Co‐variables in first trimester maternal serum screening

Abstract

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.

Second-trimester serum levels of placenta growth factor (PLGF) and inhibin A are increased in smokers. Implications for pre-eclampsia risk assessment

“…This discrepancy in comparison to our study could be explained by the difference in gestational age and the possible placental compensatory action (reduced PAPP-A levels in early pregnancy but not thereafter) which has been observed in the case of Down syndrome [17] as well as PE [11]. Moreover, the definition of smoking is not given in the mentioned study [16] and could have been less strict than ours (one or more cigarettes per day).…”

“…For SP1 and, interestingly, for activin A, this absence of an effect by smoking has not been mentioned in the literature so far. For PAPP-A, a difference (slight but significant reduction to 0.89 MoM) has been reported for smokers in the first trimester in a large study [16]. This discrepancy in comparison to our study could be explained by the difference in gestational age and the possible placental compensatory action (reduced PAPP-A levels in early pregnancy but not thereafter) which has been observed in the case of Down syndrome [17] as well as PE [11].…”

Influence of gravidity and foetal gender on the value of screening variables in the first trimester of pregnancy

“…De Graaf et al [8] observed, in women with more than one pregnancy, lower AFP, higher PAPP-A (albeit statistically non-significant) and no effect on free b-hCG.…”

“…Hence, there was a statistically significant decrease of 1-2% in the detection rate (DR) in pregnancies with female foetuses. Neither De Graaf et al [8] or Ardawi et al [9] found any differences in PAPP-A levels in relation to foetal gender.…”

Serum markers for pre-eclampsia: An update on the analytes to be determined in the first, second, and third trimester

“…On the other hand, we could not demonstrate an effect of maternal smoking on the serum levels of activin A, PAPP-A, SP1, HPL, leptin, sE-selectin, IGF-BP1, M-CSF, and VEGF at 17 weeks of gestation, and this was not influenced by the possible later development of pre-eclampsia [57]. For PAPP-A, there is a conflicting report of a slight but significant reduction (to 0.89 MoM) in the literature for smokers' levels in the first trimester [58]. The discrepancy could be explained by the different gestational age of the study populations together with the possible placental compensary action mentioned above [54].…”