Prenatal Diagnosis: Difference between revisions

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==Introduction==
==Introduction==
[[File:Chromosome-_trisomy.jpg|thumb|Trisomy 21 karyotype cartoon]]
[[File:Chromosome-_trisomy.jpg|thumb|Trisomy 21 karyotype cartoon]]
[[File:Preimplantation blastomere biopsy.jpg|thumb|alt=ART Preimplantation blastomere biopsy|ART Preimplantation blastomere biopsy<ref name="PMID24783200"><pubmed>24783200</pubmed>| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982254 PMC3982254] | [http://www.hindawi.com/journals/bmri/2014/306505 Biomed Res Int.]</ref>
This current page is a general starting point for the topic of prenatal diagnosis, the links below are to resources that give more specific information about some diagnostic techniques available at different stages of pregnancy. The two major classes of techniques are invasive and non-invasive testing and the results of these tests most commonly show normal development. When abnormal development is identified this can be due to genetic, environmental, unknown causes or a combination of these effects. (More? [[Human_Abnormal_Development|Abnormal Development]])  
This current page is a general starting point for the topic of prenatal diagnosis, the links below are to resources that give more specific information about some diagnostic techniques available at different stages of pregnancy. The two major classes of techniques are invasive and non-invasive testing and the results of these tests most commonly show normal development. When abnormal development is identified this can be due to genetic, environmental, unknown causes or a combination of these effects. (More? [[Human_Abnormal_Development|Abnormal Development]])  



Revision as of 11:03, 20 July 2015

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Introduction

Trisomy 21 karyotype cartoon

[[File:Preimplantation blastomere biopsy.jpg|thumb|alt=ART Preimplantation blastomere biopsy|ART Preimplantation blastomere biopsy[1] This current page is a general starting point for the topic of prenatal diagnosis, the links below are to resources that give more specific information about some diagnostic techniques available at different stages of pregnancy. The two major classes of techniques are invasive and non-invasive testing and the results of these tests most commonly show normal development. When abnormal development is identified this can be due to genetic, environmental, unknown causes or a combination of these effects. (More? Abnormal Development)


A trend in developed countries of an increasing maternal age, long associated with increased genetic abnormalities, has emphasised the need for good diagnostic low risk tests that allow informed decisions early in a pregnancy. (More? Genetic) In contrast, in developing countries environmental effects such as infections and nutrition can impact upon embryonic and fetal development (More? Environmental | Nutrition)


Recently with the growth in Assisted Reproductive Technologies (ART) or commonly known as In Vitro Fertilization (IVF), there is a new "form" of prenatal diagnosis that involves genetic testing of the blastocyst before implantation. (More? Assisted Reproductive Technology)


Non-Invasive Prenatal Testing (NIPT) is a new technique that analyzes cell-free fetal DNA circulating in maternal blood.


There are other pages that refer to postnatal diagnostic testing. (More? Neonatal Diagnosis)


This Embryology site is a developmental educational resource, it does not provide specific clinical details, you should always refer to a health professional.


Diagnosis Links: Prenatal Diagnosis | pregnancy test | amniocentesis | chorionic villus sampling | ultrasound | Alpha-Fetoprotein | Pregnancy-associated plasma protein-A | Fetal Blood Sampling | Magnetic Resonance Imaging | Computed Tomography | Non-Invasive Prenatal Testing | Fetal Cells in Maternal Blood | Preimplantation Genetic Screening | Comparative Genomic Hybridization | Genome Sequencing | Neonatal Diagnosis | Category:Prenatal Diagnosis | Fetal Surgery | Classification of Diseases | Category:Neonatal Diagnosis

| Assisted Reproductive Technology | In Vitro Fertilization | Journal - Prenatal diagnosis


Amniocentesis.jpg Chorionic villus sampling Ultrasound
Amniocentesis Chorionic villus sampling Ultrasound

