregnant women were administered the Symptom Questionnaire to evaluate changes in distress. Women who were offered fetoscopy had significantly more anxiety, depression, somatic symptoms and hostility than the control group. Psychological distress significantly decreased after the results of fetoscopy were communicated to the patient, and the decrease was similar in normal control women. Five other patients had a diagnosis of homozygous beta-thalassaemia and their pregnancies were terminated. Their psychological distress increased when they learned the outcome of fetoscopy, but decreased again after termination. Psychological reactions to fetoscopy and amniocentesis appear to be similar, yet women who undergo fetoscopy suffer from more psychological distress.     

Mid-trimester fetal sex determination from maternal peripheral blood by fluorescence in situ hybridization without enrichment of fetal cells

To determine the fetal sex on 30 women who were 16–20 weeks pregnant, about 100 000 maternal blood nucleated cells were analysed by means of fluorescence in situ hybridization (FISH) with a Y-chromosome-specific DNA probe. Cells with the hybridization signal were detected in 12 of the 30 women. All the 12 mothers gave birth to a male child. Of the other 18 women who had no Y-positive cells in the peripheral blood, 14 gave birth to a female child and four gave birth to a male child. These false-negative results probably occurred because the number of cells examined was inadequate. The data obtained in this study suggest that fetal sex determination using maternal peripheral blood with FISH is possible and that this diagnostic method will be clinically useful when more cells are analysed.     

Decision making during the prenatal diagnostic procedure. A questionnaire and interview study of 211 women participating in prenatal diagnosis

Counselling in connection with prenatal diagnosis (PND) is a common task for the obstetrician and the midwife. However, the decision making processes of pregnant women are not completely known, for instance, the questions of women's autonomy, the decision on how to act in the case of an abnormal test, and the partner's participation in the decision. A questionnaire and interview study was carried out among 211 women undergoing PND by amniocentesis or chorionic villus biopsy. Most women in the sample indicated that PND was completely voluntary. However, at the same time almost every woman reported that it was difficult to decline from PND when offered. Even before the visit to register at the antenatal clinic, most of the women (83 per cent) had made up their minds to have PND. At the time of the test, many of the participants (62 per cent) had decided in favour of a legal abortion if the test indicated an abnormality in the fetus. At the same time, however, the data indicate a need for reflection and ambivalence, which the medical staff have to accept. In the questionnaire most of the women stated that they and their partners had similar attitudes towards PND, but when interviewed 38 per cent of the women admitted some differences between their own attitudes and their partners'. Although some women reported considerable deliberation and ambivalence, most of them said that they would undergo PND in another pregnancy.     

Temporal changes in Ohio amniocentesis utilization during the first twelve years (1972–1983), and frequency of chromosome abnormalities observed

The history of amniocentesis utilization in the seventh largest state of the United States is documented from its inception in 1972 through the first half of 1984. Amniocentesis utilization ratios for Ohio residents aged ⩾35 have increased from 0.21 per cent (19/9091) in 1972 to 23.4 per cent (1655/7531) in 1983, representing an average annual growth rate of 43.1 per cent. Of the amniocenteses performed from January 1, 1978–July 1, 1984, 71 per cent were referred for advanced maternal age (⩾35), 15 per cent for maternal anxiety (30–34), 10 per cent for family history or previous child with a genetic defect, and 4 per cent for other reasons. Between 1978-1983 utilization by women 45 years of age was only 20 per cent higher than women 35 even though their risk of giving birth to a Down syndrome child was about one order of magnitude higher. In addition, various factors were tested as to whether they affected utilization of amniocentesis by women ⩾35 during 1978 1983. A strong correlation of +0.89 existed between county population size and utilization ratios. No difference in utilization was found between whites and nonwhites, regardless of county population size. When utilization ratios were compared separately between Protestants, Catholics and other religions in Ohio's most populated county, no statistical differences were found. From 1978–July 1, 1984, the frequency of all cytogenetically abnormal chromosome results observed in Ohio amniocenteses to women ⩾35 was 2.48 per cent (187/7536). Of these, 2.15 per cent (162/7536) had unbalanced karyotypes. Future maximum amniocentesis utilization for women ⩾35 is estimated at 60–70 per cent.     

