Predictive (screening) tests can determine whether your baby is more or less likely to have certain genetic anomalies, many of which are associated with genetic syndromes.
Screening tests do not replace diagnostic tests. If the results indicate an increased risk for a genetic syndrome, your attending physician or another healthcare professional will discuss options for confirming the diagnosis with the appropriate diagnostic test.
Categories of Screening Tests:
First-Trimester Biochemical Screening – PAPP-A Test for Down, Edwards, and Patau Syndromes
PAPP-A is produced by trophoblasts and released into the maternal bloodstream during pregnancy. Measuring PAPP-A, combined with free β-hCG levels and ultrasound measurements, is used to statistically estimate the likelihood of chromosomal abnormalities during the first-trimester screening.
In high-risk pregnancies for the most common chromosomal abnormalities (Down, Edwards, Patau syndromes), further diagnostic testing is recommended.
Placental Growth Factor (PlGF)
Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family, mainly expressed in the placenta, and increases significantly during pregnancy. PlGF is measured in women between 20 and 34+6 weeks of gestation if there is any suspicion of preeclampsia.
PlGF concentration is low in the first trimester of an uncomplicated pregnancy, rises between weeks 11–12, peaks around week 30, and then decreases. Low PlGF levels are considered a reflection of placental dysfunction and have been shown to correlate significantly with time to delivery in women suspected of preeclampsia.
sFlt-1/PlGF (soluble FMS-like tyrosine kinase / placental growth factor)
Preeclampsia is a progressive pregnancy-related disorder with serious complications for both mother and fetus. Measuring maternal serum biomarkers sFlt-1 (soluble FMS-like tyrosine kinase) and PlGF significantly improves risk stratification in women at high risk for preeclampsia.
Maternal serum levels of sFlt-1 and PlGF, measured from mid-pregnancy onward, can confirm the diagnosis of preeclampsia. The sFlt-1/PlGF ratio has higher diagnostic value compared to each biomarker alone.
Women with preeclampsia exhibit significantly higher sFlt-1/PlGF ratios compared to women with other hypertensive disorders or normal pregnancies.
PrenaTest – Non-Invasive Prenatal Testing (NIPT)
Decades of research on non-invasive prenatal testing using cell-free fetal DNA in maternal blood, combined with rapid technological advances, have finally borne fruit.
Researchers overcame the challenge of the small amount of fetal DNA in maternal circulation, making it possible to identify fetuses at high risk for numerical chromosomal abnormalities (aneuploidies) in all chromosomes, deletions and duplications in autosomal chromosomes, and nine of the most clinically significant microdeletion syndromes—all from a simple maternal blood draw, with no risk to the fetus.
At LIFE CODE, PrenaTest is the preferred non-invasive prenatal screening test because it offers:
- 1 test with 8 options
- Requires only 2% fetal DNA
- Fast, safe, and cost-effective
- Highest positive predictive value among similar tests
PrenaTest can be performed in all pregnancies, regardless of conception method (natural, assisted, egg donation, surrogate), from the 10th week of gestation in singleton or twin pregnancies, to identify fetuses at high risk for chromosomal abnormalities.
What are the limitations of the analysis?
The limitations of the PrenaTest, as with similar tests, are that it cannot detect:
a) Partial trisomies of the examined chromosomes
b) Structural chromosomal abnormalities (inversions, translocations), genetic disorders, or congenital anomalies of the fetus
c) Mosaicism (presence of both normal and abnormal cell lines) involving monosomies or trisomies of the chromosomes tested
In cases where fetal DNA represents an extremely low proportion of maternal blood, i.e., less than 2%, the test results cannot be reliably evaluated.
In such cases, the test is repeated with a new sample
What are the sensitivity rates?
The sensitivity of the method for detecting trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), trisomy 13 (Patau syndrome), and sex chromosome abnormalities is >99%.
The PPV (positive predictive value) is the highest among comparable NIPT tests. For example, the PPV for trisomy 21 is 98.4%, while overall for trisomies 13, 18, 21, and sex chromosome aneuploidies it is greater than 95%.
How long does it take to receive the results?
The results of the analysis are available within 7 business days and are always interpreted by the attending physician. The physician may recommend additional tests to confirm the findings (whether high or low risk), taking into account the PrenaTest results in combination with other clinical data and ultrasound findings.
PRENATEST OPTIONS
Option 1
Detection of Trisomy 21 and Fetal Sex
Applicable only for singleton pregnancies
Option 2
Detection of Trisomies 13, 18, 21 and Fetal Sex
Applicable for singleton and twin pregnancies.
