Pregnancy Outcome of Confined Placental Mosaicism: Meta-analysis of Cohort Studies
Authors: Spinillo Silvia L. , Farina Antonio , Sotiriadis Alexandros , Pozzoni Mirko , Giglio Sabrina , Papale Margherita , Candiani Massimo , Cavoretto Paolo I. 
Published: May 2023

Confined placental mosaicism (CPM) is a condition in which there is chromosomal abnormality in the placenta that is not present in the fetus. Confined placental mosaicism has historically been most often identified following a first-trimester chorionic villus sampling (CVS), in which there are 2 different cell lines in the placenta but a normal karyotype in the fetus based on amniocentesis or neonatal blood. As the outcome for CPM pregnancies is still debated, including the potential for adverse pregnancy and postnatal outcomes, this study aimed to evaluate the rates of adverse neonatal and obstetrical outcomes in CPM-diagnosed pregnancies, as compared with unaffected matched controls.

This meta-analysis was performed in accordance with an a priori designed protocol and was registered with the PROSPERO (International Prospective Register of Systematic Reviews) database. A search of EMBASE and MEDLINE databases from 1980 to February 2022 was performed. Included articles were published in the English language and were observational studies including singleton CPM-diagnosed pregnancies (whose controls were unaffected and with normal karyotype). Excluded were all reviews, case reports, and congress abstracts. In addition, high-risk or positive cell-free DNA screening (cfDNA) cases followed by diploid amniotic cells were excluded (because of the different methodology, which may have an effect on the analysis). Because of the paucity of data regarding mosaicism in submicroscopic copy number variants, these abnormalities were also excluded from the analysis.

Primary outcomes included the occurrence of the following: termination of pregnancy, major fetal defects (as defined by the Centers for Disease Control and Prevention), small for gestational age (SGA) neonate with birth weight (BW) <10th centile and neonatal SGA with BW less than the third centile, preterm birth (PTB), hypertensive disorders, admission to a neonatal intensive care unit, intrauterine fetal demise at <24 weeks' gestation, and >24 weeks' gestation stillbirth. All other abnormal pregnancy outcomes were searched for, including PTB, obstetrical cholestasis, amniotic infection, gestational diabetes, cesarean delivery, amniotic infection, preterm prelabor rupture of membranes, and neonatal mortality or morbidity.

Of 310 retrieved articles, 80 studies were assessed for eligibility, and 8 retrospective matched cohort studies were included. The results of the meta-analysis showed that women with CPM had a higher risk of adverse pregnancy outcomes than those without CPM. The most common adverse outcomes were fetal growth restriction (FGR), PTB, and stillbirth. The risk of FGR was significantly higher in women with CPM, with an odds ratio (OR) of 3.60 (95% confidence interval [CI], 2.40–5.39). Similarly, the risk of PTB was higher in women with CPM, with an OR of 2.64 (95% CI, 1.90–3.67), and the risk of stillbirth was also increased, with an OR of 2.58 (95% CI, 1.51–4.42). Scarcity of reporting for other obstetrical neonatal and obstetrical outcomes hindered further conclusions. In subgroup analysis, the risk of delivering an SGA infant was 3-fold higher for CPM when trisomy 16 was excluded and 11-fold higher for trisomy 16 specifically compared with unaffected controls.

The authors acknowledge that the meta-analysis has several limitations, including the heterogeneity of the included studies, the lack of information on the specific type and extent of CPM in each case, and the potential for publication bias. Nevertheless, the study provides valuable insights into the pregnancy outcomes of women with CPM and highlights the need for further research to improve our understanding of this condition.

Overall, this meta-analysis suggests that women with CPM are at increased risk of adverse pregnancy outcomes, particularly FGR, PTB, and stillbirth. The findings highlight the importance of early detection of CPM and close monitoring of pregnancies in women with this condition. The study also emphasizes the need for further research to better understand the underlying mechanisms of CPM and to identify effective interventions to improve pregnancy outcomes in affected women.