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Cited by 247Prenatal Screening and DiagnosticsDemographic Trends and Gender PreferencesMaternal and Perinatal Health Interventions

Noninvasive Fetal Sex Determination Using Cell-Free Fetal DNA: A Systematic Review and Meta-analysis

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Devaney, Stephanie A., Palomaki, Glenn E., Scott, Joan A., Bianchi, Diana W.·2011·JAMA
DOI 10.1001/jama.2011.1114PMC PMC4526182
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Abstract

CONTEXT: Noninvasive prenatal determination of fetal sex using cell-free fetal DNA provides an alternative to invasive techniques for some heritable disorders. In some countries this testing has transitioned to clinical care, despite the absence of a formal assessment of performance. OBJECTIVE: To document overall test performance of noninvasive fetal sex determination using cell-free fetal DNA and to identify variables that affect performance. DATA SOURCES: Systematic review and meta-analysis with search of PubMed (January 1, 1997-April 17, 2011) to identify English-language human studies reporting primary data. References from review articles were also searched. STUDY SELECTION AND DATA EXTRACTION: Abstracts were read independently to identify studies reporting primary data suitable for analysis. Covariates included publication year, sample type, DNA amplification methodology, Y chromosome sequence, and gestational age. Data were independently extracted by 2 reviewers. RESULTS: From 57 selected studies, 80 data sets (representing 3524 male-bearing pregnancies and 3017 female-bearing pregnancies) were analyzed. Overall performance of the test to detect Y chromosome sequences had the following characteristics: sensitivity, 95.4% (95% confidence interval [CI], 94.7%-96.1%) and specificity, 98.6% (95% CI, 98.1%-99.0%); diagnostic odds ratio (OR), 885; positive predictive value, 98.8%; negative predictive value, 94.8%; area under curve (AUC), 0.993 (95% CI, 0.989-0.995), with significant interstudy heterogeneity. DNA methodology and gestational age had the largest effects on test performance. Methodology test characteristics were AUC, 0.988 (95% CI, 0.979-0.993) for polymerase chain reaction (PCR) and AUC, 0.996 (95% CI, 0.993-0.998) for real-time quantitative PCR (RTQ-PCR) (P = .02). Gestational age test characteristics were AUC, 0.989 (95% CI, 0.965-0.998) (<7 weeks); AUC, 0.994 (95% CI, 0.987-0.997) (7-12 weeks); AUC, 0.992 (95% CI, 0.983-0.996) (13-20 weeks); and AUC, 0.998 (95% CI, 0.990-0.999) (>20 weeks) (P = .02 for comparison of diagnostic ORs across age ranges). RTQ-PCR (sensitivity, 96.0%; specificity, 99.0%) outperformed conventional PCR (sensitivity, 94.0%; specificity, 97.3%). Testing after 20 weeks (sensitivity, 99.0%; specificity, 99.6%) outperformed testing prior to 7 weeks (sensitivity, 74.5%; specificity, 99.1%), testing at 7 through 12 weeks (sensitivity, 94.8%; specificity, 98.9%), and 13 through 20 weeks (sensitivity, 95.5%; specificity, 99.1%). CONCLUSIONS: Despite interstudy variability, performance was high using maternal blood. Sensitivity and specificity for detection of Y chromosome sequences was greatest using RTQ-PCR after 20 weeks' gestation. Tests using urine and tests performed before 7 weeks' gestation were unreliable.

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  • Cell-free fetal DNA disappears from the maternal circulation shortly after delivery and therefore does not confound prenatal genetic investigations in subsequent pregnancies.

    “Unlike fetal cells, it disappears from the maternal circulation shortly after delivery (319,320) and therefore does not confound prenatal genetic investigations in subsequent pregnancies (321,322).”

    From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [321]

    The Comment section discusses fetal DNA detection during pregnancy and the need to validate negative test results, but not whether DNA from an earlier pregnancy can affect later testing. Searches for postpartum clearance, previous pregnancies, and subsequent pregnancies found no passage in our copy addressing that point; the References list alone does not establish it. (LLM, conf=0.72)

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Research works printed but not linked: 2

  1. [34]Bischoff FZ Dang DX Marquez-Do D Detecting fetal DNA from dried maternal blood spots Reprod Biomed Online 2003 6 3 349 351 12735873
  2. [88]Mortarino M Garagiola I Lotta LA Siboni SM Semprini AE Peyvandi F Non-invasive tool for foetal sex determination in early gestational age [published online ahead of print April 15, 2011] Haemophilia 2011 21492325

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Authors
Devaney, S. A., Palomaki, G. E., Scott, J. A., & Bianchi, D. W.
Affiliations
  • Johns Hopkins University (US)
  • Tufts Medical Center (US)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2011-08-10
Volume
306
Issue
6
Pages
627-36
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2011.1114
PMC
PMC4526182
OpenAlex
W2017457374
Cited by
247
References
90
Citations by year
2026: 5 · 2025: 7 · 2024: 7 · 2023: 15 · 2022: 8 · 2021: 11 · 2020: 11 · 2019: 8 · 2018: 14 · 2017: 11 · 2016: 19 · 2015: 29 · 2014: 22 · 2013: 30 · 2012: 47
FWCI
30.21
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r21hg004865-02)
  • National Human Genome Research Institute (1R21HG004865-02, R21-HG004865)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD042053)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
  • Social Sciences › Gender Studies › Demographic Trends and Gender Preferences
  • Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
Keywords
non-invasive prenatal testing, fetal sex determination, cell-free fetal DNA, Y chromosome detection, test performance, sensitivity and specificity, gestational age, real-time quantitative PCR, PCR, prenatal diagnosis, diagnostic odds ratio, positive predictive value, negative predictive value, area under the curve
MeSH terms
DNA, Female, Fetus, Humans, Male, Predictive Value of Tests, Pregnancy, Prenatal Diagnosis, Sensitivity and Specificity, Sex Determination Analysis, Polymerase Chain Reaction, Sequence Analysis, DNA, Chromosomes, Human, Y

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