Prenatal Diagnosis

From Embryology
Embryology - 25 May 2017    Facebook link Pinterest link Twitter link  Expand to Translate  
Google Translate - select your language from the list shown below (this will open a new external page)

العربية | català | 中文 | 中國傳統的 | français | Deutsche | עִברִית | हिंदी | bahasa Indonesia | italiano | 日本語 | 한국어 | မြန်မာ | Pilipino | Polskie | português | ਪੰਜਾਬੀ ਦੇ | Română | русский | Español | Swahili | Svensk | ไทย | Türkçe | اردو | ייִדיש | Tiếng Việt    These external translations are automated and may not be accurate. (More? About Translations)

Educational Use Only - Embryology is an educational resource for learning concepts in embryological development, no clinical information is provided and content should not be used for any other purpose.


Trisomy 21 karyotype cartoon
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) include new techniques that analyzes cell-free fetal DNA circulating in maternal blood or from fetal cells in the cervical canal.

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

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

Some Recent Findings

  • Fetal genome profiling at 5 weeks of gestation after noninvasive isolation of trophoblast cells from the endocervical canal [2] "We have isolated intact trophoblast cells from Papanicolaou smears collected noninvasively at 5 to 19 weeks of gestation for next-generation sequencing of fetal DNA. ...The data revealed fetal DNA fractions of 85 to 99.9%, with 100% correct fetal haplotyping. This noninvasive platform has the potential to provide comprehensive fetal genomic profiling as early as 5 weeks of gestation."
  • An Economic Analysis of Cell-Free DNA Non-Invasive Prenatal Testing in the US General Pregnancy Population[3] "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[4] "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[5] "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[6] "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[7] "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
Mark Hill.jpg
PubMed logo.gif

This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Prenatal Diagnosis Zhen Yu, Ee-Leng Tan, Dong Ni, Jing Qin, Siping Chen, Shenli Li, Baiying Lei, Tianfu Wang A Deep Convolutional Neural Network Based Framework for Automatic Fetal Facial Standard Plane Recognition. IEEE J Biomed Health Inform: 2017; PubMed 28534800

Ridha Fatnassi, Nédia Marouen, Houcem Ragmoun, Latifa Marzougui, Sabra Hammami [Collodion baby: clinical aspects and role of prenatal diagnosis]. [Le bébé collodion: aspects cliniques et intérêt du diagnostic anténatal.] Pan Afr Med J: 2017, 26;118 PubMed 28533841

O Shen, H Y Sela, H Nagar, R Rabinowitz, E Jacobovich, D Chen, E Granot Prenatal diagnosis of biliary atresia: A case series. Early Hum. Dev.: 2017, 111;16-19 PubMed 28531808

Raquel García-Delgado, Francisco Jiménez, Hipólito Falcón Prenatal Diagnosis of Anomalous Origin of the Right Pulmonary Artery. Rev Esp Cardiol (Engl Ed): 2017; PubMed 28527560

Liliana María Zuluaga, John Camilo Hernández, Carlos Felipe Castaño, Jorge Hernando Donado [Effect of antenatal spiramycin treatment on the frequency of retinochoroiditis due to congenital toxoplasmosis in a Colombian cohort]. Biomedica: 2017, 37;86-91 PubMed 28527270

Search term: Non-Invasive Prenatal Testing Fergus Perry Scott, Melody Menezes, Ricardo Palma-Dias, Debbie Nisbet, Philip Schluter, Fabricio da Silva Costa, Andrew Cameron McLennan Factors affecting cell free DNA fetal fraction and the consequences for test accuracy. J. Matern. Fetal. Neonatal. Med.: 2017;1-20 PubMed 28514925

Melissa Hill, Eugene Oteng-Ntim, Frida Forya, Mary Petrou, Stephen Morris, Lyn S Chitty Preferences for prenatal diagnosis of sickle-cell disorder: A discrete choice experiment comparing potential service users and health-care providers. Health Expect: 2017; PubMed 28504327

Xuan Ni Tan, Rosemary Harrup Follicular lymphoma in pregnancy presenting as multiple aneuploidy on non-invasive prenatal testing. Intern Med J: 2017, 47(5);601-602 PubMed 28503877

L F Johansson, E N de Boer, H A de Weerd, F van Dijk, M G Elferink, G H Schuring-Blom, R F Suijkerbuijk, R J Sinke, G J Te Meerman, R H Sijmons, M A Swertz, B Sikkema-Raddatz Novel Algorithms for Improved Sensitivity in Non-Invasive Prenatal Testing. Sci Rep: 2017, 7(1);1838 PubMed 28500333

Zandra C Deans, Stephanie Allen, Lucy Jenkins, Farrah Khawaja, Ros J Hastings, Kathy Mann, Simon J Patton, Erik A Sistermans, Lyn S Chitty Recommended practice for laboratory reporting of non-invasive prenatal testing (NIPT) of trisomies 13, 18 and 21: a consensus opinion. Prenat. Diagn.: 2017; PubMed 28497584


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

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


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).


