Editing Prenatal testing (section)

==Purpose==
There are three purposes of prenatal diagnosis: (1) to enable timely medical or surgical treatment of a condition before or after birth, (2) to give the parents the chance to abort a fetus with the diagnosed condition, and (3) to give parents the chance to prepare psychologically, socially, financially, and medically for a baby with a health problem or disability, or for the likelihood of a stillbirth. Prior information about problems in pregnancy means that healthcare staff as well as parents can better prepare themselves for the delivery of a child with a health problem. For example, Down syndrome is associated with cardiac defects that may need intervention immediately upon birth.<ref>{{cite journal | vauthors = Versacci P, Di Carlo D, Digilio MC, Marino B | title = Cardiovascular disease in Down syndrome | journal = Current Opinion in Pediatrics | volume = 30 | issue = 5 | pages = 616–622 | date = October 2018 | pmid = 30015688 | doi = 10.1097/MOP.0000000000000661 | s2cid = 51663233 }}</ref>
{{Further|Normalized chromosome value}}

{| class="wikitable"
!
!Name of test (category)'
!When
!Invasivity
!How
!Turnaround time
!Tests/Screens for
~Associated risks
|-
! rowspan="5" |Routine prenatal tests
|Maternal weight
|Every checkup appointment
|Non-invasive
|Scale
|Immediately
|Baselines, pre-pregnancy weight estimates, tracking weight gain/loss, pattern observation
|NA
|-
|Maternal blood pressure/Preeclampsia screen<ref name="o564">{{cite journal | title=Screening for Preeclampsia: Recommendation Statement | journal=American Family Physician | volume=97 | issue=2 | date=January 15, 2018 | pages=online | url=https://www.aafp.org/pubs/afp/issues/2018/0115/od1.html | access-date=2024-08-14}}</ref>
|Every checkup appointment
|Non-Invasive
|Blood pressure cuff
|Immediately
|[[Pre-eclampsia]]/[[hypertension]]
|NA
|-
|Maternal urinalysis/urine test screen<ref>{{Cite web|date=May 26, 2019 |title=Getting a Pregnancy Urinalysis: About Prenatal Urine Tests |url=https://americanpregnancy.org/prenatal-testing/urine-test-urinalysis/ |access-date=2023-12-01 |website=American Pregnancy Association |language=en-US}}</ref>
|Periodically
|Non-invasive
|Urine collection
|~a few minutes – ~1 week
|[[Human chorionic gonadotropin|hCG]], [[diabetes]], dehydration, [[Pre-eclampsia|preeclampsia]], kidney and bladder infection/disease
|NA
|-
|[[Ultrasound]]<ref>{{Cite web|date=April 26, 2020 |title=Ultrasound: Sonogram |url=https://americanpregnancy.org/healthy-pregnancy/pregnancy-health-wellness/ultrasound/ |access-date=2023-12-01 |website=American Pregnancy Association |language=en-US}}</ref>
|Periodically
|Non-invasive/Invasive
|Abdominal or Transvaginal
|~1 day – ~1 week
|Fetal development, [[neural tube defect]]s, [[birth defect]]s, and various other physical abnormalities (see below for specific ultrasound tests)
|NA
|-
|Fetal heart-rate monitoring<ref name="urmc.rochester.edu">{{Cite web |title=External and Internal Heart Rate Monitoring of the Fetus – Health Encyclopedia – University of Rochester Medical Center |url=https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=92&contentid=P07776#:~:text=With%20internal%20monitoring,%20you%20may,scalp%20or%20other%20body%20part. |access-date=2023-12-01 |website=www.urmc.rochester.edu}}</ref>
|Week 12 – onward
|Non-invasive
|Handheld abdominal doppler or [[Fetoscopy|fetoscope]]
|Immediately
|Heart rate irregularities
|NA
|-
! Genetic prenatal tests
|Carrier screening (Screen)<ref name="www.acog.org">{{Cite web |title=Carrier Screening |url=https://www.acog.org/womens-health/faqs/carrier-screening |access-date=2023-12-01 |website=www.acog.org |language=en}}</ref>
|Anytime (before or during pregnancy)
|Less invasive
|Cheek swab or [[Venipuncture|blood draw]]
|~2–4 weeks
|Determining if a parent carries specific genes associated with certain (primarily autosomal recessive) conditions
|Very low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.
|-
|[[Chorionic villus sampling]]/Biopsy, CVS (diagnostic)<ref>{{Cite web |date=November 19, 2019 |title=Chorionic Villus Sampling (CVS) |url=https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/chorionic-villus-sampling-cvs |access-date=2023-12-01 |website=www.hopkinsmedicine.org |language=en}}</ref>
|Week 8 – 14
|Invasive
|Transabdominal or transcervical insertion of a needle, forceps or syringe to obtain a fetal placenta tissue sample
|~1–2 weeks
|Chromosomal abnormalities, birth defects
|Miscarriage, preterm labor/delivery, infection, cramping, bleeding, premature rupture of amniotic membrane, baby limb defects
|-
|Cell-free fetal DNA (cfDNA) Test/Noninvasive prenatal test (NIPT) (screen)<ref name="www.acog.org-2">{{Cite web |title=Cell-Free DNA Prenatal Screening Test |url=https://www.acog.org/womens-health/infographics/cell-free-dna-prenatal-screening-test |access-date=2023-12-01 |website=www.acog.org |language=en}}</ref>
|Week 10 – onward
|Less invasive
|Blood draw
|~1–2 weeks
|Gender, chromosomal abnormalities
|Very low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.
|-
|First trimester screening<ref name="www.acog.org-3">{{Cite web |title=Prenatal Genetic Screening Tests |url=https://www.acog.org/womens-health/faqs/prenatal-genetic-screening-tests |access-date=2023-12-01 |website=www.acog.org |language=en}}</ref>
|Week 10 – 13
|Invasive
|Nuchal translucency ultrasound & blood prick/draw
|~1 week
|Chromosomal abnormalities, birth defects, heart defects
|Very low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.
|-
|Alpha-fetoprotein (AFP)/modified sequential/multiple marker/quad/triple/maternal serum test (screen)<ref>{{Cite web |title=Alpha-fetoprotein (AFP) Screening Test – Health Encyclopedia – University of Rochester Medical Center |url=https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=90&contentid=p02426 |access-date=2023-12-01 |website=www.urmc.rochester.edu}}</ref>
|Weeks 14 – 22
|Less invasive
|Blood draw
|~1–2 weeks
