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OBJECTIVE: To assess the efficiency of modified enrichment method for cell-free fetal DNA (cffDNA) through purified superparamagnetic beads during non-invasive prenatal testing (NIPT). METHODS: A total of 26 252 pregnant women undergoing NIPT at the Maternal and Child Health Care Hospital of Haidian District from December 2017 to September 2022 were recruited and randomly assigned into the conventional group (n = 10 573) and the modified enrichment group (n = 15 679), who were then subjected to the screening and enrichment of the cffDNA using a conventional and a modified technique, respectively. High-risk pregnant women detected by NIPT were subjected to invasive prenatal diagnosis. All women were followed up for their pregnancy outcomes, and the detection efficacy of the two methods was compared in terms of fragment size, concentration of cffDNA, duplicate detection rate, and indices of clinical laboratory tests. RESULTS: The fragment size of the main peak of the cell-free DNA library of the modified enrichment group was significantly lower than that of the conventional group [267 (264, 269) bp vs. 294 (292, 296) bp, P < 0.01], while the concentration of cffDNA was significantly higher [21.86% (17.61%, 26.36%) vs. 9.08% (6.87%, 11.87%), P < 0.01]. In addition, the duplicate detection rate (0.740% vs. 2.02%, X2 = 83.90, P < 0.01) and detection failure rate (0.006% vs. 0.057%, P < 0.05) in the modified enrichment group were significantly lower than those of the conventional group. The combined positive predictive value (PPV) in both high-risk (64.3% vs. 76.1%) and low-risk (35.3% vs. 45.5%) pregnant women from the modified enrichment group was slightly lower than those from the conventional group, though no significant difference was detected. There was one false negative case for trisomy 21 among the high-risk pregnant women from the conventional group, and no false negative case was found in the modified enrichment group. CONCLUSION: The modified technique to screen and enrich the cffDNA has significantly enhanced the relative concentration of cffDNA and reduced the failure and duplication detection rate of NIPT, which has significantly reduced the incidence of false negative cases due to the low concentration of cffDNA, and greatly increased the overall detection efficacy of NIPT.
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Ácidos Nucleicos Libres de Células , Pruebas Prenatales no Invasivas , Humanos , Femenino , Embarazo , Ácidos Nucleicos Libres de Células/aislamiento & purificación , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , Adulto , Pruebas Prenatales no Invasivas/métodos , Diagnóstico Prenatal/métodos , FetoAsunto(s)
Amniocentesis , Cromosomas Humanos Par 2 , Cromosomas Humanos Par 7 , Mosaicismo , Pruebas Prenatales no Invasivas , Trisomía , Humanos , Femenino , Embarazo , Trisomía/diagnóstico , Trisomía/genética , Adulto , Cromosomas Humanos Par 2/genética , Cromosomas Humanos Par 7/genética , Reacciones Falso Positivas , Pruebas Prenatales no Invasivas/métodos , Reacciones Falso Negativas , Disomía Uniparental/diagnóstico , Disomía Uniparental/genéticaRESUMEN
OBJECTIVE: To evaluate the accuracy of expanded noninvasive prenatal testing (NIPT) for maternal copy number variations. MATERIALS AND METHODS: Expanded NIPT was used to detect CNVs ≥2 Mb at a whole-genome scale. The threshold of maternal deletion was copy numbers (CN) ≤ 1.6, and the threshold of maternal duplication was CN ≥ 2.4. RESULTS: Of the 5440 pregnant women with successful expanded NIPT results, 28 maternal CNVs ≥2 Mb were detected in 27 pregnant women. Except for five cases reported as test failure, 23 CNVs ≥2 Mb were confirmed among the remaining 22 pregnant women by CNV-seq of maternal lymphocyte DNA. The genomic location, copy numbers and fragment size of maternal CNVs reported by expanded NIPT were consistent with the results of CNV-seq of maternal lymphocyte DNA. CONCLUSIONS: Maternal CNVs ≥2 Mb can be accurately evaluated according to the CN indicated by expanded NIPT results.
