Impact of introduction of noninvasive prenatal testing on uptake of genetic testing in fetuses with central nervous system anomalies.

OBJECTIVE: To evaluate the impact of introduction of noninvasive prenatal testing (NIPT) on the uptake of invasive testing in pregnancies complicated by fetal central nervous system (CNS) anomalies. METHODS: Retrospective review of all singleton pregnancies complicated by fetal CNS anomalies seen at a single tertiary center between 2010 and 2017. Cases who had undergone invasive testing or NIPT prior to the diagnosis of the CNS anomaly were excluded. Cases were segregated according to whether they were seen prior to introduction of NIPT (group A, 2010-2013) or thereafter (group B, 2014-2017). We examined the rate of invasive and noninvasive genetic testing in each group. RESULTS: We retrieved 500 cases: 308 (62%) were isolated CNS anomalies, and 192 (38%) had additional structural anomalies. In the total cohort, 165 women (33%) underwent expectant management with no further prenatal genetic testing, 166 (33%) had invasive testing, 52 (10%) had NIPT, and 117 pregnancies (23%) were terminated without further prenatal investigations. The introduction of NIPT significantly decreased the number of pregnancies having no testing (44% group A vs 22% in group B, p < .0001), particularly in the group presenting with isolated ventriculomegaly, but did not affect the uptake of invasive testing (34% vs 32%, respectively; p = .61). NIPT would have missed 4% of pathogenic copy number variants (CNVs) in the group of cases with isolated brain anomalies and 11% of CNVs in cases with complex anomalies. CONCLUSIONS: Uptake of invasive prenatal testing in fetuses with brain anomalies was not affected by NIPT. However, the incidence of no genetic testing was significantly reduced. NIPT was a suboptimal testing strategy in this population as it missed a significant number of subchromosomal genetic anomalies.

Invasive Prenatal Diagnostic Testing Recommendations are Influenced by Maternal Age, Statistical Misconception and Perceived Liability.

Funding policy and medico-legal climate are part of physicians' reality and might permeate clinical decisions. This study evaluates the influence of maternal age and government funding on obstetrician/gynecologist recommendation for invasive prenatal testing (i.e. amniocentesis) for Down syndrome (DS), and its association with the physician's assessment of the risk of liability for medical malpractice unless they recommend amniocentesis. Israeli physicians (N = 171) completed a questionnaire and provided amniocentesis recommendations for women at 18 weeks gestation with normal preliminary screening results, identical except aged 28 and 37. Amniocentesis recommendations were reversed for the younger ('yes' regardless of testing results: 6.4%; 'no' regardless of testing results: 31.6%) versus older woman ('yes' regardless of testing results: 40.9%; 'no' regardless of testing results: 7.0%; χ2 = 71.55, p < .01). About half of the physicians endorsed different recommendations per scenario; of these, 65.6% recommended amniocentesis regardless of testing results for the 37-year-old woman. Physicians routinely performing amniocentesis and those advocating for amniocentesis for all women ≥ age 35 were approximately twice as likely to vary their recommendations per scenario. Physicians who perceived risk of liability for malpractice as large were nearly one-and-a-half times more likely to vary recommendations. The results indicate physicians' recommendations are influenced by maternal age, though age is already incorporated in prenatal DS risk evaluations. The physician's assessment of the risk that they will be sued unless they recommend amniocentesis may contribute to this spurious influence.

Maternal Anxiety and the Second-Trimester Prenatal Screening: A Prospective Cohort Study.

