Prenatal Health Screening


Health Screening tests

Screening is a way of identifying apparently healthy individuals who may have a higher risk of a particular disorder. Health screenings benefit people comprehend their risk for developing chronic diseases before symptoms present, while they can still prevent the condition. The MELAL Medical Laboratory offers a range of screening tests to different sections of the population. The non-invasive screening tests provided by MELAL Medical Laboratory health screening service identify potential risk factors that can lead to genetic conditions, cardiovascular disease, stroke, cancers, osteoporosis, and other serious illnesses.

Prenatal testing

Prenatal testing, including screening and diagnostic tests, can provide valuable information about the infant’s health.

Types of prenatal testing

The two main types of prenatal testing are:

Screening tests

Prenatal screening tests can identify whether an infant is more or less likely to have certain birth defects, many of which are genetic disorders. These tests cover blood tests, ultrasound examinations and/or prenatal cell-free DNA screening (NIPT).  Prenatal screening tests are usually offered during the first or second trimester. Screening tests can’t make a definitive diagnosis. If results indicate an increased risk for a genetic disorder, the health care provider will discuss to patient about options for a diagnostic test to confirm the diagnosis.

Diagnostic tests

If a possible problem in a screening test, age, positive family or medical history puts an individual at increased risk of having a baby with a genetic disorder, an invasive prenatal diagnostic test might be considered.

Types of screening tests

Genetic testing of an embryo prior to implantation

There are two types of genetic testing of an embryo prior to transfer: preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). Both procedures require in vitro fertilization even if the couple is not sub-fertile, biopsy of in vitro embryos for genetic testing, and transfer of embryos based on the results of genetic testing. Genetic testing can also be performed on the first and second polar bodies obtained from mature oocytes prior to and after fertilization.

Preimplantation genetic screening (PGS)

The goal of preimplantation genetic screening (PGS) for aneuploidy (chromosomal abnormality, also known as PGD-A) is to identify de-novo aneuploidy, including subchromosomal deletions and additions, in embryos of couples known (or presumed) to be euploid. Forty to 60 percent of preimplantation embryos are aneuploid, which is one potential etiology for the relatively low implantation efficiency of both natural conceptions and in vitro fertilization (IVF). Theoretically, performing IVF, determining the genetic status (chromosomal copy numbers) of the preimplantation embryos, and then selecting only euploid embryos for embryo transfer should increase the rate of successful implantation per transferred embryo, and possibly reduce the chance of miscarriage. Transferring a single embryo will reduce multiple pregnancy rates by allowing efficient single embryo transfers.

Molecular genetics test:

·         Array comparative genomic hybridization and single nucleotide polymorphism arrays

  o   Array comparative genomic hybridization (CGH or microarray) and single nucleotide polymorphism (SNP) arrays are the most common methods of genetic analysis. All 23 pairs of chromosomes are evaluated and results can be available within several hours, usually overnight, which enables transfer of fresh embryos the next day. Disadvantages of array CGH are that it cannot detect polyploidies, changes in DNA sequences (eg, point mutations), or small gains and losses in regions of the genome not covered by the microarray. However, use of SNP microarrays or next generation sequencing can overcome these limitations.

·         Next generation sequencing (NGS)

  o   In next generation sequencing, segments of chromosomes are sequenced to determine ploidy and identify specific pathologic mutations in the DNA sequence. It is becoming more commonly utilized for aneuploidy detection; however, the increased detection rate along with potential sampling errors may lead to over-reading abnormalities and discard of potentially viable embryos.

  o   If genetic results are not available before the embryo must be transferred (six days following oocyte retrieval), the embryos are cryopreserved until after the results of the analysis become available. Additional embryos in excess of those being transferred can also be cryopreserved.

