Non-Invasive Prenatal Screening Guidelines

Timing and Procedure

Low fetal fraction may result in "no-call" results, occurring in approximately 1% of samples 1
The test screens primarily for common trisomies and sex chromosome abnormalities 2
No ultrasound is required for the basic NIPS procedure 2
Repeat testing for "no-call" results provides a result approximately 75-80% of the time when performed at a later gestational age 1

All positive NIPS results require diagnostic confirmation through invasive testing 3, 4
A mosaic result on CVS cannot be treated as definitive confirmation and requires follow-up amniocentesis 3

Higher detection rates for common trisomies compared to traditional screening methods 5
Lower false-positive rates, resulting in fewer unnecessary invasive procedures 5
The positive predictive value for NIPS for T21 is 50-95%, compared to only 2.2-3.6% for traditional screening 5
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 5

In twin pregnancies, NIPS screening performance is equivalent to singletons 2
Obesity, maternal malignancy, and other factors may affect test performance and should be considered when interpreting results 6

Comprehensive pre-test counseling should include discussion of the optional and screening nature of NIPS, types of conditions that can and cannot be detected, possible test results, and information about positive and negative predictive values 7
Post-test counseling for negative results should emphasize risk reduction but not elimination, and that NIPS only screens for select conditions 7
Post-test counseling for positive results should include discussion of the PPV of the result, balanced description of the condition detected, and recommendation for diagnostic confirmation before any decisions 7

Failing to confirm positive NIPS results with diagnostic testing before making clinical decisions 3, 4
Relying on CVS alone to confirm NIPS results, especially for certain aneuploidies 3
Overlooking the need for neural tube defect screening, as NIPS does not detect structural abnormalities 7
Misinterpreting "no-call" results, which may be associated with higher risk of chromosomal abnormalities in some cases 1

In singleton pregnancies, NIPT detects trisomy 21 with a sensitivity of 98.8 % (95 % CI 97.8‑99.3 %)【8】.
In singleton pregnancies, the false‑positive rate for trisomy 21 is 0.04 % (95 % CI 0.02‑0.08 %), i.e., fewer than 1 in 2,500 unaffected pregnancies screen positive【8】.
In twin gestations, NIPT maintains high accuracy with a sensitivity of 98.2 % (95 % CI 88.2‑99.7 %) and a specificity of 99.9 % for trisomy 21【9】.
Across multiple cohorts, the positive predictive value (PPV) for a trisomy 21‑positive NIPT result is 91.8 % (95 % CI 88.4‑94.2 %)【8】.

First‑trimester combined serum‑ultrasound screening detects 77‑82 % of Down‑syndrome cases with a false‑positive rate of 3‑5 %【8】.
Using NIPT, only 1.1‑2 diagnostic invasive procedures (amniocentesis or CVS) are needed to confirm one affected pregnancy, compared with 28‑45 invasive procedures required when relying on traditional screening methods【10】.

Approximately 1 % of NIPT samples yield a “no‑call” result, most often because fetal fraction is insufficient【10】.
When a no‑call occurs, repeat testing at a later gestational age provides a definitive result in 75‑80 % of cases【10】.

The American College of Obstetricians and Gynecologists (ACOG) advises that NIPT should not be performed in pregnancies with a vanishing twin, because residual fetal DNA can confound results【8】.
A known maternal malignancy is considered a relative contraindication for NIPT, as circulating tumor DNA may lead to false‑positive findings【8】.

Singleton pregnancies ≥10 weeks gestation: Offer NIPT as the first‑line screening test for trisomies 21, 18, and 13【11】.
Positive NIPT result: Proceed to confirmatory diagnostic testing (amniocentesis or CVS) before any clinical decision【11】.
No‑call result: Counsel patients to either undergo diagnostic testing directly or repeat NIPT at a later gestational age【10】.
Twin pregnancies: NIPT can be used with equivalent performance to singletons for trisomy 21 detection, allowing the same first‑line screening approach【9】.