Prenatal Screening and Diagnosis

  • Diagnosis
  • Algorithms
  • Screening
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

  • Diagnostic testing for chromosome abnormalities and open neural tube defects (ONTD) should be offered to all women; those at high risk for either a chromosome abnormality or ONTD should have more extensive counseling
    • High risk includes
      • Previous pregnancy with chromosome disorder (eg, Down syndrome [DS] or trisomy 18 [T18])
      • Either parent is a known carrier of a genetic translocation or inversion
      • Maternal age ≥35 years at estimated date of delivery (EDD)
      • Abnormal ultrasound or fetal findings
      • Increased risk of ONTD due to family history, patient use of specific medications (eg, valproic acid or carbamazepine), or diabetic status
  • Amniocentesis or chorionic villus sampling (CVS) confirms diagnosis suggested by screening tests
    • CVS – 10-13 weeks
      • Examines fetal chromosomes only; uses placental tissue
      • Not appropriate for patients at increased risk for ONTD
    • Amniocentesis – ≥15weeks
      • Examines fetal chromosomes
      • Amniotic fluid alpha-fetoprotein concentration and acetylcholinesterase testing available to assist in the diagnosis of fetal ONTD

 

Prenatal Screening Test Information
Test Recommended for Purpose

First trimester (combined) screen

Maternal screen, first trimester

Order during the first trimester (between 11w0d and 13w6d gestation)

Crown-rump length (CRL) must be between 42-85 mm and an NT measurement must be obtained

Use when mother accepts higher SPR and wants results in the first trimester

Does not detect ONTD

Sequential screen combines first and second trimester screening results

First specimen drawn between 11w0d and 13w6d gestation

CRL must be between 42-85 mm and an NT measurement must be obtained

Second specimen drawn between 15w0d and 24w6d

Specimen 1 measures PAPP-A and total hCG

Specimen 2 measures AFP, uE3, hCG, and DIA

Screens for DS, T18, ONTD

An interpretation is provided after the first draw so that pregnancies at very high risk for DS can be identified in the first trimester

Patients who are at intermediate or low risk after the first draw go on for the second draw and the complete screen

Integrated screen, combines first and second trimester screening results

First specimen drawn between 10w0d and 13w6d gestation

CRL must be between 32-85 mm (an NT measurement is optional for this test – must be obtained when the CRL is between 36-85)

Second specimen drawn between 15w0d and 24w6d

Serum-only tests – do not round gestational age to nearest week; use EDD to avoid clerical errors

Specimen 1 measures PAPP-A

Specimen 2 measures AFP, uE3, hCG, and DIA

Screens for DS, T18, ONTD

When combined with a first trimester certified US for NT, this test yields the best detection rate and lowest false-positive rate of all prenatal screens

Can be run without an NT (serum integrated) yielding the same detection rate with a slightly higher false-positive rate

Single Screen

(Maternal serum screen, alpha fetoprotein only)

Women who have had early amniocentesis, CVS, or first trimester screening

Ideal time period is 16-18 wks gestation; however, reference medians are available from 14w0d to 24w6d

Do not round gestational age to nearest week; use EDD to avoid clerical errors

Screen for fetal risk of ONTD at 14-25 wks

Quad Screen

Maternal serum screen, alpha fetoprotein, hCG, estriol, and inhibin A

ACOG recommends the quad for second trimester aneuploidy screening

Offer to patients who

  • Present initially for second trimester
  • Do not wish to have first trimester screening
  • Did not have access to first trimester screening

Quad is the most economical prenatal screening test for aneuploidy

Ideal time period is 16-18 wks gestation; however, reference medians are available from 14w0d to 24w6d

Do not round gestational age to nearest week; use EDD to avoid clerical errors

Quad screen for fetal risk of DS, T18, and ONTD

Better detection rate at a lower false-positive rate than the triple screen

Best second trimester screen available

Noninvasive prenatal testing (NIPT) for fetal aneuploidy

Can be performed as early as 9.0 wks gestation

Offer to patients who are considered to be at increased risk for one of the common fetal aneuploidy disorders: trisomy 13, 18, 21, or Turner syndrome (TS)

