Detection of maternal X chromosome abnormalities using single nucleotide polymorphism-based noninvasive prenatal testing.
Am J Obstet Gynecol MFM
; 2(3): 100152, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-33345882
ABSTRACT
BACKGROUND:
Maternal X chromosome abnormalities may cause discordant results between noninvasive prenatal screening tests and diagnostic evaluation of the fetus/newborn, leading to unnecessary invasive testing. Women with X chromosome abnormalities are at increased risk for reproductive, pregnancy, or other health complications, which may be reduced or ameliorated by early diagnosis, monitoring, and intervention.OBJECTIVE:
This study aimed to validate a single nucleotide polymorphism-based noninvasive prenatal test to identify X chromosome abnormalities of maternal origin. STUDYDESIGN:
All tests unable to evaluate fetal risk for aneuploidy because of uninformative algorithm results were eligible for inclusion. Two groups of cases were prospectively identified Group A (n=106) where a maternal X chromosome abnormality was suspected and Group B (control group, n=107) where a fetal chromosome abnormality involving chromosome 13, 18, 21, or X was suspected but did not meet criteria for reporting. Maternal DNA was isolated from the plasma-depleted cellular pellet and sent to a reference laboratory for blinded analysis using chromosomal microarray. A chromosome abnormality involving chromosomes 13, 18, 21, or X was reported by the reference laboratory if ≥5 Mb in size and present in ≥20% of the DNA.RESULTS:
A maternal X chromosome abnormality was suspected in 1/1305 tests (149/194,385; 0.08%). In Group A, a maternal X chromosome abnormality was confirmed in 100/106 cases (94.3% positive predictive value, 1-sided 97.5% confidence interval, 88.1%-100.0%). Turner syndrome was the most commonly suspected maternal abnormality (58/106, 54.7%), with confirmation of mosaic or nonmosaic 45,X by microarray in 38/58 (65.5%) cases. Noninvasive prenatal screening tests suspected the presence of maternal 47,XXX with or without mosaicism in 40/106 (37.7%) cases, confirmed by microarray in 38/40 (95.0%). In Group B (n=107), no maternal microarray abnormalities were reported, providing a negative predictive value of 100% (1-sided 97.5% confidence interval, 96.6%-100.0%).CONCLUSION:
When noninvasive prenatal testing suspected a maternal X chromosome abnormality, maternal microarray confirmed an X chromosome abnormality with 94.3% positive predictive value. Of the maternal X chromosome abnormalities detected by array, >50% were 45,X. When fetal chromosome abnormalities involving chromosomes 13, 18, 21, or X were suspected, no maternal chromosome abnormalities were reported, yielding a negative predictive value of 100%. Women with maternal X abnormalities suspected with noninvasive prenatal testing may be at increased risk for reproductive and health complications; early evaluation and treatment may prevent long-term consequences or disability.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trastornos de los Cromosomas
/
Pruebas Prenatales no Invasivas
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
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Screening_studies
Límite:
Female
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Humans
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Newborn
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Pregnancy
Idioma:
En
Año:
2020
Tipo del documento:
Article