Late first‐trimester ultrasound findings can alter management after high‐risk NIPT result

ABSTRACT Objective To evaluate the impact of detailed late first‐trimester ultrasound (LFTU) on the positive predictive value (PPV) of a high‐risk non‐invasive prenatal test (NIPT) result for various chromosomal abnormalities. Methods This was a retrospective study of all cases undergoing invasive prenatal testing from three tertiary providers of obstetric ultrasound over 4 years, each using NIPT as a first‐line screening test. Data were collected from pre‐NIPT ultrasound, NIPT, LFTU, placental serology and later ultrasound examinations. Prenatal testing for chromosomal abnormalities was performed by microarray, initially using array comparative genomic hybridization and then single nucleotide polymorphism (SNP) array for the last 2 years. Uniparental disomy testing was performed by SNP array during all 4 years. The majority of NIPT tests were analyzed using the Illumina platform, initially confined to the assessment of the common autosomal trisomies, sex chromosome aneuploidies and rare autosomal trisomies (RAT), then extending to genome‐wide analysis for the last 2 years. Results Amniocentesis or chorionic villus sampling (CVS) was performed on 2657 patients, 1352 (51%) of whom had undergone prior NIPT, with 612 (45%) of these returning a high‐risk result and meeting the inclusion criteria for the study. LFTU findings significantly affected the PPV of the NIPT result for trisomies 13 (T13), 18 (T18) and 21 (T21), monosomy X (MX) and RAT but not for the other sex chromosomal abnormalities or segmental imbalances (> 7 Mb). Abnormal LFTU increased the PPV close to 100% for T13, T18, T21, MX and RAT. The magnitude of the change in PPV was highest for the most severe chromosomal abnormalities. When LFTU was normal, the incidence of confined placental mosaicism (CPM) was highest in those with a high‐risk NIPT result for T13, followed by T18 and T21. After normal LFTU, the PPV for T21, T18, T13 and MX decreased to 68%, 57%, 5% and 25%, respectively. Conclusions LFTU after a high‐risk NIPT result can alter the PPV for many chromosomal abnormalities, assisting counseling regarding invasive prenatal testing and pregnancy management. The high PPVs of NIPT for T21 and T18 are not sufficiently modified by normal LFTU findings to alter management. These at‐risk patients should be offered CVS for earlier diagnosis, particularly given the low rate of CPM associated with these aneuploidies. Patients with a high‐risk NIPT result for T13 and normal LFTU findings often wait