Women are considered to be at increased risk when

  • Patient ≥35 yrs at EDD
  • Patient had a previous child with aneuploidy
  • Patient’s current fetus has US abnormalities associated with trisomy 13, 18, 21, or TS

Patient has screened positive by serum screening (± NT)

Highly sensitive screening test for specific fetal aneuploidies

Intended to identify women with a current pregnancy at risk for trisomy 13, 18, 21, or TS; may also identify fetuses with other sex-chromosome aneuploidies or triploidy

Women carrying a fetus with US abnormalities who screen negative by NIPT should be offered diagnostic testing (ie, fetal karyotype and/or fetal microarray by CVS or amniocentesis)

All positive NIPT results should be confirmed by fetal karyotype

 

Prenatal Diagnosis – Amniotic Fluid and Chromosome Analyses
Test Recommended for Purpose
Chromosome Analysis, Chorionic Villus Sampling (CVS)

Indications include

  • Patient desires diagnostic testing instead of screening
  • Advanced maternal age (patient ≥35 yrs at EDD)
  • Abnormal first trimester screen for DS or T18
  • Fetal US abnormalities
  • Family history of chromosome abnormality or genetic disorder
Prenatal diagnosis in pregnant patient at 10-13 wks gestation
Chorionic Villus, FISH

Rapid detection of aneuploidy involving chromosomes 13, 18, 21, X, and Y

Preliminary results usually available within 48 hours of sample receipt by lab

Order in conjunction with fetal chromosome studies
Chromosome Analysis, Amniotic Fluid

Indications include

  • Patient desires diagnostic testing instead of screening
  • Advanced maternal age (patient ≥35 yrs at EDD)
  • Abnormal maternal screen for ONTD, DS, or T18
  • Fetal ultrasound abnormalities
  • Family history of chromosome abnormality or genetic disorder

Prenatal diagnosis in patient >14 wks gestation

Amniocentesis is discouraged <15 wks gestation due to high rates of fetal loss, leakage of amniotic fluid, and increased risk of club foot

Chromosome Analysis, Prenatal FISH

Rapid detection of aneuploidy involving chromosomes 13, 18, 21, X, and Y

Preliminary results usually available within 48 hours of sample receipt by lab

Order in conjunction with fetal chromosome studies
Fetal Cytogenomic SNP Microarray

Indications include

  • Clarification of an abnormal fetal karyotype requiring further characterization
  • Abnormal ultrasound findings with a normal karyotype
  • Family history of a known or suspected chromosomal abnormality that is best evaluated by microarray

Submission of a maternal blood sample for maternal cell contamination studies is encouraged

Detection of unbalanced chromosomal abnormalities (copy number gain/loss) and absence of heterozygosity in amniotic fluid and CVS samples
Amniotic Fluid AFP with Reflex to Acetylcholinesterase

Indications include

  • Abnormal MSAFP screen
  • Family history of ONTD
  • Patient taking valproic acid or carbamazepine
  • Patient with medication-dependent diabetes or uncontrolled diabetes

Do not round gestational age to nearest wk; use EDD to avoid clerical errors

Prenatal diagnosis for ONTD at 14-25 wks gestation

Amniocentesis is discouraged <15 weeks gestation due to high rates of fetal loss, leakage of amniotic fluid, and increased risk of club foot

 

Sensitivity and Initial Positive Rates for Down Syndrome
Screening Test

% DS Detection

% Initial Positive DS cutoff
Quad

81

4-5

1/150

Integrated – serum only

85

3-4

1/110

Integrated – with NT

87

1.0

1/110

Sequential

63 (1st)
23 (2nd)
86 (total)

0.6 (1st)
1.0 (2nd)
1.6 (total)

1/25 (1st)
1/110 (2nd)

First trimester

85

5-6

1/230

Triple

75-80

5-6

1/190

 

Amniotic Fluid AChE Specificity and Sensitivity Rates for Open Neural Tube
Defects (Alpha Fetoprotein [Amniotic Fluid] with Reflex to Acetylcholinesterase)
 Testing for

Sensitivity

Open neural tube defects 95%
Anencephaly

97%

Open spina bifida

99%

Abdominal wall defects

40-79%

 

