LETTER TO THE EDITOR First trimester markers of trisomy 21 and the in ̄uence of maternal cigarette smoking status

Maternal cigarette smoking is associated with alterations in maternal serum analytes used in screening for trisomy 21 during the second trimester of pregnancy. Thus, serum free b-hCG levels in women who smoke are reduced by 11±14% in unaffected pregnancies (Spencer, 1998; Ferriman et al., 1999) and by 16% in pregnancies affected by trisomy 21 (Spencer, 1998). The consequence of this reduction in serum free bhCG levels is that in cigarette smokers there is a 10% decrease in sensitivity for trisomy 21 and a 50% reduction in the false positive rate. Although correcting for smoking status improves the detection rate by only 1±2%, the increase in accuracy of the estimated risk for an individual patient is considerable. There is now interest in moving screening for chromosomal abnormalities to the ®rst trimester of pregnancy (Grudzinskas and Ward, 1997). Combining maternal serum pregnancy associated plasma protein ± A (PAPP-A) and free b-hCG with fetal nuchal translucency thickness (NT) can identify about 90% of pregnancies affected by trisomies 21, 18 and 13, triploidy and sex chromosome aneuploidies for a false positive rate of about 5% (Spencer et al., 1999, 2000a,b,c; Tul et al., 1999). In an earlier study of 2887 unaffected pregnancies (Spencer, 1999) we observed that levels of maternal serum free b-hCG were not altered in the ®rst trimester of pregnancy, whilst PAPP-A levels were reduced by 15%. We have now had the opportunity to examine the effect of self-reported maternal cigarette smoking status on ®rst trimester maternal serum levels of free b-hCG and PAPP-A and fetal NT in normal and trisomy 21 pregnancies. For NT in the unaffected group we used NT data from the 2887 previously reported (Spencer, 1999) unaffected pregnancies screened in our OSCAR clinic (Spencer et al., in press). For pregnancies affected by trisomy 21 we used available information from our previous study of NT and maternal serum biochemical marker levels from 204 of the 210 cases (Spencer et al., 1999), supplemented with a further series of 20 cases identi®ed during prospective screening in our OSCAR clinics. All biochemical measurements were performed using the CIS Kryptor system and all markers were expressed a MoMs corrected for maternal weight when appropriate (Spencer et al., 1999). The median maternal age, weight and gestation in the trisomy 21 and unaffected pregnancies according to cigarette smoking status are shown in Table 1. In the unaffected population the median NT MoM in smokers was identical to that in non-smokersÐ0.996 (95% con®dence interval 0.975±1.017) versus 1.000 (0.990±1.010)Ðwith a log10 MoM SD of 0.1086 in smokers and 0.1155 in non-smokers. The log10 MoM distributions in the two groups were compared by t-tests assuming equal variance and no signi®cant difference ( p=0.244) was observed. In trisomy 21 pregnancies the median MoM NT in the smokers was again similar to that in non-smokersÐ2.539 (CI 2.07±3.17) versus 2.607 (CI 2.44±2.80)Ðwith a log10 MoM SD of 0.2025 in smokers and 0.1918 in nonsmokers. The log10 MoM distributions in the two groups were compared by t-tests assuming equal variance and no signi®cant difference ( p=0.334) was observed. In trisomy 21 pregnancies the median weight corrected MoM free b-hCG in the smokers was 13% lower than in non-smokersÐ1.787 (CI 1.09±2.24) versus 2.048 (CI 1.88±2.26)Ðwith a log10 MoM SD of 0.2648 in smokers and 0.2784 in non-smokers. The log10 MoM distributions in the two groups were compared by t-tests assuming equal variance but this difference did not reach statistical signi®cance ( p=0.198). The median weight corrected MoM PAPPA in the smokers was 6% higher in the smokers than in non-smokersÐ0.556 (CI 0.36±0.72) versus 0.526 (CI 0.45±0.56)Ðwith a log10 MoM SD of 0.2720 in smokers and 0.2821 in non-smokers. The log10 MoM distributions in the two groups were compared by ttests assuming equal variance but no signi®cant difference ( p=0.279) was observed. The ®ndings of this study in the ®rst trimester suggest that maternal cigarette smoking does not affect fetal NT in either trisomy 21 or unaffected pregnancies. Furthermore, the data suggest that in trisomy 21 pregnancies cigarette smoking is associated with a 13% decrease in maternal serum free b-hCG concentration, which is similar to the previously reported 16% decrease in affected pregnancies in the second trimester (Spencer, 1998). In unaffected pregnancies cigarette smokers have an 11±14% reduction in free b-hCG levels during the second trimester (Spencer, 1998; Ferriman et al., 1999), but the levels are not altered in the ®rst trimester of pregnancy (Spencer, 1999). The consequence of these ®ndings would be a decrease in the detection of trisomy 21 in cigarette smokers. In trisomy 21 pregnancies cigarette smoking is