Inclusion of sex chromosomes in noninvasive prenatal testing in Asia,Australia, Europe and the USA: A survey study

Objective

To examine the extent to which sex chromosomes are included in current noninvasive prenatal testing (NIPT) and the reporting practices with respect to fetal chromosomal sex and sex chromosome aberrations (SCAs), in addition to an update on the general implementation of NIPT.

Method

A questionnaire addressing the research objectives was distributed by email to fetal medicine and clinical genetics experts in Asia, Australia, Europe and the USA.

Results

Guidelines on NIPT are available in the majority of the included countries. Not all existing guidelines address reporting of fetal chromosomal sex and SCAs. In most settings, NIPT frequently includes sex chromosomes (five Australian states, China, Hong Kong, Israel, Singapore, Thailand, USA and 23 of 31 European countries). This occurs most often by default or when parents wish to know fetal sex. In most settings, a potential SCA is reported by stating the risk hereof as “low” or “high” and/or by naming the SCA. Less than 50% of all pregnant women receive NIPT according to respondents from three Australian states, China, Israel, Singapore, Thailand and 24 of 31 European countries. However, this percentage, the genomic coverage of NIPT and its application as primary or secondary screening vary by setting.

Conclusion

In most of the studied countries/states, NIPT commonly includes sex chromosomes. The reporting practices concerning fetal chromosomal sex and SCAs are diverse and most commonly not addressed by guidelines. In general, NIPT is variably implemented across countries/states.     

A cross-country comparison of pregnant women's decision-making and perspectives when opting for non-invasive prenatal testing in the Netherlands and Belgium

Background

The Netherlands and Belgium have been among the first countries to offer non-invasive prenatal testing (NIPT) as a first-tier screening test. Despite similarities, differences exist in counseling modalities and test uptake. This study explored decision-making and perspectives of pregnant women who opted for NIPT in both countries.

Methods

A questionnaire study was performed among pregnant women in the Netherlands (NL) (n = 587) and Belgium (BE) (n = 444) opting for NIPT, including measures on informed choice, personal and societal perspectives on trisomy 21, 18 and 13 and pregnancy termination.

Results

Differences between Dutch and Belgian women were shown in the level of informed choice (NL: 83% vs. BE: 59%, p < 0.001), intention to terminate the pregnancy in case of confirmed trisomy 21 (NL: 51% vs. BE: 62%, p = 0.003) and trisomy 13/18 (NL: 80% vs. BE: 73%, p = 0.020). More Belgian women considered trisomy 21 a severe condition (NL: 64% vs. BE: 81%, p < 0.001). Belgian women more frequently indicated that they believed parents are judged for having a child with trisomy 21 (BE: 42% vs. NL: 16%, p < 0.001) and were less positive about quality of care and support for children with trisomy 21 (BE: 23% vs. NL: 62%, p < 0.001).

Conclusion

Differences in women's decision-making regarding NIPT and the conditions screened for may be influenced by counseling aspects and country-specific societal and cultural contexts.     

State-wide increase in prenatal diagnosis of klinefelter syndrome on amniocentesis and chorionic villus sampling: Impact of non-invasive prenatal testing for sex chromosome conditions

Background

To analyze population-based trends in the prenatal diagnosis of sex chromosome aneuploidy (SCA) since the availability of non-invasive prenatal testing (NIPT).

Methods

Retrospective state-wide data for all prenatal diagnoses performed <25 weeks gestation from 2005 to 2020 in Victoria, Australia. Non-invasive prenatal testing became locally available from 2012. The prenatal diagnosis rates of SCA as proportions of all prenatal diagnostic tests and all births were calculated. Statistical significance was assessed with the χ² test for trend, with p < 0.05 considered significant.

Results

46,518 amniocentesis and chorionic villus sampling were performed during the study period, detecting 617 SCAs. There was a significant increase in the rate of prenatal SCAs from 5.8 per 10,000 births in 2005 to 8.7 per 10,000 births in 2020 (p < 0.0001). This increase was predominantly due to 47,XXY cases, 91% of which were ascertained via positive NIPT for this condition in 2020. The prenatal diagnosis rate of 47,XXY significantly increased from 0.8 per 10,000 births in 2005 to 4.3 per 10,000 births in 2020 (p < 0.0001).

Conclusion

Screening for SCAs using NIPT has directly led to an increase in their prenatal diagnosis on a population-wide basis, especially 47,XXY. This has implications for clinician education, genetic counselling, and pediatric services.     

