目的:尽管无细胞DNA(cfDNA)筛查已成为常见非整倍体的筛查方式,过去十年的进一步研究和一些出版物表明,低浓度的cfDNA与许多妊娠相关并发症之间存在一定的相关性。本系统综述和荟萃分析的主要目的是评估低ff水平在预测随后的PE/PIH中的潜在价值。GDM,SGA/FGR,和PTB。荟萃分析结果旨在总结当前可用的文献数据,并确定该生化标志物的临床相关性以及除常见非整倍体检测外,对其在并发症中的应用进行进一步研究的潜在必要性。
方法:本系统综述和荟萃分析是根据系统综述和荟萃分析(PRISMA)指南的首选报告项目设计的。它包括所有观察性研究,这些研究报告在进行非侵入性产前检测(NIPT)后低-ff水平,作为筛查染色体异常及其与不良妊娠结局的关系的一部分。即妊娠高血压疾病的后续发展,妊娠期糖尿病,早产,以及检测小于胎龄胎儿或生长受限胎儿。Medline(1966-2041),Scopus(2004-2024)Clinicaltrials.gov(2008-2024),EMBASE(1980-2024),在我们的主要搜索中使用了Cochrane中央对照试验注册中心(1999-2024)和GoogleScholar(2004-2024)数据库以及电子检索全文论文的参考列表。我们最后一次搜索的日期是2024年2月29日。
结果:我们的搜索确定了128项潜在相关研究,总的来说,本系统综述包括8项研究,共纳入72,507例患者。cfDNA低ff与HDP呈正相关(OR1.66,95%CI1.34,2.06,I平方检验:56%)。cfDNA低ff与GDM呈正相关(OR1.27,95%CI1.03,1.56,I平方检验:76%)。此外,低ff水平与SGA/FGR呈正相关(OR1.63,95%CI1.32,2.03,I平方检验:0%)。低ff水平与PTB风险呈正相关,但这种关联并未达到统计学上的显着水平(OR1.22,95%CI0.89,1.67,I平方检验:66%)。
结论:我们的研究表明低ff与不良围产期结局的风险增加有关。包括PE/PIH,GDM,和SGA/FGR。然而,由于证据相互矛盾,ff与PTB之间的关系尚不清楚.应该强调的是,需要进一步的研究来揭示低ff与不良妊娠结局的关联背后的潜在机制,并探索其在整体产前筛查中的潜在作用。这可能不仅限于检测非整倍体。
OBJECTIVE: While cell-free DNA (cfDNA) screening has emerged as a screening modality for common aneuploidies, further research and several publications over the past decade suggested some correlation between the low concentrations of cfDNA and a number of pregnancy-related complications. The primary goal of this systematic review and meta-analysis was to assess the potential value of low-ff levels in the prediction of subsequent PE/PIH, GDM, SGA/FGR, and PTB. The meta-analysis results aim at summarizing the currently available literature data and determining the clinical relevance of this biochemical marker and the potential necessity for additional investigation of its utility in complications other than the detection of common aneuploidies.
METHODS: This systematic review and meta-analysis was designed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. It included all observational studies that reported low -ff levels after the performance of non-invasive prenatal testing (NIPT) as part of the screening for chromosomal abnormalities and their association with adverse pregnancy outcomes, namely the subsequent development of hypertensive disorders of pregnancy, gestational diabetes, preterm birth, and the detection of small for gestational age fetuses or growth-restricted fetuses. The Medline (1966-2041), Scopus (2004-2024), Clinicaltrials.gov (2008-2024), EMBASE (1980-2024), Cochrane Central Register of Controlled Trials CENTRAL (1999-2024) and Google Scholar (2004-2024) databases were used in our primary search along with the reference lists of electronically retrieved full-text papers. The date of our last search was set at February 29, 2024.
RESULTS: Our search identified 128 potentially relevant studies and,overall, 8 studies were included in the present systematic review that enrolled a total of 72,507 patients. Low ff of cfDNA cfDNA was positively associated with HDP (OR 1.66, 95% CI 1.34, 2.06, I-square test: 56%). Low ff of cfDNA was positively associated with GDM (OR 1.27, 95% CI 1.03, 1.56, I-square test: 76%). Furthermore, low ff levels were positively associated with SGA/FGR (OR 1.63, 95% CI 1.32, 2.03, I-square test: 0%). Low ff levels were positively correlated with the risk for PTB but the association did not manage to reach a statistical significant level (OR 1.22, 95% CI 0.89, 1.67, I-square test: 66%).
CONCLUSIONS: Our study suggests that low ff is associated with increased risk of adverse perinatal outcomes, including PE/PIH, GDM, and SGA/FGR. However, the relationship between ff and PTB remains unclear due to conflicting evidence. It should be emphasized that further research is needed to reveal the underlying mechanisms behind the association of low ff with adverse pregnancy outcomes and explore its potential role in an overall prenatal screening, which could potentially not be limited to detecting aneuploidies.