Non-Invasive Prenatal Testing (NIPT) is a screening method used during pregnancy that analyzes small fragments of cell-free DNA (cfDNA) found in a pregnant person’s blood. This cfDNA originates primarily from the placenta. While NIPT is primarily utilized to screen for certain chromosomal conditions in the developing fetus, it can also provide information about fetal gender.
How NIPT Determines Fetal Gender
NIPT determines fetal gender by examining sex chromosomes in cell-free DNA. Humans typically have two sex chromosomes: XX for a female and XY for a male. The test specifically looks for fragments of the Y chromosome. If Y chromosome fragments are detected in the mother’s blood sample, it indicates the presence of a male fetus. Conversely, if only X chromosomes are found and no Y chromosome fragments are detected, the test indicates a female fetus. This method leverages the distinct genetic makeup associated with each gender.
The High Accuracy of NIPT for Gender
NIPT is widely recognized for its high accuracy in determining fetal gender. Studies generally report accuracy rates for gender determination ranging from approximately 98% to 99.9%. This makes NIPT a highly reliable method for identifying the baby’s sex, as it detects the presence or absence of the Y chromosome.
When NIPT Gender Results Can Be Incorrect
Despite its high accuracy, NIPT gender results can occasionally be incorrect due to several factors. These instances are rare but can cause discrepancies, and understanding them helps clarify why a NIPT result might not align with other observations or subsequent tests.
Maternal Biological Factors
One cause for an inaccurate NIPT gender result is the “vanishing twin” phenomenon. This occurs when a twin pregnancy begins, but one fetus is lost early in gestation. If the vanished twin was male, its Y-chromosome DNA can remain in the mother’s bloodstream for weeks or months, leading to a false male result for a surviving female fetus.
Maternal mosaicism, a condition where some of the mother’s cells have a different chromosomal makeup, can also affect NIPT results. For instance, if a mother has cells with a missing X chromosome (45,X mosaicism), it could lead to a false female result if the fetal DNA fraction is low or if maternal DNA influences the reading.
Similarly, a mother who has received an organ transplant from a male donor might have Y-chromosome DNA from the donor circulating in her blood, resulting in a false male gender prediction for a female fetus. Previous male pregnancies are generally not a cause for incorrect NIPT gender results, as cell-free fetal DNA from prior pregnancies clears from the mother’s bloodstream relatively quickly after birth.
Fetal Biological Factors
Certain fetal chromosomal abnormalities can also lead to discrepancies in NIPT gender determination. For example, Turner syndrome (45,XO), where a female fetus has only one X chromosome instead of the usual two, might lead to a NIPT result indicating female. In rare cases, if the NIPT specifically looks for the Y chromosome and its detection is low, it could lead to a false female result. Conversely, Klinefelter syndrome (47,XXY), where a male fetus has an extra X chromosome, could be detected as male if the Y chromosome is identified. However, if Y-chromosome fragments are present at very low levels or if the test methodology focuses on relative ratios, it could sometimes lead to ambiguous or misinterpreted results regarding the number of sex chromosomes.
Technical/Laboratory Factors
Technical aspects and laboratory processes can also contribute to NIPT inaccuracies. A low fetal fraction, referring to an insufficient amount of fetal DNA circulating in the mother’s blood, is a common reason for inconclusive or, in rare cases, inaccurate results. If the fetal DNA is too diluted, the test may not reliably detect the Y chromosome, potentially leading to a false female result or an inability to provide a gender prediction. Sample contamination with male DNA, either during blood collection or laboratory processing, can also lead to a false male result. While rare, human error in the laboratory, such as sample mislabeling or data entry mistakes, can also result in an incorrect gender report.
Confirming Fetal Gender and Next Steps
If a discrepancy arises between NIPT gender results and other clinical observations, or if there are concerns about accuracy, further steps can be taken to confirm fetal gender. The most common method for confirmation is a detailed ultrasound scan, typically performed around 18-22 weeks of pregnancy during the anatomy scan. This ultrasound can visually assess the external genitalia of the fetus, providing a clear indication of gender.
If there is a persistent discrepancy or suspicion of a chromosomal abnormality, more definitive diagnostic tests may be recommended. These include amniocentesis or chorionic villus sampling (CVS). These invasive procedures collect fetal cells directly from the amniotic fluid or placenta, respectively, allowing for a direct analysis of the fetal chromosomes. These diagnostic tests provide a definitive chromosomal analysis, which can confirm both the fetal gender and the presence of any chromosomal conditions.