Cell-Free DNA Testing (NIPT) for Fetal Sex Determination
The blood test that determines baby gender is called noninvasive prenatal testing (NIPT) or cell-free DNA screening, which analyzes fetal DNA fragments circulating in maternal blood and can be performed after 9-10 weeks of pregnancy. 1, 2
How the Test Works
- NIPT analyzes cell-free DNA (cfDNA) in maternal plasma, which consists of small DNA fragments (<200 base pairs) that are free-floating in the blood 1
- After 10 weeks of gestation, approximately 10-15% of the total cfDNA in maternal plasma is of placental origin, providing sufficient fetal DNA for accurate analysis 1, 2
- The test uses next-generation sequencing technology, including massively parallel shotgun sequencing or targeted sequencing approaches, to identify and count DNA fragments from each chromosome 1, 3
- For sex determination specifically, the test detects the presence or absence of Y chromosome sequences to determine if the fetus is male or female 2, 4
Timing and Accuracy
- The optimal timing for NIPT is after 10 weeks gestation, when fetal fraction is adequate for reliable results 1, 2
- Some laboratories offer testing as early as 9 weeks, though if a "no-call" result occurs at this early timepoint, repeat testing at a slightly later gestational age provides results in approximately 75-80% of cases 2
- Sex determination by NIPT is highly accurate when adequate fetal fraction is present, though it remains a screening test rather than a diagnostic test 1, 2
Important Limitations and Caveats
Factors that can affect test accuracy include:
- High maternal BMI is strongly associated with low fetal fraction and may result in test failure in up to 20% of women with elevated BMI 2
- Approximately 1% of initial samples result in "no-call" results, with insufficient fetal fraction being the most common cause 2
- Multiple gestations or vanishing twin syndrome can affect fetal fraction measurements and interpretation 2
- Certain chromosomal abnormalities (particularly trisomies 13 and 18) can be associated with low fetal fraction 2
Critical clinical considerations:
- While highly accurate, NIPT is a screening test, not a diagnostic test, and any abnormal or uncertain results should be confirmed with diagnostic testing such as amniocentesis or chorionic villus sampling 1, 2
- Sex designation by NIPT may occasionally be discordant with physical examination at birth, and blood chromosome analysis is recommended if discordance occurs 1
- The test should be performed in the context of appropriate pre-test and post-test genetic counseling 2
Clinical Applications Beyond Gender
- NIPT was initially developed for aneuploidy screening (Down syndrome, trisomy 13, trisomy 18) and has expanded to include sex chromosome abnormalities and some microdeletion syndromes 1
- Fetal sex determination is particularly valuable for pregnancies at risk of X-linked genetic disorders, where knowing fetal sex guides further diagnostic decisions 1, 5
- The test can also determine fetal RhD status and detect some paternally inherited single gene disorders 3, 5, 6