Clinical Value of Noninvasive Prenatal Genetic Testing for Surrogate Mothers
Non-invasive prenatal genetic testing (NIPT) has revolutionized the screening of chromosomal abnormalities in the field of precision medicine for surrogate mothers during pregnancy. The latest clinical study published in the prestigious international journal Frontiers in Laboratory Medicine reveals the true efficacy and clinical decision-making value of NIPT in screening for different types of fetal chromosomal abnormalities through an in-depth analysis of 952 high-risk singleton surrogate mothers.
Core data: Analysis of the predictive efficacy of NIPT for different chromosomal abnormalities
Efficacy of screening for common chromosomal trisomies
T21 (Down syndrome): PPV as high as 84.53% (317/375 cases diagnosed)
T18 (Edwards syndrome): PPV of 68.82% (64/93 cases diagnosed)
T13 (Patau’s syndrome): PPV of 39.00% (16/41 cases diagnosed)
Sex chromosome abnormality (SCA) screening efficacy
Overall PPV of 48.77% (119/244 cases diagnosed)
Significantly higher PPV for sex chromosome trisomies (e.g., 47,XXY, 47,XXX, 47,XYY) (60.00%, 90/150 cases)
45,X (Turner syndrome) PPV only 20.21% (19/94 cases)
Other chromosomal abnormalities (NIPT-plus extended application)
Rare chromosomal aneuploidy PPV: 64.28% (27/42 cases)
Detection of pathogenic CNV (pCNV) involved key syndromes:
Catcall syndrome (5p deletion)
1q43-q44 deletion syndrome (1q43-q44 deletion)
Prader-Willi/Angelman syndrome (5p deletion)
16p13.11 microdeletion syndrome
Breakthrough discovery: age does not affect NIPT predictive efficacy
Study confirms for the first time that surrogate mother’s age is not a key determinant of NIPT accuracy!
No statistically significant difference in PPV for T21, T18, T13, SCA and other abnormalities between the <35 and ≥35 age groups.
Older surrogate mothers need not be overly concerned about test accuracy
CLINICAL IMPLICATION: Dr. Robert Chen, Johns Hopkins University, noted, “The finding overturns traditional perceptions and implies that NIPT can be used as a universal screening protocol for surrogate mothers of all ages.”
Real-world pregnancy outcome tracking: an in-depth analysis of the impact of decision-making
Study of 840 surrogate mothers completing labor and delivery follow-up (loss rate of only 11.76%) reveals key decision-making patterns:
| Type of Exception | Number of continuing pregnancies | Number of terminations | Spontaneous abortion/stillbirth |
|---|---|---|---|
| T21 (Down’s) | 8 cases | extremely high proportion | – |
| T18/T13 | 0cases | full | 4cases |
| sex chromosome abnormality | 35cases | 51cases | – |
| Chromosomally normal fetus | 2 cases terminated due to ultrasound abnormalities | – | 1 stillbirth |
Key indicators for 401 births:
96.3% healthy newborns (396 cases)
94.3% full-term delivery rate (378 cases)
Birth defect rate 1.25% (5 cases)
Golden strategy for clinical application of NIPT: accurately avoiding screening pitfalls
Limitations of T13 testing
Lowest PPV (39.00%) stems from placenta-specific chimerism (CPM) – NIPT detects placental DNA rather than direct fetal samples. Dr. Emily White, Oxford Fetal Medicine Centre, UK, emphasizes, “T13 results need to be verified by amniocentesis CMA.”
Screening Strategies for Sex Chromosome Abnormalities
For 45,X low PPV (20.21%):
Must combine ultrasound to monitor nuchal translucency thickness
Maternal karyotyping to rule out chimerism
Genetic counselor intervention for decision making
Precise localization with NIPT-plus
Rare chromosomal aneuploidy: low detection rate and often associated with early miscarriage, not recommended as first-line screening
CNV testing:
Focus on high incidence microdeletion/duplication syndromes (e.g. 22q11.2)
When VOUS (variant of undetermined significance) is detected, it should be combined with ultrasound + tertiary genetic counseling
KEY RECOMMENDATION: The International Society for Reproductive Genetics (ISRG) 2024 guidelines are clear: “Karyotyping + Chromosome Microarray (CMA) must be performed in all high-risk cases of NIPT to minimize misdiagnosis.”
Decision Support System for Surrogate Mothers: from Genetic Data to Fertility Options
Scenario-based solution:
When NIPT suggests high risk of T21
PPV exceeds 84%, but of the 8 cases of continued pregnancy:
3 cases chose an early intervention program based on
5 cases maintained pregnancy due to religious beliefs
Essentials of counseling for sex chromosome abnormalities
Take 47,XXY (Klinefelter syndrome) as an example:
Fertility may be impaired but can be resolved with assisted reproduction
Neurodevelopmental risk < 10%
Case of surrogate mom Sarah: “Genetic counselor Dr. James Miller used 3D modeling to show spectrum of disease and ultimately decided to continue pregnancy”
Response to NIPT-plus finding of VOUS
Follow the “3C’s”:
Confirm (CMA validation)
Counsel
Choose (individualized decision-making)
AUTHORITATIVE CONCLUSION: Dr. Laura Garcia of the World Health Organization’s Commission on the Control of Genetic Diseases emphasized, “This study provides a key evidence-based rationale for the Global Plan for Combating Birth Defects 2030, confirming that NIPT is a landmark technology that will change the pathway of chromosomal disorders prevention and treatment.”