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Variaciones en el Número de Copia de ADN , Linfocitos , Pruebas Prenatales no Invasivas , Humanos , Femenino , Embarazo , Pruebas Prenatales no Invasivas/métodos , Adulto , ADN/sangre , ADN/genética , ADN/análisisRESUMEN
Non-invasive prenatal testing (NIPT) is usually performed beyond 10 weeks of gestation, because earlier in pregnancy, the fetal fraction is low, resulting in failure to obtain reliable results. This study aimed to evaluate the clinical performance of NIPT earlier in pregnancy using a method for cell-free DNA (cfDNA) analysis that eliminates the need for polymerase chain reaction (PCR), DNA sequencing, or microarrays (Vanadis® system, PerkinElmer, Waltham, MA, USA). Cell-free DNA was extracted from the maternal plasma of 30 singleton pregnancies at 6-9 weeks of gestation (group 1) and at 11-14 weeks of gestation of the same patients (group 2). The mean crown-rump length (CRL) and gestational age in group A was 16.12 mm and that in group B was 61.45 mm. In group A, results were obtained in all, but one, cases (97%). From the remaining pregnancies, one miscarried at 8 weeks and, therefore, the follow-up NIPT at 12 weeks could not be performed. The fetal sex was diagnosed correctly in the 28 cases that had a successful early test, and the results were in accordance with the examination at 12 weeks. There were no cases of aneuploidies and disomy was diagnosed correctly in all. The "Vanadis" prenatal NIPT assay can successfully be used early during the first trimester at 6-9 weeks of gestation (early NIPT) to identify the fetal sex. Further studies are needed to explore the diagnostic potential for aneuploidies.
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Ácidos Nucleicos Libres de Células , Edad Gestacional , Pruebas Prenatales no Invasivas , Primer Trimestre del Embarazo , Humanos , Embarazo , Femenino , Adulto , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , Pruebas Prenatales no Invasivas/métodos , Primer Trimestre del Embarazo/sangre , Diagnóstico Prenatal/métodos , MasculinoRESUMEN
BACKGROUND: Digital Polymerase Chain Reaction (dPCR) presents a promising approach for quantifying DNA and analyzing copy number variants, particularly in non-invasive prenatal testing. This method offers a streamlined and time-efficient procedure in contrast to the widely used next-generation sequencing for non-invasive prenatal testing. Studies have reported encouraging results for dPCR in detecting fetal autosomal aneuploidies. Consequently, this systematic review aimed to evaluate the effectiveness of dPCR in screening for trisomy 21, 18, and 13. METHODS: A systematic search was conducted in PubMed, Web of Sciences, and Embase for relevant articles published up to December 30, 2023. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was utilized for the quality assessment of the included articles. Furthermore, a bivariate random-effect regression model was used to conduct a meta-analysis on the utility of dPCR for trisomy 21 screening. RESULTS: A total of 9 articles were included in this review, with all of them assessing the utility of dPCR in trisomy 21 screening, and 2 and 1 studies conducting additional analysis on the screening abilities of dPCR for trisomy 18 and 13, respectively. A bivariate random-effects model calculated pooled sensitivity and specificity with a 95% confidence interval (CI). Meta-analysis of 6 studies comparing trisomy-21 screening with karyotyping demonstrated dPCR's pooled sensitivity of 98% [95% CI: 94 -100] and specificity of 99% [95% CI: 99 -100]. While conducting a meta-analysis for trisomy 13 and 18 proved impractical, reported values for sensitivity and specificity were favorable. CONCLUSIONS: These findings suggest that dPCR holds promise as an effective tool for non-invasive prenatal testing, presenting a less time-consuming and intricate alternative to next-generation sequencing. However, further research is necessary to evaluate dPCR's applicability in clinical settings and to delineate its specific advantages over next-generation sequencing. This study contributes valuable insights into the potential of dPCR for enhancing prenatal screening methodologies. TRIAL REGISTRATION: The protocol of this study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on 7/3/2024, with a registration code of CRD42024517523.