Targeted Ultrasound Test Results Follow-Up

Test Result Next Action
Anomaly detected on US

Perform second-tier screening:

  • NIPT for fetal aneuploidy

OR

Confirm with follow-up tests

  • Alpha Fetoprotein (Amniotic Fluid) with Reflex to Acetylcholinesterase and Fetal Hemoglobin
  • Chromosome Analysis, Amniotic Fluid
  • Chromosome Analysis FISH, Prenatal
  • Cytogenomic SNP Microarray - Fetal

OR

  • Chromosome Analysis, Chorionic Villus Sampling (CVS)
  • Chorionic Villus, FISH
  • Cytogenomic SNP Microarray - Fetal
  • Maternal Serum Screen, Alpha Fetoprotein (only)
No anomaly on US, but MSAFP MoM* 2.5-3.0

Repeat MSAFP (do not repeat aneuploidy screen, only the MSAFP) 2 wks after initial draw to see if AFP MoM level is increasing or decreasing; if increasing, treat patient per next row below (no anomaly on US, but MSAFP MoM >3.0)

If decreasing, probable transient maternal-fetal bleed; monitor pregnancy

  • Review or repeat level II US (including examination for signs of placental bleeding)

OR

  • Treat patient per next row below (no anomaly on US, but MSAFP MoM >3.0)
No anomaly on US, but MSAFP MoM* >3.0

Confirm with amniotic fluid tests

  • Alpha Fetoprotein (Amniotic Fluid) with Reflex to Acetylcholinesterase and Fetal Hemoglobin
  • Chromosome Analysis, Amniotic Fluid

If AF-AFP is normal, patient is at risk for poor pregnancy outcome (prematurity, small-for-gestational-age infant, still birth)

  • Offer counseling
  • Monitor pregnancy
No anomaly on US, but hCG MoM* >3.5

Patient is at increased risk for poor pregnancy outcome (preeclampsia, imminent fetal death, small-for-gestational-age infant)

  • Offer counseling
  • Monitor pregnancy

*MoM measures are multiples of the median, calculated as the value of the substance divided by the median value based on gestational age of the fetus.  Adjustments to MoM values are made for maternal weight, race, number of fetuses and maternal medication-dependent or uncontrolled diabetes.

 

Second Trimester Maternal Serum Screening Tests – Result Patterns

AFP

hCG

uE3

DIA

Pattern

L

H

L

H

Normal, overestimated gestation, and DS

H

L

H

N

Normal, underestimated gestation

L

L

L

*

Trisomy 18, fetal death

H

H

H

H

Multiple fetuses

H

N

N

N

Spina bifida, fetal-maternal hemorrhage, ventral wall defect

VH

N

L

N

Anencephaly, fetal death

VL

H

VL

N

Mole or partial mole

L = low; H = high; N = normal; VL = very low; VH = very high; * = may be high, low, or normal; not taken into account for risk calculation

Because most families who have a child with an open neural tube defect (ONTD), Down syndrome (DS), or trisomy 18 (T18) have no prior family history of these disorders, prenatal screening should be discussed with all pregnant women.

Open neural tube defects (ONTD)

Epidemiology

  • Incidence – 1/900 pregnancies (varies with racial background and geographical location)

Clinical Presentation

  • Most common types include spina bifida (a developmental defect of the spine and overlying skin) and anencephaly (developmental failure of the brain, skull, and overlying skin)
  • Lesions of spina bifida include the following
    • Simple meningocele
    • Lipomyelomeningocele
    • Diastematomyelia
    • Myelocystocele
    • Neuritic cyst
    • Intraspinal and intrapelvic meningoceles
    • True spina bifida occulta associated with spinal dysraphism
  • Spina bifida often results in the following sequela, but clinical severity depends on several factors, especially location and size of the lesion
    • Paralysis of the lower limbs
    • Loss of bowel and bladder control
    • Cerebral ventriculomegaly requiring shunt placement
  • Anencephaly associated with limited lifespan
    • 50% of infants are stillborn
    • Remainder of newborns die within hours or days of birth
  • Risk – independent of maternal age

Down syndrome (DS)

