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.     

Does an educational video for aneuploidy screening improve informed choice among pregnant women? A randomised controlled trial

Background

Poor knowledge and the lack of deliberation have been cited as reasons for women making uninformed choices about aneuploidy screening. Adequate pre-test counselling is of particular importance where non-invasive prenatal screening (NIPS) is being increasingly offered as a primary screening test.

Design

Women attending the antenatal clinic with a singleton pregnancy below 14 weeks were randomised to receive routine counselling or the intervention—a 16-min educational video on aneuploidy screening before their consult. The primary outcome, rate of informed choice, was assessed using an adapted multidimensional measure of informed choice questionnaire, where informed choice was defined as good knowledge and value-consistent behaviour. Secondary outcomes included informed choice with deliberation, decisional conflict and anxiety.

Results

Two hundred and eighty-six women were recruited. 69.8% of women in the intervention group made an informed choice compared with 53.6% in the control group (Risk Ratio [RR] 1.30, p = 0.014). A significantly higher number of women in the intervention group had good knowledge compared to controls (81% vs. 60.9%; RR 1.33, p = 0.001). Decisional conflict did not differ between groups, but women in the intervention group had higher anxiety scores (p < 0.001).

Conclusion

The study intervention was effective in helping women make informed choice. Qualitative studies to determine the reason for increased anxiety are needed.

Trial registration

Trial registry: ClinicalTrials.gov ; Identifier: NCT05492981.     

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.     

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.     

Association of amnioinfusion volume at the time of surgery for twin-twin transfusion syndrome and latency to delivery

Objective

To evaluate the impact of amnioinfusion and other peri-operative factors on pregnancy outcomes in the setting of Twin-twin transfusion syndrome (TTTS) treated via fetoscopic laser photocoagulation (FLP).

Methods

Retrospective study of TTTS treated via FLP from 2010 to 2019. Pregnancies were grouped by amnioinfusion volume during FLP (<1 L vs. ≥1 L). The primary outcome was latency from surgery to delivery. An amnioinfusion statistic (AIstat) was created for each surgery based on the volume of fluid infused and removed and the preoperative deepest vertical pocket. Regression analysis was planned to assess the association of AIstat with latency.

Results

Patients with amnioinfusion of ≥1 L at the time of FLP had decreased latency from surgery to delivery (61 ± 29.4 vs. 73 ± 28.8 days with amnioinfusion <1 L, p < 0.001) and increased preterm prelabor rupture of membranes (PPROM) <34 weeks (44.7% vs. 33.5%, p = 0.042). Amnioinfusion ≥1 L was associated with an increased risk of delivery <32 weeks (aRR 2.6, 95% CI 1.5–4.5), 30 weeks (aRR 2.4, 95% CI 1.5–3.8), and 28 weeks (aRR 1.9, 95% CI 1.1–2.3). Cox-proportional regression revealed that AIstat was inversely associated with latency (HR 1.1, 95% CI 1.1–1.2).

Conclusion

Amnioinfusion ≥1 L during FLP was associated with decreased latency after surgery and increased PPROM <34 weeks.     

Association between low fetal fraction in cell-free DNA screening and fetal chromosomal aberrations: A systematic review and meta-analysis

Objective

To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal chromosomal aberrations.

Method

We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS-2.

Results

Twenty-seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 [3.61–9.95], I ² of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 [3.07–6.47], I ² = 0%, n = 22 studies), monosomy X (OR 5.88 [2.34–14.78], I ² = 18%, n = 10 studies), and triploidy (OR 36.39 [9.83–134.68], I ² = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 [0.76–2.03], I ² = 36%, n = 23 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 [1.78–9.00], I ² = 2%, n = 11 studies). Meta-analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1% and 2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed.

Conclusion

An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and other specific types of fetal chromosomal aberrations.     

Calf circumferences in fetuses and neonates with and without talipes equinovares. A prospective cohort study

Objective

Children and adults with talipes equinovarus (TEV) have smaller calves and shorter feet compared to non-affected controls. Do these changes have a prenatal onset?

Methods

A prospective cohort study (January 2020–July 2021) was conducted with serial ultrasonographic measurements at 20 and 28 weeks gestation and measurements directly and 6 weeks after birth. Calf circumference and width, foot length and length of humerus, ulna, radius, femur, tibia and fibula were measured in TEV and were compared to a control population. Calculated sample size necessitated a minimal population of 10 cases with TEV and 50 controls.