The psychological effects of false-positive results in prenatal screening for fetal abnormality: A prospective study

The purpose of the study was to describe the impact of false-positive results from initial maternal serum alpha-fetoprotein (MS-AFP) screening. The analyses compared two groups of women, those receiving a negative result (n = 346) and those receiving an initial positive result (n = 26), over four time points—prior to testing, immediately after testing, later in pregnancy, and in the post-partum period. Receiving an abnormal result was associated with high levels of anxiety which were reflected in increased worry about the baby's health and a more negative attitude towards the pregnancy and the baby. Women who had an initial abnormal result were offered a variety of further tests. Those women who went on to have amniocentesis were less worried about their baby's health in the third trimester and also less anxious post-partum than those who did not have amniocentesis. In view of the increasing number of screening tests available, it is necessary to establish whether and how these levels of distress can best be reduced.     

Women's opinions on the offer and use of maternal serum screening

We studied the opinions and experiences concerning maternal serum screening of two groups of women: (A) women who were not eligible for prenatal diagnosis; and (B) women for whom prenatal diagnosis was available because of advanced maternal age, and who either underwent chorionic villus sampling or amniocentesis. Many of the women were in favour of the availability of serum screening and would apply for this test in a future pregnancy. This applied also to many respondents who had previously undergone prenatal diagnosis. Most of these women, however, did not intend to decline diagnostic amniocentesis if the screening results did not indicate an increased risk. The majority of the group of respondents of 36 years and over did not consider it acceptable if age indication was dropped altogether. A system based on serum screening will have other implications than a policy based on age indication, since specific individual risk assessment is perceived as being of more significance than a risk statistically derived from age alone. Serum screening is often seen as a means of reassurance and many women are not aware of the possible drawbacks. As technology becomes increasingly complicated, counselling has to be adjusted correspondingly. Further research is needed to establish whether and how distress can be minimized and well-considered individual choice can be achieved.     

Rh isoimmunization following genetic amniocentesis

A series of 8009 genetic amniocenteses were retrospectively examined to evaluate the relationship of the procedure to Rh isoimmunization. Of the 615 Rh negative women giving birth to Rh positive infants and estimated to be at risk, thirteen (2·1 per cent) were sensitized subsequent to the amniocentesis. Eleven of the sensitizations occurred early in the programs, and a combination of experience and ultrasound performed concurrently with the amniocentesis appear to have reduced the risk of isoimmunization to that of control data from the literature.     

Antenatal gene tests in low-risk pregnancies: molecular screening for aspartylglucosaminuria (AGU) and infantile neuronal ceroid lipofuscinosis (INCL) in Finland

Approximately one in five subjects in Finland carries some gene defect associated with 30 diseases belonging to the Finnish disease heritage, and about one in 500 children born is affected. Almost all carriers, women and men, are unaware of their condition. Recent advances in molecular medicine have offered the possibility of population-based carrier screening for recessive disorders. We studied acceptance and attitudes to antenatal screening for aspartylglucosaminuria (AGU) and infantile neuronal ceroid lipofuscinosis (INCL). From January 1995 until December 1996 carrier tests were offered at Kuopio City Health Center, free of charge to all pregnant women attending maternity care units. Women found to be carriers of AGU (n=47) or INCL (n=14) underwent detailed genetic counseling, and their male partners were also offered the test. If both partners appeared to be carriers we offered prenatal testing (n=1). No affected fetuses were detected. Attitudes towards the gene test were elicited by means of a questionnaire. Altogether 87% of pregnant women elected to undertake the gene tests. Antenatal screening for gene defects was feasible and well accepted, and it provided an effective way to find carriers of genetic diseases and to incorporate prenatal testing into this process. Copyright © 2001 John Wiley & Sons, Ltd.     

The impact of prenatal diagnosis on the occurrence of chromosome abnormalities

From the public health point of view, several formal attempts have been made to measure the impact of prenatal diagnosis (PND) on the incidence of Down's Syndrome (DS), but the results have varied widely. The impact of PND (reduction in the birth rate of chromosomally abnormal neonates) is related to utilization rates but quantitative estimates of this have not been established. In a three-year (1981–1983) total population study from Queensland, Australia, we present results to measure the impact of a voluntary PND programme on the birth incidence of DS, and also other chromosomally abnormal births. Utilization rates for the PND service were 15·5 per cent in that population of mothers 35 years and over. Numbers and rates of all cases of chromosomal abnormalities are presented, subclassified by type of diagnosis–-either by PND or by clinical diagnosis after birth. For the total population, 7·3 per cent of cases of DS were detected prenatally, and 15·4 per cent of all chromosome abnormalities. (A method for measuring the impact of PND is described.) Using this in conjunction with our demographic data, we estimate that with a 15 per cent utilization rate of PND by older mothers, 14 per cent of DS births can be prevented in this age group, or a 5 per cent overall reduction can be achieved if mothers of all ages are considered. One index–-the ratio of the percentage of DS births which are preventable compared with the population utilization rates of PND–-has potential for widespread use. Queensland data for this ratio is 0·34, a figure consistent with that from other studies. Thus a 3·5 per cent drop in the overall DS birth rate may be expected for each 10 per cent increase in the utilization rates of PND for mothers of 35 years and over. A diagram is presented which may serve as a model for improved data collection and better impact estimates in the future.     

