Prenatal diagnostic testing and atypical chromosome abnormalities following combined first‐trimester screening: implications for contingent models of non‐invasive prenatal testing

Lindquist, Anthea; Poulton, Alice; Halliday, Jane; Hui, Lisa

doi:10.1002/uog.18979

Cited by 44 publications

(68 citation statements)

References 25 publications

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“…Lindquist et al [11] also describe an association between low PAPP-A and atypical abnormalities. They find an overall prevalence of atypical abnormalities of 1.4% in those with a combined first trimester risk > 1: 300 where we find 2.8%.…”

Section: Discussionmentioning

confidence: 99%

“…They find an overall prevalence of atypical abnormalities of 1.4% in those with a combined first trimester risk > 1: 300 where we find 2.8%. Lindquist et al [11] describe that 90% of atypical abnormalities could be detected by cFTS > 1: 100, serum analytes below < 0.2 MoM or ultrasound abnormalities. This is in contrast to our finding of only 34% atypical abnormalities could be detected by cFTS > 1: 100, serum analytes below < 0.2 MoM, but without inclusion of ultrasound abnormalities.…”

Section: Discussionmentioning

confidence: 99%

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Population-Based Screening for Trisomies and Atypical Chromosomal Abnormalities: Improving Efficacy using the Combined First Trimester Screening Algorithm as well as Individual Risk Parameters

et al. 2018

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Aim: To examine the performance of the combined First Trimester Screening (cFTS) algorithm when outliers of 4 risk parameters (maternal age, nuchal translucency (NT) thickness, PAPP-A and β-hCG) were included in the classification of “high-risk”. Methods: A retrospective analysis of singleton pregnancies undergoing cFTS between 2008 and 2011 in Denmark. Abnormal karyotypes were classified as trisomy 21 (T21), trisomy 13 (T13) and trisomy 18 (T18), sex chromosome aberrations and atypical abnormal karyotypes. Results: cFTS was completed in 193,638 pregnancies. In 10,205 (5.3%) cases, cytogenetic or molecular analysis was performed pre- or postnatally. An abnormal karyotype was seen in 1,122 (11.0%). The algorithm identified 87% of T21, 80% of T13, 75% of T18, 79% of sex chromosome aberrations and 35% of atypical abnormal karyotypes. Additional classification of a single risk parameter outlier (low PAPP-A or free β-hCG (< 0.2 MoMs), high β-hCG (≥5.0 MoMs), maternal age ≥45 years or NT ≥3.5 mm) as being at high-risk would have improved detection rates to 88, 80, 81, 81 and 37% respectively. The screen positive rate increased from 4.4 to 4.8%. Discussion: Addition of outliers of the 4 parameters used in cFTS algorithm will lead to a statistically significant increase in detection rates for chromosomal abnormality.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Population-Based Screening for Trisomies and Atypical Chromosomal Abnormalities: Improving Efficacy using the Combined First Trimester Screening Algorithm as well as Individual Risk Parameters

et al. 2018

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“…Similar to case 4, cases of 5p deletion syndrome associated with a low PAPP‐A level, as well as an abnormal level of serum human chorionic gonadotrophin were reported . Recent studies suggest that atypical chromosome abnormalities are associated with a low PAPP‐A level, among other risk factors . However, cFTS showed a low‐risk result in Case 3.…”

Section: Discussionmentioning

confidence: 99%

“…Single‐nucleotide polymorphism‐based noninvasive prenatal testing was reported to be highly accurate for five microdeletion syndromes including 5p deletion syndrome . However, case 4 illustrates the importance of offering IPD for scan abnormalities or a positive cFTS with a low PAPP‐A level despite a negative cfDNA testing result …”

Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of 5p deletion syndrome: Report of five cases

Mak

Teresa

Chan

et al. 2019

J of Obstet and Gynaecol

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It is difficult to prenatally identify 5p deletion (−) syndrome. Here, we report five cases of 5p‐ syndrome diagnosed by invasive prenatal diagnosis. Of them, three had a small cerebellum in the second trimester. In one case, a prominent renal pelvis and an absent nasal bone were also found in the first trimester. However, there were no abnormal ultrasound findings in the other two cases. Two cases had noninvasive prenatal testing and one showed a ‘5p‐ syndrome positive result’ because of reduced amount of cell‐free DNA in 5p. Two had combined first‐trimester screening performed where one had a high‐risk result for trisomy 18 and a low pregnancy‐associated plasma protein‐A level. Two cases of 5p‐ syndrome resulted from a parental balanced translocation. Prenatal diagnosis will only be made on invasive prenatal diagnosis for abnormal ultrasound findings with small cerebellum, abnormal prenatal screening or a parental reciprocal translocation involving 5p.

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“…These other abnormalities included trisomy 18 (11%), pathogenic CNVs (10%), level III mosaicism (9%), sex chromosome abnormalities (7%), triploidy (4%), and trisomy 13 (4%) . When the state cohort of 100,418 women undergoing CFTS during the years 2014 to 2015 was analysed, 90% of major chromosome abnormalities not detectable by standard cfDNA (ie other than trisomies 21, 18, and 13 and sex chromosome abnormalities) would have been detected if diagnostic testing was performed in women with CFTS risk >1 in 100, serum PaPP‐A or beta‐HCG <0.2 MoM, or fetal abnormality on first or second trimester ultrasound …”

Section: Have Women Really “Paid a Price” For Embracing Cfdna?mentioning

confidence: 99%

What is the real “price” of more prenatal screening and fewer diagnostic procedures? Costs and trade‐offs in the genomic era

Hui

Norton

2018

Prenatal Diagnosis

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Any screening approach, including with cell-free DNA, will have an inferior detection rate compared with 100% diagnostic testing with chromosomal microarrays. Cell-free DNA-based screening, however, should not be seen as a threat to informed choice or maximising the benefits of diagnostic testing. Screening methods have become so much better that more women are now comfortable relying on such screening and do not need the certainty of a diagnostic test. This has not lead to a decline in detection of fetal chromosome abnormalities-in fact, we are now seeing historically high yields from prenatal screening. There are both economic and ethical consequences of offering universal diagnostic testing and abandoning the presumption of a normal infant in otherwise uncomplicated pregnancies. However, for some women, comprehensive information and diagnostic accuracy are important. Offering these women all options, with a careful and comprehensive explanation of the risks and benefits of each, results in outcomes that are best aligned with woman's preferences while at the same time requiring fewer diagnostic tests and lowering costs. It is one of the primary challenges of the modern era of prenatal testing to ensure that women receive sufficient information on which to make informed decisions.

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Prenatal diagnostic testing and atypical chromosome abnormalities following combined first‐trimester screening: implications for contingent models of non‐invasive prenatal testing

Cited by 44 publications

References 25 publications

Population-Based Screening for Trisomies and Atypical Chromosomal Abnormalities: Improving Efficacy using the Combined First Trimester Screening Algorithm as well as Individual Risk Parameters

Population-Based Screening for Trisomies and Atypical Chromosomal Abnormalities: Improving Efficacy using the Combined First Trimester Screening Algorithm as well as Individual Risk Parameters

Prenatal diagnosis of 5p deletion syndrome: Report of five cases

What is the real “price” of more prenatal screening and fewer diagnostic procedures? Costs and trade‐offs in the genomic era

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