Potential Diagnostic Consequences of Applying Noninvasive Prenatal Testing: Population-Based Study From a Country With Existing First-Trimester Screening

作者：Petersen O B^*; Vogel I; Ekelund C; Hyett J; Tabor A

来源：Obstetrical and Gynecological Survey, 2014, 69(6): 321-323.

DOI：10.1002/uog.13270

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p><jats:italic>Targeted non‐invasive prenatal testing (<jats:styled-content style="fixed-case">NIPT</jats:styled-content>) tests for trisomies 21, 18 and 13 and sex chromosome aneuploidies and could be an alternative to traditional karyotyping. The aim of this study was to determine the risk of missing other abnormal karyotypes of probable phenotypic significance by <jats:styled-content style="fixed-case">NIPT</jats:styled-content></jats:italic>.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p><jats:italic>This was a retrospective population‐based analysis of all singleton pregnancies booked for combined first‐trimester screening (<jats:styled-content style="fixed-case">cFTS</jats:styled-content>) in Denmark over a 4‐year period. Data concerning maternal demographics, <jats:styled-content style="fixed-case">cFTS</jats:styled-content> and prenatal or postnatal karyotypes were collected from the Danish Fetal Medicine database. Karyotypes were classified according to whether the chromosomal anomaly would have been detected by <jats:styled-content style="fixed-case">NIPT</jats:styled-content> and whether it was likely to affect phenotype</jats:italic>.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:italic><jats:styled-content style="fixed-case">cFTS</jats:styled-content> was completed in 193 638 pregnancies. 10 205 (5.3%) had cytogenetic or molecular analysis performed. Of these, 1122 (11.0%) had an abnormal karyotype, of which 262 (23.4%) would have been missed by <jats:styled-content style="fixed-case">NIPT</jats:styled-content>, but would probably have been clinically significant. The prevalence of such ‘atypical abnormal karyotypes’ was increased in women above 45 years of age, in pregnancies with increased nuchal translucency (<jats:styled-content style="fixed-case">NT</jats:styled-content>) thickness (≥ 3.5 mm), with abnormal levels of free β‐human chorionic gonadotropin (&lt; 0.2 or ≥ 5.0 multiples of the median (<jats:styled-content style="fixed-case">MoM</jats:styled-content>)) or pregnancy‐associated plasma protein‐A &lt; 0.2 <jats:styled-content style="fixed-case">MoM</jats:styled-content>. One or more of these factors was present in 3% of women, and the prevalence of atypical abnormal karyotypes in this high‐risk cohort was 1.6%</jats:italic>.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p><jats:italic>A significant proportion of karyotypic abnormalities will be missed by targeted <jats:styled-content style="fixed-case">NIPT</jats:styled-content>. Women of advanced maternal age, or with increased fetal <jats:styled-content style="fixed-case">NT</jats:styled-content> or abnormal biochemistry, have a higher risk of having a fetus affected by an atypical abnormal karyotype and need to be counseled accordingly when considering <jats:styled-content style="fixed-case">NIPT</jats:styled-content>.

• 出版日期2014-6