·         Karyomapping 

  o   Karyomapping to detect embryos at risk for a specific disorder may be an option when the specific molecular defects have not been characterized. It involves SNP genotyping the parents and a close relative, such as an existing child, for a known disease and identifying the disease loci on the chromosome. The section of parental DNA closely linked with the disease mutation is subsequently compared with the same section of DNA from the embryo (obtained by blastomere or trophectoderm biopsy). If the DNA segments match, the embryo has a significantly greater likelihood of being a carrier (one copy of that mutation) or affected with the disorder (two copies of the mutation).

  o   SNP information from karyomapping may give chromosome copy number assessment, but the accuracy is dependent on the number of “key” SNPs obtained from each individual and its clinical use has not been validated. Karyomapping is often used in conjunction with the other methods to determine chromosome copy number.

·         Fluorescence in situ hybridization

  o   Fluorescence in situ hybridization (FISH) is another technique for genetic testing but has several disadvantages that have made FISH testing in PGS obsolete

Preimplantation genetic diagnosis (PGD)

The goal of PGD is to establish a pregnancy that is unaffected by a specific gene mutation(s) when one or both biologic parents is a known carrier of a specific gene mutation(s). Additionally, PGD can be used to identify an unbalanced chromosomal complement when one parent is a carrier of a balanced translocation or chromosomal rearrangement. It is also used to select embryos for transfer that have a specific genetic complement, such as particular sex chromosomes or human leukocyte antigen (HLA) type. There are two types of preimplantation genetic testing:

·         Preimplantation genetic testing for monogenic (single-gene) disorders (PGT-M) is performed on cell(s) removed from a preimplantation embryo or a polar body from an oocyte. The goal is to establish a pregnancy that is unaffected by specific genetic characteristics, such as a known heritable genetic mutation or chromosomal abnormality (eg, translocations) carried by one or both biological parents. It is also used to select embryos for transfer that have specific characteristics, such as a particular gender or compatible HLA type.

·         Preimplantation genetic testing for aneuploidy (PGT-A) (formerly called preimplantation genetic screening) is performed on cell(s) removed from a preimplantation embryo or a polar body from an oocyte. The aim is to distinguish de-novo aneuploidy in the embryo(s) of parents considered to be chromosomally normal. Theoretically, avoiding the transfer of aneuploid embryos will reduce the risk of miscarriage and increase the chance of conceiving a successful pregnancy.

Molecular genetics tests:

·         Polymerase chain reaction (PCR)

  o   To detect differences in gene sequences between cells, PCR is used to amplify the segment of the genome that contains the specific gene of interest. Nested primer PCR provides the means to obtain millions of copies of the gene of interest and test for mutations using mutation-specific primers, digestion with restriction enzymes, or heteroduplex analysis.

·         Gene sequencing

·         Single nucleotide polymorphism arrays

·         KaryoMapping


1.    Glenn L Schattman and Kangpu Xu, Preimplantation genetic screening, UpToDate, 2018.
2.    Glenn L Schattman and Kangpu Xu, Preimplantation genetic testing, UpToDate, 2018.
3.    https://crgh.co.uk/pgs-aneuploidy-screening/. The Centre for Reproductive & Genetic Health. Accessed February 20, 2021.
First trimester screening tests
Through the first trimester, the health care provider will recommend a blood test and an ultrasound to measure the size of the clear space in the tissue at the back of a baby’s neck (nuchal translucency). In Down syndrome, Edwards’ syndrome, and Patau’s syndrome, the nuchal translucency measurement is abnormally increased. Typically, first trimester screening is done between weeks 11 and 14 of pregnancy.
First-trimester screening, also called the first trimester combined test, has two steps:
·        A blood test to measure levels of two pregnancy-specific substances in the mother’s blood — pregnancy-associated plasma protein-A (PAPP-A) and human chorionic gonadotropin (HCG)
·        An ultrasound exam to measure the size of the clear space in the tissue at the back of the baby’s neck (nuchal translucency)
You might choose to follow the first-trimester screening with another test that’s more definitive if results show that your risk level is moderate or high.
Second trimester screening tests
·         The quad screen, also known as the second-trimester screen, is a prenatal test that determines levels of four factors in pregnant women’s serum:
·         Alpha-fetoprotein (AFP), a protein made by the developing baby
·         Human chorionic gonadotropin (HCG), a hormone made by the placenta
·         Estriol, a hormone made by the placenta and the baby’s liver
·         Inhibin A, another hormone made by the placenta