Prenatal diagnosis of carnitine palmitoyltransferase 2 deficiency in chorionic villi: a novel approach

Carnitine palmitoyltransferase 2 (CPT2) deficiency, the most common autosomal recessive inherited disease of the mitochondrial long-chain fatty acid (LCFA) β-oxidation, may result in three distinct clinical phenotypes, namely, a mild adult muscular form, a severe infantile hepatocardiomuscular disease, and a neonatal form, which includes dysmorphic features in addition to hepatocardiomuscular symptoms. Both the latter forms are life-threatening diseases, and prenatal diagnosis (PND) can be offered to couples at a one-fourth risk of having an affected child. PND of CPT2 deficiency hitherto relied mostly on mutation detection from fresh chorionic villi (10 weeks' gestation), since CPT2 activity could be assayed on cultured amniocytes only (16–17 weeks' gestation). We devised a CPT2 activity assay from 10 mg of chorionic villi sampling (CVS). Combining this enzymatic assay to haplotype study using polymorphic markers linked to the CPT2 gene, we were able to carry out within 2 days, CPT2 deficiency PND, in two unrelated families, using a CVS performed at the 11th week of gestation. Copyright © 2003 John Wiley & Sons, Ltd.     

The impact of non-invasive prenatal testing on anxiety in women considered at high or low risk for aneuploidy after combined first trimester screening

Objective: The aim of this study was to (1) examine the psychological impact of non-invasive prenatal testing (NIPT) in women with a high-risk (≥1 : 300) and low-risk (≤1 : 301) result on combined first trimester screening (cFTS) and (2) to examine factors influencing anxiety and decision-making in both risk populations. Method: Questionnaires and structured interviews were administered to low (n = 50) and high (n = 63) risk women at the time of NIPT blood draw (point A) and again at least 1 week after receiving their NIPT result (point B). Anxiety levels were measured at these two time points using the State–Trait Anxiety Inventory. Results: Both high-risk and low-risk cFTS groups demonstrated similar intrinsic (trait) anxiety levels (36 ± 10 vs 35 ± 10; p = 0.70). High-risk women had significantly higher levels of state anxiety at point A than low-risk women (42 ± 11 vs 36 ± 11; p < 0.01). Both groups had a statistically significant reduction (p < 0.01), to similar final levels of state anxiety at point B (30 ± 11 vs 29 ± 8; p = 0.61). Conclusion: Women receiving a high-risk result on cFTS have higher levels of state anxiety than their low-risk counterparts. Following a low-risk NIPT result, the anxiety levels in both populations are reduced to similar levels. © 2017 John Wiley & Sons, Ltd.     

Detection rates and residual risk for a postnatal diagnosis of an atypical chromosome aberration following combined first-trimester screening

Objectives

To determine the detection rates of all types of chromosome aberrations and the residual risk for postnatal diagnosis of an atypical chromosome aberration depending on the strategy for further investigation with either noninvasive prenatal testing (NIPT) or invasive testing in pregnancies with increased risk following combined first-trimester screening (cFTS).

Methods

A review of all pregnancies examined with cFTS during 2010 to 2017.

Results

The cohort consisted of 129 493 pregnancies. There were 852 (0.7%) clinically significant chromosome aberrations, including aberrations detected later on or after birth. A total of 12% were atypical chromosome aberrations. Considering that 40% were detected due to a miscarriage/intrauterine fetal death or a malformation on ultrasound there is a 0.05% (1:2000) background risk of a postnatal diagnosis of a liveborn child with an atypical chromosome aberration if no further invasive test is performed during pregnancy. If all women with an increased risk (≥1:200) had an invasive test and NIPT was performed up to a risk of 1:1000, 95% of common trisomies/sex chromosome aberrations and 55% of atypical aberrations would be detected.

