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Perinatal outcomes in euploid pregnancies with ‘double-positive’ first trimester prenatal screening for trisomy 18 and 21

Journal of Perinatology volume 33, pages 836–840 (2013)Cite this article

Subjects

Abstract

Objective:

The objective of this study was to investigate whether women who screened positive for both trisomy 18 (T18) and trisomy 21 (T21) yet had euploid karyotypes were at increased risk for adverse pregnancy outcomes.

Study Design:

This was a retrospective cohort study of women who had first trimester aneuploidy screening. Double-positive subjects had risks greater than screening cutoffs for T21 and T18 and confirmed euploid karyotypes. Singleton subjects were matched 1:2 by maternal age to controls with normal screening. Perinatal outcomes were investigated using t-tests and χ2-tests; statistical significance was set at P<0.05.

Result:

Of 9733 women who had first trimester screening, 33 euploid pregnancies screened positive for both T21 and T18. Compared with controls, these study subjects were more likely to have abnormalities identified by prenatal ultrasounds, including renal, fetal membrane and fluid, as well as multiple anomalies (P=0.01). In addition, double-positive subjects had a lower mean gestational age at birth (P=0.02) and lower mean birth weight (P=0.03) than controls. Maternal outcomes were not significantly different.

Conclusion:

Pregnancies with double false-positive first trimester aneuploidy screening were associated with pregnancy/fetal abnormalities.

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References

  1. Nakata N, Wang Y, Bhatt S . Trends in prenatal screening and diagnostic testing among women referred for advanced maternal age. Prenat Diagn 2010; 30 (3): 198–206.

    PubMed  Google Scholar 

  2. Reddy UM, Wapner RJ . Comparison of first and second trimester aneuploidy risk assessment. Clin Obstet Gynecol 2007; 50 (2): 442–453.

    Article  PubMed  Google Scholar 

  3. Wapner RJ, Thom EA, Simpson JL, Pergament E, Silver R, Filkins K et alfor the First Trimester Maternal Serum Biochemistry and Fetal Nuchal Translucency Screening (BUN) Study Group. First-trimester screening for trisomies 21 and 18. N Engl J Med 2003; 349: 1405–1413.

    Article  CAS  PubMed  Google Scholar 

  4. 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: 2001–2011.

    Article  CAS  PubMed  Google Scholar 

  5. Wald NJ, Rodeck C, Hackshaw AK, Walters J, Chitty L, Mackinson AM . First and second trimester antenatal screening for Down’s syndrome: the results of the Serum, Urine, and Ultrasound Screening Study (SURUSS). J Med Screen 2003; 10: 56–104.

    CAS  PubMed  Google Scholar 

  6. 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: 281–286.

    Article  CAS  PubMed  Google Scholar 

  7. Kagan KO, Wright D, Maiz N, Pandeva I, Nicolaides KH . Screening for trisomy 18 by maternal age, fetal nuchal translucency, free beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol 2008; 32: 488–492.

    Article  CAS  PubMed  Google Scholar 

  8. Goetzl L . Adverse pregnancy outcomes after abnormal first-trimester screening for aneuploidy. Clin Lab Med 2010; 30: 613–628.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gagnon A, Wilson RD, Audibert F, Allen VM, Blight C, Brock JA et al. Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can 2008; 30: 918–949.

    Article  PubMed  Google Scholar 

  10. Pergament E, Stein AK, Fiddler M, Cho NH, Kupferminc MJ . Adverse pregnancy outcome after a false-positive screen for Down syndrome using multiple markers. Obstet Gynecol 1995; 86 (2): 255–258.

    Article  CAS  PubMed  Google Scholar 

  11. Spencer K, Cowans NJ, Avgidou K, Nicolaides KH . First-trimester ultrasound and biochemical markers of aneuploidy and the prediction of impending fetal death. Ultrasound Obstet Gynecol 2006; 28 (5): 637–643.

    Article  CAS  PubMed  Google Scholar 

  12. Ong CY, Liao AW, Spencer K, Munim S, Nicolaides KH . First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications. BJOG 2000; 107 (10): 1265–1270.

