First trimester Down's syndrome screening marker values and cigarette smoking: new data and a meta-analysis on free beta human chorionic gonadotophin, pregnancy-associated plasma protein-A and nuchal translucency.
OBJECTIVE
To examine the effect of smoking on three first trimester screening markers for Down's syndrome that constitute the Combined test, namely nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotophin (free beta-hCG) and to use the results to determine which of these markers need to be adjusted for smoking and by how much.


METHODS
The difference in the median multiple of the median (MoM) values in smokers compared to non-smokers was determined for NT, PAPP-A and free beta-hCG in 12,517 unaffected pregnancies that had routine first trimester Combined test screening. These results were then included in a meta-analysis of published studies and the effect of adjusting for smoking on screening performance of the Combined test was estimated.


RESULTS
The results using the routine screening data were similar to the summary estimates from the meta-analysis of all studies. The results from the meta-analysis were; median MoM in smokers compared to non-smokers: 1.06 NT (95% confidence interval 1.03 to 1.10), 0.81 PAPP-A (0.80 to 0.83) and 0.94 free beta-hCG (0.89 to 0.99). The effect of adjusting for smoking on the Combined test is small, with an estimated less than half percentage point increase in the detection rate (the proportion of affected pregnancies with a positive result) for a 3% false-positive rate (the proportion of unaffected pregnancies with a positive result) and less than 0.2 percentage point decrease in the false-positive rate for an 85% detection rate.


CONCLUSIONS
Adjusting first trimester screening markers for smoking has a minimal favourable effect on screening performance, but it is simple to implement and this paper provides the adjustment factors needed if a decision is made to make such an adjustment.
Bestwick
Jonathan P
JP
Wolfson Institute of Preventive Medicine, Barts and the London Queen Marys School of Medicine and Dentistry, Charterhouse Square London EC1M 6BQ. j.p.bestwick@qmul.ac.uk
Huttly
Wayne J
WJ
Wald
Nicholas J
NJ
D015415:Biomarkers / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000032:analysis*; D004314:Down Syndrome / Q000175:diagnosis* / Q000196:embryology; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D048208:Nuchal Translucency Measurement / Q000379:methods*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011296:Prenatal Diagnosis; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A