Conclusions

If NIPT was offered to all women with an increased risk following cFTS it would imply that three times as many children would be born with an atypical chromosome aberration.     

Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome

An Erratum has been published for this article in Prenatal Diagnosis 21(7) 2001, 605. Prenatal diagnosis (PD) of fetal cytomegalovirus (CMV) infection was performed in 242 pregnancies, with known outcome in 189 cases. In 141/189 pregnancies, PD was carried out on account of suspicious maternal CMV serology up to gestational week (WG) 23, and in 48 cases on account of abnormal ultrasonic findings detected between WG 18 and 39. Chorionic villus samples (n=6), amniotic fluid (AF, n=176) and/or fetal blood specimens (n=80) were investigated for detection of virus by cell culture, shell vial assay, PCR and/or CMV-specific IgM antibodies. Of 189 fetuses correctly evaluated by CMV detection either in fetal tissue following therapeutic abortion/stillbirth (n=24) or in urine of neonates within the first 2 weeks of life (n=33), 57 were congenitally infected. In women with proven or suspected primary infection, the intrauterine transmission rates were 20.6% (7/34) and 24.4% (10/41), respectively. Of the congenitally infected live-born infants, 57.6% (19/33) had symptoms of varying degree. The overall sensitivity of PD in the serologic and ultrasound risk groups was 89.5% (51/57). A sensitivity of 100% was achieved by combining detection of CMV-DNA and CMV-specific IgM in fetal blood or by combined testing of AF and fetal blood for CMV-DNA or IgM antibodies. There was no instance of intrauterine death following the invasive procedure. The predictive value of PD for fetal infection was 95.7% (132/138) for negative results and 100% (51/51) for positive results. Correct results for congenital CMV infection by testing AF samples can be expected with samples obtained after WG 21 and after a time interval of at least 6 weeks between first diagnosis of maternal infection and PD. In case of negative findings in AF or fetal blood and the absence of ultrasound abnormalities at WG 22–23, fetal infection and neonatal disease could be excluded with high confidence. Positive findings for CMV infection in AF and/or fetal blood in combination with CMV suspicious ultrasound abnormalities predicted a high risk of cytomegalic inclusion disease (CID). Furthermore, detection of specific IgM antibodies in fetal blood was significantly correlated with severe outcome for the fetus or the newborn (p=0.0224). However, normal ultrasound of infected fetuses at WG 22–23 can neither completely exclude an abnormal ultrasound at a later WG and the birth of a severely damaged child nor the birth of neonates which are afflicted by single manifestations at birth or later and of the kind which are not detectable by currently available ultrasonographic techniques. Copyright © 2001 John Wiley & Sons, Ltd.     

Fetal and neonatal alloimmune thrombocytopenia: prenatal interventions

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating condition, which may lead to intracranial haemorrhage (ICH) in the fetus or neonate, often with death or major neurological damage as consequence. In the absence of screening, preventive measures are only possible in the next pregnancy of women with an affected child. Controversy exists on the best intervention to minimise the risk of ICH. Most centres have abandoned treatment with serial fetal blood sampling (FBS) and platelet transfusions, because of a high rate of complications and the availability of quite effective non-invasive alternatives. In pregnancies with FNAIT and a previous affected child without ICH, weekly intravenous administration of immunoglobulins to the mother appears close to 100% effective to prevent fetal or neonatal ICH. Some centres add prednisone; this combination leads to slightly higher platelet counts at birth. In pregnant women with a previous child with ICH, the recurrence risk seems particularly high, and more aggressive maternal medical treatment is recommended, starting earlier with immunoglobulins. Whether a higher intravenous immunoglobulin dose or the addition of prednisone is really necessary is unclear. What does seem to be clear is that the use of FBS should be minimised, possibly even abandoned completely. Copyright © 2011 John Wiley & Sons, Ltd.     

Fetal chromosome analysis: Screening for chromosome disease?

The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocenteses performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were compared to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25–34 years of age, in whom all heritable diseases were excluded (group Q. The risk of unbalanced chromosome abnormality in group A (women with elevated risk) is significantly higher than in group B + C (women without elevated risk) (relative risk 2–4). Women with a known familial translocation and women 40 years or more have a relative risk of 5–7 of having an unbalanced chromosome abnormality compared with women without elevated risk. Spontaneous abortion rate and prematurity rate did not differ from rates expected without amniocentesis. It is concluded that current indications may be characterized as a mixture of evident high risk factors and factors with only a minor influence on risk. Indications for amniocentesis should therefore be reconsidered. Because it must be considered impractical and ethically wrong to limit amniocentesis to the two mentioned real high risk groups, and illogical to continue the present policy, which is not based on clearcut evidence, the possibility of offering amniocentesis to all who want it, is discussed. Screening for chromosome disease in all pregnancies is not without problems, but may be reasonable in some localities.     

