Confined placental mosaicism and pregnancy

The authors noted that chromosomal mosaicism can be detected at various stages of early life, starting within cleavage stage embryos, followed by blastocysts and biopsied cells from blastocysts during preimplantation genetic testing for aneuploidies (PGT-A), during prenatal testing and in cord blood after birth.

Mosaicism at any of these different stages may be linked to adverse pregnancy outcomes, according to the authors.

Meanwhile, discussion persists about whether blastocysts diagnosed as chromosomally mosaic by PGT-A should be deemed safe for transfer. “An accurate diagnosis of mosaicism remains technically challenging and the fate of abnormal cells within an embryo remains largely unknown,” the authors wrote. But if aneuploid cells remain in the extraembryonic tissues, CPM might occur.

To facilitate the detection of CPM, noninvasive prenatal testing (NIPT) using cell-free DNA (cfDNA) released from the placenta in maternal blood can be employed.

However, there is conflicting evidence in the literature about whether CPM is connected to fetal growth restriction (FGR) and/or other pregnancy outcomes. Hence, patient counseling by clinicians is challenging. Also, increased knowledge for clinical decisions and policy making is needed.

The authors searched Embase, PubMed, Medline Ovid, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases for relevant articles, with a publishing cutoff date of July 16, 2020.

Among the 70 articles included in the review, there were 328 fetuses and 14 different chromosomes evaluated, with 100 cases involving chromosome 16.

For CPM in 8 of the chromosomes, birth weight was often below the 5th percentile of fetal growth standards.

FGR occurred in 71.7% of CPM cases and preterm birth (<37 weeks of delivery) in 31.0% of cases.

There was also a 24.2% rate of structural fetal anomalies in cases of CPM.

In addition, high levels of mosaicism in CVS and the presence of uniparental disomy (UPD) were significantly associated with adverse pregnancy outcomes.

Overall, there were 12 cases of intrauterine fetal death (IUFD), with 8 of these deaths CPM trisomy 16. In 1 case, IUFD happened at 15 weeks of gestational age, with multiple structural fetal anomalies and growth below the third percentile.

Parents selected termination of pregnancy after diagnosis of CPM in 15 cases, of which 12 also had FGR and 6 had structural fetal anomalies.

The review found that in cases of CPM involving trisomy for chromosomes 9, 10, 12, 18 and 20, there is no indication of adverse pregnancy outcomes.

“Based on the literature, the advice to clinicians is to monitor fetal growth intensively from first trimester onwards in case of CPM, especially when chromosome 2, 3, 7, 13, 15, 16 and 22 are involved,” wrote the authors.

They also advocate examining the fetus thoroughly for structural fetal anomalies, as well as raising awareness of a higher likelihood of premature birth, possibly extreme.

Despite prematurity in nearly a fifth of the cases analyzed, long-term follow-up of people with CPM appears positive, according to the authors.

“More understanding of the biological mechanisms behind CPM will help in prioritizing embryos for transfer after the detection of mosaicism in embryos through PGT-A,” they said.

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Reference

1. Eggenhuizen GM, Go A, Koster MPH, et al. Confined placental mosaicism and the association with pregnancy outcome and fetal growth: a review of the literature. Hum Reprod Update. Published online May 13, 2021. doi:10.1093/humupd/dmab009