|Maternal hormone levels, risk of gestational hypertension and preeclampsia, chromosome abnormalities, neural tube defects
|Very low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.
|-
|Second trimester screening (screen)<ref>{{Cite web |title=Second Trimester Prenatal Screening Tests – Health Encyclopedia – University of Rochester Medical Center |url=https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=90&contentid=P08956 |access-date=2023-12-01 |website=www.urmc.rochester.edu}}</ref>
|Week 15 – 22
|Invasive
|Ultrasound and multiple markers or quad screen blood draw
|~1–2 weeks
|Chromosomal abnormalities, neural tube defects, abdominal wall defects, heart defects, other major physical defects
|Very low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.
|-
|[[Amniocentesis]] (diagnostic)<ref>{{Cite web |title=Weekly appointments – Obstetrics {{!}} Northwell Health |url=https://www.northwell.edu/obstetrics-and-gynecology/obstetrics/what-to-expect/weekly-appointments |access-date=2023-12-01 |website=www.northwell.edu |language=en}}</ref><ref>{{Cite web |date=August 8, 2021 |title=Amniocentesis |url=https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/amniocentesis |access-date=2023-12-01 |website=www.hopkinsmedicine.org |language=en}}</ref>  
|Week 15 – 20
|Invasive
|Transabdominal needle insertion to obtain an amniotic fluid sample
|~2 weeks
|Chromosomal abnormalities, autosomal recessive conditions, neural tube defects, abdominal wall defects, birth defects
|Miscarriage (1%), preterm labor/delivery, infection, cramping, bleeding, premature rupture of amniotic membrane
|-
|[[Percutaneous umbilical cord blood sampling|Cordocentesis/Percutaneous umbilical cord blood sampling]] (PUBS) (diagnostic)<ref name="American Pregnancy Association-2020">{{Cite web|date=August 26, 2020 |title=Cordocentesis : Percutaneous Umbilical Blood Sampling (PUBS) |url=https://americanpregnancy.org/prenatal-testing/cordocentesis/ |access-date=2023-12-01 |website=American Pregnancy Association |language=en-US}}</ref>
|Week 17 – onward
|Invasive
|Fetal blood sample from umbilical cord
|~3 days
|Chromosomal abnormalities, blood disorders (fetal hemolytic disease)
|Miscarriage (1–2%), preterm labor/delivery, infection, bleeding, decreased fetal heart rate, premature rupture of amniotic membrane, death
|-
|[[Preimplantation genetic diagnosis]] (PGD) (screen)<ref>{{Cite web |last=England |first=Care New |title=Embryo Preimplantation Genetic Testing (PGT) {{!}} Fertility Center |url=https://fertility.womenandinfants.org/treatment/preimplantation-genetic-testing |access-date=2023-12-01 |website=fertility.womenandinfants.org |language=en}}</ref>
|During IVF, prior to implantation
|Non-invasive
|IVF ebryo examination
|~1–2 weeks
|Chromosomal abnormalities, autosomal recessive conditions
|NA
|-
! Additional prenatal tests
|Glucose challenge test (screen)
|Week 26 – 28
|Less invasive
|Maternal blood draw after ingestion of glucose drink
|~1–2 days
|To indicate the possibility of gestational diabetes
|Very low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.
|-
|[[Glucose tolerance test|Oral Glucose Tolerance Test]] (Screen)<ref>{{Cite web |title=Tests & Diagnosis for Gestational Diabetes – NIDDK |url=https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes/gestational/tests-diagnosis |access-date=2023-12-01 |website=National Institute of Diabetes and Digestive and Kidney Diseases |language=en-US}}</ref>
|Week 26 – 28
|Less invasive
|Maternal blood draws before and after ingestion of glucose drink, requires fasting
|~2–3 days
|To properly diagnose gestational diabetes following an abnormal result from the glucose challenge screen
|Very low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.
|-
|Non-stress test<ref>{{Cite web|date=April 26, 2012 |title=Fetal Non-Stress Test (NST) |url=https://americanpregnancy.org/healthy-pregnancy/pregnancy-health-wellness/non-stress-test/ |access-date=2023-12-01 |website=American Pregnancy Association |language=en-US}}</ref>
|Week 28 – onward
|Non-invasive
|Abdominal contraction/Fetal heart rate belt
|Immediately
|Fetal heart rate vs movement, oxygen levels (indicating problems stemming from the placenta or umbilical cord), fetal distress
|NA
|-
|Group B Strep Test<ref>{{Cite web |title=Group B Strep and Pregnancy |url=https://www.acog.org/womens-health/faqs/group-b-strep-and-pregnancy |access-date=2023-12-01 |website=www.acog.org |language=en}}</ref>
|Week 36 – 38
|Invasive
|Vaginal swab
|~1–2 days
|Bacteria indicating Group B Strep
|NA
|-
|Cervix dialation check<ref>{{Citation |last1=Hutchison |first1=Julia |title=Stages of Labor |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK544290/ |work=StatPearls |access-date=2023-12-01 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31335010 |last2=Mahdy |first2=Heba |last3=Hutchison |first3=Justin}}</ref>
|Week 37 – onward
|Invasive
|The doctor takes a manual measurement inside the cervix
|Immediately
|Signs or progress of dialation, prodromal labor
|Infection, premature rupture of amniotic membrane
|-
|External fetal monitoring<ref name="urmc.rochester.edu"/>
|During Labor, after rupture of amnioatic sac
|Invasive
|Spiral wire electrode attached to body part (typically the scalp) of fetus via cervical insertion
|Immediately
|Heart rate irregularities, monitoring fetal heart rate
|Fetal bruising/infection at attachment site
|-
|[[Kleihauer–Betke test|Kleihauer-Betke/Fetal cells in maternal blood]] (FCMB) test (screen)<ref>{{Cite web |title=Kleihauer test |url=https://www.gloshospitals.nhs.uk/our-services/services-we-offer/pathology/tests-and-investigations/kleihauer-test/ |access-date=2023-12-01 |website=Gloucestershire Hospitals NHS Foundation Trust |language=en}}</ref>
|Situational
|Less invasive
|Blood draw
|<1 day
|Fetal red blood cells in the mother's blood, fetomaternal hemorrhage
|Very low risk, however there is the potential for bruising, pain, nerve damage, fainting, haematoma, bacterial infection, and bloodborne pathogen exposure.
|}