Prenatal cystic fibrosis carrier screening: Factors in a woman's decision to decline testing

Among 2207 women eligible to be screened for cystic fibrosis (CF) carrier status during pregnancy, 325 (15 per cent) declined to be tested. Of these, 260 (80 per cent) answered a questionnaire soliciting their reasons for not participating. The main factor was opposition to termination of pregnancy, with 43 per cent being against termination for any reason and another 11 per cent against termination of a CF fetus. Other reasons given were partner's disapproval or non-participation (10 per cent), perceived risk of a CF child being low (7 per cent), the error rate of the test (6 per cent), and the generation of unacceptable levels of anxiety (5 per cent). Eleven women (4 per cent) said that they did not wish to be tested during pregnancy, but only six of these would have accepted screening at another time.     

Optimising the timing for nuchal translucency measurement

It appears from current evidence that the most effective screening strategy for Down syndrome will involve a combination of first trimester nuchal translucency and serum biochemistry, whether performed in the first or second trimester. The aim of this study was to determine the optimum gestation based upon menstrual dates at which to schedule nuchal translucency (NT) measurement for the evaluation of fetal Down syndrome risk. Five thousand eight hundred and thirty-five pregnancies had an ultrasound scan scheduled between 11 and 14 completed weeks of gestation based upon either the last menstrual period (n = 3199) or a prior ultrasound scan (n = 2636). For last menstrual period-based ultrasound scans, with advancing gestation the frequency of missed miscarriage significantly decreased (p = 0.009, chi squared test), as did the need to reschedule a further scan because the gestation of the scheduled scan was too early to measure NT (p < 0.0001, Chi-squared test). In contrast, with advancing gestation the rate of unsuccessful NT measurement because the crown–rump length (CRL) was greater than 84 mm significantly increased (p < 0.0001, Chi-squared test). Of the women who had had an earlier ultrasound, 42 (1.6%) had a missed miscarriage and 9 (0.3%) were over gestation at the time of the NT scan. These data suggest that when only the last menstrual period is known the optimum time to schedule a nuchal translucency measurement is at 12 to 13 weeks' gestation. Copyright © 2002 John Wiley & Sons, Ltd.     

Risk for chromosome abnormality at amniocentesis following a child with a non-inherited chromosome aberration a european collaborative study on prenatal diagnoses 1981

Based on 2890 prenatal diagnoses from 12 European countries the risk for a chromosomally abnormal fetus at amniocentesis after the birth of a child with a chromosome abnormality has been estimated to be 1.3 per cent when the mother's age is 34 years or less at amniocentesis and 1.8 per cent if the mother is older. This risk does not depend on paternal age, and it is independent of the type of the chromosome abnormality of the index child. Some geographical heterogeneities were detected. Therefore, the overall risk has to be considered as a rough estimate. The chromosome constitution of the abnormal fetus differed from that of the index patient in 21 of 41 cases. Several explanations for the higher risk have been discussed. If the index child had trisomy 18, 13 or a sex chromosome abnormality, the fetus tended to be a female. If the index child was a trisomy 21, the fetal sex ratio was normal.     

Reasons for women's non-uptake of amniocentesis

More than 10 years after a chromosomal anomaly screening programme was set up in France for pregnant women of advanced age, amniocentesis is still a controversial issue. The reasons why eligible women did not utilize the test and whether or not the existence of social welfare coverage determined women's access to prenatal diagnosis were studied. A group of 291 women aged ⩾35 years who recently gave birth to normal liveborns was interviewed by telephone. Among those aged 38 years and over, who automatically qualified for social security coverage, 75 per cent had undergone amniocentesis as opposed to 23 per cent in the 35 to 37-year-old non-covered age group who did not qualify for social security coverage. In both groups, access to amniocentesis was found to depend on the physicians', women's and male partners' attitudes towards prenatal diagnosis and abortion. Among the younger group, the uptake depended mainly on socio-economic factors. Institutional policies should ensure greater equality of access while allowing for individual preferences.