Non-invasive prenatal testing (NIPT): Combination of copy number variant and gene analyses using an “in-house” target enrichment next generation sequencing—Solution for non-centralized NIPT laboratory?

Objective

Recent studies have integrated copy number variant (CNV) and gene analysis using target enrichment. Here, we transferred this concept to our routine genetics laboratory, which is not linked to centralized non-invasive prenatal testing (NIPT) facilities.

Method

From a cohort of 100 pregnant women, 22 were selected for the analysis of maternal genomic DNA (gDNA) along with fetal cell-free DNA. Using targeted enrichment, 135 genes were analyzed, combined with aberrations of chromosomes 21, 18, 13, X, and Y. The data were subjected to specificity and sensitivity analyses, and correlated with the results from invasive testing methods.

Results

The sensitivity/specificity was determined for the CNV analysis of chromosomes: 21 (80%/75%), 18 (-/82%), 13 (100%/67%), and Y (100%/100%). The gene detection was valid for maternal gDNA. However, for cell-free fetal DNA, it was not possible to determine the boundary between an artifact and a real sequence variant.

Conclusion

The target enrichment method combining CNV and gene detection seems feasible in a regular laboratory. However, this method can only be responsibly optimized with a sufficient number of controls and further validation on a strong bioinformatic background. The present results showed that NIPT should be performed in specialized centers, and that its introduction to isolated laboratories may not provide valid data.     

Noninvasive prenatal screening for cystic fibrosis using circulating trophoblasts: Detection of the 50 most common disease-causing variants

Objectives

Cystic fibrosis (CF) is one of the most common severe autosomal recessive disorders. Prenatal or preconception CF screening is offered in some countries. A maternal blood sample in early pregnancy can provide circulating trophoblasts and offers a DNA source for genetic analysis of both the mother and the fetus. This study aimed to develop a cell-based noninvasive prenatal test (NIPT) to screen for the 50 most common CF variants.

Methods

Blood samples were collected from 30 pregnancies undergoing invasive diagnostics and circulating trophoblasts were harvested in 27. Cystic fibrosis testing was conducted using two different methods: by fragment length analysis and by our newly developed NGS-based CF analysis.

Results

In all 27 cases, cell-based NIPT provided a result using both methods in agreement with the invasive test result.

Conclusion

This study shows that cell-based NIPT for CF screening provides a reliable result without the need for partner- and proband samples.     

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.     

Current controversies in prenatal diagnosis 1: NIPT for chromosome abnormalities should be offered to women with low a priori risk

In its successful annual cycle of controversies and debates, the International Society of Prenatal Diagnosis and Therapy once again addressed non-invasive prenatal testing (NIPT) by following up on the 2013 controversy, ‘Should non-invasive DNA testing be the standard screening test for Down syndrome in all pregnant women’? with the proposition, ‘NIPT for chromosomel abnormalities should be offered to women with low a priori risk’. © 2014 John Wiley & Sons, Ltd.     

The cell-free DNA virome of 108,349 Dutch pregnant women

Objective

Viral infections during pregnancy are a major health concern to mother and fetus. By repurposing cell-free Non Invasive Prenatal Testing (NIPT) sequencing data, we investigated prevalence and abundance of viral DNA in a cohort of 108,349 pregnant women.

Method

Cell-free DNA (cfDNA) sequencing reads that did not map to any of the human chromosomes or mitochondrial DNA of the human reference genome build GRCh38 were aligned to 224 DNA viruses selected from the NCBI refseq viral database.

Results

In total 443,665 reads of viral origin were detected across 42,273 samples representing 165 viral species. Several are known to be potentially harmful during pregnancy and/or childbirth, including Cytomegalovirus, Parvovirus B19 and Hepatitis B. Viral sequences were mostly detected at very low abundance. However, several cases had exceptionally high viral loads for Parvovirus B19, Hepatitis B and others. We found statistically significant associations between presence of viral DNA and gestational age, maternal age, fetal fraction, cfDNA concentration and others.

Conclusion

We demonstrate the feasibility to detect viral DNA from typical genome-wide NIPT cfDNA sequencing and describe the main characteristics of the viral DNA in our cohort. Our dataset of detected viral sequence reads is made publicly available to guide future clinical implementations.     

