Cell‑free fetal DNA at 11‑13 weeks of gestation is not altered in complicated pregnancies

Abstract

Non-invasive maternal cell-free fetal DNA (cffDNA) is a promising biomarker for screening common genetic syndromes. Alterations in the expression levels of cffDNA in the maternal circulation have been demonstrated in abnormal pregnancies. However, the results are conflicting. The present study aimed to investigate whether cffDNA levels are associated with pregnancy complications. The study group comprised pregnant women who presented with pregnancy complications, such as preterm birth, gestational hypertension, intrauterine growth retardation, gestational diabetes, polyhydramnios, oligohydramnios, vaginal bleeding and placental abruption. The control group comprised women who had a normal pregnancy course. Blood samples were obtained from 500 pregnant women between 11-13 weeks of gestation. cffDNA was amplified, sequenced and analyzed using the next-generation aneuploidy test of a Panorama-Natera kit. Nuchal translucency (NT) thickness as well as pregnancy associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG) levels were also assessed. Statistical analysis was performed in 494 out of the 500 samples collected with SPSS v.26 using non-parametric methods. The parameters were normalized by the multiples of median (MoM) method. The expression levels of PAPP-A, β-hCG, and the NT mean MoM values were significantly different between the study and control groups (P=0.005, P<0.001 and P=0.007, respectively). However, the expression levels of cffDNA and the mean MoM values were not significantly different between these two groups (P=0.687). The findings of the present study support the conclusion that cffDNA expression is not altered in a series of pregnancy complications. The prognostic value of cffDNA in predicting adverse pregnancy outcomes requires further investigation.

Keywords: cell-free fetal DNA; gestational diabetes mellitus; gestational hypertension; intrauterine growth retardation; oligohydramnios; placenta abruption; polyhydramnios; preeclampsia; pregnancy; preterm birth.

Figure 1

(A) Log scale histogram of weight distribution according to each pathological condition. (B) Bar charts of cffDNA, PAPP-A, β-hCG and NT MoM distribution according to the presence of each pathological feature. *, Outlier value. cffDNA, cell-free fetal DNA; PAPP-A, pregnancy associated plasma protein-A; β-hCG, β-human chorionic gonadotropin; NT, nuchal translucency; MoM, multiples of median; IUGR, intrauterine growth retardation.