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Aneuploidia , Síndrome de Down , Reacción en Cadena de la Polimerasa , Humanos , Femenino , Embarazo , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Reacción en Cadena de la Polimerasa/métodos , Pruebas Prenatales no Invasivas/métodos , Diagnóstico Prenatal/métodos , Síndrome de la Trisomía 13/diagnóstico , Sensibilidad y Especificidad , Síndrome de la Trisomía 18/diagnóstico , Síndrome de la Trisomía 18/genética , Variaciones en el Número de Copia de ADNRESUMEN
The author describes the results and implications of a study on noninvasive prenatal test results that indicate maternal malignancies.
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Pruebas Prenatales no Invasivas , Humanos , Femenino , Embarazo , Pruebas Prenatales no Invasivas/métodos , Pruebas Prenatales no Invasivas/estadística & datos numéricos , Estudios de Seguimiento , Pruebas Genéticas/métodos , Adulto , Neoplasias/genética , Neoplasias/diagnóstico , Diagnóstico Prenatal/métodos , Complicaciones Neoplásicas del Embarazo/diagnóstico , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: As a screening method, inaccuracies in noninvasive prenatal screening (NIPS) exist, which are often attributable to biological factors. One such factor is the history of transplantation. However, there are still limited reports on such NIPS cases. METHODS: We report an NIPS case of a pregnant woman who had received a stem cell transplant from a male donor. To determine the karyotype in the woman's original cell, we performed chromosome microarray analysis (CMA) on her postnatal blood and oral mucosa. To comprehensively estimate the cell-free DNA (cfDNA) composition, we further performed standard NIPS procedures on the postnatal plasma. Moreover, we reviewed all published relevant NIPS case reports about pregnant women with transplantation history. RESULTS: NIPS showed a low-risk result for common trisomies with a fetal fraction of 65.80%. CMA on maternal white blood cells showed a nonmosaic male karyotype, while the oral mucosa showed a nonmosaic female karyotype. The proportion of donor's cfDNA in postnatal plasma was 94.73% based on the Y-chromosome reads ratio. The composition of cfDNA in maternal plasma was estimated as follows: prenatally, 13.60% maternal, 65.80% donor, and 20.60% fetal/placental, whereas postnatally, 5.27% maternal and 94.73% donor. CONCLUSIONS: This study expanded our understanding of the influence of stem cell transplantation on NIPS, allowing us to optimize NIPS management for these women.
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Ácidos Nucleicos Libres de Células , Pruebas Prenatales no Invasivas , Humanos , Femenino , Embarazo , Masculino , Adulto , Ácidos Nucleicos Libres de Células/genética , Ácidos Nucleicos Libres de Células/sangre , Pruebas Prenatales no Invasivas/métodos , Trasplante de Células Madre , Donantes de Tejidos , Trisomía/genéticaRESUMEN
BACKGROUND: The analysis of haplotypes of variants is important for pharmacogenomics analysis and noninvasive prenatal testing for monogenic diseases. However, there is a lack of robust methods for targeted haplotyping. METHODS: We developed digital PCR haplotype sequencing (dHapSeq) for targeted haplotyping of variants, which is a method that compartmentalizes long DNA molecules into droplets. Within one droplet, 2 target regions are PCR amplified from one template molecule, and their amplicons are fused together. The fused products are then sequenced to determine the phase relationship of the single nucleotide polymorphism (SNP) alleles. The entire haplotype of 10s of SNPs can be deduced after the phase relationship of individual SNPs are determined in a pairwise manner. We applied dHapSeq to noninvasive prenatal testing in 4 families at risk for thalassemia and utilized it to detect NUDT15 diplotypes for predicting drug tolerance in pediatric acute lymphoblastic leukemia (72 cases and 506 controls). RESULTS: For SNPs within 40â kb, phase relation can be determined with 100% accuracy. In 7 trio families, the haplotyping results for 97 SNPs spanning 185â kb determined by dHapSeq were concordant with the results deduced from the genotypes of both parents and the fetus. In 4 thalassemia families, a 19.3-kb Southeast Asian deletion was successfully phased with 97 downstream SNPs, enabling noninvasive determination of fetal inheritance using relative haplotype dosage analysis. In the NUDT15 analysis, the variant status and phase of the variants were successfully determined in all cases and controls. CONCLUSIONS: The dHapSeq represents a robust and scalable haplotyping approach with numerous clinical and research applications.