Some Recent Findings

  • An Economic Analysis of Cell-Free DNA Non-Invasive Prenatal Testing in the US General Pregnancy Population[2] "Analyze the economic value of replacing conventional fetal aneuploidy screening approaches with non-invasive prenatal testing (NIPT) in the general pregnancy population. METHODS: Using decision-analysis modeling, we compared conventional screening to NIPT with cell-free DNA (cfDNA) analysis in the annual US pregnancy population. Sensitivity and specificity for fetal aneuploidies, trisomy 21, trisomy 18, trisomy 13, and monosomy X, were estimated using published data and modeling of both first- and second trimester screening. Costs were assigned for each prenatal test component and for an affected birth. ...Based on our analysis, universal application of NIPT would increase fetal aneuploidy detection rates and can be economically justified. Offering this testing to all pregnant women is associated with substantial prenatal healthcare benefits."
  • Increasing Live Birth Rate by Preimplantation Genetic Screening of Pooled Polar Bodies Using Array Comparative Genomic Hybridization[3] "To overcome this disadvantage, we tested a strategy involving the pooling of DNA from both polar bodies before DNA amplification. We retrospectively studied 351 patients, of whom 111 underwent polar body array-CGH before embryo transfer. In the group receiving pooled polar body array-CGH (aCGH) analysis, 110 embryos were transferred, and 29 babies were born, corresponding to live birth rates of 26.4% per embryo and 35.7% per patient. In contrast, in the control group, the IVF treatment was performed without preimplantation genetic screening (PGS). For this group, 403 embryos were transferred, and 60 babies were born, resulting in live birth rates of 14.9% per embryo and 22.7% per patient. In conclusion, our data show that in the aCGH group, the use of aneuploidy screening resulted in a significantly higher live birth rate compared with the control group, supporting the benefit of PGS for IVF couples in addition to the suitability and effectiveness of our polar body pooling strategy."
  • Noninvasive Prenatal Testing: The Future Is Now[4] "Prenatal detection of chromosome abnormalities has been offered for more than 40 years, first by amniocentesis in the early 1970s and additionally by chorionic villus sampling (CVS) in the early 1980s. ...The ability to isolate fetal cells and fetal DNA from maternal blood during pregnancy has opened up exciting opportunities for improved noninvasive prenatal testing (NIPT). Direct analysis of fetal cells from maternal circulation has been challenging given the scarcity of fetal cells in maternal blood (1:10,000-1:1,000,000) and the focus has shifted to the analysis of cell-free fetal DNA, which is found at a concentration almost 25 times higher than that available from nucleated blood cells extracted from a similar volume of whole maternal blood. There have now been numerous reports on the use of cell-free DNA (cfDNA) for NIPT for chromosomal aneuploidies-especially trisomy (an extra copy of a chromosome) or monosomy (a missing chromosome)-and a number of commercial products are already being marketed for this indication. This article reviews the various techniques being used to analyze cell-free DNA in the maternal circulation for the prenatal detection of chromosome abnormalities and the evidence in support of each."
  • Noninvasive whole-genome sequencing of a human fetus[5] "Analysis of cell-free fetal DNA in maternal plasma holds promise for the development of noninvasive prenatal genetic diagnostics. Previous studies have been restricted to detection of fetal trisomies, to specific paternally inherited mutations, or to genotyping common polymorphisms using material obtained invasively, for example, through chorionic villus sampling. Here, we combine genome sequencing of two parents, genome-wide maternal haplotyping, and deep sequencing of maternal plasma DNA to noninvasively determine the genome sequence of a human fetus at 18.5 weeks of gestation. "
  • A noninvasive test to determine paternity in pregnancy[6] "Our approach shows that noninvasive prenatal paternity testing can be performed within the first trimester with the use of a maternal blood sample."
More recent papers
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Search term: Prenatal Diagnosis <pubmed limit=5>Prenatal Diagnosis</pubmed>

Search term: Non-Invasive Prenatal Testing <pubmed limit=5>Non-Invasive Prenatal Testing</pubmed>

Amniocentesis

Amniocentesis.jpg Amniocentesis is a prenatal diagnostic test carried out mainly between 14th to 18th week of pregnancy. Amniotic fluid is taken from the uterus, sent to a diagnostic laboratory and embryonic cells isolated from the amniotic fluid. No anaesthetic is required, and a result is usually obtained in about three to four weeks. When the test is carried out by an obstetrician experienced in the technique, the risk of a miscarriage related to the test is about 1 %.


Links: Amniocentesis | Placenta - Amnionic Sac | Ultrasound

Chorionic Villus Sampling

Cvs.jpg
Chorionic Villus Sampling (CVS) test is done in the 10th to 12th week after the first day of the mother's last menstrual period. The test is done by looking at cells taken from the chorionic membrane or placenta. No anaesthetic is required, and a test result is usually available in two to three weeks.


When the test is carried out by an obstetrician experienced in the technique, the risk of miscarriage related to the test is about 2 %. (Modified from: Checking your baby's health before birth. State Health Publication Number (PA) 94-090)


Potential disadvantages include maternal cell contamination, placental mosaicism and failure to obtain an adequate specimen. This may result in the need for a repeat procedure or amniocentesis.


