First Trimester Screening
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Population Covered By The Guidance
This pathway provides guidance on the screening of pregnant women to detect fetal abnormalities in early pregnancy.
Date reviewed: September 2018
Date of next review: June 2023
Published: April 2019
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| SYMBOL | RRL | EFFECTIVE DOSE RANGE |
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None | 0 |
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Minimal | < 1 millisieverts |
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Low | 1-5 mSv |
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Medium | 5-10 mSv |
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High | >10 mSv |
Teaching Points
Teaching Points
- There are two screening tests available for the antenatal detection of Down Syndrome and other fetal aneuploidies: the combined first trimester screen and non-invasive prenatal testing (NIPT) with cell-free DNA (cfDNA)
- Combined first trimester screening identifies 86-93% of Down Syndrome cases at a false positive rate of 3-5% in studies using a risk cut-off of 1:300. The components of the test include:
- Age and past obstetric history
- Serum β-hCG and PAPP-A
- Fetal ultrasound scan with measurement of nuchal translucency thickness
- If the calculated risk is higher than 1:300 then further testing is recommended, either with secondary screening with cfDNA if available, or with invasive diagnostic testing (chorionic villus sampling or amniocentesis)
- NIPT is a maternal blood test that detects chromosomal abnormalities using cell-free fetal DNA in the maternal circulation. cfDNA has demonstrated high accuracy in the detection of common fetal autosomal trisomies (T21, T18 and T13) and has been clinically validated in both high-risk and general obstetric populations with a sensitivity >99% and false positive rate ≤0.1%
- If undertaken as an initial screening test, measurement of NT is not necessary with cfDNA but an ultrasound examination should be undertaken prior to confirm viability, gestational number and to assess for significant structural abnormalities
- cfDNA is not a diagnostic test, so a high-probability result requires confirmation with chorionic villus sampling or amniocentesis
- Increased NT thickness and low PAPP-A are risk factors for fetal structural anomalies, so further investigation may be warranted even in normal karyotype fetuses
References
References
Date of literature search: August 2018
The search methodology is available on request. Email
References are graded from Level I to V according to the Oxford Centre for Evidence-Based Medicine, Levels of Evidence. Download the document
- Gabbett M, Halliday J, Hyett J, White S, Hui L, McGillivray G. Prenatal assessment of fetal structural conditions. Australia: Royal Australian and New Zealand College of Obstetricians and Gynaecologists; 2018. (Guideline). View the reference
- Salomon LJ, Alfirevic Z, Audibert F, Kagan KO, Paladini D, Yeo G, et al. ISUOG updated consensus statement on the impact of cfDNA aneuploidy testing on screening policies and prenatal ultrasound practice. Ultrasound Obstet Gynecol. 2017;49(6):815-6. (Guideline). View the reference
- Rieder W, White S, McGillivray G, Hui L. Contemporary prenatal aneuploidy screening practice in Australia: Frequently asked questions in the cell-free DNA era. Aust N Z J Obstet Gynaecol. 2018;58(4):397-403. (Guideline). View the reference
- Whitlow BJ, Economides DL. The optimal gestational age to examine fetal anatomy and measure nuchal translucency in the first trimester. Ultrasound Obstet Gynecol. 1998;11(4):258-61. (Level II evidence). View the reference
- Mulvey S, Baker L, Edwards A, Oldham J, Shekleton P, Wallace EM. Optimising the timing for nuchal translucency measurement. Prenat Diagn. 2002;22(9):775-7. (Level II evidence). View the reference
- Nicolaides KH. Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol. 2004;191(1):45-67. (Review article). View the reference
- Wright D, Spencer K, Kagan KK, Torring N, Petersen OB, Christou A, et al. First-trimester combined screening for trisomy 21 at 7-14 weeks' gestation. Ultrasound Obstet Gynecol. 2010;36(4):404-11. (Level II evidence). View the reference
- Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH, Bukowski R, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. 2005;353(19):2001-11. (Level II evidence). View the reference
- Spencer K, Spencer CE, Power M, Dawson C, Nicolaides KH. 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(3):281-6. (Level II evidence). View the reference
- Hadlow NC, Hewitt BG, Dickinson JE, Jacoby P, Bower C. Community-based screening for Down's Syndrome in the first trimester using ultrasound and maternal serum biochemistry. BJOG. 2005;112(11):1561-4. (Level II-III evidence). View the reference
- Ekelund CK, Jørgensen FS, Petersen OB, Sundberg K, Tabor A. Impact of a new national screening policy for Down’s syndrome in Denmark: population based cohort study. BMJ. 2008;337 (Level II-III evidence). View the reference
- Bindra R, Heath V, Liao A, Spencer K, Nicolaides KH. One-stop clinic for assessment of risk for trisomy 21 at 11-14 weeks: a prospective study of 15 030 pregnancies. Ultrasound Obstet Gynecol. 2002;20(3):219-25. (Level II evidence). View the reference
- Maxwell S, Brameld K, Bower C, Dickinson JE, Goldblatt J, Hadlow N, et al. Socio-demographic disparities in the uptake of prenatal screening and diagnosis in Western Australia. Aust N Z J Obstet Gynaecol. 2011;51(1):9-16. (Level II evidence). View the reference
- Alldred SK, Takwoingi Y, Guo B, Pennant M, Deeks JJ, Neilson JP, 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;3:Cd012600. (Level I evidence). View the reference
- Lindquist A, Poulton A, Halliday J, Hui L. Prenatal diagnostic testing and atypical chromosome abnormalities following combined first-trimester screening: implications for contingent models of non-invasive prenatal testing. Ultrasound Obstet Gynecol. 2018;51(4):487-92. (Level II evidence). View the reference
- Nicolaides KH, Syngelaki A, Ashoor G, Birdir C, Touzet G. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am J Obstet Gynecol. 2012;207(5):374.e1-6. (Level II evidence).
