title: The impact of correcting for smoking status when screening for chromosomal anomalies using maternal serum biochemistry and fetal nuchal translucency thickness in the first trimester of pregnancy.
abstract: OBJECTIVE
  To evaluate the influence of cigarette smoking status on maternal serum free beta-hCG, PAPP-A and fetal nuchal translucency (NT) thickness at 11 to 14 weeks of gestation in a large cohort of women screened prospectively for chromosomal anomalies.
  
  
  METHODS
  Information on maternal cigarette smoking status, maternal age, maternal serum biochemical marker levels and fetal NT were collected from the prenatal screening computer records in two OSCAR screening centres. Data was available from 32,730 unaffected pregnancies and from 124 with Down syndrome. Statistical analysis of the marker levels in the smoking and non-smoking group were carried out. The impact on false-positive rate of correcting for smoking status was assessed from a modelling exercise.
  
  
  RESULTS
  Prevalence of smoking was significantly affected by maternal age with an overall incidence of 11.5%, which varied from 35% in women under 20 to 7% in women over 35. In the unaffected population, the median free beta-hCG MoM was significantly lower in the smoking group (0.97 vs 1.00) as was that for PAPP-A (0.84 vs 1.02). The standard deviation of the log(10) MoM free beta-hCG was lower in the smoking group and that for PAPP-A was higher in the smoking group. The difference in median marker levels did not seem to be related to the number of cigarettes smoked per day. In the group with Down syndrome, the median MoM free beta-hCG was not significantly different in the smokers (1.69 vs 1.86) as was that for PAPP-A (0.53 vs 0.57). Fetal delta NT was not significantly different in the unaffected smokers (0.11 vs 0.0 mm) or in those with Down syndrome (1.96 vs 2.25 mm). In the smoking group, when screening using maternal serum biochemistry and age alone, the false-positive rate was 6.17%, compared to 4.67% in an age-matched group of non-smokers. Correcting for smoking status by dividing the measured MoM by the median found in the smoking group resulted in the false-positive rate falling to 4.40%. When screening using NT, maternal serum biochemistry and age, the false-positive rate in smokers was 4.48%, which reduced to 3.46% after correction-in line with the 3.76% in the non-smoking group. The impact on detection rate was too small to be accurately measured.
  
  
  CONCLUSIONS
  The impact of smoking on first-trimester biochemical marker levels does not seem to be dose related. Whilst correcting first-trimester biochemical markers for maternal smoking status has little impact at the population level for detection rates, a considerable reduction in false-positive rate can be achieved, reducing the level to that seen in non-smokers. However, the effect on the individual patient-specific risk can be substantial and could certainly make a difference to the patient's decision on whether to have an invasive test.
authors.affiliation: Clinical Biochemistry Department, Harold Wood Hospital, Gubbins Lane, Romford, Essex, UK. KevinSpencer1@aol.com
authors.forename: Kevin
authors.initials: K
authors.lastname: Spencer
authors.forename: Renu
authors.initials: R
authors.lastname: Bindra
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Cacho
authors.forename: Kypros H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D002869:Chromosome Aberrations; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011296:Prenatal Diagnosis; D015995:Prevalence; D011446:Prospective Studies; D012907:Smoking / Q000009:adverse effects / Q000097:blood*
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A