    Article  CAS  PubMed  Google Scholar 

  13. Goetzinger KR, Cahill AG, Kemma J, Odibo L, Macones GA, Odibo AO . First-trimester prediction of preterm birth using ADAM12, PAPP-A, uterine artery Doppler, and maternal characteristics. Prenat Diagn 2012; 31: 1–6.

    Google Scholar 

  14. DiLorenzo G, Ceccarello M, Cecotti V, Ronfani L, Monasta L, Vecchi Brumatti L et al. First trimester maternal serum PIGF, free bHCG, PAPP-A, PP-13, uterine artery Doppler and maternal history for the prediction of preeclampsia. Placenta 2012; 33 (6): 495–501.

    Article  CAS  Google Scholar 

  15. Piazze J, Anceschi MM, Cerekja A, La Torre R, Pala A, Papa A et al. Nuchal translucency as a predictor of adverse pregnancy outcome. Int J Gynaecol Obstet 2007; 98 (1): 5–9.

    Article  CAS  PubMed  Google Scholar 

  16. 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: 9–17.

    Article  CAS  PubMed  Google Scholar 

  17. Pergament E, Alamillo C, Sak K, Fiddler M . Genetic assessment following increased nuchal translucency and normal karyotype. Prenat Diagn 2011; 31 (3): 307–310.

    Article  PubMed  Google Scholar 

  18. Alamillo C, Fiddler M, Pergament E . Increased nuchal translucency in the presence of normal chromosomes: what’s next? Curr Opin Obstet Gynecol 2012; 24: 102–108.

    Article  PubMed  Google Scholar 

  19. Summers AM, Huang T, Wyatt PR . Pregnancy outcomes of women with positive serum screening results for Down syndrome and trisomy 18. Letter to the Editor. Prenat Diagn 2002; 22: 266–271.

    Article  Google Scholar 

  20. Breathnach FM, Malone FD, Lambert-Messerlian G, Cuckle HS, Porter TF, Nyberg DA et al. for the First and Second Trimester Evaluation of Risk (FASTER) Research Consortium. First- and second-trimester screening: Detection of aneuploidies other than Down Syndrome. Obstet Gynecol 2007; 110: 651–657.

    Article  PubMed  Google Scholar 

  21. Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 2012; 367: 2175–2184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 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 (137): e1–e8.

    Google Scholar 

  23. Allyse M, Sayres LC, King JS, Norton ME, Cho MK . Cell-free fetal DNA testing for fetal aneuploidy and beyond: clinical integration challenges in the US context. Hum Reprod 2012; 27 (11): 3123–3131.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 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–e6.

    Article  Google Scholar 

  25. Vora NL, Johnson KL, Lambert-Messerlian G, Tighiouart H, Peter I, Urato AC et al. Relationships between cell-free DNA and serum analytes in first and second trimesters of pregnancy. Obstet Gynecol 2010; 116 (3): 673–678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Dr Katherine Bianco is supported by the Reproductive Scientist Development Program Award, NIH, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD000849) and Clinical investigator Award, NIH, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K08HD069518-01). Dr Yvonne Cheng is supported by the UCSF Women’s Reproductive Health Research Career Development Award, NIH, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12 HD001262).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    L M Yee

  2. Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA

    S G Valderramos, S Pena, Y W Cheng & K Bianco

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  1. L M Yee
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  2. S G Valderramos
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  3. S Pena
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  4. Y W Cheng
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  5. K Bianco
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Corresponding author

Correspondence to K Bianco.

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The authors declare no conflict of interest.

Additional information

The results of this study were presented at 32nd Annual meeting of the Society of Maternal Fetal Medicine in Dallas, Texas on 11 February 2012.

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Yee, L., Valderramos, S., Pena, S. et al. Perinatal outcomes in euploid pregnancies with ‘double-positive’ first trimester prenatal screening for trisomy 18 and 21. J Perinatol 33, 836–840 (2013). https://doi.org/10.1038/jp.2013.88

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