Fetal Resolution Clinic
Screening For Fetal Aneuploidies
A healthy pregnancy includes a healthy mother and a healthy baby. To ensure a healthy baby, proper prenatal screening, good antenatal follow up and care is essential. 1 in 1000 live births are associated with chromosomal aneuploidies in India. Chromosomal aneuploidies account for 5 – 10 % of mental retardation among children affecting their quality of life. Therefore, proper prenatal screening and counselling regarding chromosomal aneuploidies during pregnancy is highly essential. In India, a lot of screening tests are available to the parents such as first trimester biochemical screening, second trimester biochemical screening, cell free fetal DNA testing etc.
When we talk about screening for fetal chromosomal abnormalities, we need to first understand that every pregnant woman carries a risk of having a fetus with chromosomal abnormalities – this risk is called the “Background Risk” or “A Priori” risk and depends on maternal age and some factors in her medical history. Screening – Screening is a process applied on apparently healthy individuals to detect the risk of any particular problem. It is offered to a general population and the results of screening will determine whether the individual is at “High Risk” or “Low Risk” for a given condition. Women with “Low Risk” can be reassured while those with ”High Risk” can be offered confirmatory tests to check fetal chromosomes. Therefore, a screening test helps in optimizing the need for invasive testing while increasing the pick-up rate for fetal chromosomal problems.
The following tests can be offered to any pregnant woman who opts for “Fetal Aneuploidy Screening”
1. First Trimester Combined Screening Test
This test involves a blood test and the Nuchal translucency scan.
First trimester screening blood test (also called “double test”)
- This test involves a blood test that measures the quantity of two chemicals in the mother’s blood – free beta-hCG(Human Chorionic gonadotrophin) and PAPP-A(Pregnancy Associated Plasma Protein-A).
- PAPP-A is a protein produced first by the outer layer of the developing pregnancy (Trophoblast) and then by the growing placenta. During a normal pregnancy, levels of this protein increase in the mother's blood until delivery. Human chorionic gonadotropin (hCG) is a hormone produced by the developing early pregnancy and then large quantities by the placenta.The free beta subunit of hCG is used in first trimester screening. Concentrations hCG usually rise rapidly in the mother's circulation for the first 8 to 10 weeks, then decrease and stabilize at a lower level for the remainder of the pregnancy
- The first trimester screening blood test can be done at any time from 10-13+6 weeks of pregnancy. The sensitivity of the test is better around 10 weeks than around 13 weeks.
Nuchal translucency scan
- The NT scan is a highly specialized scan done by doctors who are certified by the Fetal Medicine Foundation (UK) for these scans. These doctors have a valid license which allows them to calculate individual numerical risk of Down syndrome and other chromosomal abnormalities in the fetus. In addition to the nuchal translucency, there are other first trimester markers that can be checked on this scan such as – the flow across the tricuspid valve, the Ductus venosus Doppler, the presence/absence of the fetal nasal bone and the fetal facial angle. These markers add to the sensitivity of the NT scan in detecting the risk for Down syndrome. The first trimester combined screening test gives a risk reassessment to the woman as to whether her risks of having a fetus with Down Syndrome have increased or decreased as compared to her age related risk.
2. Second Trimester Maternal Serum Biochemistry (Quadruple Test)
- When we talk about screening for fetal chromosomal abnormalities, we need to first understand that every pregnant woman carries a risk of having a fetus with chromosomal abnormalities – this risk is called the “Background Risk” or “A Priori” risk and depends on maternal age and some factors in her medical history. Screening – Screening is a process applied on apparently healthy individuals to detect the risk of any particular problem. It is offered to a general population and the results of screening will determine whether the individual is at “High Risk” or “Low Risk” for a given condition. Women with “Low Risk” can be reassured while those with ”High Risk” can be offered confirmatory tests to check fetal chromosomes. Therefore, a screening test helps in optimizing the need for invasive testing while increasing the pick-up rate for fetal chromosomal problems.
- Traditionally, the triple serum test was performed which evalated maternal serum alfa-fetoprotein, hCG and unconjugated estriol to assess the risk for Down syndrome. Now, the quadruple test has been known to have a better sensitivity with a lower false positive rate and hence is the preferred modality of second trimester maternal serum biocheistry.
- The quadruple test checks for the maternal serum inhibin A in addition to alfa-fetoprotein, hCG and unconjugated estriol to assess the risk for Down syndrome.
- The quadruple test is also a “Screening Test” and the results generally indicated a “Low Risk” or “High Risk” for fetal aneuploidies. The “Low Risk” patients can be reassured and the “High Risk” patients are explained that they need to be further evalauted to establish the need for definitive diagnostic tests to confirm fetal karyotype.
3. The Genetic Sonogram
- This is a systematic ultrasound evaluation of the fetus to look for any obvious “Markers” for fetal aneuploidy done at 18-19 weeks. There are “Major Markers” or “Minor Markers” that can be seen at the time of the scan. The major markers are major structural anomalies which definitely increase the risk for associated chromosomal abnormalities and hence justify the need for invasive testing to confirm fetal karyotype. The “Minor Markers” are subtle features which can be detected by trained sonographers and although they may not cause any functional implications to the fetus as such, their presence or absence alters the risk for fetal aneuploidies.
4. NIPT (Non-Invasive Prenatal Test / Screening)
- NIPT (cell free fetal DNA testing) is a non-invasive prenatal testing with higher sensitivity for predicting chromosomal aneuploidies. It is an advanced screening test that does not “Invade” the gestational sac – a maternal blood test. It is based on cell free fetal DNA analysis through next generation genome sequencing. NIPT was first released in Hong Kong since then NIPT (Non-Invasive Prenatal Testing) has become an intermediate step between serum screening and invasive diagnostic testing. NIPT is based on the analysis of cell free fetal DNA present in the sample of maternal blood to determine the likelihood of chromosomal aneuploidies. Good pre-test and post-test counseling is essential for better use of NIPT. It is useful to reassure the couple as it is a good screening test with good negative predictive value and is very reliable. The amount of cffDNA in maternal blood increases with gestational age34.So at later gestational age, the amount of fetal fraction obtained is also more ensuring better results and avoiding invasive testing.
