BACKGROUND Chromosomal mosaicism can be detected in different stages of early life: in cleavage stage embryos, in blastocysts and biopsied cells from blastocysts during preimplantation genetic testing for aneuploidies (PGT-A) and later during prenatal testing, as well as after birth in cord blood. Mosaicism at all different stages can be associated with adverse pregnancy outcomes. There is an onward discussion about whether blastocysts diagnosed as chromosomally mosaic by PGT-A should be considered safe for transfer. An accurate diagnosis of mosaicism remains technically challenging and the fate of abnormal cells within an embryo remains largely unknown. However, if aneuploid cells persist in the extraembryonic tissues, they can give rise to confined placental mosaicism (CPM). Non-invasive prenatal testing (NIPT) uses cell-free (cf) DNA released from the placenta in maternal blood, facilitating the detection of CPM. In literature, conflicting evidence is found about whether CPM is associated with fetal growth restriction (FGR) and/or other pregnancy outcomes. This makes counselling for patients by clinicians challenging and more knowledge is needed for clinical decision and policy making. OBJECTIVE AND RATIONALE The objective of this review is to evaluate the association between CPM and prenatal growth and adverse pregnancy outcomes. All relevant literature has been reviewed in order to achieve an overview on merged results exploring the relation between CPM and FGR and other adverse pregnancy outcomes. SEARCH METHODS The following Medical Subject Headings (MESH) terms and all their synonyms were used: placental, trophoblast, cytotrophoblast, mosaicism, trisomy, fetal growth, birth weight, small for gestational age and fetal development. A search in Embase, PubMed, Medline Ovid, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases was conducted. Relevant articles published until 16 July 2020 were critically analyzed and discussed. OUTCOMES There were 823 articles found and screened based on their title/abstract. From these, 213 articles were selected and full text versions were obtained for a second selection, after which 70 publications were included and 328 cases (fetuses) were analyzed. For CPM in eight different chromosomes (of the total 14 analyzed), there was sufficient evidence that birth weight was often below the 5th percentile of fetal growth standards. FGR was reported in 71.7% of CPM cases and preterm birth (<37 weeks of delivery) was reported in 31.0% of cases. A high rate of structural fetal anomalies, 24.2%, in cases with CPM was also identified. High levels of mosaicism in CVS and presence of uniparental disomy (UPD) were significantly associated with adverse pregnancy outcomes. WIDER IMPLICATIONS 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. In addition to this, it is advised to examine the fetuses thoroughly for structural fetal anomalies and raise awareness of a higher chance of (possibly extreme) premature birth. Despite prematurity in nearly a fifth of cases, the long-term follow-up of CPM life borns seems to be positive. 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.

中文翻译：

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局限性胎盘嵌合体及其与妊娠结局和胎儿生长的关系：文献综述

背景 染色体嵌合体可在生命早期的不同阶段检测到：在卵裂期胚胎中、在胚胎植入前非整倍体基因检测 (PGT-A) 期间的囊胚和来自囊胚的活检细胞中，随后在产前检测期间以及出生后的脐带血中检测到。 . 所有不同阶段的镶嵌现象都可能与不良妊娠结局有关。关于通过 PGT-A 诊断为染色体嵌合的囊胚是否应该被认为是安全的转移存在进一步的讨论。嵌合体的准确诊断在技术上仍然具有挑战性，胚胎内异常细胞的命运在很大程度上仍然未知。然而，如果非整倍体细胞持续存在于胚胎外组织中，它们会导致局限的胎盘嵌合体 (CPM)。无创产前检测 (NIPT) 使用母体血液中胎盘释放的无细胞 (cf) DNA，有助于检测 CPM。在文献中，关于 CPM 是否与胎儿生长受限 (FGR) 和/或其他妊娠结局相关的证据相互矛盾。这使得临床医生为患者提供咨询具有挑战性，临床决策和政策制定需要更多的知识。目的和理由 本综述的目的是评估 CPM 与产前生长和不良妊娠结局之间的关联。对所有相关文献进行了审查，以对探索 CPM 和 FGR 与其他不良妊娠结局之间关系的合并结果进行概述。搜索方法 使用了以下医学主题词 (MESH) 术语及其所有同义词：胎盘、滋养层、细胞滋养层、嵌合体、三体性、胎儿生长、出生体重、小于胎龄和胎儿发育。在 Embase、PubMed、Medline Ovid、Web of Science、Cochrane Central Register of Controlled Trials (CENTRAL) 和 Google Scholar 数据库中进行了搜索。对截至 2020 年 7 月 16 日发表的相关文章进行了批判性分析和讨论。结果 根据标题/摘要找到并筛选了 823 篇文章。从中筛选出 213 篇文章，并获得全文版本进行二次筛选，随后纳入 70 篇出版物，分析了 328 例病例（胎儿）。对于 8 条不同染色体中的 CPM（共分析 14 条），有充分证据表明出生体重通常低于胎儿生长标准的第 5 个百分位。森林遗传资源报告于 71 年。31.0% 的病例报告了 7% 的 CPM 病例和早产（小于 37 周分娩）。在 CPM 病例中，胎儿结构异常的发生率也很高，为 24.2%。CVS 中高水平的嵌合体和单亲二体 (UPD) 的存在与不良妊娠结局显着相关。更广泛的影响 根据文献，临床医生的建议是在 CPM 的情况下从孕早期开始密切监测胎儿生长，尤其是涉及 2、3、7、13、15、16 和 22 号染色体时。除此之外，建议彻底检查胎儿的结构性胎儿异常，并提高对（可能是极端的）早产可能性更高的认识。尽管近五分之一的病例早产，但对 CPM 终生婴儿的长期随访似乎是积极的。