Potential diagnostic consequences of applying non-invasive prenatal testing: population-based study from a country with existing first-trimester screening

TY - JOUR

T1 - Potential diagnostic consequences of applying non-invasive prenatal testing

T2 - population-based study from a country with existing first-trimester screening

AU - Petersen, O B

AU - Vogel, I

AU - Ekelund, C

AU - Hyett, J

AU - Tabor, A

AU - Danish Fetal Medicine Study Group

N1 - Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

PY - 2014/3

Y1 - 2014/3

N2 - Objectives Targeted non-invasive prenatal testing (NIPT) 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 NIPT. Methods This was a retrospective population-based analysis of all singleton pregnancies booked for combined first-trimester screening (cFTS) in Denmark over a 4-year period. Data concerning maternal demographics, cFTS 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 NIPT and whether it was likely to affect phenotype. Results cFTS 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 NIPT, 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 (NT) thickness (≥ 3.5 mm), with abnormal levels of free β-human chorionic gonadotropin (< 0.2 or ≥ 5.0 multiples of the median (MoM)) or pregnancy-associated plasma protein-A < 0.2 MoM. 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%. Conclusions A significant proportion of karyotypic abnormalities will be missed by targeted NIPT. Women of advanced maternal age, or with increased fetal NT 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 NIPT.

AB - Objectives Targeted non-invasive prenatal testing (NIPT) 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 NIPT. Methods This was a retrospective population-based analysis of all singleton pregnancies booked for combined first-trimester screening (cFTS) in Denmark over a 4-year period. Data concerning maternal demographics, cFTS 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 NIPT and whether it was likely to affect phenotype. Results cFTS 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 NIPT, 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 (NT) thickness (≥ 3.5 mm), with abnormal levels of free β-human chorionic gonadotropin (< 0.2 or ≥ 5.0 multiples of the median (MoM)) or pregnancy-associated plasma protein-A < 0.2 MoM. 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%. Conclusions A significant proportion of karyotypic abnormalities will be missed by targeted NIPT. Women of advanced maternal age, or with increased fetal NT 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 NIPT.

KW - Adult

KW - Biological Markers

KW - Chorionic Gonadotropin, beta Subunit, Human

KW - Chromosome Disorders

KW - Denmark

KW - Female

KW - Humans

KW - Infant, Newborn

KW - Maternal Age

KW - Nuchal Translucency Measurement

KW - Practice Guidelines as Topic

KW - Pregnancy

KW - Pregnancy Trimester, First

KW - Pregnancy-Associated Plasma Protein-A

KW - Prenatal Diagnosis

KW - Retrospective Studies

KW - Risk Factors

U2 - 10.1002/uog.13270

DO - 10.1002/uog.13270

M3 - Journal article

C2 - 24375770

SN - 0960-7692

VL - 43

SP - 265

EP - 271

JO - Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology

JF - Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology

IS - 3

ER -