OBJECTIVE: Assessing the effects of maternal anxiety on the markers and results of quadruple screening and on maternal anxiety after receiving positive results. METHODS: This prospective cohort study evaluated 1,595 pregnant women referred for prenatal visits. Maternal state/trait anxiety levels were measured, then quadruple screening was performed by measuring serum α-fetoprotein (AFP), ß-human chorionic gonadotropin, inhibin A, and unconjugated estriol (UE3). After receiving the results, the state/trait anxiety was remeasured. Amniocentesis was performed for screening-positive mothers. RESULTS: High prescreening maternal anxiety was associated with lower rates of elevated AFP (OR, 0.27; 95% CI, 0.1-0.74) and elevated inhibin A (OR, 0.38; 95% CI, 0.15-0.98). High maternal anxiety was associated with higher rates of decreased UE3 (OR, 1.8; 95% CI, 1.06-3.08). There were no significant associations between prescreening maternal anxiety and the final screening or amniocentesis results. Among the screening-positive mothers, those who had high state/trait anxiety before screening had higher anxiety scores after receiving positive results compared to those with low prescreening anxiety levels (52.9 ± 10.8 vs. 43.7 ± 10.3). CONCLUSION: High prescreening maternal anxiety is associated with lower rates of elevated AFP and inhibin A and higher rates of decreased UE3. However, maternal anxiety does not affect the final screening or amniocentesis result. High maternal state/trait anxiety before screening is associated with significantly higher maternal anxiety after the receipt of positive results.

The evolving role of genetics in reproductive medicine.

As medicine has evolved over the last century, medical genetics has grown from nonexistence to one of the most visible aspects of how we understand and treat disease. This increased role of genetics within medicine will only increase in the coming years, and its role in reproductive medicine will be significant. Genetics has emerged as a primary focus of research with translational applications within reproductive medicine. The aim of this article is to outline the applications of genetics currently available, and how these technologies can provide a positive impact on patient care.

Trait anxiety, information modality, and responses to communications about prenatal genetic testing.

Decisions to undergo invasive prenatal diagnostic procedures can be anxiety provoking. Individuals receive information about these procedures in one of three modalities: written text, audio (verbal description), or video. We examined whether modality influences emotional responses and testing decisions, and whether trait anxiety, a disposition linked with heightened sensitivity to threatening information, moderates these effects. New Zealand adults (N = 176) completed a trait anxiety measure before random allocation to view a text, audio, or video message about amniocentesis and chorionic villus sampling. Participants completed measures of child related worry, anticipated emotional distress, anticipated coping efficacy, perceived likelihood of miscarriage, and testing interest. High-anxious individuals reported greater distress and lower coping efficacy in response to the video message compared to the audio message. They also reported greater miscarriage likelihood in response to the video message compared to the text message. These findings suggest that use of video, assumed to be most informative for educating patients, could induce greater distress about prenatal testing in individuals prone to anxiety.

[Amniocentesis trainer: development of a cheap and reproducible new training model]. / Simulateur d'amniocentèse : intérêts et développement d'un nouveau modèle reproductible et économique.

Amniocentesis is the most common invasive procedure for prenatal diagnosis. It is essential to master this sampling technique prior to performing more complex ultrasound-guided interventions (cordocentesis, drain insertion). Training is a challenge because of the risks associated with the procedure, as well as the impact on the patient's anxiety. An amniocentesis simulator allows for safe training and repeats interventions, thus accelerating the learning curve, and also allows for periodic evaluation of proficiency. We present here a new, simple, and cost-effective amniotrainer model that reproduces real life conditions, using chicken breast and condoms filled with water.

Clinical correlates of pain and anxiety in prenatal diagnostic procedures.

OBJECTIVE: To study patient perception of pain and anxiety before and after amniocentesis (AC) and transabdominal chorionic villus sampling (CVS) and the clinical correlates of pain and anxiety. METHODS: 92 women underwent AC and 78 CVS. Visual analog scale was used to quantify pain and anxiety, immediately before and after the procedure. Factors which could affect pain and anxiety were noted. RESULTS: The pain and anxiety anticipated before the procedures were significantly less than actually perceived. The pre-procedure anxiety did not correlate with post-procedure pain. There was no correlation between anticipated pain or anxiety and age, parity, education, socioeconomic status, and history of procedure in previous pregnancy in both the AC and CVS groups. Post-procedure pain did not correlate with age, parity, education, socioeconomic status, abdominal scar, placental location, number of needle insertion, repeat procedure or abdominal wall thickness in either group. However, on multiple linear regression the overall post-procedure pain was associated with the number of needle insertions. CONCLUSION: Though pre-procedure pain and anxiety levels are high, most patient experience less pain and anxiety after the procedure.

