title: Dose dependency between cigarette consumption and reduced maternal serum PAPP-A levels at 11-13+6 weeks of gestation.
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 log(10) MoM). The respective values for beta-hCG MoM were 1.003 for smokers and 1.035 for nonsmokers (p < 0.0001 for log(10) 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 beta-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.
  
  
  CONCLUSIONS
  In first-trimester screening for Down syndrome by maternal serum PAPP-A and free beta-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.
authors.affiliation: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital Medical School, London, UK.
authors.forename: K O
authors.initials: KO
authors.lastname: Kagan
authors.forename: V
authors.initials: V
authors.lastname: Frisova
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
authors.forename: K
authors.initials: K
authors.lastname: Spencer
mesh_terms: D000293:Adolescent; D000328:Adult; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008875:Middle Aged; D048208:Nuchal Translucency Measurement; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D012189:Retrospective Studies; D012907:Smoking / Q000097:blood*
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A