The Non-Invasive Prenatal Paternity (NIPP) test establishes biological fatherhood before a child is born using technology that poses no risk to the pregnancy. This method is highly sought after for its safety and convenience, providing answers that once required invasive procedures. Although NIPP tests are often advertised with accuracy rates exceeding 99%, errors are possible. Understanding the science behind the test reveals the specific circumstances that can compromise a result, making it inaccurate or inconclusive.
The Mechanism of Non-Invasive Prenatal Paternity Testing
The science behind NIPP relies on analyzing cell-free DNA (cfDNA), which consists of small fragments of genetic material circulating in the mother’s bloodstream. During pregnancy, the mother’s blood contains cfDNA originating from both her own cells and the cells of the developing fetus, primarily shed from the placenta. The test requires a blood sample from the expectant mother and a buccal (cheek) swab from the presumed father.
Specialized laboratories isolate the cfDNA from the maternal blood and use advanced sequencing techniques to separate the fetal DNA profile from the mother’s own DNA. The lab then compares the genetic markers of the fetus against the markers provided by the mother and the presumed father. This comparison checks for shared markers that statistically confirm or exclude paternity.
A defining factor in this analysis is the “fetal fraction,” the percentage of total cfDNA in the mother’s blood sample that belongs to the fetus. This fraction typically needs to be above a threshold, often 2% to 4%, for a reliable result. Since fetal DNA naturally increases as the pregnancy progresses, testing is usually recommended no earlier than seven to nine weeks of gestation.
Biological and Technical Causes of Inaccurate Results
The majority of issues that lead to inaccurate or inconclusive NIPP results are directly linked to biological variations or technical limitations in the sample analysis process. These factors introduce ambiguity into the cfDNA mixture, making it difficult for the lab to definitively match the fetal DNA profile.
Low Fetal Fraction
The most common reason for an inconclusive test is an insufficient amount of fetal DNA, known as a low fetal fraction. If the test is performed too early, the fetal material may not have accumulated enough to meet the 2-4% minimum threshold required for accurate analysis. A high maternal Body Mass Index (BMI) can also dilute the concentration of fetal cfDNA, contributing to a lower fraction and potentially causing the test to fail.
Maternal Factors
Certain biological conditions unique to the mother can introduce extraneous DNA into the bloodstream, confusing the analysis. For instance, a mother who has undergone a bone marrow or stem cell transplant may have donor DNA permanently circulating in her blood. This donor DNA can interfere with the results, particularly if the donor was male, as the test may incorrectly identify the donor’s Y chromosome fragments.
A recent blood transfusion can temporarily introduce foreign DNA into the mother’s system, especially if the transfusion occurred within two weeks of the blood draw. While this is not a permanent change, it can contaminate the cfDNA pool and lead to an inconclusive or erroneous finding. Labs must be informed of any recent medical procedures to account for these complicating factors.
Multiple Gestation
The presence of a twin pregnancy presents a significant challenge to the NIPP process, even if only one fetus is being tested. Current NIPP technology is designed to compare a single fetal DNA profile. When two fetuses are present, the cfDNA is a mixture from both, making it nearly impossible to isolate a specific profile for paternity determination.
The “vanishing twin” phenomenon occurs when one fetus dies early and is reabsorbed. Although the fetus is no longer developing, its cfDNA can persist in the mother’s bloodstream for several weeks. This residual DNA creates a mixed profile that can lead to misattribution or a failed test result.
Timing and Sample Integrity
Technical errors, such as improper labeling, contamination of samples, or degradation of genetic material due to poor storage, can compromise the integrity of the test. Another consideration is testing two presumed fathers who are close biological relatives, such as brothers. Because they share significant DNA, an ordinary test may not be able to differentiate between them, resulting in an inconclusive or false positive result.
Legal Standards and the Role of Invasive Testing Methods
While NIPP tests are highly accurate for personal knowledge, they are generally not the standard for legal cases, such as child support or custody. The primary obstacle to legal admissibility is the lack of a strict, court-mandated chain-of-custody protocol for the maternal blood draw and paternal cheek swab.
For a paternity result to hold up in court, the entire process must be meticulously documented and controlled to prevent tampering or misidentification. NIPP results frequently lack the necessary legal documentation because the test focuses on informational results. If a legally binding result is required, the test must be performed under specific, court-admissible protocols, often requiring a third-party witness to the collection.
In contrast to the NIPP test, two older, more certain methods exist: Chorionic Villus Sampling (CVS) and Amniocentesis. CVS samples the placenta between 10 and 13 weeks, while Amniocentesis draws amniotic fluid, typically after 15 weeks. Both procedures sample the baby’s actual cells, providing direct and highly definitive genetic profiles suitable for legal proceedings. However, these methods are invasive and carry a small risk of complications, including miscarriage, which is why the NIPP test was developed as a safe alternative.