Influence of maternal smoking on the birth prevalence of Down syndrome and on second trimester screening performance.
OBJECTIVE
To determine the influence of maternal smoking on the birth prevalence of Down syndrome and on second trimester screening performance.


METHODS
First, a meta-analysis of cohort and case-control studies was performed to estimate the effect of maternal smoking on the live birth prevalence of Down syndrome. Then, data from 8779 women screened using the quadruple test (alphafetoprotein (AFP), unconjugated estriol (uE(3)), human chorionic gonadotrophin (free beta-hCG), and inhibin-A levels with maternal age) were used to determine the effect of smoking on the serum markers. A Monte Carlo simulation was used to assess the impact of adjusting for smoking status on screening performance.


RESULTS
The relative risk of Down syndrome in smokers (versus non-smokers) was 0.95 (95% confidence interval (CI) 0.87 to 1.03). Serum marker levels were determined as multiples of the median for non-smokers of the same gestational age and adjusted for maternal weight (MoM). The MoM values for AFP were 5% higher (95% CI 2-7%), uE(3) 4% lower (95% CI 2-5%), free beta-hCG 20% lower (95% CI 17-23%) and inhibin-A 62% higher (95% CI 57-67%) in smokers compared with non-smokers. Adjusting marker levels for smoking resulted in less than a 1 percentage point increase in the detection rate for a 5% false positive rate with the double, triple or quadruple tests.


CONCLUSIONS
There is no evidence of an association between the birth prevalence of Down syndrome and maternal smoking. The case for adjusting screening marker levels for smoking is not compelling. But if smoking data are collected routinely adjustment could be made and this would yield similar detection and false positive rates in smokers and non-smokers.
Rudnicka
Alicja R
AR
Department of Environmental and Preventive Medicine, Wolfson Institute of Preventive Medicine, Charterhouse Square, London EC1M 6BQ, UK. a.r.rudnicka@qmul.ac.uk
Wald
Nicholas J
NJ
Huttly
Wayne
W
Hackshaw
Allan K
AK
D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D015331:Cohort Studies; D004314:Down Syndrome / Q000175:diagnosis / Q000453:epidemiology*; D004964:Estriol / Q000097:blood; D005189:False Positive Reactions; D005260:Female; D005865:Gestational Age; D006801:Humans; D007265:Inhibins / Q000097:blood; D016239:MEDLINE; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D012907:Smoking / Q000009:adverse effects*; D000509:alpha-Fetoproteins / Q000032:analysis
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D000509:alpha-Fetoproteins; C422362:inhibin A; D007265:Inhibins; D004964:Estriol