Outcomes in Pregnancies with a Confined Placental Mosaicism and Implications for Prenatal Screening Using Cell-Free DNA

The most common type of confined placental mosaicism (CPM), the presence of a chromosomal abnormality in the placenta but not in the fetus, involves trisomy/disomy. Confined placental mosaicism occurs in 97% of rare autosomal trisomy (RAT) cases detected by chorionic villus sampling (CVS). Despite this relatively common finding, the association between CPM and adverse outcomes of pregnancy remains unclear. The aim of this study was to assess the association between CPM and adverse pregnancy outcomes. This was a retrospective study, based on the medical records of women who underwent CVS at 7 Italian referral centers between May 2000 and January 2018. The study included singleton pregnancies with no abnormalities and the presence of abnormal cell lines showing a RAT, tetraploidy, or whole autosomal arm imbalance in 1 or both of the 2 placental layers, and whose follow-up amniocentesis showed a normal karotype. Excluded were twin pregnancies, confirmed true fetal mosaicism, incomplete CVS analysis, and CPM for common trisomies or sex chromosome aneuploidies. Control subjects had a singleton pregnancy with no evidence of CPM. The outcomes considered were birth weight, gestational age, fetal growth restriction, Apgar score, neonatal intensive care unit admission, hypertensive disorders, and preterm birth. Data sets with known outcomes were identified for 124 pregnancies with CPM and 468 control subjects. There was a statistically significant association between CPMs involving RATs (excluding T16) and fetal growth restriction (odds ratio [OR], 3.4%; 95% confidence interval [CI], 1.3-9.3). Confined placental mosaicism involving T16 showed significant associations with the incidence of birth weight of less than third centile (OR, 11.2; 95% CI, 2.7-47.1; P = 0.007), preterm delivery (OR, 10.2; 95% CI, 1.9-54.7; P = 0.029), and Apgar score (P = 0.006). For other RATs, birth weight data did not support an association with fetal growth restriction. No other strong associations with adverse outcomes were found. The data suggest the incidence of adverse pregnancy outcomes in women identified with CPM is low. In terms of genome-wide cell-free DNA (cfDNA) screening, the yield of low-birth-weight infants identified through RAT is minimal, and therefore, this screening would unlikely be an effective test.