Ideally, the quad screen is done between weeks 15 and 18 of pregnancy; however, the test can be taken up to week 22.
The quad screen is used to evaluate whether the pregnancy has an increased chance of being affected with certain conditions, such as Down syndrome or neural tube defects. If your risk is low, the quad screen can offer reassurance that there is a decreased chance for Down syndrome, trisomy 18, trisomy 1 neural tube defects and abdominal wall defects.
If the quad screen indicates an increased chance of one of these conditions, pregnant woman might consider additional screening or testing.


Mayo clinic labs, Low Risk Pregnancy Aneuploidy Screening and Diagnostic Testing Options
Mayo clinic labs, Low Risk Pregnancy Aneuploidy Screening and Diagnostic Testing Options
ARUP, First and Second Trimester Screening Options


1.    Iranian national guidelines for organizing the prevention of chromosomal abnormalities in Down syndrome and trisomy 13 and 18, 2020

2.    https://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/prenatal-testing/art-20045177. Accessed February 21, 2021.

3.    https://www.aruplab.com/, Accessed February 21, 2021.


Noninvasive Prenatal Testing (NIPT)

Prenatal cell-free DNA (cfDNA) testing, also known as noninvasive prenatal testing (NIPT), is a method to screen for certain chromosomal abnormalities of a fetus. Herein, DNA from the mother and fetus is extracted from a maternal blood sample and screened for the increased chance of specific chromosome problems, such as Down syndrome, trisomy 13 and trisomy 18. This screening can also report fetal gender. NIPT is suggested for women who are at least 10 weeks pregnant and have sufficient counseling concerning the alternatives, advantages, and limits of first and second-trimester screening and diagnostic testing. The health care provider or a genetic counselor will discuss whether NIPT might benefit you and how to interpret the results. NIPT can be performed using next-generation sequencing of cell-free DNA (cfDNA) in the maternal circulation.

NIPT might be more sensitive and specific than traditional first and second trimester screening. Also, prenatal cell-free DNA screening might benefit women who have particular risk factors make them consider invasive testing that brings a little risk of miscarriage, including amniocentesis and chorionic villus sampling (CVS).

NIPT is available to anyone who is pregnant. It can be used to screen for certain chromosomal disorders, including:

·         Down syndrome (trisomy 21)

·         Trisomy 18

·         Trisomy 13

·         It can also be used to screen for fetal sex.


Some NIPT might also screen for the increased chance of:

·         Trisomy 16

·         Trisomy 22

·         Triploidy

·         Sex chromosome aneuploidy

·         Certain disorders caused by a chromosomal deletion (microdeletion syndrome)

·         Certain single-gene disorders

Molecular genetics tests:

·         next-generation sequencing of cell-free DNA (cfDNA) in the maternal circulation

NIPT specificity and sensitivity

ARUP, cfDNA Specificity and Sensitivity comparisons

The accuracy of NIPT 

Sian Taylor-Phillips, BMJ open, 2016.


1.    https://www.mayoclinic.org/tests-procedures/noninvasive-prenatal-testing/about/pac-20384574. Accessed February 15, 2021

2.    https://arupconsult.com/content/prenatal-screening-and-diagnosis. Accessed February 20, 2021.

3.    Palomaki G., Messerlian G., Halliday J., Prenatal screening for common aneuploidies using cell-free DNA, UpToDate, 2018.

4.    Taylor-Phillips, Sian, et al. “Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes: a systematic review and meta-analysis.” BMJ open 6.1 (2016).

5.    Mackie, F. L., et al. “The accuracy of cell‐free fetal DNA‐based non‐invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta‐analysis.” BJOG: An International Journal of Obstetrics & Gynaecology 124.1 (2017): 32-46.

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