Ethnic differences in determinants of participation and non-participation in prenatal screening for Down syndrome: A theoretical framework

Objective To develop a theoretical framework for analysing ethnic differences in determinants of participation and non-participation in prenatal screening for Down syndrome. Methods We applied Weinstein's Precaution Adoption Process (PAP) Model to the decision of whether or not to participate in prenatal screening for Down syndrome. The prenatal screening stage model was specified by reviewing the empirical literature and by data from seven focus group interviews with Dutch, Turkish and Surinamese pregnant women in the Netherlands. Results We identified 11 empirical studies on ethnic differences in determinants of participation and non-participation in prenatal screening for Down syndrome. The focus group interviews showed that almost all stages and determinants in the stage model were relevant in women's decision-making process. However, there were ethnic variations in the relevance of determinants, such as beliefs about personal consequences of having a child with Down syndrome or cultural and religious norms. Discussion The prenatal screening stage model can be applied as a framework to describe the decision-making process of pregnant women from different ethnic backgrounds. It provides scope for developing culturally sensitive, tailored methods to guide pregnant women towards informed decision-making on participation or non-participation in prenatal screening for Down syndrome. Copyright © 2007 John Wiley & Sons, Ltd.     

Prenatal diagnosis of congenital head,face, and neck malformations—Is complementary fetal MRI of value?

Objectives

The aim of this study was to evaluate the role of fetal magnetic resonance imaging (MRI) as a complement to ultrasound (US) in the prenatal diagnosis of craniofacial anomalies.

Methods

A historical cohort study including all pregnant women who were referred for fetal MRI because of antenatal diagnosis of craniofacial anomalies on screening US. Prenatal diagnostic US, MRI, and postnatal diagnosis were compared for consistencies and discrepancies.

Results

Forty-five pregnant women with 73 suspected fetal craniofacial anomalies diagnosed by US underwent MRI. In 40 out of 73 anomalies (54.8%), US and MRI findings were in complete agreement with postnatal diagnoses. MRI correctly ruled out the diagnosis of 24 anomalies suspected on US and diagnosed four additional pathologies that were not demonstrated by US. Out of the 85 anomalies (suspected by imaging or confirmed postnatally), confident diagnosis could be made by MRI in 68 anomalies (80%), not diagnosed in 10 (11.8%), and over-diagnosed in seven (8.2%). By US, confident diagnosis could be made in 44 anomalies (51.8%), not diagnosed in 11 (12.9%), and over-diagnosed in 30 (35.3%).

Conclusion

MRI is valuable in the antenatal evaluation of fetal craniofacial anomalies and may be useful as an adjunct to US in the prenatal work-up of craniofacial anomalies.     

Antenatal screening for fetal trisomies using microarray-based cell-free DNA testing: A systematic review and meta-analysis

Objective

To evaluate the test accuracy of non-invasive prenatal testing (NIPT) for fetal trisomy 21, 18, and 13 using cell-free (cf) DNA analysis in maternal plasma with microarray quantitation.

Method

Systematic review and meta-analysis. Searches in MEDLINE, Pre-MEDLINE, EMBASE, Web of Science, and the Cochrane Library to 09.07.2018.

Results

Five studies analyzing 3074 samples, including 187 trisomy 21, 43 trisomy 18, and 19 trisomy 13 cases, were identified. Risk of bias was high in all studies, introduced particularly by exclusions from analysis and by the role of the sponsor. Sensitivity of microarray-based cfDNA testing was 99.5% (95%CI 96.3%-99.9%) for trisomy 21, 97.7% (95%CI 87.9%-99.6%) for trisomy 18, and 100% (95%CI 83.2%-100%) for trisomy 13. Specificity was 100% (95% CI 99.87%-100%) for trisomy 21, 99.97% (95%CI 99.81%-99.99%) for trisomy 18, and 99.97% (95%CI 99.81%-99.99%) for trisomy 13. Pooled test failure rate was 1.1%. A direct comparison of microarray- and sequencing-based cfDNA found equivalent test accuracy.

Conclusion

Included studies suggest that NIPT using microarray-based cfDNA testing has high sensitivity and specificity for detecting fetal trisomy 21, 18, and 13. However, the evidence base is small and at high risk of bias.     

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.     

Performance of single-gene noninvasive prenatal testing for autosomal recessive conditions in a general population setting

Objective

Carrier screening with reflex to single-gene noninvasive prenatal testing (sgNIPT) is an alternative approach for identifying pregnancies at risk for inherited autosomal recessive conditions without the need for a sample from the reproductive partner. This study is the largest clinical validation of this approach in a general population setting.