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Haplotipos , Pruebas Prenatales no Invasivas , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Humanos , Reacción en Cadena de la Polimerasa/métodos , Femenino , Pruebas Prenatales no Invasivas/métodos , Embarazo , Pruebas de Farmacogenómica/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Análisis de Secuencia de ADN/métodos , Talasemia/genética , Talasemia/diagnósticoRESUMEN
OBJECTIVE: To explore the perspectives of pregnant women on broadening the scope of noninvasive prenatal testing (NIPT) from screening for foetal aneuploidies to prediction of adverse pregnancy outcomes. METHODS: Four online focus groups (n = 23 participants) and 14 individual semi-structured interviews were conducted. Participants included pregnant women with and without a history of adverse pregnancy outcomes. RESULTS: Both women at low and high risk of adverse pregnancy outcomes had a positive attitude towards using NIPT to predict adverse pregnancy outcomes. Perceived benefits included the possibility to potentially improve maternal and foetal outcomes by taking risk-reducing measures and/or intensified monitoring during pregnancy and the ability to mentally prepare for the potential adverse outcome. Perceived concerns included anxiety and stress caused by a high-risk test result, a false sense of control over pregnancy, and potential false reassurance. Additionally, women reasoned that broadening the scope of NIPT could increase the complexity of prenatal screening and raised concerns on the combined screening aims in one test (prediction of adverse pregnancy outcomes to improve foetal and maternal health vs. screening for foetal aneuploidies to increase reproductive autonomy). On a societal level, considerations on the risk of medicalising pregnancy and overall pressure to opt for NIPT were mentioned. CONCLUSION: In general, pregnant women have a positive attitude towards broadening the scope of NIPT to the prediction of pregnancy outcomes, although some concerns are acknowledged.
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Aneuploidia , Pruebas Prenatales no Invasivas , Resultado del Embarazo , Investigación Cualitativa , Humanos , Femenino , Embarazo , Adulto , Pruebas Prenatales no Invasivas/métodos , Resultado del Embarazo/epidemiología , Grupos Focales , Mujeres Embarazadas/psicología , Adulto JovenRESUMEN
RATIONALE: With advances in prenatal diagnostic techniques, chromosomal microdeletions and microduplications have become the focus of prenatal diagnosis. 7q partial monosomy or trisomy due to a deletion or duplication of the 7q end is relatively rare and usually originates from parents carrying a balanced translocation. PATIENT CONCERNS: Noninvasive prenatal screening (NIPT) showed a fetus with partial deletion and duplication of chromosome 7q. It was not possible to determine whether the fetus was normal. DIAGNOSES: Conventional chromosome G-banding and chromosome microarray analysis (CMA) were performed on fetal amniotic fluid samples and parental peripheral blood samples. INTERVENTIONS: The pregnant women were given detailed genetic counseling by clinicians. OUTCOMES: The fetal karyotype was 46, XY on conventional G-banding analysis. The CMA test results showed a deletion of approximately 7.8 Mb in the 7q36.1q36.3 region and a duplication of 6.6Mb in the 7q35q36.1 region. The parents' karyotype analysis and CMA results were normal, indicating a new mutation. LESSONS: CMA molecular diagnostic analysis can effectively detect chromosomal microdeletions or microduplications, clarify the relationship between fetal genotype and clinical phenotype, and provide a reference for prenatal diagnosis of chromosomal microdeletion-duplication syndrome.
