From the Guidelines
Non-Invasive Prenatal Testing (NIPT) can be a valuable tool in antenatal care screening when a fetus has ambiguous or unclear genitalia, as it can determine the presence of Y chromosome material with high accuracy, typically >99%. This information can be particularly useful when ultrasound visualization of external genitalia is difficult or inconclusive. According to the American College of Medical Genetics and Genomics (ACMG) guideline published in 2023 1, NIPT is recommended for all pregnant individuals over traditional screening for common trisomies and single nucleotide variants (SNVs) due to its superior screening characteristics.
Some key points to consider when using NIPT for screening in cases of ambiguous genitalia include:
- NIPT analyzes cell-free fetal DNA in the maternal bloodstream to determine genetic sex (XX or XY) with high accuracy.
- The test is typically performed between 10-22 weeks of pregnancy, with results available within 1-2 weeks.
- While NIPT can identify genetic sex, it does not provide information on anatomical development, and in cases of disorders of sex development (DSDs), the genetic sex may not align with genital appearance.
- For definitive diagnosis of complex cases, more invasive testing like amniocentesis or chorionic villus sampling may be necessary to examine chromosomal structure in detail or test for specific genetic conditions affecting genital development.
It is essential to note that NIPT should be considered one tool in comprehensive antenatal care rather than a standalone solution for evaluating ambiguous genitalia, and careful counseling is imperative to provide the highest level of care and meaningful recommendations, as emphasized by the ACMG guideline 1.
From the Research
Non-Invasive Prenatal Testing (NIPT) for ANC Screening
- NIPT is a screening test for fetal chromosomal abnormalities, including trisomy 21,18, and 13 2, 3.
- The test can also determine the sex of the fetus, which raises concerns about potential selective termination of pregnancy by prospective parents who desire a child of a particular sex 4, 5.
- In cases where the fetus has no clear genitalia, NIPT may not be directly helpful in determining the sex or identifying the underlying cause of the ambiguous genitalia.
Limitations of NIPT for Ambiguous Genitalia
- A study published in the American Journal of Medical Genetics found that prenatal diagnostic testing for disorders of sex development (DSD) has a low yield, especially in the absence of a family history of DSD 6.
- The study suggests that prenatal karyotype with fluorescence in situ hybridization for the SRY gene is the most useful test when ambiguous genitalia is suspected, but further testing for rare DSD conditions may not be practical.
- NIPT is not specifically designed to diagnose ambiguous genitalia or DSD, and its use in this context is limited.
Clinical Use of NIPT
- NIPT is an established option for antenatal screening for trisomy 21,18,13, and other selected chromosomal abnormalities 2, 3.
- The test can increase the detection rate for fetal chromosomal abnormalities while decreasing the number of invasive tests required.
- However, NIPT is not a diagnostic test, and its results must be interpreted with caution, as they may yield false negatives, false positives, or inconclusive results 3.