NIPS, or noninvasive prenatal screening, is a blood test that checks for chromosomal conditions in a developing baby. It primarily screens for three major conditions: Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13). Depending on the panel your provider orders, it can also screen for sex chromosome conditions, certain microdeletion syndromes, fetal sex, and Rh blood type.
How NIPS Works
During pregnancy, tiny fragments of DNA from the placenta break off and enter the pregnant person’s bloodstream. This cell-free DNA, or cfDNA, carries genetic information that reflects the baby’s chromosomes. NIPS analyzes a standard blood draw from the mother to measure these fragments and look for signs of extra or missing chromosomes.
The baby’s DNA makes up only about 10% of the total cfDNA circulating in maternal blood during the second trimester, and even less earlier in pregnancy. That small proportion is why NIPS typically isn’t offered until at least 10 weeks of gestation. Below about 4% fetal DNA, results become unreliable. In twin pregnancies, each baby contributes even less individual DNA, which can reduce the test’s sensitivity.
The Three Core Conditions
Every standard NIPS panel screens for the three most common autosomal trisomies, conditions where the baby has an extra copy of a specific chromosome:
- Trisomy 21 (Down syndrome): The most common chromosomal condition and the one NIPS detects most reliably. Sensitivity is essentially 100%, with specificity around 99.9%. In a large study of over 20,000 pregnancies, the positive predictive value for Down syndrome was about 71%, meaning roughly 7 out of 10 positive results were confirmed by diagnostic testing.
- Trisomy 18 (Edwards syndrome): A serious condition affecting multiple organ systems. NIPS detects it with high sensitivity, and confirmation rates in one study reached about 86%.
- Trisomy 13 (Patau syndrome): The rarest of the three and the hardest to screen for accurately. In one study, only 33% of positive NIPS results for trisomy 13 were confirmed, meaning false positives are more common for this condition.
The American College of Obstetricians and Gynecologists (ACOG) recommends that cfDNA screening for these three trisomies be routinely available to all pregnant patients, regardless of age or risk level.
Sex Chromosome Conditions
Many NIPS panels offer optional screening for sex chromosome aneuploidies. These are conditions where a baby has an extra or missing sex chromosome. Collectively, they occur in about 1 in 500 births. ACOG recommends this screening be available as an opt-in choice with appropriate counseling beforehand.
The conditions screened include:
- Turner syndrome (monosomy X): Affects females born with only one X chromosome. NIPS confirmation rates for Turner syndrome are around 50%, making false positives relatively common.
- Klinefelter syndrome (47,XXY): Affects males born with an extra X chromosome. This is the most frequently identified sex chromosome condition through prenatal screening.
- Triple X syndrome (47,XXX): Affects females born with an extra X chromosome.
- XYY syndrome (47,XYY): Affects males born with an extra Y chromosome.
The overall detection rate for sex chromosome conditions is lower than for the three main trisomies, ranging from about 79% to 92%. Confirmation through diagnostic testing occurred in roughly two-thirds of cases in one study.
Microdeletion Syndromes
Some expanded NIPS panels screen for microdeletions, which are conditions caused by a small missing piece of a chromosome rather than a whole extra chromosome. These are optional add-ons, not part of standard screening. ACOG currently does not recommend routine population-wide screening for microdeletions and advises that patients interested in this information consider diagnostic testing (amniocentesis or CVS) instead, since NIPS performs less reliably for these conditions.
The microdeletion syndromes most commonly included on expanded panels are:
- 22q11.2 deletion (DiGeorge syndrome): The most commonly offered microdeletion screen, associated with heart defects, immune problems, and developmental differences.
- 15q11 deletions (Angelman and Prader-Willi syndromes): Two different conditions caused by deletions in the same region of chromosome 15, depending on which parent’s copy is affected.
- 5p deletion (Cri du chat syndrome): Named for the distinctive high-pitched cry in affected newborns.
- 4p deletion (Wolf-Hirschhorn syndrome): Associated with growth delays and intellectual disability.
False positive rates for microdeletions are high. In one study, seven out of eight microdeletion results that were followed up with diagnostic testing turned out to be false positives.
Fetal Sex and Rh Factor
Beyond chromosomal conditions, NIPS can determine the baby’s biological sex as early as 10 weeks, since the test is already analyzing sex chromosomes. Many parents learn the sex through NIPS before an anatomy ultrasound, which typically happens around 18 to 20 weeks.
NIPS can also identify the baby’s Rh blood type. This is particularly useful for Rh-negative mothers, because knowing whether the baby is Rh-positive helps guide decisions about preventive treatment during pregnancy.
NIPS Is a Screening Test, Not a Diagnosis
One of the most important things to understand about NIPS is that it flags risk. It does not confirm a condition. A “positive” or “high-risk” result means further testing is needed, typically through amniocentesis or chorionic villus sampling (CVS), both of which analyze fetal cells directly and provide a definitive answer.
The gap between a positive screen and a confirmed diagnosis can be significant. For Down syndrome, about 71% of positive results are true positives. For trisomy 13, that number drops to roughly 33%. For microdeletions, confirmations are even rarer. These numbers mean that a positive NIPS result, especially for rarer conditions, is often a false alarm.
Several factors influence how likely a positive result is to be accurate. Maternal age plays a role: in one study, pregnancies with advanced maternal age (over 35) had a 61% confirmation rate for high-risk NIPS results overall, compared to lower rates in younger populations. The underlying prevalence of a condition in the population directly affects how many positive screens turn out to be real, which is why more common conditions like Down syndrome have higher confirmation rates than rare ones like microdeletions.
A negative NIPS result is highly reassuring for the three main trisomies, given the near-100% sensitivity. But no screening test catches everything, and NIPS does not screen for all possible genetic conditions, structural birth defects, or developmental differences. It examines specific chromosomal targets and nothing more.