First trimester Down’s syndrome screening marker values and cigarette smoking: new data and a meta-analysis on free β human chorionic gonadotophin, pregnancy-associated plasma protein-A and nuchal translucency

J Med Screen 2008;15:204-206
doi:10.1258/jms.2008.008049
© 2008 Medical Screening Society

 

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Short Communications


Jonathan P Bestwick, Statistician 
,


Wolfson Institute of Preventive Medicine, Barts and the London Queen Marys School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ


Wayne J Huttly, Antenatal screening manager
,


Wolfson Institute of Preventive Medicine, Barts and the London Queen Marys School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ


Nicholas J Wald, Professor
,


Wolfson Institute of Preventive Medicine, Barts and the London Queen Marys School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ

Correspondence to: Jonathan P Bestwick, Wolfson Institute of Preventive Medicine Barts and the London Queen Marys School of Medicine and Dentistry Charterhouse Square London EC1M 6BQ; j.p.bestwick{at}qmul.ac.uk


Objectives To examine the effect of smoking on three first trimester screeningmarkers for Down’s syndrome that constitute the Combined test,namely nuchal translucency (NT), pregnancy-associated plasmaprotein-A (PAPP-A) and free β human chorionic gonadotophin(free β-hCG) and to use the results to determine whichof these markers need to be adjusted for smoking and by howmuch.

Methods The difference in the median multiple of the median (MoM) valuesin smokers compared to non-smokers was determined for NT, PAPP-Aand free β-hCG in 12,517 unaffected pregnancies that hadroutine first trimester Combined test screening. These resultswere then included in a meta-analysis of published studies andthe effect of adjusting for smoking on screening performanceof the Combined test was estimated.

Results The results using the routine screening data were similar tothe summary estimates from the meta-analysis of all studies.The results from the meta-analysis were; median MoM in smokerscompared to non-smokers: 1.06 NT (95% confidence interval 1.03to 1.10), 0.81 PAPP-A (0.80 to 0.83) and 0.94 free β-hCG(0.89 to 0.99). The effect of adjusting for smoking on the Combinedtest is small, with an estimated less than half percentage pointincrease in the detection rate (the proportion of affected pregnancieswith a positive result) for a 3% false-positive rate (the proportionof unaffected pregnancies with a positive result) and less than0.2 percentage point decrease in the false-positive rate foran 85% detection rate.

Conclusion Adjusting first trimester screening markers for smoking hasa minimal favourable effect on screening performance, but itis simple to implement and this paper provides the adjustmentfactors needed if a decision is made to make such an adjustment.


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Home page J Med ScreenHome page

G. Lambert-Messerlian, G. E Palomaki, and J. A Canick
Adjustment of serum markers in first trimester screening
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