Feasibility of noninvasive prenatal testing for common fetal aneuploidies in an early gestational window.

BACKGROUND

Noninvasive prenatal testing (NIPT) by massively parallel sequencing (MPS) of the circulating cell free fetal (cff) DNA during the second trimester of pregnancy is now a frontline test for detecting common fetal chromosomal abnormalities. However, the availability of an earlier test result in the first trimester would enable better clinical management of high-risk pregnancies. The aim of the study was to determine the feasibility of early gestational NIPT.

METHODS

Plasma DNA libraries were subjected to MPS and chromosomal read counts normalized to reference. Chromosomal aneuploidy was determined by z-scores (-3<z<3, normal range). The cff DNA fraction in 96 male pregnancies was calculated by the relative proportion of Y chromosomal reads.

RESULTS

NIPT results were obtained in the first (8-12 weeks) and second (15-18 weeks) trimester for 182 high-risk women. NIPT identified T21, T13 and 45,X in 3 pregnancies that were confirmed by karyotyping, but missed a T15 pregnancy that eventually miscarried. In the remaining 178 pregnancies, results for first and second trimester NIPT were normal. The median fetal fraction in the first trimester was 7.6 ± 4.18% and 15% of samples were identified with a cff fraction below 4%. Different trends of cff DNA fraction change were observed between the first and second trimester, with 59% of pregnancies showing an increase, 17% showing no change and 24% showing a decrease.

CONCLUSIONS

Although NIPT was highly reliable and accurate at an earlier gestational age, clinical implementation should proceed with caution due to a small, but significant, number of pregnancies associated with a low cff DNA fraction.