Prenatal Screening Strategies in Localities with Limited Resources

Abstract

Several important developments have been made in prenatal screening and diagnosis of serious fetal abnormalities, and prevention of common adverse pregnancy outcomes. However, full implementation is not cost-neutral and in localities with limited resources, compromises are needed. This review considers options for maternal plasma cell free DNA (cfDNA); prenatal microarray analysis; and multi-marker screening for preeclampsia (PE). Although not new, use of first trimester nuchal translucency and additional ultrasound markers is also considered as this is not routinely available in many limited resource localities. In order to benefit from recent advances in prenatal screening, even in adequately resourced localities, public health decision-makers have to make difficult choices. Options include: secondary and contingent cfDNA screening following a positive conventional test, microarray only when there are ultrasound indications, first trimester PE and screening using biochemistry alone, ideally with additional serum markers.

This is a preview of subscription content, access via your institution.

References

  1. 1.

    Cuckle HS, Benn P, Pergament E. Cell-free DNA screening for aneuploidy as a clinical service. Clin Biochem. 2015;48:932–41.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Wapner RJ, Martin CL, Levy B, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012;367:2175–84.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    American College of Obstetricians and Gynecologists. Report of the task force on hypertension in pregnancy. Obstet Gynecol. 2013;122:1122.

    Article  Google Scholar 

  4. 4.

    Roberge S, Nicolaides K, Demers S, Hyett J, Chaillet N, Bujold E. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis. Am J Obstet Gynecol. 2017;216:110-20.e6.

    Google Scholar 

  5. 5.

    Akolekar R, Syngelaki A, Poon L, Wright D, Nicolaides KH. Competing risks model in early screening for preeclampsia by biophysical and biochemical markers. Fetal Diagn Ther. 2013;33:8–15. Erratum. Fetal Diagn Ther. 2013;34:43.

    Article  Google Scholar 

  6. 6.

    Sonek J, Nicolaides K. Additional first-trimester markers. Clin Lab Med. 2010;30:573–92.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    American College of Obstetricians and Gynecologists. Noninvasive prenatal testing for fetal aneuploidy. Committee Opinion No. 545. Obstet Gynecol. 2012;120:1532–4.

    Article  Google Scholar 

  8. 8.

    Benn P, Borrell A, Chiu R, et al. Position statement from the aneuploidy screening committee on behalf of the board of the international society for prenatal diagnosis. Prenat Diagn. 2013;33:622–9.

    Article  PubMed  Google Scholar 

  9. 9.

    Ginsberg GM, Cuckle H. Cost-utility analysis of cfDNA screening for Down’s syndrome in Israel. In: Studd J, Tan SL, Chevenak FA, editors. Current Progress in Obstetrics and Gynecology, vol. 4. Mumbai: Kothari Medical; 2017.

    Google Scholar 

  10. 10.

    Harper LM, Sutton AL, Longman RE, Odibo AO. An economic analysis of prenatal cytogenetic technologies for sonographically detected fetal anomalies. Am J Med Genet A. 2014;164A:1192–7.

    Article  PubMed  Google Scholar 

  11. 11.

    Wapner RJ, Babiarz JE, Levy B, et al. Expanding the scope of non-invasive prenatal testing: detection if fetal microdeletion syndromes. Am J Obstet Gynecol. 2015;212:332.e1–9.

    Article  Google Scholar 

  12. 12.

    WHO Recommendations for Prevention and Treatment of Pre-Eclampsia and Eclampsia. Geneva: World Health Organization; 2011.

  13. 13.

    National Institute for Health and Clinical Excellence Clinical Guideline 107. Hypertension in pregnancy: the management of hypertensive disorders during pregnancy. 2010. Available at: www.nice.org.uk/guidance/CG107. Accessed 22 Sep 2017.

  14. 14.

    American College of Obstetricians and Gynecologists. Practice advisory on low-dose aspirin and prevention of preeclampsia: updated recommendations. 2016.

  15. 15.

    Park F, Russo K, Williams P, et al. Prediction and prevention of early-onset pre-eclampsia: impact of aspirin after first-trimester screening. Ultrasound Obstet Gynecol. 2015;46:419–23.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Cuckle HS, Pergament E, Benn P. Multianalyte maternal serum screening for chromosomal abnormalities and neural tube defects. In: Milunsky A, Milunsky JM, editors. Genetic disorders and the fetus: diagnosis, prevention and treatment. 7th ed. Hoboken: Wiley; 2015.

    Google Scholar 

  17. 17.

    Xu C, Wang T, Liu C, et al. Noninvasive prenatal screening of fetal aneuploidy without massively parallel sequencing. Clin Chem. 2017. doi:10.1373/clinchem.2016.266247.

    Google Scholar 

  18. 18.

    Mulvey S, Baker L, Edwards A, Oldham J, Shekleton P, Wallace EM. Optimising the timing for nuchal translucency measurement. Prenat Diagn. 2002;22:775–7.