Maternal anxiety and pain during prenatal diagnostic techniques: a prospective study.

OBJECTIVE: To explore anxiety and pain felt by women undergoing chorionic villus sampling (CVS) and amniocentesis (AC). METHOD: We prospectively questioned 254 women (67 undergoing CVS, 187 AC) before the procedure on their anxiety, after the procedure on their pain felt, and the support they received or desired. The medical team collected technical information concerning each procedure. RESULTS: The level of anxiety was significantly higher in women undergoing CVS than AC, in those who had received complete information before the procedure, and when indication for the procedure was fetal structural abnormalities. The level of pain was significantly higher in cases of anxious women, those undergoing a CVS rather than AC, those who had undergone invasive prenatal diagnostic procedures in previous pregnancies, in procedures deemed difficult by the operator, and with needle insertion in the lateral part of the uterus. About 30% of women undergoing CVS and 8% of those undergoing AC would have desired some form of pain prevention, mostly with nonpharmacologic therapy. CONCLUSION: Prenatal diagnosis is frequently associated with anxiety and pain. We identified factors that could exacerbate either one. When questioned, patients would desire a nonpharmacologic means for pain prevention.

Communication in genetic counseling: cognitive and emotional processing.

The profession of genetic counseling has received limited guidance from theoretical models in how to communicate complex health information so that clients can actively use the information. In this study of a national sample of 145 genetic counselors conducting sessions with simulated clients, we apply two different approaches for analyzing and describing verbal health communication. The Roter interaction analysis system (RIAS) and linguistic inquiry word count (LIWC) were used to identify evidence of communication behaviors consistent with tenets of the social cognitive processing model (SCPM). These tools revealed descriptive evidence of counselor facilitation of client emotional processing and, to a lesser extent, facilitation of client cognitive processing and understanding. Conversely, descriptive analysis of client communication revealed evidence of cognitive processing, but less affective processing. Second, we assessed whether genetic counselor facilitative communication predicted simulated client responses consistent with the cognitive and emotional processing inherent in SCPM. These analyses revealed that counselor attempts to promote emotional expression and client insight were positively associated with client word usage indicative of expression of negative affect and cognitive processing. This study is the first to our knowledge to apply RIAS and LIWC in tandem and gives us a description of current practices within genetic counseling within a theoretical framework. Additionally, it provides suggestions for education and communication goals to improve providers' responses to patient emotions as well as skills to engender patient understanding and personal meaning-making of complex medical information.

Beyond the first trimester screen: can we predict who will choose invasive testing?

PURPOSE: The purpose of this study is to determine what factors, in addition to a positive first trimester aneuploidy screen, correlate with a pregnant patient's decision to undergo invasive prenatal testing. METHODS: We conducted a retrospective cohort study of singleton pregnancies referred to the Johns Hopkins Prenatal Diagnosis and Treatment Center between 2001 and 2009 with an indication of positive first trimester screen. We compared demographic factors and numerical first trimester screen results with invasive testing uptake. Risk difference calculations and linear modeling were used for analysis. RESULTS: A total of 171 eligible patients were identified. Maternal age, race, residual risk, marital status, and year of first trimester screen correlated significantly with invasive testing uptake. Family history was predictive of invasive testing uptake for patients younger than 35 years only. Type of elevated risk (trisomy 21 vs. 18 and 13), assisted reproductive technology status, parity, and increase from age-related risk were not predictive. A general linear model for relative risk with Gaussian error showed significant interaction between the variables of age and family history, so the two traits were analyzed separately (P = 0.009). CONCLUSIONS: Among patients with positive first trimester screen results, several demographic traits are predictive of invasive testing uptake. This information can help providers to identify patients at increased risk of declining invasive testing and can help providers anticipate educational needs. Further investigation should be conducted to elucidate the causes of these differences, which may relate to misinformation about the testing options and differences in values systems.

[Assessment of anxiety, pain and its management in prenatal diagnosis procedures]. / Évaluation de l'anxiété, de la douleur, et de leur prise en charge dans les gestes de diagnostic anténatal.