- Dan S, Wang W, Ren J, Li Y, Hu H, Xu Z, et al. Clinical application of massively parallel sequencing-based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11,105 pregnancies with mixed risk factors. Prenat Diagn. 2012;32(13):1225-32. (Level II evidence). View the reference
- Badeau M, Lindsay C, Blais J, Nshimyumukiza L, Takwoingi Y, Langlois S, et al. Genomics-based non-invasive prenatal testing for detection of fetal chromosomal aneuploidy in pregnant women. Cochrane Database Syst Rev. 2017;11:Cd011767. (Level I evidence). View the reference
- Norton ME, Brar H, Weiss J, Karimi A, Laurent LC, Caughey AB, et al. Non-Invasive Chromosomal Evaluation (NICE) Study: results of a multicenter prospective cohort study for detection of fetal trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012;207(2):137.e1-8. (Level II evidence). View the reference
- Gil MM, Accurti V, Santacruz B, Plana MN, Nicolaides KH. Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol. 2017;50(3):302-14. (Level I evidence). View the reference
- Zhang H, Gao Y, Jiang F, Fu M, Yuan Y, Guo Y, et al. Non-invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146,958 pregnancies. Ultrasound Obstet Gynecol. 2015;45(5):530-8. (Level II evidence). View the reference
- Iwarsson E, Jacobsson B, Dagerhamn J, Davidson T, Bernabe E, Heibert Arnlind M. Analysis of cell-free fetal DNA in maternal blood for detection of trisomy 21, 18 and 13 in a general pregnant population and in a high risk population - a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2017;96(1):7-18. (Level I evidence). View the reference
- McGillivray G, Hui L, Halliday J. Prenatal screening and diagnosis of chromosomal and genetic conditions in the fetus in pregnancy. Australia: Royal Australian and New Zealand College of Obstetricians and Gynaecologists; 2016. (Guideline). View the reference
- Revello R, Sarno L, Ispas A, Akolekar R, Nicolaides KH. Screening for trisomies by cell-free DNA testing of maternal blood: consequences of a failed result. Ultrasound Obstet Gynecol. 2016;47(6):698-704. (Level II evidence). View the reference
- Chan N, Smet ME, Sandow R, da Silva Costa F, McLennan A. Implications of failure to achieve a result from prenatal maternal serum cell-free DNA testing: a historical cohort study. BJOG. 2018;125(7):848-55. (Level II evidence). View the reference
- Martinez-Payo C, Bada-Bosch I, Martinez-Moya M, Perez-Medina T. Clinical results after the implementation of cell-free fetal DNA detection in maternal plasma. J Obstet Gynaecol Res. 2018 (Level II evidence). View the reference
- Hui L, Norton M. What is the real "price" of more prenatal screening and fewer diagnostic procedures? Costs and trade-offs in the genomic era. Prenat Diagn. 2018;38(4):246-9. (Level III evidence). View the reference
- Oepkes D, Page-Christiaens GC, Bax CJ, Bekker MN, Bilardo CM, Boon EMJ, et al. Trial by Dutch laboratories for evaluation of non‐invasive prenatal testing. Part I—clinical impact. Prenat Diagn. 2016;36(12):1083-90. (Level II evidence). View the reference
- Malan V, Bussières L, Winer N, et al. Effect of cell-free DNA screening vs direct invasive diagnosis on miscarriage rates in women with pregnancies at high risk of trisomy 21: A randomized clinical trial. JAMA. 2018;320(6):557-65. (Level II evidence). View the reference
- Liao H, Liu S, Wang H. Performance of non-invasive prenatal screening for fetal aneuploidy in twin pregnancies: a meta-analysis. Prenat Diagn. 2017;37(9):874-82. (Level I evidence). View the reference
- Fosler L, Winters P, Jones KW, Curnow KJ, Sehnert AJ, Bhatt S, et al. Aneuploidy screening by non-invasive prenatal testing in twin pregnancy. Ultrasound Obstet Gynecol. 2017;49(4):470-7. (Level II evidence). View the reference
- Huang X, Zheng J, Chen M, Zhao Y, Zhang C, Liu L, et al. Noninvasive prenatal testing of trisomies 21 and 18 by massively parallel sequencing of maternal plasma DNA in twin pregnancies. Prenat Diagn. 2014;34(4):335-40. (Level II evidence). View the reference
- Bevilacqua E, Gil MM, Nicolaides KH, Ordonez E, Cirigliano V, Dierickx H, et al. Performance of screening for aneuploidies by cell-free DNA analysis of maternal blood in twin pregnancies. Ultrasound Obstet Gynecol. 2015;45(1):61-6. (Level II evidence). View the reference
