Co-variables in first trimester maternal serum screening.

The objective of this study was to determined the influence of maternal weight, maternal smoking habits, gravidity, parity and fetal gender on the level of maternal serum marker used in first trimester screening for Down syndrome. A total of 2449 singleton unaffected pregnancies from two centres were studied. Maternal serum free beta-human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) concentrations had been measured in all pregnancies, and pregnancy associated plasma protein (PAPP)-A levels had been measured in 924. All results were expressed as multiples of the gestation specific median (MoM) values after regression, using each centre's own medians. Information on maternal weight was available in 2259 pregnancies, on self-reported current cigarette smoking in 1364 (of whom 117 (8.6%) were smokers), on gravidity in 1371, parity in 1303 and fetal gender in 253. All three markers showed a statistically significant negative association with maternal weight (p<0.0005) and in the subsequent analyses MoM values were weight adjusted using standard methods. The median PAPP-A level in smokers was 0.81 MoM, a significant reduction (p<0.005); free beta-hCG was also reduced (median 0.89 MoM) but not significantly (p=0.17), and AFP was unaltered. The median AFP level in primagravidas was highly significantly greater than that in gravid women (p<0.0005). In PAPP-A the reverse effect was seen but it did not reach statistical significance (p=0.15) and there was no effect for free beta-hCG. Results of a similar magnitude and direction were found for parity. The median level of free beta-hCG was higher (p=0.0005), and the median AFP lower in female pregnancies. Maternal weight and, for PAPP-A, maternal smoking are important first trimester screening co-variables. Gravidity, parity and fetal gender also seem to influence one or more first trimester markers.

de Graaf IM ，Cuckle HS ，Pajkrt E ，Leschot NJ ，Bleker OP ，van Lith JM ... -  《PRENATAL DIAGNOSIS》

Maternal serum free-beta-chorionic gonadotrophin, pregnancy-associated plasma protein-A and fetal nuchal translucency thickness at 10-13(+6) weeks in relation to co-variables in pregnant Saudi women.

To establish normative values and distribution parameters of first-trimester screening markers, namely, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A), at 10 to 13(+6) weeks of gestation in Saudi women and to evaluate the effect of co-variables including maternal body weight, gravidity, parity, fetal gender, twin pregnancy, smoking and ethnicity on these markers. A cohort of Saudi women (first cohort n = 1616) with singleton pregnancies prospectively participated in the present study, and fetal NT together with maternal serum free beta-hCG and PAPP-A were determined at 10 to 13(+6) weeks of gestation. The distribution of gestational age-independent multiples of the median (MoM) of the parameters was defined and normative values were established, and correction for maternal body weight was made accordingly. The influence of various co-variables was examined using the data collected from the first and the second (n = 1849) cohorts of women and 62 twin pregnancies, and compared with other studies. All markers exhibited log-normally distributed MoMs. Gestational age-independent normative values were established. Maternal body weight was corrected, particularly for maternal free beta-hCG and PAPP-A using standard methods. Fetal NT showed a negative relationship with increasing gravidity (r = -0.296) or parity (r = -0.311), whereas both free beta-hCG and PAPP-A exhibited a significant positive relationship. There was a significant increase in the MoM of free beta-hCG in female fetuses. Smoking decreased MoM values of free beta-hCG (by 14.6%; P < 0.01) and PAPP-A (by 18.8%; P < 0.001). Twin pregnancy showed significant increases in MoM values of free beta-hCG (by 1.87-fold) and PAPP-A (by 2.24-fold), with no significant changes in fetal NT MoM values. Fetal NT MoM values were lower in Africans and Asians but higher in Orientals, as compared to Saudi women (P < 0.05; in each case). MoM values (body weight-corrected) of free beta-hCG were 25.2% higher in Africans and 19.4% higher in Orientals but 6.8% lower in other Arabian and Asian (by 5.8%) women as compared to Saudi women (P < 0.05; in each case). The normative values and distribution parameters for fetal NT, maternal serum free beta-hCG and PAPP-A were established in Saudi singleton pregnancies, the maternal body weight together with smoking, twin pregnancy and ethnicity being important first-trimester screening co-variables. Gravidity, parity and fetal gender are also considered to influence one or more of the first-trimester markers examined.

Ardawi MS ，Nasrat HA ，Rouzi AA ，Qari MH ，Al-Qahtani MH ，Abuzenadah AM ... -  《PRENATAL DIAGNOSIS》

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.

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. 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. 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. 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.

Spencer K ，Bindra R ，Cacho AM ，Nicolaides KH ... -  《PRENATAL DIAGNOSIS》

[Effect of maternal smoking on concentrations of the pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of chorionic gonadotropin (beta hCG) in the first trimester of pregnancy].

Gajewska J ，Ceran A ，Chełchowska M ，Borowski D ，Ambroszkiewicz J ，Jaczyńska R ，Zwoliński J ，Laskowska-Klita T ... -  《-》

First trimester maternal serum screening for Down's syndrome: an evaluation of the DPC Immulite 2000 free beta-hCG and pregnancy-associated plasma protein-A assays.

Spencer K 《ANNALS OF CLINICAL BIOCHEMISTRY》