=== Prenatal screening ===

==== Maternal serum screening ====
First-trimester maternal serum screening can check levels of free β-[[human chorionic gonadotropin|hCG]], [[Pregnancy-associated plasma protein A|PAPP-A]], intact or beta hCG, or h-hCG in the woman's [[blood plasma|serum]], and combine these with the measurement of [[nuchal translucency]] (NT). Some institutions also look for the presence of a fetal nasalbone on the ultrasound.{{cn|date=February 2025}}

Second-trimester maternal serum screening ([[AFP screening]], triple screen, quad screen, or penta screen) can check levels of [[alpha fetoprotein]], β-[[human chorionic gonadotropin|hCG]], [[inhibin]]-A, [[estriol]], and h-hCG (hyperglycosolated hCG) in the woman's [[blood plasma|serum]].{{cn|date=February 2025}}

The [[triple test]] measures [[Blood serum|serum]] levels of [[Alpha-fetoprotein|AFP]], [[estriol]], and [[beta-hCG]], with a 70% [[sensitivity and specificity|sensitivity]] and 5% [[false-positive]] rate. It is complemented in some regions of the United States, as the ''Quad test'' (adding inhibin A to the panel, resulting in an 81% sensitivity and 5% false-positive rate for detecting [[Down syndrome]] when taken at 15–18 weeks of [[Gestational age (obstetrics)|gestational age]]).<ref>{{cite journal |vauthors=Lao MR, Calhoun BC, Bracero LA, Wang Y, Seybold DJ, Broce M, Hatjis CG |year=2009 |title=The ability of the quadruple test to predict adverse perinatal outcomes in a high-risk obstetric population |journal=[[Journal of Medical Screening]] |volume=16 |issue=2 |pages=55–9 |doi=10.1258/jms.2009.009017 |pmid=19564516 |s2cid=23214929}}</ref>