Epidemiology

  • Incidence – 1/600 births (regardless of race or geographical location)

Risk Factors

  • Risk increases with maternal age in a sigmoid fashion
    • 20s – risk for a child born with DS is ~1:1,500
    • 30s – risk rises dramatically
    • 40s – risk levels out to ~1:100
  • ~50% of babies with DS are born to mothers <35 years

Pathophysiology

  • Extra chromosome 21 found in all nucleated cells
  • Mosaic DS
    • Caused by an extra chromosome 21 in some, but not all, cells
    • Clinical phenotype
      • Usually milder than non-mosaic DS
      • Can vary from normal to severely affected

Clinical Presentation

  • Moderate to severe intellectual disability
  • Characteristic facial features
    • Down-slanting palpebral fissures
    • Epicanthic folds
    • Depressed nasal bridge
    • Flat mid-face
    • Low-set ears
  • Cardiac abnormalities
    • Ventricular septal defect (VSD)
    • Endocardial cushion defect
  • Hypothyroidism
  • Leukemia

Trisomy 18 (T18)

Epidemiology

  • Incidence – 1/3,000 births
  • Survival
    • 90% stillborn
    • Most infants die within the first year of life

Pathophysiology

  • Extra chromosome 18 found in all nucleated cells

Clinical Presentations

  • Severe intellectual disability
  • Heart defects
  • Failure to thrive
  • Clenched fists
  • Rocker bottom feet
  • Spina bifida
  • Nonambulatory
  • Inarticulate
    • Survivors can learn sign language
  • Risk – increases with maternal age

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Maternal Serum Screening, Integrated, Specimen #1 0081062
Method: Quantitative Chemiluminescent Immunoassay

Limitations

Ultrasound (US) for nuchal thickness is optional for this test; if an NT measurement is submitted to the lab, the sonographer must be FMF- or NTQR-certified

Sample may be drawn as early as 10w0d (CRL of 32mm) but NT, if done, must be measured when CRL is 36-85 mm

Sample draw and US do not have to be done on the same day

Final interpretive report available only when the second specimen test results are complete

A screen interpreted as “normal” misses approximately 10-20% of DS cases, 15% of ONTD cases, and 10-20% of T18 cases, depending on the test and maternal age

Follow Up

When NT is included, this test yields the best detection rate and lowest false-positive rate of all prenatal screens

Final results are available after the second trimester sample is received by the lab

Maternal Serum Screening, Integrated, Specimen #2 0081064
Method: Quantitative Chemiluminescent Immunoassay

Limitations

Requires a previously submitted first trimester specimen, Maternal Serum Screening, Integrated, Specimen #1

A screen interpreted as “normal” misses approximately 10-20% of DS cases, 15% of ONTD cases, and 10-20% of T18 cases, depending on the test and maternal age

AFP false positives occur with multiple gestation pregnancies, underestimated gestational age

Follow Up

Genetic counseling for abnormal results recommended

Maternal Serum Screen, First Trimester 0081150
Method: Quantitative Chemiluminescent Immunoassay

Limitations

Requires NT measurement performed by an FMF- or NTQR-certified ultrasonographer

This test does not screen for ONTD

A screen interpreted as “normal” misses approximately 10-20% of DS cases and 10-20% of T18 cases, depending on the test and maternal age

Follow Up

Maternal Serum Screen, Alpha Fetoprotein (only) test is recommended in the second trimester to screen for ONTD

Genetic counseling for abnormal results recommended

Maternal Screening, Sequential, Specimen #1 0081293
Method: Quantitative Chemiluminescent Immunoassay

Limitations

Requires an NT measurement that has been performed by an FMF- or NTQR-certified ultrasonographer

Most expensive screening test (a combination of the required ultrasound, and the first and second trimester lab tests)

A screen interpreted as “normal” misses approximately 10-20% of DS cases and 10-20% of T18 cases, depending on the test and maternal age

Follow Up

Interpretation is provided after first draw so pregnancies at very high risk for DS can be identified in the first trimester

Genetic counseling for abnormal results recommended

Patients at intermediate or low risk after first draw go on for second draw to complete the screen