Methods

The clinical performance of carrier screening with reflex to sgNIPT for cystic fibrosis, spinal muscular atrophy, alpha thalassemias, and beta hemoglobinopathies was assessed by collecting pregnancy outcome data on patients who underwent this testing and comparing the neonatal outcome to the assay-predicted fetal risk.

Results

Of 42,067 pregnant individuals who underwent screening, 7538 carriers (17.9%) had reflex sgNIPT, and neonatal or fetal outcomes were obtained for 528 cases, including 25 affected pregnancies. Outcomes demonstrated high concordance with sgNIPT, for example, all pregnancies with 9 in 10 personalized fetal risk results were affected (positive predictive value (PPV) of 100% for the sub-group) and the sgNIPT assay showed a sensitivity of 96.0% (95% CI: 79.65%–99.90%), specificity of 95.2% (95% CI: 92.98%–96.92%), average PPV of 50.0% (95% CI: 35.23%–64.77%), and negative predictive value (NPV) of 99.8% (95% CI: 98.84%–99.99%). The end-to-end performance of carrier screening with reflex to sgNIPT was calculated to have a sensitivity of 92.4% and specificity of 99.9%, which are unaffected by partner carrier screening or misattributed paternity unlike a traditional carrier screening workflow, which has a 35% sensitivity and a maximum of 25% PPV (1 in 4) in a real-life setting.

Conclusion

This study builds upon earlier findings to confirm that carrier testing with reflex to sgNIPT is highly accurate for general population screening. Given this high accuracy and an NPV of 99.8%, this workflow should be considered as an option for most of the general pregnant population. When the biological partner sample is unavailable, this workflow should be recommended as the first-line approach.     

Overview of the impact of noninvasive prenatal testing on diagnostic procedures

Noninvasive prenatal testing (NIPT) has had a profound influence in the field of prenatal diagnosis since the 1997 discovery of cell-free fetal DNA in maternal blood. Research has progressed rapidly, with clinical data supporting laboratory studies showing that NIPT is highly sensitive and specific for fetal aneuploidy, resulting in marked uptake in the high-risk patient population. The superior accuracy of NIPT compared with conventional screening methods has led to significant decreases in the number of invasive diagnostic procedures, in addition to a concomitant decrease in the number of procedure-related fetal losses. Yet, NIPT has been described as a ‘disruptive innovation’ due to the considerable changes the technology has commanded on current prenatal screening and diagnostic practices. This review summarizes both institutional and global experience with NIPT uptake, its effect on reducing diagnostic invasive procedures, and the unique challenges that reduced procedural volume may have on physician and trainee proficiency, cytogenetic laboratories, and neonatal outcome. © 2015 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.     

Short-term outcome after the prenatal diagnosis of right aortic arch

Objectives

To determine the proportion of children that require surgery in the first year of life and thereafter in order to improve the counseling of parents with a fetus with a right aortic arch (RAA).

Methods

Fetuses diagnosed with isolated RAA, defined as the absence of intra- or extracardiac anomalies, between 2007 and 2021 were extracted from the prospective registry PRECOR.

Results

In total, 110 fetuses were included, 92 with a prenatal diagnosis of RAA and 18 with double aortic arch (DAA). The prevalence of 22q11 deletion syndrome was 5.5%. Six pregnancies were terminated and five cases were false-positive; therefore, the follow-up consisted of 99 neonates. Surgery was performed in 10 infants (10%) in the first year of life. In total, 25 (25%) children had surgery at a mean age of 17 months. Eight of these 25 (32%) had a DAA. Only one child, with a DAA, required surgery in the first week of life due to obstructive stridor.

Conclusions

Children with a prenatally diagnosed RAA are at a low risk of acute respiratory postnatal problems. Delivery in a hospital with neonatal intensive care and pediatric cardiothoracic facilities seems only indicated in cases with suspected DAA. Expectant parents should be informed that presently 25% of the children need elective surgery and only incidentally due to acute respiratory distress.     