The biomarkers [[PAPP-A]] and β-[[human chorionic gonadotropin|hCG]] seem to be altered for pregnancies resulting from ICSI, causing a higher false-positive rate. Correction factors have been developed and
should be used when screening for Down's syndrome in singleton pregnancies after ICSI,<ref name="Gjerris2012">{{cite journal |vauthors=Gjerris AC, Tabor A, Loft A, Christiansen M, Pinborg A |date=July 2012 |title=First trimester prenatal screening among women pregnant after IVF/ICSI |journal=Human Reproduction Update |volume=18 |issue=4 |pages=350–9 |doi=10.1093/humupd/dms010 |pmid=22523111 |doi-access=free}}</ref> but in twin pregnancies such correction factors have not been fully elucidated.<ref name="Gjerris2012" /> In [[vanishing twin]] pregnancies with a second gestational sac with a dead fetus, first-trimester screening should be based solely on the maternal age and the nuchal translucency scan as biomarkers are altered in these cases.<ref name="Gjerris2012" />

==== Advances in prenatal screening ====
Measurement of [[fetal protein]]s in maternal serum is a part of standard prenatal screening for [[Diagnosis of fetal aneuploidy|fetal aneuploidy]] and [[neural tube defects]].<ref>{{cite journal |display-authors=6 |vauthors=Ball RH, Caughey AB, Malone FD, Nyberg DA, Comstock CH, Saade GR, Berkowitz RL, Gross SJ, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, Emig D, D'Alton ME |date=July 2007 |title=First- and second-trimester evaluation of risk for Down syndrome |journal=Obstetrics and Gynecology |volume=110 |issue=1 |pages=10–7 |doi=10.1097/01.AOG.0000263470.89007.e3 |pmid=17601890 |s2cid=10885982}}</ref><ref>{{cite journal |vauthors=Dashe JS, Twickler DM, Santos-Ramos R, McIntire DD, Ramus RM |date=December 2006 |title=Alpha-fetoprotein detection of neural tube defects and the impact of standard ultrasound |url=http://rc.kfshrc.edu.sa/rcf/E_Library/NTDR/Alphafeto%20protein%20detection..pdf |url-status=dead |journal=American Journal of Obstetrics and Gynecology |volume=195 |issue=6 |pages=1623–8 |doi=10.1016/j.ajog.2006.03.097 |pmid=16769022 |archive-url=https://web.archive.org/web/20111001101304/http://rc.kfshrc.edu.sa/rcf/E_Library/NTDR/Alphafeto%20protein%20detection..pdf |archive-date=October 1, 2011 |access-date=November 12, 2010}}</ref> Computational predictive model shows that extensive and diverse feto-maternal protein trafficking occurs during pregnancy and can be readily detected non-invasively in maternal [[whole blood]].<ref>{{cite journal |vauthors=Maron JL, Alterovitz G, Ramoni M, Johnson KL, Bianchi DW |date=December 2009 |title=High-throughput discovery and characterization of fetal protein trafficking in the blood of pregnant women |journal=Proteomics. Clinical Applications |volume=3 |issue=12 |pages=1389–96 |doi=10.1002/prca.200900109 |pmc=2825712 |pmid=20186258}}</ref> This computational approach circumvented a major limitation, the abundance of maternal proteins interfering with the detection of fetal proteins, to fetal proteomic analysis of maternal blood. Entering fetal gene transcripts previously identified in maternal whole blood into a computational predictive model helped develop a comprehensive proteomic network of the term neonate. It also shows that the fetal proteins detected in pregnant woman's blood originate from a diverse group of tissues and organs from the developing fetus. Development proteomic networks dominate the functional characterization of the predicted proteins, illustrating the potential clinical application of this technology as a way to monitor normal and abnormal fetal development.{{cn|date=February 2025}}