UNLABELLED: Invasive prenatal diagnosis procedures are numerous and more or less painful and stressful. The purpose of this study was to investigate maternal perception of both anxiety and pain before and after amniocentesis (AC) or transabdominal chorionic villus sampling (CVS), to determine factors associated with pain and anxiety, and to evaluate the pain support. This is a prospective study evaluating the professional practices at CHRU of Lille between March and May 2009 with 132 AC and 22 CVS by aspiration. An original questionnaire has been elaborated in three parts: the first one fulfilled by patients before the procedure, the second one, after the procedure, and the last one by the medical team. Statistical comparisons have used the Chi(2) test, the Fisher exact test, the Student's t test and the U test of Mann Whitney. RESULTS: The anxiety level is high but does not differ between the two groups AC and CVS. CVS are more painful than AC (EVA 5.77 versus 3.07, P<0.0001). No predisposing factor for anxiety has been found. On the other side, procedures are more painful when they are long lasting, considered difficult by the medical team, when needles used are large, the number of needle insertions increases, puncture is performed along a side of the uterus, patients are anxious, and then procedure indication is an hygroma. Patients are satisfied in 98.7% of cases of the support of the medical team. Few drug treatments was prescribed (only 4.5%), however, patients are generally applicant. CONCLUSION: An analgesic, anxiolytic, or a relaxation technique can be proposed to anxious and applicant patients undergoing CVS. Technical conditions of the procedure are more difficult to improve, however, we should use if possible thinner needles, and avoid, wherever technically possible, the punctures on the lateral side of the uterus. Finally, further studies seem necessary for the evaluation of a treatment protocol.

Different communication strategies for disclosing results of diagnostic prenatal testing.

BACKGROUND: Any screening program aiming to reassure pregnant women that their unborn baby is healthy will cause anxiety while waiting for the test results. OBJECTIVES: 1) To determine if revealing amniocentesis or chorionic villous sampling (CVS) results on a fixed date alters maternal anxiety during the waiting period, compared with a policy of revealing the result "when available" (i.e. variable date). 2) To evaluate whether issuing early results from a rapid molecular test alters maternal anxiety during the waiting period. 3) To evaluate whether different methods of communication (telephone, fax, email, face to face) have any impact on the parents' satisfaction and anxiety levels. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2010). SELECTION CRITERIA: All published and unpublished randomised trials, in which methods of issuing prenatal test results are compared. DATA COLLECTION AND ANALYSIS: Two review authors (Faris Mujezinovic and Zarko Alfirevic) assessed eligibility and trial quality and performed data extraction. MAIN RESULTS: Two studies (involving 286 women) from amniocentesis (but none from CVS) compared the impact of communicating results of rapid testing with waiting for definitive karyotype. Unfortunately, it was not possible to perform pooled analysis because one study reported only median (interquartile range) data, presumably because the data were not normally distributed.One study reported a statistically significant reduction in the average anxiety during the waiting period for women who had had a rapid test compared with those who had not (mean difference (MD) -2.30, 95% confidence intervals (CI) -3.08 to - 1.52). The other study compared median (interquartile range) for the trait- and state-anxiety scores and found no difference between the two groups. AUTHORS' CONCLUSIONS: 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.

Ethnic and socio-economic differences in uptake of prenatal diagnostic tests for Down's syndrome.

OBJECTIVE: The objective of this study was to assess ethnic and socio-economic differences in the uptake of maternal age-based prenatal diagnostic testing for Down's syndrome by amniocentesis or chorionic villus sampling. STUDY DESIGN: The study population consisted of 12,340 women aged 36 years or over, who lived in a geographically defined region in the Southwest of The Netherlands and who gave birth to a live born infant in the period 2000-2004. Data were obtained from the Department of Clinical Genetics Erasmus MC and Statistics Netherlands. Logistic regression analyses were done to assess ethnic and socio-economic differences in uptake. RESULTS: The overall uptake of prenatal diagnostic tests was 28.5%. Women of Turkish and Caribbean origin participated in prenatal diagnostic tests equally or more often than Dutch women. Women of North-African origin and women from low socio-economic background had a lower uptake than others. Ethnic differences in uptake could not be attributed to differences in socio-economic background. CONCLUSIONS: Uptake of prenatal diagnostic tests for Down's syndrome in The Netherlands was low and varied among ethnic and socio-economic groups of advanced maternal age. The finding that women of Turkish and Caribbean origin participated in prenatal diagnostic tests equally or more often than Dutch women was unexpected. The low uptake among Dutch women may be related to the Dutch pregnancy culture. The finding that women of North-African origin and women from low socio-economic background had a lower uptake may be related to barriers in access to prenatal diagnostic tests.