Links: Chorionic Villus Sampling | Placenta - Amnionic Sac | Ultrasound

Non-Invasive Prenatal Testing

A published survey of clinicians from 28 countries worldwide[7] reported that NIPT is available in their country (n=43) and that they offer NIPT in their current practice (n=38). Eighteen respondents from 14 countries reported that there are plans to introduce NIPT into routine antenatal care in their country. Test prices varied widely, ranging from $US 350 - $US 2900, and several respondents observed that high test prices limited or restricted widespread use of NIPT.


See also recent Non-Invasive Prenatal Testing (NIPT) articles in Australian Family Physician[8] and JAMA (USA).

Cordocentesis

Percutaneous umbilical blood sampling (PUBS, fetal blood sampling, umbilical vein sampling)

This chromosome analysis test is done at in the 18th week or later of high-risk pregnancies. The technique may be used when either alternative tests (amniocentesis, CVS, ultrasound) are either inconclusive or not achievable (severe oligohydramnios).

The risk of a miscarriage related to the test is about 3 per cent (occurring in 3 in 100 pregnancies).

Coelocentesis

This is a technique of sampling of extracoelomic fluid usually for an early prenatal diagnostic technique.

Fetal Fibronectin

As a prenatal diagnostic test, a positive fetal fibronectin test result can indicate a higher risk of preterm delivery, but may also has false positive results. The negative result is more reliable as an indicator of reduced risk of preterm birth.

(fFN) is an extracellular matrix glycoprotein produced by fetal cells. Fetal fibronectin appears to act as an adhesive between the interface of the chorion and the decidua (fetal membrane and uterine lining).

Genetic Testing

There are clinically more and more tests becoming available as we learn more about the genetic basis of some diseases. The most common diagnostic test relates to the current trend in an increasing maternal age, which has long been associated with an increase in genetic abnormalities, the most frequent of these is trisomy 21 or Down syndrome.

Inheritance Genetics

Pedigree chart


Links: Genetic risk maternal age | Trisomy 21

Australia

A recent publication from NHMRC Medical Genetic Testing: information for health professionals (2010). This paper covers background information on all types of genetic tests, not just those associated with prenatal diagnosis.

Types of genetic tests

  • Somatic cell genetic testing involves testing tissue (usually cancer) for non-heritable mutations. This may be for diagnostic purposes, or to assist in selecting treatment for a known cancer.
  • Diagnostic testing for heritable mutations involves testing an affected person to identify the underlying mutation(s) responsible for the disease. This typically involves testing one or more genes for a heritable mutation.
  • Predictive testing for heritable mutations involves testing an unaffected person for a germline mutation identified in genetic relatives. The risk of disease will vary according to the gene, the mutation and the family history.
  • Carrier testing for heritable mutations involves testing for the presence of a mutation that does not place the person at increased risk of developing the disease, but does increase the risk of having an affected child developing the disease.
  • Pharmacogenetic testing for a genetic variant that alters the way a drug is metabolised. These variants can involve somatic cells or germline changes. Even if these variants are heritable (that is germline changes), the tests are usually of relevance to genetic relatives only if they are being treated with the same type of medication.


Links: NHMRC - Medical Genetic Testing: information for health professionals

USA

A new site developed by NIH "GeneTests" provides medical genetics information resources available at no cost to all interested persons. It contains educational information, a directory of genetic testing laboratories and links to other databases such as OMIM.


Links: GeneTests | Medline Plus - Genetic Testing

Comparative Genomic Hybridization

This new test under development is based upon microarray-based comparative genomic hybridization (array CGH).

All fetal cells should have complete copies of maternal and paternal genomes. The test compares regions of fetal DNA that deviate from this "pattern" due to either too much or too little DNA, alterations reflect regions of the genome that are either copied or deleted. These genetic changes may therefore cause disease.

Links: Comparative Genomic Hybridization

Ethics of Testing

Major developmental abnormalities detected early enough can be resolved far more easily than those discovered late in a pregnancy.

What are the ethical questions that are raised by prenatal testing? Future individual rights or parents rights? But what about diseases, like Huntington's, where a diagnostic test can be made but there are no current treatments for the postnatal (95% of cases adult onset) disease?

Huntington's disease

Guidelines for the molecular genetics predictive test

Recommendation 2.1 "the test is available only to individuals who have reached the age of majority."
Recommendation 7.2 "the couple requesting antenatal testing must be clearly informed that if they intend to complete the pregnancy if the fetus is a carrier of the gene defect, there is no valid reason for performing the test."

(excerpt from: IHA and the World Federation of Neurology Research Group on Huntington's Chorea. Guidelines for the molecular genetics predictive test in Huntington's disease.)