- Kagan KO, Avgidou K, Molina FS, Gajewska K, Nicolaides KH. Relation between increased fetal nuchal translucency thickness and chromosomal defects. Obstet Gynecol. 2006;107(1):6-10. (Level II-III evidence). View the reference
- Snijders RJ, Noble P, Sebire N, Souka A, Nicolaides KH. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10-14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group. Lancet. 1998;352(9125):343-6. (Level II evidence). View the reference
- Huang LY, Pan M, Han J, Zhen L, Yang X, Li DZ. What would be missed in the first trimester if nuchal translucency measurement is replaced by cell free DNA foetal aneuploidy screening? J Obstet Gynaecol. 2018:1-4. (Level III evidence). View the reference
- Souka AP, Krampl E, Bakalis S, Heath V, Nicolaides KH. Outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency in the first trimester. Ultrasound Obstet Gynecol. 2001;18(1):9-17. (Level III evidence). View the reference
- Westin M, Saltvedt S, Bergman G, Almstrom H, Grunewald C, Valentin L. Is measurement of nuchal translucency thickness a useful screening tool for heart defects? A study of 16,383 fetuses. Ultrasound Obstet Gynecol. 2006;27(6):632-9. (Level II evidence). View the reference
- Bahado-Singh RO, Wapner R, Thom E, Zachary J, Platt L, Mahoney MJ, et al. Elevated first-trimester nuchal translucency increases the risk of congenital heart defects. Am J Obstet Gynecol. 2005;192(5):1357-61. (Level II evidence). View the reference
- Makrydimas G, Sotiriadis A, Ioannidis JP. Screening performance of first-trimester nuchal translucency for major cardiac defects: a meta-analysis. Am J Obstet Gynecol. 2003;189(5):1330-5. (Level I evidence). View the reference
- Nicolaides KH, Heath V, Cicero S. Increased fetal nuchal translucency at 11-14 weeks. Prenat Diagn. 2002;22(4):308-15. (Level III evidence). View the reference
- Simpson LL, Malone FD, Bianchi DW, Ball RH, Nyberg DA, Comstock CH, et al. Nuchal translucency and the risk of congenital heart disease. Obstet Gynecol. 2007;109(2 Pt 1):376-83. (Level II evidence). View the reference
- American College of Obstetricians and Gynecologists. Practice Bulletin No. 163: Screening for Fetal Aneuploidy. Obstet Gynecol. 2016;127(5):e123-37. (Guideline). View the reference
- Papatheodorou SI, Evangelou E, Makrydimas G, Ioannidis JP. First-trimester ductus venosus screening for cardiac defects: a meta-analysis. BJOG. 2011;118(12):1438-45. (Level I evidence). View the reference
- Whitworth M, Bricker L, Mullan C. Ultrasound for fetal assessment in early pregnancy. Cochrane Database Syst Rev. 2015(7):Cd007058. (Level I evidence). View the reference
- McLennan A, Walker S. Prenatal assessment of fetal structural conditions. Australia: Royal Australian and New Zealand College of Obstetricians and Gynaecologists; 2016. (Guideline). View the reference
- Edwards L, Hui L. First and second trimester screening for fetal structural anomalies. Semin Fetal Neonatal Med. 2018;23(2):102-11. (Review article). View the reference
- Carlson LM, Vora NL. Prenatal diagnosis: screening and diagnostic tools. Obstet Gynecol Clin North Am. 2017;44(2):245-56. (Review article). View the reference
- Baffero GM, Somigliana E, Crovetto F, Paffoni A, Persico N, Guerneri S, et al. Confined placental mosaicism at chorionic villous sampling: risk factors and pregnancy outcome. Prenat Diagn. 2012;32(11):1102-8. (Level II-III evidence). View the reference
- Akolekar R, Beta J, Picciarelli G, Ogilvie C, D'Antonio F. Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2015;45(1):16-26. (Level I evidence). View the reference
- Beta J, Lesmes-Heredia C, Bedetti C, Akolekar R. Risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review of the literature. Minerva Ginecol. 2018;70(2):215-9. (Level I evidence). View the reference
- Wulff CB, Gerds TA, Rode L, Ekelund CK, Petersen OB, Tabor A. Risk of fetal loss associated with invasive testing following combined first-trimester screening for Down syndrome: a national cohort of 147,987 singleton pregnancies. Ultrasound Obstet Gynecol. 2016;47(1):38-44. (Level II evidence). View the reference
- Bilardo CM, Muller MA, Pajkrt E, Clur SA, van Zalen MM, Bijlsma EK. Increased nuchal translucency thickness and normal karyotype: time for parental reassurance. Ultrasound Obstet Gynecol. 2007;30(1):11-8. (Level III evidence). View the reference
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