Knowledge and attitudes towards prenatal diagnostic procedures among pregnant women in Greece.

OBJECTIVE: To assess knowledge and attitudes towards prenatal diagnostic procedures among pregnant women living in Greece who underwent amniocentesis or chorionic villus sampling in relation to underlying demographic, lifestyle and medical history predictors. METHOD: 354 women, upon receiving the results, were interviewed in person. A structured questionnaire was answered based upon sociodemographic, educational, lifestyle and medical history variables, as well as questions pertaining to the women's knowledge, use and opinion of prenatal tests. Summary statistics and multiple logistic regression analyses were performed. RESULTS: No prior information on prenatal diagnostic procedures was reported in 29% or on prenatal screening tests in 50% of the study subjects. Women with no history of inherited diseases were about threefold more likely to have inadequate knowledge (OR = 2.72, p = 0.01) as were women of non-Greek nationality (OR = 3.27, p = 0.02) as well as those who reported being unaware of the health consequences of smoking during pregnancy (OR = 2.50, p = 0.005). By contrast, women of higher education were over twofold more likely to attain a higher level of knowledge of prenatal diagnostic procedures (OR = 0.51, p = 10(-4)) as were those reported reading the popular press (OR = 0.44, p = 10(-4)). CONCLUSION: In spite of the increased availability of prenatal diagnosis, much more is needed to be done in order to improve the efficiency of prenatal counseling, especially in immigrants and women with a low educational background.

The role of attitudes towards the targets of behaviour in predicting and informing prenatal testing choices.

Research considering the role of attitudes in prenatal testing choices has commonly focused on the relationship between the attitude towards undergoing testing and actual testing behaviour. In contrast, this study focused on the relationship between testing behaviour and attitudes towards the targets of the behaviour (in this case people with Down syndrome (DS) and having a baby with DS). A cross-sectional, prospective survey of 197 pregnant women measured attitudes towards the targets of prenatal testing along with intentions to use screening and diagnostic testing, and the termination of an affected pregnancy. Screening uptake was established via patient records. Although attitudes towards DS and having a baby with DS were significantly associated with screening uptake and testing and termination intentions, unfavourable attitudes were better than favourable ones at predicting these outcomes. For example, in the quartile of women with the 'most favourable' attitude towards people with DS 67% used screening although only 8% said they would terminate an affected pregnancy. Qualitative data suggested that not all women considered personal attitudes towards DS to be relevant to their screening decisions. This finding has implications for the way in which informed choice is currently understood and measured in the prenatal testing context.

Women's accounts of the physical sensation of chorionic villus sampling and amniocentesis: expectations and experience.

OBJECTIVE: to understand women's expectations and experience of discomfort during chorionic villus sampling (CVS) and amniocentesis, and relate them to aspects of clinical practice. DESIGN: thematic analysis of narrative interviews. Interviews were recorded and transcribed verbatim, coded and analysed using computer-assisted qualitative data analysis software. PARTICIPANTS AND SETTING: sample recruited nationally for two wider studies of experiences of antenatal screening (n=47) and experiences of ending a pregnancy for fetal abnormality (n=40). Of these, 31 women had experienced amniocentesis and/or CVS at least once. FINDINGS: most women found the procedures less painful than expected. A smaller group were shocked or surprised at the sensation, and were worried that they had jumped and that the needle might have damaged the baby. A few found it very painful, using vivid imagery of being stabbed or punctured. However, even those who found it worse than expected felt it was worth the pain to get a definite diagnosis. Women identified a range of factors affecting their experience, including levels of anxiety, prior experience or knowledge of the procedures, levels of information provided, trust in the skill of the operator, or reassurance and empathy of the staff involved. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the needs of a small minority of women who find CVS or amniocentesis shocking and/or painful may be overlooked. A review of pre-test information and procedures is recommended to ensure that women are better prepared for possible physical sensations during the procedures to address the needs of this minority.