References

  1. <pubmed>24783200</pubmed>| PMC3982254 | Biomed Res Int.
  2. <pubmed>26158465</pubmed>| PLoS One.
  3. Feichtinger M, Stopp T, Göbl C, Feichtinger E, Vaccari E, Mädel U, et al. (2015) Increasing Live Birth Rate by Preimplantation Genetic Screening of Pooled Polar Bodies Using Array Comparative Genomic Hybridization. PLoS ONE 10(5): e0128317.
  4. <pubmed>24466384</pubmed>
  5. <pubmed>22674554</pubmed>
  6. <pubmed>22551147</pubmed>
  7. <pubmed>26085345</pubmed>
  8. [Noninvasive prenatal testing Noninvasive prenatal testing] Volume 43, No.7, July 2014 Pages 432-434.


Journals

Prenatal Diagnosis communicates the results of clinical and basic research in prenatal and preimplantation diagnosis in humans, and animal and in vitro models,

http://www.ncbi.nlm.nih.gov/pubmed?term=%22Prenat+Diagn%22[jour]

Articles

<pubmed>17845745</pubmed>

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November 2010 "Prenatal Diagnosis" All (63715) Review (8631) Free Full Text (6349)

Search Pubmed: Prenatal Diagnosis




Prenatal Diagnosis Terms

  • blastomere biopsy - An ART preimplantation genetic diagnosis technique carried out at cleavage stage (day 3), excluding poor quality embryos, detects chromosomal abnormalities of both maternal and paternal origin. May not detect cellular mosaicism in the embryo.
  • blastocyst biopsy - An ART preimplantation genetic diagnosis technique carried out at blastocyst stage (day 4-5), removes several trophoblast (trophoderm) cells, detects chromosomal abnormalities of both maternal and paternal origin and may detect cellular mosaicism.
  • cell-free fetal deoxyribonucleic acid - (cfDNA) refers to fetal DNA circulating and isolated from the plasma portion of maternal blood. Can be performed from GA 10 weeks as a first-tier test or as a second-tier test, with women with increased probability on combined first trimester screening offered cfDNA or diagnostic testing.
  • false negative rate - The proportion of pregnancies that will test negative given that the congenital anomaly is present.
  • false positive rate - The proportion of pregnancies that will test positive given that the congenital anomaly is absent.
  • free β human chorionic gonadotrophin - beta-hCG subunit of hCG used as a diagnostic marker for: early detection of pregnancy, Trisomy 21, spontaneous abortion, ectopic pregnancy, hydatidiform mole or choriocarcinoma.
  • multiples of the median - (MoM) A multiple of the median is a measure of how far an individual test result deviates from the median and is used to report the results of medical screening tests, particularly where the results of the individual tests are highly variable.
  • negative predictive value - The probability that a congenital anomaly is absent given that the prenatal screening test is negative.
  • Non-Invasive Prenatal Testing - (NIPT) could refer to ultrasound or other imaging techniques, but more frequently used to describe analysis of cell-free fetal DNA circulating in maternal blood.
  • polar body biopsy - (PB biopsy) An ART preimplantation genetic diagnosis technique that removes either the first or second polar body from the zygote. As these are generated by oocyte meiosis they detects chromosomal abnormalities only on the female genetics.
  • positive predictive value - The probability that a congenital anomaly is present given that the prenatal screening test is positive.
  • prenatal screening sensitivity - (detection rate) The probability of testing positive on a prenatal screening test if the congenital anomaly is present.
  • prenatal screening specificity - The probability of testing negative on a prenatal screening test if the congenital anomaly is absent.
  • quadruple test (maternal serum testing of a-fetoprotein Template:AFP, free B-hCG or total hCG, unconjugated estriol, and inhibin A) is a fetal chromosomal anomaly test usually carried out later in pregnancy (GA 14 to 20 weeks).
  • single nucleotide polymorphisms - (SNPs) the variation in a single DNA nucleotide that occurs at a specific position in the genome.
  • triple test - (maternal serum testing of a-fetoprotein Template:AFP, free B-hCG or total hCG, and unconjugated estriol) is a fetal chromosomal anomaly test usually carried out later in pregnancy (GA 14 to 20 weeks).


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  • Mayo Clinic [www.mayoclinic.org/tests-procedures/noninvasive-prenatal-testing/basics/definition/prc-20012964 Noninvasive Prenatal Testing]

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Cite this page: Hill, M.A. (2024, March 28) Embryology Prenatal Diagnosis. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Prenatal_Diagnosis

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G