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Deleción Cromosómica , Duplicación Cromosómica , Cromosomas Humanos Par 7 , Diagnóstico Prenatal , Humanos , Femenino , Cromosomas Humanos Par 7/genética , Embarazo , Adulto , Duplicación Cromosómica/genética , Diagnóstico Prenatal/métodos , Pruebas Prenatales no Invasivas/métodos , Bandeo Cromosómico , Cariotipificación , Análisis por Micromatrices/métodosRESUMEN
Non-invasive prenatal testing (NIPT) is a quite popular approach for detecting fetal genomic aneuploidies. However, due to the limitations on sequencing read length and coverage, NIPT suffers a bottleneck on further improving performance and conducting earlier detection. The errors mainly come from reference biases and population polymorphism. To break this bottleneck, we proposed NIPT-PG, which enables the NIPT algorithm to learn from population data. A pan-genome model is introduced to incorporate variant and polymorphic loci information from tested population. Subsequently, we proposed a sequence-to-graph alignment method, which considers the read mis-match rates during the mapping process, and an indexing method using hash indexing and adjacency lists to accelerate the read alignment process. Finally, by integrating multi-source aligned read and polymorphic sites across the pan-genome, NIPT-PG obtains a more accurate z-score, thereby improving the accuracy of chromosomal aneuploidy detection. We tested NIPT-PG on two simulated datasets and 745 real-world cell-free DNA sequencing data sets from pregnant women. Results demonstrate that NIPT-PG outperforms the standard z-score test. Furthermore, combining experimental and theoretical analyses, we demonstrate the probably approximately correct learnability of NIPT-PG. In summary, NIPT-PG provides a new perspective for fetal chromosomal aneuploidies detection. NIPT-PG may have broad applications in clinical testing, and its detection results can serve as a reference for false positive samples approaching the critical threshold.
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Aneuploidia , Pruebas Prenatales no Invasivas , Humanos , Femenino , Embarazo , Pruebas Prenatales no Invasivas/métodos , Algoritmos , Genómica/métodos , Diagnóstico Prenatal/métodos , Análisis de Secuencia de ADN/métodosRESUMEN
OBJECTIVE: This study aims to perform a prenatal genetic diagnosis of a high-risk fetus with trisomy 7 identified by noninvasive prenatal testing (NIPT) and to evaluate the efficacy of different genetic testing techniques for prenatal diagnosis of trisomy mosaicism. METHODS: For prenatal diagnosis of a pregnant woman with a high risk of trisomy 7 suggested by NIPT, karyotyping and chromosomal microarray analysis (CMA) were performed on an amniotic fluid sample. Low-depth whole-genome copy number variation sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were used to clarify the results further. In addition, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was performed to analyze the possibility of uniparental disomy(UPD). RESULTS: Amniotic fluid karyotype analysis revealed a 46, XX result. Approximately 20% mosaic trisomy 7 was detected according to the CMA result. About 16% and 4% of mosaicism was detected by CNV-seq and FISH, respectively. MS-MLPA showed no methylation abnormalities. The fetal ultrasound did not show any detectable abnormalities except for mild intrauterine growth retardation seen at 39 weeks of gestation. After receiving genetic counseling, the expectant mother decided to continue the pregnancy, and follow-up within three months of delivery was normal. CONCLUSION: In high-risk NIPT diagnosis, a combination of cytogenetic and molecular genetic techniques proves fruitful in detecting low-level mosaicism. Furthermore, the exclusion of UPD on chromosome 7 remains crucial when NIPT indicates a positive prenatal diagnosis of trisomy 7.