The difference in [[DNA methylation|methylation]] of specific DNA sequences between mother and fetus can be used to identify fetal-specific DNA in the blood circulation of the mother. In a study published in the March 6, 2011, online issue of ''[[Nature (journal)|Nature]]'', using this non-invasive technique a group of investigators from Greece and UK achieved correct diagnosis of 14 [[trisomy 21]] ([[Down syndrome]]) and 26 normal cases.<ref>{{cite journal |vauthors=Papageorgiou EA, Karagrigoriou A, Tsaliki E, Velissariou V, Carter NP, Patsalis PC |date=April 2011 |title=Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21 |journal=Nature Medicine |volume=17 |issue=4 |pages=510–3 |doi=10.1038/nm.2312 |pmc=3977039 |pmid=21378977}}</ref><ref>{{cite web |title=A New Non-invasive Test for Down Syndrome:Trisomy 21 Diagnosis using Fetal-Specific DNA Methylation |url=http://www.sciguru.com/newsitem/6740/A-New-Non-invasive-Test-for-Down-SyndromeTrisomy-21-Diagnosis-using-Fetal-Specific-DNA-Methylation/ |access-date=March 8, 2011 |publisher=SciGuru.com}}</ref> Using [[massive parallel sequencing]], a study testing for trisomy 21 only, successfully detected 209 of 212 cases (98.6%) with 3 false-positives in 1,471 pregnancies (0.2%).<ref name="Palomaki" /> With commercially available non-invasive (blood) testing for Down syndrome having become available to patients in the United States and already available in China, in October 2011, the International Society for Prenatal Diagnosis created some guidance. Based on its [[sensitivity and specificity]], it constitutes an advanced screening test and that positive results require confirmation by an invasive test, and that while effective in the diagnosis of Down syndrome, it cannot assess half the abnormalities detected by invasive testing. The test is not recommended for general use until results from broader studies have been reported, but may be useful in high-risk patients in conjunction with genetic counseling.<ref name="ISPD" />

A study in 2012 found that the maternal plasma cell-free DNA test was also able to detect trisomy 18 (Edwards syndrome) in 100% of the cases (59/59) at a false-positive rate of 0.28%, and trisomy 13 (Patau syndrome) in 91.7% of the cases (11/12) at a false-positive rate of 0.97%. The test interpreted 99.1% of samples (1,971/1,988); among the 17 samples without an interpretation, three were trisomy 18. The study stated that if z-score cutoffs for trisomy 18 and 13 were raised slightly, the overall false-positive rates for the three aneuploidies could be as low as 0.1% (2/1,688) at an overall detection rate of 98.9% (280/283) for common aneuploidies (this includes all three trisomies: Down, Edwards and Patau).<ref>{{cite journal |display-authors=6 |vauthors=Palomaki GE, Deciu C, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Grody WW, Nelson SF, Canick JA |date=March 2012 |title=DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study |journal=Genetics in Medicine |volume=14 |issue=3 |pages=296–305 |doi=10.1038/gim.2011.73 |pmc=3938175 |pmid=22281937}}</ref>

=== Prenatal genetic testing ===
{{Multiple issues|section=yes|{{more medical citations needed|section|date=July 2015}}
{{more citations needed section|date=July 2015}}
{{original research|section|date=July 2015}}}}
The goal of prenatal genetic testing is to identify pregnancies at high risk of abnormalities, allowing for early intervention, termination or appropriate management and preparation measures.<ref>{{Cite journal |last1=Jelin |first1=Angie C. |last2=Sagaser |first2=Katelynn G. |last3=Wilkins-Haug |first3=Louise |date=April 1, 2019 |title=Prenatal Genetic Testing Options |url=https://www.sciencedirect.com/science/article/pii/S0031395518302037 |journal=Pediatric Clinics of North America |series=Current Advances in Neonatal Care |language=en |volume=66 |issue=2 |pages=281–293 |doi=10.1016/j.pcl.2018.12.016 |issn=0031-3955 |pmid=30819336 |s2cid=73470036|url-access=subscription }}</ref> Prenatal genetic testing can be subdivided into two categories: screening and diagnostic testing. Screening informs an individual of the potential for certain abnormalities occurring, whereas, diagnostic testing is used to confirm/diagnose that specific abnormalities exist within the fetus. Prenatal screens are typically less invasive than prenatal diagnostic tests. Screening comes with much lower risks, however, the results are not as definitive as diagnostic tests. Providers often recommend following up with a diagnostic test upon receipt of a positive result from a specific screen.<ref>{{Cite journal |last1=Jenkins |first1=Morgan |last2=Seasely |first2=Angela R. |last3=Subramaniam |first3=Akila |date=December 2022 |title=Prenatal genetic testing 1: screening tests |url=https://journals.lww.com/co-pediatrics/abstract/2022/12000/prenatal_genetic_testing_1__screening_tests.5.aspx. |journal=Current Opinion in Pediatrics |language=en-US |volume=34 |issue=6 |pages=544 |doi=10.1097/MOP.0000000000001172 |issn=1040-8703|url-access=subscription }}</ref>

