What is the recommended timing and procedure for Non-Invasive Prenatal Screening (NIPS) tests?

Recommended Timing and Procedure for Non-Invasive Prenatal Screening (NIPS)

Non-Invasive Prenatal Screening (NIPS) should be performed between 9-12 weeks of gestation, with diagnostic confirmation via amniocentesis rather than chorionic villus sampling (CVS) for any positive results to ensure accurate fetal karyotyping. 1, 2

Timing of NIPS

• NIPS can be performed from the 10th week of gestation onward, allowing for early detection of fetal chromosomal abnormalities without invasive procedures 3
• The optimal timing for NIPS is typically between 9-12 weeks of gestation in the first trimester 1
• Test success rates increase with gestational age, with studies showing improved reliability after 7 weeks of gestation 4
• Low fetal fraction (proportion of placental DNA in maternal plasma) may result in "no-call" results, occurring in approximately 1% of samples 2

Procedure for NIPS

• NIPS involves a maternal blood sample that analyzes cell-free DNA fragments from the placenta circulating in maternal plasma 1
• The test screens primarily for common trisomies (13,18, and 21) and sex chromosome abnormalities 2
• No ultrasound is required for the basic NIPS procedure, unlike traditional screening methods that may require nuchal translucency measurements 2
• Repeat testing for "no-call" results provides a result approximately 75-80% of the time when performed at a later gestational age 2

Confirmatory Testing for Positive Results

• All positive NIPS results require diagnostic confirmation through invasive testing 2
• While CVS can be performed earlier (10-13 weeks), amniocentesis (performed after 15.5 weeks) is the preferred confirmatory test 5
• This is because NIPS analyzes placental DNA, and CVS also samples placental tissue, which may not always represent the true fetal karyotype due to confined placental mosaicism 5
• A mosaic result on CVS cannot be treated as definitive confirmation and requires follow-up amniocentesis 2

Advantages of NIPS Over Traditional Screening

• Higher detection rates for common trisomies compared to traditional screening methods 2
• Lower false-positive rates, resulting in fewer unnecessary invasive procedures 2
• The positive predictive value (PPV) for NIPS for T21 is 50-95%, compared to only 2.2-3.6% for traditional screening 2
• This translates to needing only 1.1-2 amniocentesis procedures to confirm trisomy in an affected pregnancy with NIPS, versus 28-45 diagnostic procedures with traditional screening 2

Special Considerations

• For pregnancies with ultrasound soft markers, NIPS can serve as a second-line complementary screening tool 6
• Certain soft markers like absent/hypoplastic nasal bone, echogenic bowel, or multiple soft markers warrant further evaluation even in low-risk pregnancies 6
• In twin pregnancies, NIPS screening performance is equivalent to singletons, unlike traditional screening which has diminished performance in twins 2
• Obesity, maternal malignancy, and other factors may affect test performance and should be considered when interpreting results 2, 1

Pre-test and Post-test Counseling

• Comprehensive pre-test counseling should include discussion of:

  • The optional and screening nature of NIPS 2
  • Types of conditions that can and cannot be detected 2
  • Possible test results including "no-call" results 2
  • Information about positive and negative predictive values 2
  • Recommendation for confirmation of abnormal results 2

• Post-test counseling for negative results should emphasize:

  • Risk reduction but not elimination 2
  • NIPS only screens for select conditions 2
  • Need for neural tube defect screening as NIPS doesn't detect structural abnormalities 2

• Post-test counseling for positive results should include:

  • Discussion of the PPV of the result 2
  • Balanced description of the condition detected 2
  • Recommendation for diagnostic confirmation before any decisions 2

Common Pitfalls to Avoid

• Failing to confirm positive NIPS results with diagnostic testing before making clinical decisions 2
• Relying on CVS alone to confirm NIPS results, especially for certain aneuploidies like trisomy 13 and monosomy X that are more likely to be mosaic on CVS 2
• Overlooking the need for neural tube defect screening, as NIPS does not detect structural abnormalities 2
• Inadequate counseling about the limitations of NIPS, including the possibility of false-positive and false-negative results 3
• Misinterpreting "no-call" results, which may be associated with higher risk of chromosomal abnormalities in some cases 2