Cell free fetal DNA fraction in the first trimester: a sign for abnormally invasive placenta?

We report about a pregnancy complicated by an abnormally invasive placenta (AIP) treated with a planned caesarean-hysterectomy at 34 weeks GA (Gestational Age). At 12+5 weeks GA noninvasive prenatal testing (NIPT) showed a low risk for all trisomies, but cell free-fetal (cff) DNA fraction was highly elevated with 35.3%. We repeated NIPT at 26+6 weeks GA. At that time the cff DNA fraction was still very increased with 26.1%.

Median cff DNA fraction at 10+6 GA is reported with 10.2%, between 10 and 21 weeks gestation, fetal fraction (ff) increases at 0.10% per week. After the first half of pregnancy the ff increases at a rate of 1% per week. So far there have been published inconsistent data about increased level of cff DNA as a biomarker for AIP during the third trimester. No data exist about the first trimester. Our case supports the theory that cff DNA fraction as biomarker for AIP maybe better in the first trimester than later in pregnancy. Our patient with AIP had a very elevated level of cff DNA fraction of 35.3% at the end of the first trimester. According to the published data by Wang E. et al. the median level of cff DNA fraction in normal pregnancies at this GA is only around 10.4%. Probably due to increased apoptosis of placental cells in the second half of pregnancy, median cff DNA-fraction increases about 1% per week and is around 25% at 34 wks GA. These results of our case support and Samuel's theory that cff DNA fraction as biomarker for AIP maybe better in the first trimester than later in pregnancy. Our case report and previous data from Sekizawa et al. should, therefore, prompt further studies on diagnostic value of cff DNA fraction in early pregnancy. Abnormally invasive Placenta (AIP) is one of the most dangerous conditions associated with pregnancy, because hemorrhage may result in severe acute maternal morbidity. Cff DNA as a possible marker of subsequent AIP could help to improve accuracy of prenatal diagnosis of morbidly invasive placenta.

Fig. 1: 3D-Ultrasound-Color-Doppler (HDlive technology) and Glass Body rendering shows intraplacental hypervascularity: complex, irregular arrangement of numerous placental vessels, exhibiting tortuous courses and varying calibers11.