Pregnancy outcome of confined placental mosaicism: meta-analysis of cohort studies

Abstract

Objective: This study aimed to assess the rate of adverse obstetrical and neonatal outcomes in pregnancies diagnosed with confined placental mosaicism relative to that of unaffected controls.

Data sources: Web-based databases were searched using relevant key words, and articles published from 1980 to February 2022 were retrieved.

Study eligibility criteria: Observational studies in English language including ≥10 cases of singleton pregnancies with diagnosis of confined placental mosaicism were included. The diagnosis was established after detection of any chromosomal abnormality at chorionic villus sampling for any indication, followed by normal karyotype from amniotic fluid or neonatal leukocyte culture.

Methods: Two authors independently screened the references for eligibility, data extraction, and assessment of methodological quality using the Newcastle-Ottawa scale. All available obstetrical and neonatal outcomes were recorded. Random-effect meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals of available outcomes in pregnancies with and without confined placental mosaicism. Statistical heterogeneity was evaluated with I² statistics (International Prospective Register of Systematic Reviews registration number: CRD42021260319).

Results: Of the 80 articles reviewed, 8 retrospective matched-cohort studies (708 cases of confined placental mosaicism and 11,599 unaffected controls) compared cases with and without confined placental mosaicism and were included in the meta-analysis. The risk of delivering small-for-gestational-age neonates was significantly increased in confined placental mosaicism pregnancies according to crude analysis (odds ratio, 2.45; 95% confidence interval, 1.23-4.89; I²=72%) and to sensitivity analysis of high-quality studies (odds ratio, 3.65; 95% confidence interval, 2.43-5.57; I²=0%). Similarly, confined placental mosaicism resulted in an increased risk of birthweight below the third centile (odds ratio, 5.33; 95% confidence interval, 1.19-24.19; I²= 83%). Subgroup analysis revealed that the risk of delivering small-for-gestational-age neonates was 3-fold higher for confined placental mosaicism excluding trisomy 16, and 11-fold higher for cases including trisomy 16 only vs unaffected controls, respectively. No difference was found in the risk of low birthweight and preterm birth (at <37 weeks' gestation). Other outcomes were insufficiently reported, therefore they were not analyzed.

Conclusion: Pregnant women prenatally diagnosed with confined placental mosaicism have an increased risk of impaired fetal growth, suggesting the need for intensified antenatal surveillance.

Keywords: chorionic villus sampling; confined placental mosaicism; fetal growth restriction; genetics; placenta; pregnancy outcome; prenatal diagnosis; small for gestational age.