Medically invasive techniques are those in which a tool is used to access something inside the body. There are varying degrees of invasiveness, depending on what specimen is required to complete the test. The typical blood draw administered by a healthcare professional is one of the most common invasive medical practices.<ref>{{Citation |title=Best practice in phlebotomy and blood collection |date=March 2010 |url=https://www.ncbi.nlm.nih.gov/books/NBK138496/ |work=WHO Best Practices for Injections and Related Procedures Toolkit |access-date=2023-12-01 |publisher=World Health Organization |language=en}}</ref> Since it causes minimal discomfort and there is very low risk associated with the sample collection, a blood draw is considered less invasive. Chorionic villus sampling (CVS) and Amniocentesis are the most invasive prenatal tests because there is greater associated risk and the sample is more difficult to access. These procedures are done via needle insertion into the abdomen to collect a sample within the uterus, meaning exceptional care/precision is required.<ref>{{Cite web |last=Medicine |first=Northwestern |title=Prenatal Genetic Testing |url=https://www.nm.org/conditions-and-care-areas/womens-health/obgyn/obstetrics/prenatal-care/prenatal-genetic-testing |access-date=2023-12-01 |website=Northwestern Medicine |language=en-US}}</ref>
Prenatal genetic testing can identify various chromosomal abnormalities, autosomal conditions, various birth defects, and some fetal blood disorders.

[[Chromosomal abnormalities]] are when the chromosomes differ in either structure or number when compared to a typical reference genome. This includes chromosomal deletions, duplications, inversions, and translocations.<ref>{{Cite web |title=What is a chromosome condition? |url=https://www.yourgenome.org/theme/what-is-a-chromosome-condition/ |access-date=2025-03-25 |website=@yourgenome · Science website |language=en-GB}}</ref>  Some examples of chromosomal abnormalities include:
* [[Down syndrome]] (trisomy 21)
* [[Edwards syndrome]] (trisomy 18)
* [[Patau syndrome]] (trisomy 13)
* [[Turner syndrome]] (monosomy X)
* [[Klinefelter syndrome]] (XXY)
* [[Trisomy X]] (XXX)
* [[Jacobs syndrome]] (XYY)
* [[Pallister–Killian syndrome]]
* [[Wolf–Hirschhorn syndrome]]
* [[Cri du chat syndrome|Cri-du-chat syndrome]]
* [[WAGR syndrome]]
* [[DiGeorge syndrome]]
* [[Fragile X syndrome]]
– Prader-Willi/Angelman syndrome

[[Dominance (genetics)|Autosomal recessive]] conditions occur when both parents pass on a mutation within an autosomal (non-sex) chromosome.<ref>{{Cite web |title=Carrier Test for Autosomal Recessive Conditions Video & Image |url=https://www.columbiadoctors.org/health-library/multimedia/carrier-test-autosomal-recessive-conditions/ |access-date=2023-12-01 |website=www.columbiadoctors.org}}</ref>  Some examples of autosomal recessive conditions are:
* [[Cystic fibrosis]]
* [[Sickle cell disease|Sickle cell anemia]]
* [[Tay–Sachs disease]]
* [[Spinal muscular atrophy]]
* [[Autosomal recessive polycystic kidney disease]]
* [[Phenylketonuria]]

[[Neural tube defect]]s are a type of birth defect that occurs when the neural tube of a fetus does not form/close properly, potentially effecting other systems throughout the body.<ref>{{Cite web |title=Neural Tube Defects – Causes, Types, Treatment & More {{!}} CHOC |url=https://www.choc.org/neuroscience/neural-tube-defects/ |access-date=2023-12-01 |website=Children's Hospital of Orange County |language=en}}</ref>  Some examples of neural tube defects are:
* [[Spina bifida]]
* [[Anencephaly]]
* [[Encephalocele]]
* [[Tethered spinal cord syndrome]]

[[Abdominal wall defect]]s are a type of birth defect that occur when the abdominal wall of a fetus does not form properly, potentially effecting other organs throughout the body.<ref>{{Cite web |title=List of fetal abdominal wall defects with links to each condition |url=https://www.fetalhealthfoundation.org/fetal-syndromes/abdominal-wall-defect/ |access-date=2023-12-01 |website=Fetal Health Foundation |language=en-US}}</ref>  Some examples of abdominal wall defects are:
* [[Gastroschisis]]
* [[Omphalocele]]
* [[Bladder exstrophy]]
* [[Cloacal exstrophy]]
* [[Ectopia cordis]]
* [[Pentalogy of Cantrell]]
* Body-stalk anomaly

Blood disorders can occur from a negative interaction between the maternal blood and the fetal blood.<ref>{{Cite web |title=Hemolytic Disease of the Fetus and Newborn (HDFN) |url=https://www.nationwidechildrens.org/conditions/hemolytic-disease-of-the-fetus-and-newborn-hdfn |access-date=2023-12-01 |website=www.nationwidechildrens.org |language=en}}</ref> An example of a fetal blood disorder is [[Hemolytic disease of the newborn|Hemolytic disease of the fetus]].