Second-trimester prenatal screening markers for Down syndrome in women with insulin-dependent diabetes mellitus

Published studies have shown that some serum markers used in screening for Down syndrome tend to be lower among women with insulin-dependent diabetes mellitus (IDDM). On this basis, many screening programmes adjust the marker levels to take account of this difference. Recent studies suggested that the marker levels were not different, and so adjustment may no longer be needed, possibly because of better diabetic control. Data from a prenatal screening programme for Down syndrome were examined to see whether the median values of second-trimester screening markers were still reduced in pregnant women with IDDM. A total of 366 women with IDDM singleton pregnancies without Down syndrome were identified from the screening programme at Barts from 1989 to 2002. After allowing for maternal weight, the median multiples of the median (MoM) for IDDM-unaffected singleton pregnancies were as follows: 0.88 (95% confidence interval 0.84–0.93) for alphafetoprotein (AFP), 0.95 (0.91–0.99) for unconjugated oestriol (uE₃), 0.90 (0.80–1.01) for total human chorionic gonadotrophin (total hCG), 0.98 (0.88–1.08) for free β-hCG, and 0.99 (0.89–1.10) for inhibin-A. The median levels for AFP and uE₃ were statistically significantly lower in pregnant women with IDDM. The other markers were not significantly different in women with and without IDDM. There remains a case for adjusting AFP and uE₃ levels in women with IDDM in prenatal screening programmes for Down syndrome. Copyright © 2004 John Wiley & Sons, Ltd.     

Socio-cultural inequities in access to prenatal diagnosis: The role of insurance coverage and regulatory policies

The article presents the results of a 4-month-period survey by questionnaire among all women attending the Marseille Centre for Prenatal Diagnosis for amniocentesis. Socio-cultural status of women getting access to amniocentesis is significantly higher than in the general population of pregnant women in the same geographic area of south-eastern France. Sociocultural status is also higher among women who have to cover costs of procedure to get access to amniocentesis than among those who benefit from it free-of-charge according to French Social Security regulations. In contrast, risk perception and attitudes toward termination of pregnancy are similar in these two groups. A total of 24·4 per cent of respondents declared that they got access to amniocentesis ‘on their own initiative’, the remaining 75·6 per cent declaring that they ‘were following medical advice’. Multidimensional analysis shows that the women who do not benefit from free-of-charge amniocentesis, and who have a high level of education and no antecedents of fetal and perinatal deaths, are more likely to perceive themselves as ‘self-referring’. The study indicates that institutional coverage may be effective in reducing socio-cultural inequities in access to prenatal diagnosis. But such a policy may conflict with the respect of women' s individual autonomy in the amniocentesis decision.     

Comprehensive prenatal diagnostics: Exome versus genome sequencing

Objective

This study aimed to assess the diagnostic yield of prenatal genetic testing using trio whole exome sequencing (WES) and trio whole genome sequencing (WGS) in pregnancies with fetal anomalies by comparing the results with conventional chromosomal microarray (CMA) analysis.

Methods

A total of 40 pregnancies with fetal anomalies or increased nuchal translucency (NT ≥ 5 mm) were included between the 12th and 21st week of gestation. Trio WES/WGS and CMA were performed in all cases.

Results

The trio WES/WGS analysis increased the diagnostic yield by 25% in cases with negative CMA results. Furthermore, all six chromosomal aberrations identified by CMA were independently detected by WES/WGS analysis. In total, 16 out of 40 cases obtained a genetic sequence variant, copy number variant, or aneuploidy explaining the phenotype, resulting in an overall WES/WGS diagnostic yield of 40%. WES analysis provided a more reliable identification of mosaic sequence variants than WGS because of its higher sequencing depth.

Conclusions

Prenatal WES/WGS proved to be powerful diagnostic tools for fetal anomalies, surpassing the diagnostic yield of CMA. They have the potential to serve as standalone methods for prenatal diagnosis. The study highlighted the limitations of WGS in accurately detecting mosaic variants, which is particularly relevant when analyzing chorionic villus samples.     

Ethical issues associated with prenatal screening using non-invasive prenatal testing for sex chromosome aneuploidy

Prenatal screening for sex chromosome aneuploidies (SCAs) is increasingly available through expanded non-invasive prenatal testing (NIPT). NIPT for SCAs raises complex ethical issues for clinical providers, prospective parents and future children. This paper discusses the ethical issues that arise around NIPT for SCAs and current guidelines and protocols for management. The first section outlines current practice and the limitations of NIPT for SCAs. It then outlines key guidelines before discussing the ethical issues raised by this use of NIPT. We conclude that while screening for SCAs should be made available for people seeking to use NIPT, its implementation requires careful consideration of what, when and how information is provided to users.