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First trimester biochemical screening for Down's syndrome

N J Wald1, A Kennard, D Smith

  • 1Wolfson Institute of Preventive Medicine, St Bartholomew's Hospital Medical College, London, UK.

Annals of Medicine
|February 1, 1994
PubMed
Summary
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First trimester screening for Down's syndrome shows promise using four key biochemical markers: pregnancy-associated plasma protein A (PAPP-A), free beta human chorionic gonadotrophin (hCG), unconjugated estriol (uE3), and alpha-fetoprotein (AFP). Combined with maternal age, these markers may detect 70% of affected pregnancies with a 5% false-positive rate.

Area of Science:

  • Biochemistry
  • Genetics
  • Maternal-Fetal Medicine

Background:

  • First-trimester screening for Down's syndrome is crucial for early detection.
  • Several biochemical markers in maternal serum have been investigated for this purpose.

Purpose of the Study:

  • To evaluate the effectiveness of specific biochemical markers for first-trimester Down's syndrome screening.
  • To assess the potential of combining these markers with maternal age for improved detection rates.

Main Methods:

  • Literature analysis of published studies on first-trimester screening markers.
  • Evaluation of pregnancy-associated plasma protein A (PAPP-A), free beta human chorionic gonadotrophin (hCG), unconjugated estriol (uE3), and alpha-fetoprotein (AFP).
  • Statistical assessment of detection rates and false-positive rates when markers are combined with maternal age.

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Main Results:

  • A combination of PAPP-A, free beta hCG, uE3, and AFP with maternal age suggests a potential 70% detection rate for Down's syndrome at a 5% false-positive rate.
  • This performance level is comparable to second-trimester screening methods.
  • Other markers like total hCG, free alpha-hCG, CA125, PLAP, and SP1 showed less promise or insufficient data.

Conclusions:

  • First-trimester screening using the four identified markers and maternal age is a promising approach.
  • Further research is necessary to confirm these findings due to assumptions of independence and potential publication bias.
  • Screening can be initiated around 9-10 weeks of pregnancy, aligning with the safety window for chorionic villus sampling.