What is the accuracy of non-invasive prenatal testing (NIPT) for fetal sex determination at 9 weeks gestation?

Accuracy of Non-Invasive Prenatal Testing (NIPT) for Fetal Sex Determination at 9 Weeks

Non-invasive prenatal testing (NIPT) using cell-free DNA (cfDNA) at 9 weeks gestation demonstrates high accuracy for fetal sex determination, with sensitivity of approximately 96.6% and specificity of 98.9%. 1

NIPT Performance for Fetal Sex Determination

• NIPT for fetal sex determination can be performed after 9-10 weeks gestation, as approximately 10-15% of the total cell-free DNA in maternal plasma is of placental origin by this time 2
• The accuracy of NIPT for fetal sex determination does not significantly vary by trimester or week of testing after 9 weeks, maintaining reliably high performance throughout pregnancy 1
• Meta-analysis of studies incorporating 9,965 pregnancies showed overall mean sensitivity of 96.6% (95% CI: 95.2-97.7%) and mean specificity of 98.9% (95% CI: 98.1-99.4%) for fetal sex determination using cfDNA 1

Factors Affecting NIPT Accuracy at 9 Weeks

• Approximately 1% of initial samples submitted for NIPT result in "no-call" results, with insufficient fetal fraction being the most common cause 2
• Maternal factors that can reduce accuracy at 9 weeks include:
  • High maternal BMI, which is strongly associated with low fetal fraction and may result in test failure in up to 20% of women with high BMI 3
  • Use of certain anticoagulants that can interfere with cfDNA analysis 3
  • Maternal autoimmune conditions that have been linked to higher rates of no-call results 3
• Fetal factors that may affect accuracy include:
  • Presence of certain chromosomal abnormalities, particularly trisomies 13 and 18, which can be associated with low fetal fraction 3
  • Multiple gestations or vanishing twin syndrome, which can affect fetal fraction measurements and interpretation 2, 3

Comparison with Ultrasound for Fetal Sex Determination

• Ultrasound determination of fetal sex at 9 weeks (equivalent to 11 weeks gestational age) has significantly lower accuracy than NIPT:
  • Ultrasound accuracy at 11 weeks is only 46-70.3% 4, 5
  • Ultrasound accuracy increases with gestational age: 98.7% at 12 weeks and 100% at 13 weeks 4
  • Male fetuses are frequently misidentified as female (56% error rate) at 11 weeks by ultrasound 4

Clinical Implications

• NIPT provides a reliable non-invasive alternative to invasive testing for sex determination in pregnancies at risk of sex-linked genetic disorders 2
• For pregnancies requiring sex determination at 9 weeks, NIPT is significantly more accurate than ultrasound at this early gestational age 4, 1
• If a "no-call" result occurs with NIPT at 9 weeks, repeat testing at a slightly later gestational age provides a result in approximately 75-80% of cases 2
• The American College of Obstetricians and Gynecologists recommends offering diagnostic testing to individuals with persistent no-call results 2

Important Considerations

• NIPT for fetal sex determination should be performed in the context of appropriate pre-test and post-test genetic counseling 2
• Patients should be informed that while highly accurate, NIPT is a screening test, not a diagnostic test, and any abnormal or uncertain results should be confirmed with diagnostic testing 2
• The American College of Medical Genetics and Genomics (ACMG) strongly recommends NIPT over traditional screening methods for both singleton and twin pregnancies 2
• Alternative screening methods should be considered for women with factors predisposing to low fetal fraction, such as high BMI 3