Dose dependency between cigarette consumption and reduced maternal serum PAPP‐A levels at 11–13+6 weeks of gestation

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Abstract
Objective To examine whether in smokers there is a significant dose dependency between the number of cigarettes per day and levels of free ß‐hCG and pregnancy‐associated plasma protein A (PAPP‐A) at 11–13+6 weeks of gestation. Methods This was a retrospective analysis of the maternal serum free ß‐hCG and PAPP‐A levels in relation to the maternal smoking status in 109 263 chromosomally normal singleton pregnancies that had undergone first‐trimester screening for Down syndrome by a combination of fetal nuchal translucency thickness and maternal serum biochemistry. Results There were 95 287 nonsmokers and 13 976 cigarette smokers. The overall median PAPP‐A MoM among cigarette smokers was 0.827, which was 19.6% lower than the value of 1.029 in nonsmokers (p < 0.0001 for log10 MoM). The respective values for β‐hCG MoM were 1.003 for smokers and 1.035 for nonsmokers (p < 0.0001 for log10 MoM) which corresponds to a reduction of 3.1%. There was a significant inverse relationship between the number of cigarettes per day and the level of PAPP‐A MoM (r = 0.989, p < 0.0001) but not the level of free β‐hCG MoM (r = 0.733; p = 0.098). Using a statistical modeling approach we found that the screen‐positive rate when correcting the PAPP‐A MoM by an all or nil smoking factor was reduced by only 0.1% (3.75 vs 3.85%) when compared to correcting with a factor related to the smoking dose per day. Conclusion In first‐trimester screening for Down syndrome by maternal serum PAPP‐A and free β‐hCG the impact of correcting for the dose dependant rather than the all or nil effect of smoking is marginal. However, a dose dependent correction improves the accuracy of the individual patient‐specific risk. Copyright © 2007 John Wiley & Sons, Ltd.

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