    Article  PubMed  Google Scholar 

  19. 19.

    Wright D, Spencer K, Nix B. First trimester screening for Down syndrome using free β hCG, total hCG and PAPP-A: an exploratory study. Prenat Diagn. 2007;27:1118–22.

    Article  PubMed  Google Scholar 

  20. 20.

    Huang T, Dennis A, Meschino WS, Rashid S, Mak-Tam E, Cuckle H. First trimester screening for Down syndrome using nuchal translucency, maternal serum pregnancy-associated plasma protein A, free-β human chorionic gonadotrophin, placental growth factor and α-fetoprotein. Prenat Diagn. 2015;35:709–16.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Palomaki GE, Eklund EE, Neveux LM, Lambert Messerlian GM. Evaluating first trimester maternal serum screening combinations for Down syndrome suitable for use with reflexive secondary screening via sequencing of cell free DNA: high detection with low rates of invasive procedures. Prenat Diagn. 2015;35:789–96.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Wald NJ, Cuckle H; UK collaborative AFP study. maternal serum alpha fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Lancet. 1977;i:1323–32.

    Google Scholar 

  23. 23.

    Wald NJ, Cuckle HS, Densem JW, Kennard A, Smith D. Maternal serum screening for down’s syndrome: the effect of routine ultrasound scan determination of gestational age and adjustment for maternal weight. Br J Obstet Gynaecol. 1992;99:144–9.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Cuckle HS, Thornton JG. Antenatal diagnosis and management of neural tube defects. In: Levene MI, Lilford RJ, editors. Fetal and Neonatal Neurology and Neurosurgery. London: Churchill Livingstone; 1995. p. 295–309.

    Google Scholar 

  25. 25.

    Maruotti GM, Saccone G, D’Antonio F, et al. Diagnostic accuracy of intracranial translucency in detecting spina bifida: a systematic review and meta-analysis. Prenat Diagn. 2016;36:991–6.

    Article  PubMed  Google Scholar 

  26. 26.

    Bernard J-P, Cuckle HS, Bernard M, et al. Combined screening for open spina bifida at 11–14 weeks using fetal biparietal diameter and maternal serum markers. Am J Obstet Gynecol. 2013;209:223.e1–5.

    Article  Google Scholar 

  27. 27.

    Simon EG, Arthuis CJ, Haddad G, et al. A biparietal/transverse abdominal diameter (BPD/TAD) ratio ≤ 1: a potential hint for open spina bifida at 11–13 weeks scan. Ultrasound Obstet Gynecol. 2015;45:267–72.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Grandjean H, Larroque D, Levi S. The performance of routine ultrasonographic screening of pregnancies in the Eurofetus study. Am J Obstet Gynecol. 1999;181:446–54.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Rossi AC, Prefumo F. Accuracy of ultrasonography at 11–14 weeks of gestation for detection of fetal structural anomalies: a systematic review. Obstet Gynecol. 2013;122:1160–7.

    Article  PubMed  Google Scholar 

  30. 30.

    Sotiriadis A, Papatheodorou S, Eleftheriades M, Makrydimas G. Nuchal translucency and major congenital heart defects in fetuses with normal karyotype: a meta-analysis. Ultrasound Obstet Gynecol. 2013;42:383–9.

    CAS  PubMed  Google Scholar 

  31. 31.

    Pereira S, Ganapathy R, Syngelaki A, Maiz N, Nicolaides K. Contribution of fetal tricuspid regurgitation in first-trimester screening for major cardiac defects. Obstet Gynecol. 2011;117:1384–91.

    Article  PubMed  Google Scholar 

  32. 32.

    Cheleman T, Syngelaki N, Maiz N, Allan L, Nicolaides K. Contribution of ductus venosus Doppler in first trimester screening for major cardiac defects. Fetal Diagn Ther. 2011;29:127–34.

    Article  Google Scholar 

  33. 33.

    Papatheodorou SI, Evangelou E, Makrydimas G, Ioannidis JP. First-trimester ductus venosus screening for cardiac defects: a meta-analysis. Br J Obstet Gynaecol. 2011;118:1438–45.

    CAS  Article  Google Scholar 

  34. 34.

    Borrell A, Grande M, Bennasar M, et al. First trimester detection of cardiac defects with the use of the ductus venosus blood flow. Ultrasound Obstet Gynecol. 2013;42:51–7.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Howard Cuckle.

Ethics declarations

Conflict of Interest

None.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Cuckle, H., Neiger, R. Prenatal Screening Strategies in Localities with Limited Resources. J. Fetal Med. 4, 165–170 (2017). https://doi.org/10.1007/s40556-017-0140-4

Download citation

Keywords

  • cfDNA
  • Screening
  • CVS
  • Amniocentesis
  • Microarray
  • aCGH
  • Down syndrome
  • Preeclampsia
  • Markers
  • Spina bifida