=== Ultrasound imaging and serum markers as indications for genetic testing ===
Ultrasound imaging provides the opportunity to conduct a nuchal translucency (NT) scan screening for chromosomal abnormalities such as [[Down syndrome]] (trisomy 21), Edwards syndrome (trisomy 18), and [[Patau syndrome]] (trisomy 13). Using the information from the NT scan the mother can be offered an invasive diagnostic test for fetal chromosomal abnormalities. Serum markers are used in a similar fashion to identify gestations that should be recommended for further testing. When the NT scan or serum markers arouse suspicion for chromosomal abnormalities the following genetic tests may be conducted on fetal or placental tissue samples: Interphase-[[fluorescence in situ hybridization]] (FISH), [[quantitative PCR]] and [[Chorionic villus sampling|direct preparation of chromosomes from chorionic villi]].<ref name="Ref2">{{cite journal |vauthors=Miny P, Tercanli S, Holzgreve W |date=April 2002 |title=Developments in laboratory techniques for prenatal diagnosis |journal=Current Opinion in Obstetrics & Gynecology |volume=14 |issue=2 |pages=161–8 |doi=10.1097/00001703-200204000-00010 |pmid=11914694 |s2cid=40591216}}</ref>

=== Screens ===

====Carrier screening  ====
Carrier screening is a general DNA test that uses a blood or cheek swab sample to determine if the parents carry certain genetic conditions. This test can be done anytime, whether the individual(s) are considering starting a family or have already become pregnant. Various types of carrier screens are available that test for progressively more genetic abnormalities. The single gene/condition screen will test for a specific condition, whereas, the expanded carrier screen will test for hundreds of different abnormalities that can be inherited by a fetus. There are also three gene/condition and ethnic specific carrier tests. In the case of a positive test result, further testing is often recommended, as the carrier test only determines if the parent(s) is a carrier, not if the gene has definitively been passed to the fetus.<ref name="www.acog.org" />

==== Placental acellular DNA (pa-DNA) ====
Placental acellular (fetal cell-free) DNA testing (pa-DNA) allows for the detection of apoptotic placental cells and placental DNA circulating in maternal blood for the noninvasive diagnosis of fetal aneuploidy.<ref name="Ref2" /><ref name="Taglauer-2014">{{cite journal |vauthors=Taglauer ES, Wilkins-Haug L, Bianchi DW |date=February 2014 |title=Review: cell-free fetal DNA in the maternal circulation as an indication of placental health and disease |journal=Placenta |volume=35 Suppl |issue=Suppl |pages=S64-8 |doi=10.1016/j.placenta.2013.11.014 |pmc=4886648 |pmid=24388429}}</ref> A meta-analysis that investigated the success rate of using placental acellular DNA from maternal blood to screen for aneuploidies found that this technique detected trisomy 13 in 99% of the cases, trisomy 18 in 98% of the cases and trisomy 21 in 99% of the cases.<ref name="Taglauer-2014" /><ref>{{Cite journal |last1=Gil |first1=M. M. |last2=Galeva |first2=S. |last3=Jani |first3=J. |last4=Konstantinidou |first4=L. |last5=Akolekar |first5=R. |last6=Plana |first6=M. N. |last7=Nicolaides |first7=K. H. |date=June 2019 |title=Screening for trisomies by cfDNA testing of maternal blood in twin pregnancy: update of The Fetal Medicine Foundation results and meta-analysis |journal=Ultrasound in Obstetrics & Gynecology |volume=53 |issue=6 |pages=734–742 |doi=10.1002/uog.20284 |issn=1469-0705 |pmid=31165549 |doi-access=free|hdl=10641/1656 |hdl-access=free }}</ref> Failed tests using placental acellular DNA are more likely to occur in fetuses with trisomy 13 and trisomy 18 but not with trisomy 21.<ref>{{cite journal |vauthors=Revello R, Sarno L, Ispas A, Akolekar R, Nicolaides KH |date=June 2016 |title=Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result |journal=Ultrasound in Obstetrics & Gynecology |volume=47 |issue=6 |pages=698–704 |doi=10.1002/uog.15851 |pmid=26743020 |doi-access=free}}</ref> Previous studies found elevated levels of acellular placental DNA for trisomy 13 and 21 from maternal serum when compared to women with euploid pregnancies.<ref name="Wataganara-2003">{{Cite journal |last1=Wataganara |first1=T |last2=LeShane |first2=ES |display-authors=etal |year=2003 |title=Maternal serum cell-free fetal DNA levels are increased in cases of trisomy 13 but not trisomy 18. – PubMed – NCBI |journal=Human Genetics |language=en |volume=112 |issue=2 |pages=204–8 |doi=10.1007/s00439-002-0853-9 |pmid=12522563 |s2cid=9721963}}</ref><ref>{{cite journal |vauthors=Lee T, LeShane ES, Messerlian GM, Canick JA, Farina A, Heber WW, Bianchi DW |date=November 2002 |title=Down syndrome and cell-free fetal DNA in archived maternal serum |journal=American Journal of Obstetrics and Gynecology |volume=187 |issue=5 |pages=1217–21 |doi=10.1067/mob.2002.127462 |pmid=12439507 |s2cid=31311811}}</ref><ref>{{cite journal |display-authors=6 |vauthors=Lo YM, Lau TK, Zhang J, Leung TN, Chang AM, Hjelm NM, Elmes RS, Bianchi DW |date=October 1999 |title=Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21 |journal=Clinical Chemistry |volume=45 |issue=10 |pages=1747–51 |doi=10.1093/clinchem/45.10.1747 |pmid=10508120 |doi-access=free}}</ref><ref name="Lo-2009">{{cite journal |vauthors=Lo YM |date=January 2009 |title=Noninvasive prenatal detection of fetal chromosomal aneuploidies by maternal plasma nucleic acid analysis: a review of the current state of the art |journal=BJOG |volume=116 |issue=2 |pages=152–7 |doi=10.1111/j.1471-0528.2008.02010.x |pmid=19076946 |s2cid=6946087}}</ref> However, an elevation of acellular DNA for trisomy 18 was not observed.<ref name="Wataganara-2003" /> Circulating placental nucleated cells comprise only three to six percent of maternal blood plasma DNA, reducing the detection rate of fetal developmental abnormalities.<ref name="Lo-2009" /> Two alternative approaches have been developed for the detection of fetal aneuploidy. The first involves the measuring of the [[Allele|allelic ratio]] of [[single nucleotide polymorphism]]s (SNPs) in the [[mRNA]] coding region in the [[placenta]]. The next approach is analyzing both maternal and placental DNA and looking for differences in the [[DNA methylation]] patterns.<ref name="www.acog.org-2" /><ref name="Lo-2009" />