Results

Twenty cases with TEV and 62 controls were included. Fetal calf circumference (p < 0.001) and width (p < 0.001) were smaller in the TEV group in comparison to the control group, which persisted after birth. Growth in foot length (p < 0.001) and calf width (p 0.003) declined prenatally over time. The bone lengths and upper leg circumference were not smaller or shorter in TEV compared to controls.

Conclusion

This prospective cohort study demonstrated the prenatal onset of reduced calf and foot size in fetuses with TEV from 20 weeks and onwards, which persists directly after birth. To investigate whether reduction in circumference initiates TEV or is caused by TEV, further examination is needed.     

How does cell-based non-invasive prenatal test (NIPT) perform against chorionic villus sampling and cell-free NIPT in detecting trisomies and copy number variations? A clinical study from Denmark

Objectives

We aimed to compare cell-based NIPT (cbNIPT) to chorionic villus sampling (CVS) and to examine the test characteristics of cbNIPT in the first clinical validation study of cbNIPT compared to cell-free NIPT (cfNIPT).

Material and Methods

Study 1: Women (N = 92) who accepted CVS were recruited for cbNIPT (53 normal and 39 abnormal). Samples were analyzed with chromosomal microarray (CMA). Study 2: Women (N = 282) who accepted cfNIPT were recruited for cbNIPT. cfNIPT was analyzed using sequencing and cbNIPT by CMA.

Results

Study 1: cbNIPT detected all aberrations (32/32) found in CVS: trisomies 13, 18 and 21 (23/23), pathogenic copy number variations (CNVs) (6/6) and sex chromosome aberrations (3/3). cbNIPT detected 3/8 cases of mosaicism in the placenta. Study 2: cbNIPT detected all trisomies found with cfNIPT (6/6) and had no false positive (0/246). One of the three CNVs called by cbNIPT was confirmed by CVS but was undetected by cfNIPT, two were false positives. cbNIPT detected mosaicism in five samples, of which two were not detected by cfNIPT. cbNIPT failed in 7.8% compared to 2.8% in cfNIPT.

Conclusion

Circulating trophoblasts in the maternal circulation provide the potential of screening for aneuploidies and pathogenic CNVs covering the entire fetal genome.     

Prenatal detection of aortic coarctation in a well-organized screening setting: Are we there yet?

Objective

We aimed to assess current prenatal detection rate (DR) of aortic coarctation (CoA) and its impact on neonatal outcome in the Netherlands to evaluate the efficacy of the Dutch screening protocol in which the cardiac four-chamber view, outflow tracts and three-vessel view are compulsory.

Methods

All prenatally and postnatally diagnosed CoA cases between 2012 and 2021 were extracted from our PRECOR-registry. Annual DRs were calculated with a focus on the trend over time and attributing factors for detection. Postnatal outcome was compared between prenatally detected and undetected cases.

Results

49/116 cases (42.2%) were detected prenatally. A higher chance of detection was found for cases with extracardiac malformations (71.4%; p = 0.001) and the more severe cases with an aortic arch hypoplasia and/or ventricular septal defect (63.2%; p = 0.001). Time-trend analysis showed no improvement in DR over time (p = 0.33). Undetected cases presented with acute circulatory shock in 20.9% and were more likely to have severe lactic acidosis (p = 0.02) and impaired cardiac function (p < 0.001) before surgery.

Conclusion

Even in a well-organized screening program, the DR of CoA still requires improvement, especially in isolated cases. The increased risk of severe lactic acidosis in undetected cases stresses the need for urgent additions to the current screening program, such as implementation of the three-vessel trachea view and measurement of outflow tracts.     

Droplet digital PCR is a cost-effective method for analyzing long cell-free DNA in maternal plasma: Application in preeclampsia

Objective

Long cell-free DNA (cfDNA) can be found in the plasma of pregnant women and cancer patients. We investigated if droplet digital PCR (ddPCR) can analyze such molecules for diagnostic purposes using preeclampsia as a model.

Method

Plasma samples from ten preeclamptic and sixteen normal pregnancies were analyzed. Two ddPCR assays targeting a single-copy gene, VCP, and one ddPCR assay targeting LINE-1 repetitive regions were used to measure the percentages of long cfDNA >533, 1001, and 170 bp, respectively. The LINE-1 assay was developed as guided by in silico PCR analyses to better differentiate preeclamptic and normal pregnancies.