DiGeorge Syndrome: Applicable only for singleton pregnancies.
Option 2 Plus
Detection of Trisomies & Autosomal Monosomies (Chromosomes 1–22), Autosomal Deletions/Duplications >7 Mb, and Fetal Sex
Applicable for singleton and twin pregnancies.
DiGeorge Syndrome: Applicable only for singleton pregnancies.
Option 3
Detection of Trisomies 13 / 18 / 21, Detection of Sex Chromosome Aneuploidies (X & Y), and Fetal Sex
DiGeorge Syndrome
Applicable for singleton pregnancies.
Option 3 Plus
Detection of Trisomies & Autosomal Monosomies (Chromosomes 1-22), Sex Chromosome Aneuploidies (X & Y), Deletions / Duplications >7 Mb, and Fetal Sex
DiGeorge Syndrome
Applicable for singleton pregnancies.
Option 4
Detection of Trisomies of Autosomal Chromosomes 13 / 18 / 21 / 9 / 16, Sex Chromosome Aneuploidies (X & Y), Fetal Sex, and 6 Microdeletion Syndromes: 22q11.2 deletion (DiGeorge), 15q11.2 deletion (Angelman/Prader-Willi), 1p36 deletion, 4p16.3 deletion (Wolf-Hirschhorn), 5p15.3 deletion (Cri-du-chat)
Applicable for singleton pregnancies.
Option 5 Plus
Detection of Trisomies & Monosomies of Autosomal Chromosomes (1-22), Sex Chromosome Aneuploidies (X & Y), Autosomal Chromosome Deletions/Duplications >7 MB, Fetal Sex, and 9 Microdeletion Syndromes: 22q11.2 deletion (DiGeorge), 15q11.2 deletion (Angelman/Prader-Willi), 1p36 deletion, 4p16.3 deletion (Wolf-Hirschhorn), 5p15.3 deletion (Cri-du-chat), 11q23-q24.3 deletion (Jacobsen), 8q24.11-q24.13 deletion (Langer-Giedion), 17p11.2 deletion (Smith-Magenis)
Applicable for singleton pregnancies.
NIPT Fetal Rhesus
Detection of Fetal Rhesus in Pregnant Women with Negative Rhesus Factor
Applicable for singleton pregnancies.
For more information about the options available with PrenaTest, please contact us at +30 210 6917172 or +30 210 6993730.
References
Palomaki GE, Kloza EM, Lambert-Messerlian GM, et al. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med. 2011;13:913-920.
Sparks, A.B., Wang, E.T., Struble, C.A., Barrett, W., et al, Selective analysis of cell-free DNA in maternal blood for evaluation of fetal trisomy. Prenat Diagn (2012);32(1):3-9. doi: 10.1002/pd.2922. Epub 2012 Jan 6.
Sparks, A.B., Struble, C.A., Wang, E.T., Song, K., Oliphant, A., Non-invasive Prenatal Detection and Selective Analysis of Cell-free DNA Obtained from Maternal Blood: Evaluation for Trisomy 21 and Trisomy 18, Am J Obstet Gynecol. (2012), doi: 10.1016/j.ajog.2012.01.030.
Norton, M., Brar, H., Weiss, J., Karimi, A., et al. Non-Invasive Chromosomal Evaluation (NICE) Study: Results of a Multicenter, Prospective, Cohort Study for Detection of Fetal Trisomy 21 and Trisomy 18, Am J Obstet Gynecol. (2012), doi:10.1016/j.ajog.2012.05.021.
Brar H, Wang E, Struble C, et al. The fetal fraction of cell-free DNA in maternal plasma is not affected by a priori risk of fetal trisomy. J Matern Fetal Neonatal Med (2012), DOI: 10.3109/14767058.2012.722731
Ashoor G, Syngelaki A, Nicolaides KH, et al. Trisomy 13 detection in the first trimester of pregnancy using a chromosome-selective cell-free DNA analysis method, ULTRASOUND Obstet Gynecol. (2012), DOI: 10.1002/uog.12299.
Nicolaides KH, Syngelaki A, Ashoor G, et al. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am J Obstet Gynecol 2012;207:374.e1-6
Nicolaides KH, Syngelaki A, Gil M, Atanasova V, Markova D. Validation of targeted sequencing of single-nucleotide polymorphisms of non-invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X and Y. Prenat Diagn (2013);33:1-5.