The clinical usefulness of biochemical (free β-hCg, PaPP-a) and ultrasound (nuchal translucency) parameters in prenatal screening of trisomy 21 in the first trimester of pregnancy

Abstract

Objectives: The aim of the study was to analyze the correlation of multiples of the normal median of PAPP-A, free β-hCG levels and nuchal translucency values in prenatal, first trimester screening of trisomy 21 in pregnant women. Material and methods: 251 pregnant women underwent antenatal screening at 11-13 +6 weeks of pregnancy which was composed of the measurement of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein (PAPP-A) levels in the maternal serum and an ultrasound assessment of nuchal translucency (NT). The pregnant women with a high risk of trisomy 21 (≥ 1:300) were given amniocentesis to verify fetal defects. There were 217 cases of normal fetal karyotype and 34 cases of trisomy 21. PAPP-A, β-hCGMoM and NT values were analyzed for the predefined ranges. Results: 85% cases of trisomy 21 had elevated free β-hCGMoM (> 1.5) and only 53% of these had a PAPP-AMoM result below 0.5 (p < 0.05). Analysis of NT in selected ranges of β-hCG (> 1.5) and PAPP-AMoM (< 0.05), which are typical for Down Syndrome values, showed that not all fetuses with Down Syndrome presented with an increased NT. Respectively 44.15% and 26.5% of fetuses presented with increased NT. Characteristic for trisomy 21, a correlation with all 1st trimester screening tests' parameters occurred in only 23.5% of cases. In 53% of cases the results were atypical. Conclusions: The PAPP-A and β-hCG values in the selected MoM ranges did not shown a correlation to the NT measurement, therefore they are independent factors in the diagnosis of trisomy 21. Simultaneous biochemical and ultrasound testing is an indispensable condition for prenatal diagnosis of trisomy 21 in the 1st trimester of pregnancy.

Low first trimester maternal serum PAPP‐A concentrations in women with non‐cavity‐distorting intramural uterine fibroids

“…We defined "low PAPP-A" as PAPP-A <0.5 MoM, based on findings derived from previous studies. 12 Calculations revealed leiomyoma size of 5.5 cm diameter as a cut-off value with 90% (86.7-92.7) specificity and 40% (22.7-59.4) sensitivity for low PAPP-A (Figure 2). Results of ROC curve analysis demonstrated that area under the curve value for leiomyoma size is 0.675 (0.63-0.72) (p < 0.001).…”

Evaluation of indications for amniocentesis in cases of normal fetal ultrasound results

“…They established that although the mean NT was significantly higher in fetuses with confirmed trisomy 21 than in euploid fetuses, a considerable proportion of the former group showed normal NT values. For cases with PAPP-A concentrations of less than 0.5 and β-hCG levels of over 1.5 MoM, the figure was 44.15% and 26.5%, respectively [9].…”

An Assessment of Selected Molecular and Biochemical Markers of the Folate Pathway as Potential Risk Factors for Fetal Trisomy 21 during the First Trimester of Pregnancy in the Polish Population

“…Our results were not statistically significant; however, this issue also occurred in other studies [ 17 , 25 , 28 , 29 , 30 ]. Some authors observed that, in a population of white American, Chinese and Italian women, the combination of the CT and TT genotypes of the c.665C>T MTHFR variant and the GG genotype for the c.66A>G variant in the MTRR (OR = 6.0, p < 0.025; Wang) significantly increased the risk for trisomy 21 in fetuses of women carriers of these alternative genotypes [ 2 , 4 , 21 ]. The lack of statistical significance in our research may depend on the size of the groups and the studied population, because in the Polish population, there are no significant differences in the frequency of the alleles and genotypes of the studied alternative variants between women with fetal trisomy 21 and without the abnormality.…”

“…The ultrasound examination was performed using the Voluson E8 ultrasound (General Electric Company (GE), Fairfield, CT, USA) and included the assessment of fetal anatomy with fetal heart rate (FHR) and measurement of nuchal translucency (NT) as a marker of the risk of chromosomal abnormalities (trisomy 21, 18 and 13), according to the standards of the Fetal Medicine Foundation and recommendations of the Ultrasound Section of the Polish Society of Gynecologists and Obstetricians [ 1 , 2 , 3 , 4 ].…”

“…Since the 1990s, there has been a main diagnostic scheme, implemented between 11 and 13 + 6 weeks of pregnancy, created by Professor Kypros Nicolaides, a world expert in fetal medicine. It consists of the assessment of the concentration of free β-subunit of human chorionic gonadotropin β (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in the mother’s serum, with maternal age and measurement of nuchal translucency (NT) and the heart rate (FHR) in a fetus by ultrasound evaluation, which enable the detection of approximately 80–90% of T21 cases at false-positive rate results (FPR) of about 5% [ 1 , 2 , 3 , 4 ]. There are also other additional ultrasound markers to increase the sensitivity of prenatal screening, such as nasal bone (NB), tricuspid flow (TF) and ductus venosus (DV).…”