The influence of smoking on maternal serum AFP and free beta hCG levels and the impact on screening for Down syndrome

Abstract

I have studied the impact of maternal smoking on the levels of maternal serum alpha-fetoprotein (AFP) and free beta human chorionic gonadotrophin (hCG) during the second trimester in a large series (30,727) of self-reported smokers and non-smokers whose pregnancy resulted in the birth of a normal fetus. I have confirmed in a smaller subset of this population that self-reporting is an accurate method of assessing smoking status as confirmed by biochemical (serum cotinine) assessment. In addition, I have investigated marker levels among 195 pregnancies affected by Down syndrome with smoking status confirmed by measurement of serum cotinine. In both unaffected and Down syndrome groups, the incidence of smoking was 19 per cent but a considerable variation was observed with maternal age when the incidence in younger women (under 25) was 32 per cent. AFP median levels in unaffected smokers were 3 per cent higher, whilst in the Down syndrome group smoker medians were increased by 10 per cent compared with the non-smoker group. Free beta hCG levels in unaffected smokers were reduced by 14 per cent, whilst in the Down syndrome group smoker median levels were decreased by 16 per cent. In the smoker group, the Down syndrome detection rate was 10 per cent lower than in the non-smoker group, whilst the false-positive rate was also 2 per cent lower. Correcting for smoking status would redress this inequality and produce an overall 2 per cent increase in the detection rate for a 0.4 per cent increase in the false-positive rate. This increase in screening performance may be worth building into screening programmes, particularly in populations with a high smoking incidence.