No risk estimate is provided after first sample unless patient is at very high risk for either DS or T18; all patients receive a risk estimate after second sample is received

Maternal Screening, Sequential, Specimen #2 0081294
Method: Quantitative Chemiluminescent Immunoassay

Limitations

Requires a previously submitted first trimester specimen (Maternal Screening, Sequential Specimen #1)

A screen interpreted as “normal” misses approximately 10-20% of DS cases, 15% of ONTD cases, and 10-20% of T18 cases, depending on the test and maternal age

AFP false positives occur with multiple gestation pregnancies, underestimated gestational age

Follow Up

Genetic counseling for abnormal results recommended

Maternal Serum Screen, Alpha Fetoprotein, hCG, Estriol, and Inhibin A 0080269
Method: Quantitative Chemiluminescent Immunoassay

Limitations

Better detection rate and lower false-positive rate than triple screen

Best second trimester screen available

A screen interpreted as “normal” misses approximately 10-20% of DS cases, 15% of ONTD cases, and 10-20% of T18 cases, depending on the test and maternal age

AFP false positives occur with multiple gestation pregnancies, underestimated gestational age

Follow Up

Request recalculation only if ultrasound exam reveals a due date discrepancy >10 days

Genetic counseling for abnormal results recommended

Maternal Serum Screen, Alpha Fetoprotein (Only) 0080434
Method: Quantitative Chemiluminescent Immunoassay

Limitations

Does not screen for DS or T18

Follow Up

If AFP is between 2.5 and 3.0 MoMs, repeat AFP test (no earlier than 2 wks after original test was drawn) and offer targeted US and amniocentesis for chromosomes and AF-AFP

If AFP ≥3.0 MoMs, offer US and amniocentesis

Genetic counseling for abnormal results recommended

Non-Invasive Prenatal Testing for Fetal Aneuploidy (Panorama) 2007537
Method: Targeted sequencing with SNPs

Limitations

Test not appropriate for

  • Women carrying >1 fetus
  • Women who are not the genetic mother of the fetus
  • Women who have undergone allogeneic bone marrow transplant

Screens only for chromosomes 13, 18, 21, X, Y, and triploidy

Fetal mosaicism may not be detected

Low fetal fraction (FF) may occur normally in some pregnancies and can affect the ability to report a result

Individuals with elevated BMI are at increased risk of having a low FF; may result in increased chance of a false-positive, false-negative, or no-call test result

Follow Up

Women carrying a fetus with US abnormalities who screen negative by NIPT should be offered diagnostic testing: fetal karyotype +/- fetal microarray by CVS or amniocentesis

All positive NIPT results should be confirmed by fetal karyotype

Chromosome Analysis, Chorionic Villus 2002291
Method: Giemsa Band

Limitations

Time-sensitive test

Patient may have a higher rate of spontaneous fetal loss post-procedure than with amniocentesis

Follow Up

Genetic counseling for abnormal results recommended

Chorionic Villus, FISH 0040203
Method: Fluorescence in situ Hybridization

Limitations

Does NOT detect structural chromosome abnormalities, mosaicism or aneuploidy involving chromosomes other than 13, 18, 21, X, or Y

Follow Up

Genetic counseling for abnormal results 

Irreversible therapeutic action should not be initiated on the basis of FISH results alone

Chromosome FISH, Chorionic Villus with Reflex to Chromosome Analysis or Genomic Microarray 2011131
Method: Fluorescence in situ Hybridization

Limitations

Will not detect base pair mutations, very small deletions/duplications; tetraploidy; balanced rearrangements, such as translocations, inversions, and balanced insertions; low-level mosaicism; imbalances of mitochondrial genome

Failure of the array to detect an imbalance at any specific locus does not exclude the diagnosis of any disorder associated with that locus

Duplications <2 MB and deletions <1 MB may not be reported if they contain only a few genes that have no compelling association with the disease

Test results are often complex, and a CNV of uncertain clinical significance may be detected

Chromosome Analysis, Amniotic Fluid 2002293
Method: Giemsa Band

Limitations

Time-sensitive test

Follow Up

Genetic counseling for abnormal results 

Chromosome Analysis, Amniotic Fluid, with Reflex to Genomic Microarray 2008367
Method: Giemsa Band/Genomic Microarray (Oligo-SNP Array)