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Cromosomas Humanos Par 7 , Variaciones en el Número de Copia de ADN , Hibridación Fluorescente in Situ , Cariotipificación , Mosaicismo , Trisomía , Disomía Uniparental , Humanos , Femenino , Mosaicismo/embriología , Embarazo , Hibridación Fluorescente in Situ/métodos , Cromosomas Humanos Par 7/genética , Trisomía/diagnóstico , Trisomía/genética , Cariotipificación/métodos , Adulto , Disomía Uniparental/diagnóstico , Disomía Uniparental/genética , Diagnóstico Prenatal/métodos , Análisis por Micromatrices/métodos , Pruebas Prenatales no Invasivas/métodos , Reacción en Cadena de la Polimerasa Multiplex/métodos , Líquido AmnióticoRESUMEN
Trisomy 7 is the most common observed type of rare autosomal trisomies (RATs) detected at expanded genome-wide non-invasive prenatal testing (NIPT). Genetic counseling of NIPT trisomy 7-positive pregnancies remains to be not easy because the parents may worry about the likelihood of adverse pregnancy outcomes, fetal abnormality and the necessity of invasive procedures for confirmation of fetal mosaic trisomy 7 and uniparental disomy (UPD) 7. This review provides a comprehensive information on the update issues concerning genetic counseling of NIPT trisomy 7-positive pregnancies.
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Cromosomas Humanos Par 7 , Asesoramiento Genético , Pruebas Prenatales no Invasivas , Trisomía , Humanos , Femenino , Embarazo , Trisomía/diagnóstico , Trisomía/genética , Pruebas Prenatales no Invasivas/métodos , Cromosomas Humanos Par 7/genética , Disomía Uniparental/diagnóstico , Disomía Uniparental/genética , Pruebas Genéticas/métodos , Diagnóstico Prenatal/métodosAsunto(s)
Variaciones en el Número de Copia de ADN , Humanos , Variaciones en el Número de Copia de ADN/genética , Femenino , Estudios de Cohortes , Embarazo , Distrofina/genética , Pruebas Genéticas/métodos , Pruebas Genéticas/estadística & datos numéricos , Pruebas Prenatales no Invasivas/métodos , Pruebas Prenatales no Invasivas/estadística & datos numéricos , Diagnóstico Prenatal/métodos , Diagnóstico Prenatal/estadística & datos numéricosRESUMEN
INTRODUCTION: Confined placental mosaicism (CPM) is thought to be one of the main sources of false-positive prenatal cell-free DNA (cfDNA) screening results, but extensive and systematic studies to prove this statement are limited. We evaluate the contribution of CPM to false-positive prenatal cfDNA screening results in the largest cohort published to date. METHOD: We systematically offered postnatal analysis on placenta and umbilical cord to women who had a negative amniocentesis following a positive prenatal cfDNA screening result. A standardized protocol was used in which (when available) biopsies were taken at five locations in the placenta and umbilical cord. RESULTS: We analyzed a series of 99 placentas. CPM could be confirmed in 32.3 % of cases (32/99). CPM was detected across all subtypes of chromosomal aberrations (common and rare autosomal trisomies, sex chromosome abnormalities, copy number variations and autosomal monosomies). A lower detection rate was present in umbilical cord biopsies in comparison with placental biopsies. When comparing different sections of the placenta, no clear difference could be observed with regard to the probability of CPM being present nor to the grade of mosaicism. DISCUSSION: We confirm an important role for CPM in explaining false-positive prenatal cfDNA screening results. Placental regional differences are common. Given its limited clinical relevance, we do however not advocate placental studies in a diagnostic setting.
