Antenatal screening for fetal chromosomal conditions
The American College of Obstetricians and Gynecologists (ACOG) recommends that all pregnant women, regardless of maternal age, be offered antenatal screening and invasive diagnostic testing for aneuploidy.[36]American College of Obstetricians and Gynecologists. Practice bulletin no. 77: screening for fetal chromosomal abnormalities. Oct 2020 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2020/10/screening-for-fetal-chromosomal-abnormalities
Importantly, the ACOG guidelines encourage pre-test and post-test counselling. Women should be counselled regarding the differences between screening and invasive diagnostic testing. The UK National Screening Committee also recommends antenatal screening for DS, Edwards' syndrome and Patau's syndrome.[37]NHS England. Screening for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome. Dec 2024 [internet publication].
https://www.gov.uk/government/publications/fetal-anomaly-screening-programme-handbook/289099d7-ded0-43be-a901-600b78fb727e
First-trimester screening, a combination of nuchal translucency measurement, serum markers (pregnancy-associated plasma protein A and free or total beta-human chorionic gonadotropin [hCG]), and maternal age, is 79% to 90% sensitive in detecting DS.[38]Wapner R, Thom E, Simpson JL, et al. First-trimester screening for trisomies 21 and 18. N Engl J Med. 2003;349:1405-13.
http://www.nejm.org/doi/full/10.1056/NEJMoa025273
http://www.ncbi.nlm.nih.gov/pubmed/14534333?tool=bestpractice.com
[39]Spencer K, Spencer CE, Power M, et al. Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one-stop clinic: a review of three years prospective experience. BJOG. 2003;110:281-6.
http://onlinelibrary.wiley.com/doi/10.1046/j.1471-0528.2003.02246.x/full
http://www.ncbi.nlm.nih.gov/pubmed/12628268?tool=bestpractice.com
[40]Alldred SK, Takwoingi Y, Guo B, et al. First trimester serum tests for Down's syndrome screening. Cochrane Database Syst Rev. 2015;(11):CD011975.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011975/full
http://www.ncbi.nlm.nih.gov/pubmed/26617074?tool=bestpractice.com
[41]Alldred SK, Takwoingi Y, Guo B, et al. First trimester ultrasound tests alone or in combination with first trimester serum tests for Down's syndrome screening. Cochrane Database Syst Rev. 2017 Mar 15;3(3):CD012600.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6464518
http://www.ncbi.nlm.nih.gov/pubmed/28295158?tool=bestpractice.com
[42]Alldred SK, Takwoingi Y, Guo B, et al. First and second trimester serum tests with and without first trimester ultrasound tests for Down's syndrome screening. Cochrane Database Syst Rev. 2017 Mar 15;3(3):CD012599.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6464364
http://www.ncbi.nlm.nih.gov/pubmed/28295159?tool=bestpractice.com
If a woman is discovered to be at an increased risk of fetal aneuploidy, then genetic counselling and chorionic villus sampling (CVS) is offered, or she may choose to have a second-trimester amniocentesis (invasive diagnostic testing).[36]American College of Obstetricians and Gynecologists. Practice bulletin no. 77: screening for fetal chromosomal abnormalities. Oct 2020 [internet publication].
https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2020/10/screening-for-fetal-chromosomal-abnormalities
The integrated screening approach uses both the first and second-trimester markers to adjust a woman's age-related risk of having a child with DS. The integrated approach is more sensitive, with lower false-positive rates than first-trimester screening alone. It provides a detection rate of 94% to 96%.[43]Malone FD, Canick JA, Ball RH, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. 2005;353:2001-11.
http://www.nejm.org/doi/full/10.1056/NEJMoa043693
http://www.ncbi.nlm.nih.gov/pubmed/16282175?tool=bestpractice.com
A second method is the sequential screening approach, in which the patient is informed of the first-trimester screening results, then is given the option to receive further diagnostic testing in the second trimester.
First-trimester ultrasonographic markers, such as a non-visualised nasal bone, tricuspid regurgitation, crown-rump length, femur and humeral length, head and trunk volumes, and umbilical cord diameters, need further investigation regarding utility for screening protocols. Second-trimester ultrasonographic markers such as echogenic bowel, intracardiac echogenic focus, and dilated renal pelvis have a low sensitivity and specificity for DS.[44]Smith-Bindman R, Hosmer W, Feldstein VA, et al. Second-trimester ultrasound to detect fetuses with Down syndrome: a meta-analysis. JAMA. 2001;285:1044-55.
http://www.ncbi.nlm.nih.gov/pubmed/11209176?tool=bestpractice.com
Additionally, in North America and the UK, non-invasive prenatal (antenatal) screening (NIPS) is recommended as part of the antenatal care screen in high-risk patients for fetal aneuploidy.[37]NHS England. Screening for Down’s syndrome, Edwards’ syndrome and Patau’s syndrome. Dec 2024 [internet publication].
https://www.gov.uk/government/publications/fetal-anomaly-screening-programme-handbook/289099d7-ded0-43be-a901-600b78fb727e
[45]Dungan JS, Klugman S, Darilek S, et al. Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023 Feb;25(2):100336.
https://www.gimjournal.org/article/S1098-3600(22)01004-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36524989?tool=bestpractice.com
The clinical use of NIPS has become increasingly common as it provides women with a more sensitive non-invasive screening option, with positive predictive values around 80% and negative predictive values reported to be as high as 99% to 100% in higher prevalence populations such as those with advanced maternal age.[46]Smith M, Visootsak J. Noninvasive screening tools for Down syndrome: a review. Int J Womens Health. 2013;5:125-31.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655554
http://www.ncbi.nlm.nih.gov/pubmed/23687453?tool=bestpractice.com
[47]Porreco RP, Garite TJ, Maurel K, et al. Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and the common sex chromosome aneuploidies from maternal blood using massively parallel genomic sequencing of DNA. Am J Obstet Gynecol. 2014;211:365.
http://www.ajog.org/article/S0002-9378%2814%2900270-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/24657131?tool=bestpractice.com
Other clinical non-invasive screening modalities for DS include: the first-trimester screen, with a detection rate of 75% to 80%; and the maternal serum screen, with a detection rate of 80%. NIPS evaluates cell-free DNA that circulates in maternal blood, and can be done as early as 9 weeks' gestation. While numerous studies have shown NIPS to be both highly sensitive and highly specific, conclusive confirmation of NIPS screening results can only be done via amniocentesis and CVS.[46]Smith M, Visootsak J. Noninvasive screening tools for Down syndrome: a review. Int J Womens Health. 2013;5:125-31.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655554
http://www.ncbi.nlm.nih.gov/pubmed/23687453?tool=bestpractice.com
[48]Badeau M, Lindsay C, Blais J et al. Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women. Cochrane Database Syst Rev. 2017 Nov 10;11:CD011767.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011767.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/29125628?tool=bestpractice.com
Physicians should discuss the risks, benefits, and limitations of antenatal screening and diagnostic testing with patients.[48]Badeau M, Lindsay C, Blais J et al. Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women. Cochrane Database Syst Rev. 2017 Nov 10;11:CD011767.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011767.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/29125628?tool=bestpractice.com
[49]American College of Obstetricians and Gynecologists. Committee opinion no. 640: cell-free DNA screening for fetal aneuploidy. Obstet Gynecol. 2015;126:e31-7.
http://www.ncbi.nlm.nih.gov/pubmed/26287791?tool=bestpractice.com