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).

Non-Invasive Prenatal Testing

A published survey of clinicians from 28 countries worldwide[8] 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[9] and JAMA (USA).

Cervical Canal Trophoblasts

Beginning in 2009, a diagnostic trial indicated that fetal cytotrophoblast cells could be collected by transcervical sampling for genetic analysis.[10] A recent 2016 study[2] has identified fetal genome profiling as early as gestation weeK 5 GA using this technique.

Links: Trophoblast

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


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


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.)


  1. Tanya Milachich New advances of preimplantation and prenatal genetic screening and noninvasive testing as a potential predictor of health status of babies. Biomed Res Int: 2014, 2014;306505 PubMed 24783200 | PMC3982254 | Biomed Res Int.
  2. 2.0 2.1 Chandni V Jain, Leena Kadam, Marie van Dijk, Hamid-Reza Kohan-Ghadr, Brian A Kilburn, Craig Hartman, Vicki Mazzorana, Allerdien Visser, Michael Hertz, Alan D Bolnick, Rani Fritz, D Randall Armant, Sascha Drewlo Fetal genome profiling at 5 weeks of gestation after noninvasive isolation of trophoblast cells from the endocervical canal. Sci Transl Med: 2016, 8(363);363re4 PubMed 27807286
  3. Peter Benn, Kirsten J Curnow, Steven Chapman, Steven N Michalopoulos, John Hornberger, Matthew Rabinowitz An Economic Analysis of Cell-Free DNA Non-Invasive Prenatal Testing in the US General Pregnancy Population. PLoS ONE: 2015, 10(7);e0132313 PubMed 26158465 | PLoS One.
  4. 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.
  5. Errol R Norwitz, Brynn Levy Noninvasive prenatal testing: the future is now. Rev Obstet Gynecol: 2013, 6(2);48-62 PubMed 24466384
  6. Jacob O Kitzman, Matthew W Snyder, Mario Ventura, Alexandra P Lewis, Ruolan Qiu, Lavone E Simmons, Hilary S Gammill, Craig E Rubens, Donna A Santillan, Jeffrey C Murray, Holly K Tabor, Michael J Bamshad, Evan E Eichler, Jay Shendure Noninvasive whole-genome sequencing of a human fetus. Sci Transl Med: 2012, 4(137);137ra76 PubMed 22674554
  7. Xin Guo, Philip Bayliss, Marian Damewood, John Varney, Emily Ma, Brett Vallecillo, Ravinder Dhallan A noninvasive test to determine paternity in pregnancy. N. Engl. J. Med.: 2012, 366(18);1743-5 PubMed 22551147
  8. Mollie A Minear, Celine Lewis, Subarna Pradhan, Subhashini Chandrasekharan Global perspectives on clinical adoption of NIPT. Prenat. Diagn.: 2015; PubMed 26085345
  9. [Noninvasive prenatal testing Noninvasive prenatal testing] Volume 43, No.7, July 2014 Pages 432-434.
  10. Anthony N Imudia, Yoko Suzuki, Brian A Kilburn, Frank D Yelian, Michael P Diamond, Roberto Romero, D Randall Armant Retrieval of trophoblast cells from the cervical canal for prediction of abnormal pregnancy: a pilot study. Hum. Reprod.: 2009, 24(9);2086-92 PubMed 19497946


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


Robert Liston, Diane Sawchuck, David Young, Society of Obstetrics and Gynaecologists of Canada, British Columbia Perinatal Health Program Fetal health surveillance: antepartum and intrapartum consensus guideline. J Obstet Gynaecol Can: 2007, 29(9 Suppl 4);S3-56 PubMed 17845745

Search Pubmed

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

Search Pubmed: Prenatal Diagnosis

Prenatal Diagnosis Terms

  • ART - Assisted Reproductive Technology a general term to describe all the clinical techniques used to aid fertility.
  • 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 - (cffDNA) refers to fetal DNA circulating and isolated from the plasma portion of maternal blood.
  • 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.
  • 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.
  • pre-implantation genetic diagnosis - (PGD, pre-implantation genetic screening) a diagnostic procedure for embryos produced through Assisted Reproductive Technology (ART, in vitro fertilisation, IVF) for genetic diseases that would generate developmental abnormalities or serious postnatal diseases.
  • 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.
  • single nucleotide polymorphisms - (SNPs) the variation in a single DNA nucleotide that occurs at a specific position in the genome.
Other Terms Lists  
Terms Lists: ART | Birth | Bone | Cardiovascular | Cell Division | Gastrointestinal | Genetic | Hearing | Heart | Immune | Integumentary | Neural | Oocyte | Palate | Placenta | Renal | Spermatozoa | Ultrasound | Vision | Historic | Glossary

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

  • Mayo Clinic [ Noninvasive Prenatal Testing]

Glossary Links

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols

Cite this page: Hill, M.A. 2017 Embryology Prenatal Diagnosis. Retrieved May 25, 2017, from

What Links Here?
© Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G