Results

Preeclamptic patients had a significantly lower median percentage of long cfDNA than healthy pregnant controls, as determined by the LINE-1 170 bp assay (28.9% vs. 35.1%, p < 0.0001) and the VCP 533 bp assay (6.6% vs. 8.7%, p = 0.014). The LINE-1 assay provided a better differentiation than the VCP 533 bp assay (area under ROC curves, 0.94 vs. 0.79).

Conclusion

ddPCR is a cost-effective approach for unlocking diagnostic information carried by long cfDNA in plasma and may have applications for the detection of preeclampsia. Further longitudinal studies with larger cohorts are required to assess the clinical utility of this test.     

Brain cortical assessment by MRI in fetuses with left congenital diaphragmatic hernia

Objective

To evaluate fetal brain development using MRI (magnetic resonance imaging) in CDH (congenital diaphragmatic hernia).

Methods

52 isolated left CDH and 104 control fetuses were imaged using MRI. Brain morphometry (Biparietal diameter—BPD, brain fronto-occipital diameter—BFOD, third ventricle, posterior ventricles, transcerebellar diameter—TCD, anteroposterior and craniocaudal cerebellar vermis diameter—AP and CC) and cortical structures (bilateral cingulate fissure—CF, insular fissure—IF, insular depth - ID) were compared with controls using Mann–Whitney test.

Results

Median gestational age at MRI (p = 0.95)and the median biparietal diameter (p = 0.737) were comparable. Among morphometric parameters, only the brain fronto-occipital diameter was significantly smaller in CDH (p = 0.001) and the third ventricle was significantly greater in CDH (<0.0001). Among cortical structures, the cingulate and insular fissures were significantly deeper in CDH fetuses (p < 0.0001) as the insular depth ID was smaller in CDH (p < 0.03).

Conclusions

CDH fetuses have a smaller fronto-occipital diameter, reduced insular depth, deeper cingulate and insular fissure, and greater third ventricle width as compared to controls. These findings suggest that left CDH may have an impact on fetal brain development with an overall reduction in brain volume.     

Presentation of ventriculomegaly at 11–14 weeks of gestation: An analysis of longitudinal data

Objectives

The aim of this study was to examine the value of the sonographic measurements of the choroid plexus and the lateral ventricles at 11–14 gestational weeks in fetuses that had the diagnosis of second-trimester ventriculomegaly (VM) as a clinical reference.

Methods

The standard axial plane used for biparietal diameter measurement from 2D stored images in the first trimester was used to calculate the ratio between the choroid plexus and lateral ventricle diameter (PDVDR), the choroid plexus and lateral ventricle length (PLVLR) and the choroid plexus and lateral ventricle area (PAVAR) in 100 normal and 15 fetuses diagnosed with second-trimester VM.

Results

In fetuses with VM, the measurements of PDVDR, PLVLR and PAVAR were all significantly smaller compared to normal fetuses (p = < 0.001, <0.001, <0.01). Four out of seven cases with mild VM had measurements below the 5th percentile (57%). 75% of cases with moderate or severe VM had at least one measurement below the 5th percentile.

Conclusions

Since the axial plane of the fetal head is obtained in all first-trimester routine screenings, the measurements of PDVDR, PLVLR and PAVAR could easily be integrated into routine examinations for an early detection of VM.     

Rapid and radical amniodrainage in the treatment of severe twin–twin transfusion syndrome†

We have evaluated the role of a rapid and radical method of amniodrainage in the treatment of severe twin–twin transfusion. The outcome of 15 patients with severe twin–twin transfusion for which a amniodrainage was performed by means of a vacuum bottle system was compared with the outcome of 15 patients with a similar condition, matched for gestational age at the time of the initial procedure and drained using a standard procedure. In the study group the amniodrainage ended when no amniotic fluid could be aspirated, whereas the women in the standard group were drained with a syringe system and the fluid was removed until the deepest amniotic fluid pool was <8 cm. At the initial procedure, the mean volume of amniotic fluid drained was significantly (p<0.05) higher (3252 vs 2153 ml) and the length of the procedure significantly (p<0.001) shorter (21 vs 41 min) in the study group than in the standard group. The mean post-procedure amniotic fluid index was significantly (p<0.001) smaller (2.9 vs 7.7 cm) after radical amniodrainage than after the standard amniodrainage. The mean number of procedures was significantly (p<0.001) lower (1.5 vs 5.6) in the study group compared to the standard group. In the study group the mean placental thickness increased significantly (p<0.001) from 9 mm before the procedure to 49 mm after, and the overall perinatal survival rate was 80% and the proportion of pregnancies with at least one survivor was 93%. The present data indicate that early, rapid and radical amniodrainage is an effective and low-cost therapy for severe twin–twin transfusion syndrome. Compared to the standard amniodrainage technique it also appears to reduce the need for multiple procedures. Copyright © 2001 John Wiley & Sons, Ltd.     