Decision-making about reproductive choices among individuals at-risk for Huntington's disease.

We explored how individuals at-risk for HD who have or have not been tested make reproductive decisions and what factors are involved. We interviewed 21 individuals (8 with and 4 without the mutation, and 9 un-tested) in-depth for 2 hours each. At-risk individuals faced a difficult series of dilemmas of whether to: get pregnant and deliver, have fetal testing, have pre-implantation genetic diagnosis, adopt, or have no children. These individuals weighed competing desires and concerns: their own desires vs. those of spouses vs. broader moral concerns (e.g., to end the disease; and/or follow dictates against abortion) vs. perceptions of the interests of current or future offspring. Quandaries arose of how much and to whom to feel responsible. Some changed their perspectives over time (e.g., first "gambling," then being more cautious). These data have critical implications for genetic counselors and other health care workers and future research, particularly as more genetic tests become available.

Informed choice of pregnant women in prenatal screening tests for Down's syndrome.

BACKGROUND: Although maternal serum screening (MSS) for Down's syndrome has become routinely available in most obstetric clinics in many countries, few studies have addressed the reasons why women agree to undergo the MSS test. OBJECTIVES: The aims of this study were to describe the circumstances in which MSS was offered to pregnant women and their reasons for undertaking it. METHODS: Participant observation and in depth interviews were used in this study; specifically, the experiences of women who had a positive result for MSS and who then followed this up with amniocentesis were examined. The interviewees were twenty six mothers aged between 22 and 35 years. The interviews were audio taped and transcribed for analysis. The results were analysed by the constant comparative method. RESULTS: This study identified the reasons on which pregnant women appeared to base their decisions when undergoing MSS. The reasons were first, the recognition that the procedure was a prenatal routine procedure; second, the need to avoid the risk of giving birth to a baby with Down's syndrome, and third, a trust in modern technology and in the professional authorities. CONCLUSIONS: This study offers insights into the informed choice made by women with a positive MSS result. The reasons for undergoing MSS might help health professionals and policy makers to reflect on their practice and this may, in turn, improve the quality of prenatal care during MSS.

Pregnant women's responses to information about an increased risk of carrying a baby with Down syndrome.

BACKGROUND: Fetal screening for Down syndrome by an ultrasound examination, including measurement of fetal nuchal translucency, at 12 to14 weeks' gestation is presently being evaluated in a Swedish randomized controlled trial. Women at high risk were offered an amniocentesis to obtain a definite diagnosis. The aim of this study was to explore women's reactions and responses to information about being at high risk after the scan, with a special focus on reactions to a false positive test. METHOD: Interviews were conducted with 24 women within 1 week after the scan, in midpregnancy, and 2 months after the birth. The interviews were analyzed qualitatively. Down syndrome was confirmed in 4 women, who chose to terminate the pregnancy. The remaining 20 women had a false positive test. RESULTS: For the majority, the risk information caused strong reactions of anxiety and worries about the future. A typical way for women to cope was to "withhold" the pregnancy, to take a "timeout," and try to live as if they were not pregnant any longer. Some weeks later, when the women received normal results from the chromosome analysis, they resumed being pregnant. Six women ages more than 35 years who had a risk score lower than their age-related risk did not express similarly strong reactions. Two months after the birth of a healthy baby, most stated they would undergo the same procedure in a subsequent pregnancy. One woman still suffered from the experience when interviewed at 2 months after the birth, and another said she regretted participating in the fetal screening program. CONCLUSIONS: A false positive test of fetal screening for Down syndrome by ultrasound examination may cause strong reactions of anxiety and even rejection of the pregnancy. The prevalence of such reactions and possible long-term effects need further investigation.