Limitations

Does not detect base pair mutations, very small deletions/duplications; tetraploidy; balanced rearrangements, such as translocations, inversions, and balanced insertions; low-level mosaicism; imbalances of mitochondrial genome

Failure of the array to detect an imbalance at any specific locus does not exclude the diagnosis of any disorder associated with that locus

Duplications <2 MB and deletions <1 MB may not be reported if they contain only a few genes that have no compelling association with the disease

Test results are often complex, and a CNV of uncertain clinical significance may be detected

Chromosome FISH, Prenatal 2002297
Method: Fluorescence in situ Hybridization

Limitations

Does NOT detect structural chromosome abnormalities, mosaicism or aneuploidy involving chromosomes other than 13, 18, 21, X, or Y

Follow Up

Genetic counseling for abnormal results

Irreversible therapeutic action should not be initiated on the basis of FISH results alone

Chromosome FISH, Amniotic Fluid with Reflex to Chromosome Analysis or Genomic Microarray 2011130
Method: Fluorescence in situ Hybridization

Limitations

Will not detect base pair mutations, very small deletions/duplications; tetraploidy; balanced rearrangements, such as translocations, inversions, and balanced insertions; low-level mosaicism; imbalances of mitochondrial genome

Failure of the array to detect an imbalance at any specific locus does not exclude the diagnosis of any disorder associated with that locus

Duplications <2 MB and deletions <1 MB may not be reported if they contain only a few genes that have no compelling association with the disease

Test results are often complex, and a CNV of uncertain clinical significance may be detected

Cytogenomic SNP Microarray - Fetal 2002366
Method: Genomic Microarray (Oligo-SNP Array)

Limitations

Time-sensitive test

Will not detect balanced rearrangements, such as translocations, inversions, and balanced insertions

Most intragenic alterations, such as point mutations and very small deletions or duplications, are not detected

Imbalances of the mitochondrial genome, genomic imbalances below the resolution of this array platform, and aberrations in regions of the genome not represented on the array platform are not detected

Test results are often complex, and a CNV of uncertain clinical significance may be detected

Follow Up

Genetic counseling for abnormal results

Alpha Fetoprotein (Amniotic Fluid) with Reflex to Acetylcholinesterase and Fetal Hemoglobin 0080427
Method: Chemiluminescent Immunoassay/Electrophoresis

Limitations

AFP amniotic fluid test results are confounded by contamination with fetal blood which occurs in approximately 8% of samples collected

AChE is much less affected by fetal blood

Cannot be performed until second trimester

Follow Up

Positive tests will automatically reflex to testing that will check for the presence of ACHE and/or fetal blood

Genetic counseling for abnormal results

Related Tests

Guidelines

ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol. 2007; 109(1): 217-27. PubMed

American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 545: Noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol. 2012; 120(6): 1532-4. PubMed

Benn P, Borell A, Chiu R, Cuckle H, Dugoff L, Faas B, Gross S, Johnson J, Maymon R, Norton M, Odibo A, Schielen P, Spencer K, Huang T, Wright D, Yaron Y. Position statement from the Aneuploidy Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat Diagn. 2013; 33(7): 622-9. PubMed

Gregg AR, Gross SJ, Best RG, Monaghan KG, Bajaj K, Skotko BG, Thompson BH, Watson MS. ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genet Med. 2013; 15(5): 395-8. PubMed

Invasive prenatal testing for aneuploidy. American College of Obstetricians and Gynecologists - Medical Specialty Society. 2007 December NGC: 006537

Wilson KL, Czerwinski JL, Hoskovec JM, Noblin SJ, Sullivan CM, Harbison A, Campion MW, Devary K, Devers P, Singletary CN. NSGC practice guideline: prenatal screening and diagnostic testing options for chromosome aneuploidy. J Genet Couns. 2013; 22(1): 4-15. PubMed

General References

American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. 2013; 122(6): 1374-7. PubMed

Ashwood ER, Palomaki GE. A new era in noninvasive prenatal testing. N Engl J Med. 2013; 369(22): 2164. PubMed