Factors involved in the decision to decline prenatal screening with noninvasive prenatal testing (NIPT)

Objective

To investigate factors involved in the decision to decline prenatal screening with noninvasive prenatal testing (NIPT).

Method

A questionnaire study was conducted among 219 pregnant women in the Netherlands who had declined prenatal screening with NIPT (TRIDENT-2 study). Respondents were selectively recruited from three hospitals and 19 midwifery practices, primarily located in or near socioeconomically disadvantaged neighborhoods. 44.3% of the respondents were of non-Western ethnic origin and 64.4% were religious.

Results

Most respondents (77.2%) found the decision to decline NIPT easy to make, and 59.8% had already made the decision before information about NIPT was offered. These respondents were more often religious, multigravida, and had adequate health literacy. The main reasons to decline NIPT were “I would never terminate my pregnancy” (57.1%) and “every child is welcome” (56.2%). For 16.9% of respondents, the out-of-pocket costs (175 euros) played a role in the decision, and the women in this group were more often nonreligious, primigravida, and had inadequate health literacy.

Conclusion

The primary factors involved in the decision to decline NIPT were related to personal values and beliefs, consistent with autonomous choice. Out-of-pocket costs of NIPT hinder equal access for some pregnant women.     

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.     

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.     

Three- versus two-dimensional ultrasound for nuchal translucency thickness measurements: comparison of feasibility and levels of agreement

We have determined feasibility and levels of agreement for visualizing the nuchal translucency within a time limit with three-dimensional (3D) and two-dimensional (2D) transvaginal ultrasound. A total of 213 women of median gestational age 13 weeks (range 11–14 weeks) undergoing first-trimester nuchal translucency (NT) thickness measurements with 2D transabdominal ultrasound were included in the study. Additionally all women underwent 2D and 3D transvaginal NT examination within a time limit of 90 s. These two methods were compared with each other and with our standard method (2D transabdominal ultrasound) with respect to visualization of fetal nuchal fold and to the levels of agreement. The nuchal fold was visualized by 3D and 2D transvaginal ultrasound in 85.9% (95% CI: 80.5%, 90.3%) and 25.8% (95% CI: 20.1%, 32.2%), respectively (p<0.001). There was a statistically significant underestimation of the NT by 2D transabdominal as compared with 3D transvaginal ultrasound of 0.1 mm (p<0.001), and by 3D transvaginal as compared with 2D transvaginal ultrasound of even 0.1 mm (p<0.001). 3D transvaginal ultrasound of the nuchal fold has increased feasibility to 2D transvaginal ultrasound within a short examination time and with minimal, but significant, measurement differences. Copyright © 2001 John Wiley & Sons, Ltd.     

Fetal intestinal loop dilatation: Follow-up and outcome of a series of 133 consecutive cases (the DILDIG study)

Objectives

To define the prognostic markers of fetal dilated bowel loops.

Methods

National non-interventional study of 133 consecutive prenatal observations of dilated loops including ultrasound examinations, complementary laboratory tests, magnetic resonance imaging (MRI), outcomes, and postnatal diagnosis.

Results

One hundred twenty seven cases were classified according to outcome: Group 1, very severe (n = 43), Group 2, children needing specific care (n = 39), and Group 3, healthy children (n = 45). Prenatal ultrasound scan suggested duodenal obstruction in 30 cases, small bowel obstruction in 81, colonic obstruction in 11, and diffuse dilatation in 5. Diameter of dilated loops did not significantly differ between the groups. A poor prognosis was significantly associated with duodenal obstruction, genetic anomalies (53% vs. 21.8%), including aneuploidies or CFTR gene mutations and abnormal amniotic fluid biochemistry (86.4% vs. 38.7%). A good prognosis was associated with regression of dilatation and normal MRI.

Conclusion

In this study, postnatal outcomes for fetuses with intestinal dilatation were best predicted by assessing the level of obstruction with prenatal ultrasound and MRI, determining the presence of associated malformations, amniotic fluid biochemical and genetic testing, and monitoring for regression of bowel dilatation. These results should help inform future guidelines on the prenatal and neonatal management of congenital intestinal obstruction.     

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.