From the Guidelines
A patient with a low-risk Non-Invasive Prenatal Screening (NIPS) result still has a residual risk of approximately 0.1-1.2% for common chromosomal syndromes such as Down syndrome, Trisomy 13, and Trisomy 18 1.
Key Points to Consider
- The detection rate for fetal trisomy 21 (T21) using NIPS is 98.8% with a corresponding false-positive rate (FPR) of 0.04% 1.
- The positive predictive value (PPV) of NIPS for T21 is 91.8% 1, while the PPVs for T18 and T13 are lower, at 65.8% and 37.2% respectively 1.
- Certain pregnancy factors, such as a vanishing twin gestation, can interfere with the performance and interpretation of NIPS 1.
Recommendations for Patients with Low-Risk NIPS Results
- Patients with a low-risk NIPS result should continue with standard prenatal care and consider additional diagnostic testing, such as a detailed anatomy ultrasound and possibly invasive testing like amniocentesis or chorionic villus sampling, if clinically indicated.
- It is essential to counsel patients that a low-risk NIPS result does not completely eliminate the risk of chromosomal abnormalities, and additional testing may be necessary to confirm the results 1.
Important Considerations
- The American College of Medical Genetics and Genomics (ACMG) recommends NIPS over traditional screening methods for all pregnant patients with singleton gestation for fetal trisomies 21,18, and 13 1.
- The ACMG also notes that NIPS has consistently higher screening performance in the detection of fetal T21/18/13 in singleton pregnancies than any of the traditional screening approaches 1.
From the Research
Residual Risk of Syndrome in Low-Risk NIPS
The residual risk of syndrome in a patient with a low-risk Non-Invasive Prenatal Screening (NIPS) result is a critical consideration in prenatal care. Several studies have investigated this issue, providing insights into the limitations of NIPS and the potential for false-negative results.
False-Negative Results in Low-Risk NIPS
- A study published in 2023 2 reported four cases of trisomy 18 in patients who had received low-risk NIPS results, highlighting the possibility of false-negative results due to placental mosaicism or other factors.
- Another study from 2020 3 analyzed false-negative results in low-risk NIPS cases and found that mosaicism was a major contributor to these errors.
- These findings suggest that NIPS is not foolproof and that patients with low-risk results may still be at risk for certain syndromes.
Residual Risk of Clinically Significant Copy Number Variations
- A 2024 study 4 evaluated the residual risk of clinically significant copy number variations in fetuses with nasal bone absence or hypoplasia after excluding NIPS-detectable findings.
- The study found that the residual risk of clinically significant copy number variations was higher in fetuses with non-isolated nasal bone absence or hypoplasia compared to those with isolated findings.
- These results highlight the importance of considering the residual risk of syndrome in patients with low-risk NIPS results, particularly in cases with additional risk factors.
Patient Perception of Residual Risk
- A 2016 study 5 investigated patient perception of residual risk after receiving a negative NIPS result and found that the majority of participants understood the residual risk.
- However, the study also noted that individuals with less formal education may require alternative communication strategies to ensure understanding of the limitations of NIPS.
- This highlights the need for clear and effective communication of residual risk to patients with low-risk NIPS results.
Limitations of NIPS
- A 2018 study 6 discussed the limitations of NIPS, including the potential for false-positive and false-negative results.
- The study proposed a method for improving the accuracy of NIPS by incorporating a cell-free fetal DNA size selection step.
- These findings emphasize the importance of understanding the limitations of NIPS and the need for ongoing research to improve the accuracy and reliability of this screening tool.