Bahado-Singh RO, Argoti P. An overview of first-trimester screening for chromosomal abnormalities. Clin Lab Med. 2010; 30(3): 545-55. PubMed

Bianchi DW, Parker L, Wentworth J, Madankumar R, Saffer C, Das AF, Craig JA, Chudova DI, Devers PL, Jones KW, Oliver K, Rava RP, Sehnert AJ, CARE Study Group. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med. 2014; 370(9): 799-808. PubMed

Bianchi DW, Platt LD, Goldberg JD, Abuhamad AZ, Sehnert AJ, Rava RP, MatErnal BLood IS Source to Accurately diagnose fetal aneuploidy (MELISSA) Study Group. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol. 2012; 119(5): 890-901. PubMed

Bornstein E, Lenchner E, Donnenfeld A, Barnhard Y, Seubert D, Divon MY. Advanced maternal age as a sole indication for genetic amniocentesis; risk-benefit analysis based on a large database reflecting the current common practice. J Perinat Med. 2009; 37(2): 99-102. PubMed

Chetty S, Garabedian MJ, Norton ME. Uptake of noninvasive prenatal testing (NIPT) in women following positive aneuploidy screening. Prenat Diagn. 2013; 33(6): 542-6. PubMed

Faas BH W, Cirigliano V, Bui T. Rapid methods for targeted prenatal diagnosis of common chromosome aneuploidies. Semin Fetal Neonatal Med. 2011; 16(2): 81-7. PubMed

Greene MF, Mello MM, Morain S. A new era in noninvasive prenatal testing. N Engl J Med. 2013; 369(22): 2165. PubMed

Gregg AR, Gross SJ, Best RG, Monaghan KG, Bajaj K, Skotko BG, Thompson BH, Watson MS. ACMG statement on noninvasive prenatal screening for fetal aneuploidy. Genet Med. 2013; 15(5): 395-8. PubMed

Gregg AR, Van den Veyver IB, Gross SJ, Madankumar R, Rink BD, Norton ME. Noninvasive prenatal screening by next-generation sequencing. Annu Rev Genomics Hum Genet. 2014; 15: 327-47. PubMed

Hung EC W, Chiu RW K, Lo YM D. Detection of circulating fetal nucleic acids: a review of methods and applications. J Clin Pathol. 2009; 62(4): 308-13. PubMed

Krantz DA, Hallahan TW, Sherwin JE. Screening for open neural tube defects. Clin Lab Med. 2010; 30(3): 721-5. PubMed

Mennuti MT, Cherry AM, Morrissette JJ D, Dugoff L. Is it time to sound an alarm about false-positive cell-free DNA testing for fetal aneuploidy? Am J Obstet Gynecol. 2013; 209(5): 415-9. PubMed

Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn. 2011; 31(1): 7-15. PubMed

Norton ME. First-trimester screening for chromosomal abnormalities: advantages of an instant results approach. Clin Lab Med. 2010; 30(3): 565-71. PubMed

Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Deciu C, Grody WW, Nelson SF, Canick JA. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med. 2011; 13(11): 913-20. PubMed

Sheppard C, Platt LD. Nuchal translucency and first trimester risk assessment: a systematic review. Ultrasound Q. 2007; 23(2): 107-16. PubMed

van Lith JM M, Benacerraf BR, Yagel S. Current controversies in prenatal diagnosis 2: Down syndrome screening: is ultrasound better than cell-free nucleic acids in maternal blood? Prenat Diagn. 2011; 31(3): 231-4. PubMed

Zhong Y, Tuuli M, Odibo AO. First-trimester assessment of placenta function and the prediction of preeclampsia and intrauterine growth restriction. Prenat Diagn. 2010; 30(4): 293-308. PubMed

Zimmermann B, Hill M, Gemelos G, Demko Z, Banjevic M, Baner J, Ryan A, Sigurjonsson S, Chopra N, Dodd M, Levy B, Rabinowitz M. Noninvasive prenatal aneuploidy testing of chromosomes 13, 18, 21, X, and Y, using targeted sequencing of polymorphic loci. Prenat Diagn. 2012; 32(13): 1233-41. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

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Last Update: March 2016