==== First/Second/Third trimester Screen ====
The first, second, combined, and third trimester screens typically consist of an ultrasound (abdominal and/or transvaginal) and maternal blood/serum testing. The ultrasound is used to visually assess the growth, development, and activity of the fetus through imaging observations and measurements. The ultrasound portion of the first trimester screen can include a nuchal translucency screen and a fetal nasal bone determination screen. The available blood tests from the first trimester screen can test for plasma protein A and human chorionic gonadotropin. The second trimester screen looks at specific blood markers, to include the estriol, inhibin and human chorionic gonadotropin hormones and often consists of Alpha-fetoprotein (AFP) screening. Any abnormal results from these screening tests can indicate the possibility of abnormal conditions such as Trisomy 18, Trisomy 21 (Down syndrome), and spina bifida.<ref name="www.acog.org-3" />

==== Alpha-fetoprotein (AFP)/multiple marker test ====
The AFP test is often done in the second trimester using the serum from the maternal blood draw. This test looks at a specific protein that is formed in the liver of the fetus and released into the fluid contents of the womb, which is then absorbed into the mother's blood stream. Multiple determinations stem from the results of AFP testing. Genetically, it can expose chromosomal and neural defects.<ref name="www.hopkinsmedicine.org-2021">{{Cite web |date=August 8, 2021 |title=Common Tests During Pregnancy |url=https://www.hopkinsmedicine.org/health/wellness-and-prevention/common-tests-during-pregnancy |access-date=2023-12-01 |website=www.hopkinsmedicine.org |language=en}}</ref>

=== Diagnostic tests ===

==== Chorionic Villus Sampling (CVS) ====
CVS is an invasive diagnostic test that can be done during the first trimester of pregnancy for individuals that are looking to identify or are at higher risk of passing chromosomal abnormalities. A tissue cell sample of the placenta is obtained abdominally via needle or via vaginal insertion of a catheter/syringe into the cervix in combination with ultrasound to guide the procedure. Positive results from CVS require blood testing for confirmation.<ref name="www.hopkinsmedicine.org-2021" />

==== Amniocentesis ====
Amniocentesis is an invasive diagnostic test that can be done during the second trimester of pregnancy for individuals that are looking to identify or are at higher risk of passing chromosomal and/or neural tube abnormalities. The procedure is typically done via needle, in combination with ultrasound for guidance, to obtain a sample of the amniotic fluid surrounding the fetus.<ref name="www.hopkinsmedicine.org-2021" />

==== Cordocentesis/Percutaneous umbilical blood sampling (PUBS) ====
PUBS is an invasive diagnostic test that can be done during the second trimester of pregnancy for individuals that are looking to identify or are at higher risk of passing chromosomal and/or blood abnormalities. The demand for cordocentesis tests is diminishing because it has been replaced with CVS and Amniocentesis, which carry less risk. The procedure is typically done via needle into the mother's abdomen, in combination with ultrasound for guidance, to obtain a blood sample from the umbilical cord of the fetus.<ref name="American Pregnancy Association-2020" />