Non-Invasive Prenatal Testing (NIPT) is a screening method available early in pregnancy that uses a sample of the mother’s blood to gather information about the developing fetus. This non-invasive test analyzes small fragments of cell-free DNA (cfDNA) that circulate in the mother’s bloodstream, originating from both the mother and the placenta. Although NIPT is primarily designed to screen for certain genetic conditions, it also yields information about the sex chromosomes, allowing for fetal sex determination.
The Primary Purpose of NIPT
NIPT was developed primarily as a screening tool for common fetal aneuploidies, which are conditions caused by an atypical number of chromosomes. The test focuses on detecting the risk of Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome), and Trisomy 13 (Patau syndrome). These conditions result from having an extra copy of the 21st, 18th, or 13th chromosome, respectively.
The analysis works by examining the relative amounts of DNA fragments from each chromosome. If the test detects an overrepresentation of DNA fragments from a specific chromosome, it suggests a higher risk that the fetus has an extra copy of that chromosome. This process provides a risk assessment, not a definitive diagnosis, for these chromosomal disorders. NIPT is typically performed beginning around 10 weeks of gestation, when there is a sufficient amount of fetal cfDNA in the maternal blood for reliable analysis.
How NIPT Determines Fetal Sex
Fetal sex determination is an automatic secondary result of the chromosomal analysis performed by NIPT. This determination is achieved by looking for the presence or absence of DNA fragments from the Y chromosome within the cell-free DNA sample. A fetus that develops as male has both an X and a Y chromosome, while a fetus that develops as female has two X chromosomes.
If the laboratory analysis detects Y chromosome material, the fetus is classified as male; conversely, if no Y chromosome fragments are detected, the fetus is classified as female. Since the mother’s own DNA does not contain Y chromosomes, any Y-specific DNA detected must originate from the fetus or the placenta, allowing for a highly accurate prediction of fetal sex early in the pregnancy.
Reliability and Potential for Ambiguity
The accuracy of NIPT for fetal sex determination is very high, often reported to be greater than 99%. However, the result is not guaranteed to be 100% accurate, and the test may sometimes be unable to provide a result. The reliability of any NIPT result depends heavily on the fetal fraction, which is the percentage of total cell-free DNA in the mother’s blood belonging to the fetus.
If the fetal fraction is too low, typically below a threshold of 2% to 4%, the test may result in a “no-call” or inconclusive result. This low amount of fetal DNA makes it difficult for the laboratory to confidently distinguish the fetal chromosomes, including the Y chromosome, from the mother’s own DNA. Low fetal fraction is often associated with early gestational age or a high maternal body mass index. In rare instances, biological factors like sex chromosome aneuploidies in the fetus or a vanishing twin can also lead to an ambiguous or incorrect sex determination.