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Ácidos Nucleicos Libres de Células , Mosaicismo , Placenta , Humanos , Femenino , Embarazo , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , Placenta/patología , Adulto , Pruebas Prenatales no Invasivas/métodos , Reacciones Falso PositivasRESUMEN
OBJECTIVE: To explore the feasibility of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal copy number variants (CNV). METHODS: A retrospective analysis was carried out on NIPT positive samples in Suzhou Municipal Hospital from January 1, 2019 to December 31, 2021. The effect of NIPT on fetal CNV detection was assessed by comparison with the results of karyotype analysis and/or chromosomal microarray analysis (CMA). RESULTS: Among the 525 NIPT positive samples, 146 were CNV cases, of which 84 were further verified by karyotyping and/or CMA, 29 (34.5%) were true positive. Among them, 12 cases were pathogenic variants, 2 cases were likely pathogenic variants and 15 cases were variants of uncertain significance. CONCLUSION: NIPT could detect CNV with high accuracy, and to combine CNV detection and chromosomal aneuploidy detection has great significance to improve the prenatal and postnatal care.
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Variaciones en el Número de Copia de ADN , Cariotipificación , Pruebas Prenatales no Invasivas , Diagnóstico Prenatal , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Pruebas Prenatales no Invasivas/métodos , Diagnóstico Prenatal/métodos , Adulto , Aneuploidia , Feto , Estudios de FactibilidadAsunto(s)
Cardiomegalia , Síndrome de Dandy-Walker , Retardo del Crecimiento Fetal , Derrame Pericárdico , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Ultrasonografía Prenatal , Femenino , Humanos , Embarazo , Anomalías Múltiples/genética , Anomalías Múltiples/diagnóstico por imagen , Cardiomegalia/diagnóstico por imagen , Cardiomegalia/genética , Síndrome de Dandy-Walker/diagnóstico por imagen , Síndrome de Dandy-Walker/embriología , Síndrome de Dandy-Walker/genética , Reacciones Falso Negativas , Retardo del Crecimiento Fetal/diagnóstico , Retardo del Crecimiento Fetal/diagnóstico por imagen , Megalencefalia/genética , Pruebas Prenatales no Invasivas/métodos , Derrame Pericárdico/diagnóstico por imagen , Arteria Umbilical Única/diagnóstico por imagen , Triploidía , Ultrasonografía Prenatal/métodosRESUMEN
BACKGROUND: Non-invasive prenatal testing (NIPT) has been clinically available in Australia on a user-pays basis since 2012. There are numerous providers, with available tests ranging from targeted NIPT (only trisomies 21, 18, and 13 +/- sex chromosome aneuploidy) to genome-wide NIPT. While NIPT is being implemented in the public health care systems of other countries, in Australia, the implementation of NIPT has proceeded without public funding. The aim of this study was to investigate how NIPT has been integrated into antenatal care across Australia and reveal the successes and challenges in its implementation in this context. METHODS: An anonymous online survey was conducted from September to October 2022. Invitations to participate were sent to healthcare professionals (HCPs) involved in the provision of NIPT in Australia through professional society mailing lists and networks. Participants were asked questions on their knowledge of NIPT, delivery of NIPT, and post-test management of results. RESULTS: A total of 475 HCPs responded, comprising 232 (48.8%) obstetricians, 167 (35.2%) general practitioners, 32 (6.7%) midwives, and 44 (9.3%) genetic specialists. NIPT was most commonly offered as a first-tier test, with most HCPs (n = 279; 60.3%) offering it to patients as a choice between NIPT and combined first-trimester screening. Fifty-three percent (n = 245) of respondents always offered patients a choice between NIPT for the common autosomal trisomies and expanded (including genome-wide) NIPT. This choice was understood as supporting patient autonomy and informed consent. Cost was seen as a major barrier to access to NIPT, for both targeted and expanded tests. Equitable access, increasing time demands on HCPs, and staying up to date with advances were frequently reported as major challenges in delivering NIPT. CONCLUSIONS: Our findings demonstrate substantial variation in the clinical implementation of NIPT in Australia, including in the offers of expanded screening options. After a decade of clinical use, Australian clinicians still report ongoing challenges in the clinical and equitable provision of NIPT.