NIPT screens for Trisomy 18, offering expectant parents an early screening option for this serious chromosomal condition. Prenatal screening now uses a precise analysis of cell-free DNA circulating in the mother’s blood, replacing older serum-based methods. This technology provides a “high-risk” or “low-risk” assessment, guiding the next steps in prenatal care and decision-making.
Understanding Trisomy 18
Trisomy 18, or Edwards Syndrome, occurs when an individual has three copies of chromosome 18 instead of two. This extra genetic material disrupts fetal development, causing severe abnormalities across multiple body systems. It is the second most common autosomal trisomy among live-born children, following Trisomy 21 (Down syndrome).
The condition involves severe intellectual disability, developmental delays, and significant congenital malformations. Physical features include a small head, a small jaw, and clenched fists with overlapping fingers. Affected infants often have serious structural heart defects, kidney malformations, and feeding difficulties.
The prognosis for Trisomy 18 is poor, with a high mortality rate; many affected fetuses do not survive to term. Most infants born alive pass away within the first month due to medical problems. Early prenatal screening is a priority for many families.
The Scope of Non-Invasive Prenatal Testing
NIPT is a blood test performed on the pregnant person, typically starting around the tenth week of gestation. This screening analyzes cell-free DNA (cfDNA) fragments, which originate from the placenta and circulate in the maternal bloodstream. Since placental DNA is similar to the fetus’s DNA, measuring the relative amount of cfDNA from specific chromosomes can indicate an extra copy.
The primary targets of NIPT are the three most common autosomal trisomies: Trisomy 21 (Down syndrome), Trisomy 18 (Edwards Syndrome), and Trisomy 13 (Patau Syndrome). Most NIPT panels also screen for sex chromosome aneuploidies, such as Turner Syndrome or Klinefelter Syndrome, and sometimes certain microdeletion syndromes. NIPT offers higher accuracy and a lower false-positive rate compared to older screening methods.
Accuracy and Reliability for Trisomy 18 Screening
NIPT is an effective screening tool for Trisomy 18, demonstrating high sensitivity (96% to 98%) in correctly identifying affected pregnancies. Specificity—the ability to correctly identify unaffected pregnancies—is often above 99.5%. These metrics mean that a “low-risk” result is reassuring.
The Positive Predictive Value (PPV) is the chance that a “high-risk” result truly indicates the fetus has the condition. The PPV for Trisomy 18 is lower than for Trisomy 21, partly due to the lower prevalence of Trisomy 18 and the phenomenon of confined placental mosaicism.
Confined placental mosaicism occurs when the extra chromosome is present only in the placental cells, which are the source of the cfDNA, but not in the fetus. Since NIPT analyzes placental DNA, this can lead to a false positive result for Trisomy 18. NIPT remains a screening test and cannot provide a definitive diagnosis.
Interpreting NIPT Results and Next Steps
A “low-risk” NIPT result for Trisomy 18 is reliable and suggests a low probability of the condition. For most parents, this result provides reassurance, and no further testing is recommended. However, even with high accuracy, a screening test never offers a 100% guarantee.
If the NIPT returns a “high-risk” or “positive” result, this means there is an increased chance the fetus is affected. Because of potential false positives from factors like placental mosaicism, a high-risk NIPT result must always be confirmed by a diagnostic test. Genetic counseling is recommended to discuss the implications and available options.
The two main diagnostic options are Chorionic Villus Sampling (CVS) and Amniocentesis, both of which analyze fetal cells directly. CVS is performed earlier, typically between 10 and 13 weeks, by sampling placental tissue. Amniocentesis is usually performed later, after 15 or 16 weeks, by sampling the amniotic fluid. Both procedures carry a small, procedure-related risk of miscarriage, estimated to be less than 0.5%.