Abstract：
To perform a systematic review and meta-analysis of the available literature on low fetal fraction (LFF) in cell-free DNA (cfDNA) screening and the risk of fetal chromosomal aberrations.
We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS-2.
Twenty-seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 [3.61-9.95], I 2 of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 [3.07-6.47], I 2 = 0%, n = 22 studies), monosomy X (OR 5.88 [2.34-14.78], I 2 = 18%, n = 10 studies), and triploidy (OR 36.39 [9.83-134.68], I 2 = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 [0.76-2.03], I 2 = 36%, n = 23 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 [1.78-9.00], I 2 = 2%, n = 11 studies). Meta-analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1% and 2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed.
An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and other specific types of fetal chromosomal aberrations.
We searched articles published between January 2010 and May 2021 in PubMed and EMBASE databases. Risk of bias was assessed using QUADAS-2.
Twenty-seven studies met the inclusion criteria, comprising data of 243,700 singleton pregnancies. Compared to normal fetal fraction, LFF was associated with a higher risk of trisomy 13 (OR 5.99 [3.61-9.95], I 2 of heterogeneity = 0%, n = 22 studies), trisomy 18 (OR 4.46 [3.07-6.47], I 2 = 0%, n = 22 studies), monosomy X (OR 5.88 [2.34-14.78], I 2 = 18%, n = 10 studies), and triploidy (OR 36.39 [9.83-134.68], I 2 = 61%, n = 6 studies), but not trisomy 21 (OR 1.25 [0.76-2.03], I 2 = 36%, n = 23 studies). LFF was also associated with a higher risk of various other types of fetal chromosomal aberrations (OR 4.00 [1.78-9.00], I 2 = 2%, n = 11 studies). Meta-analysis of proportions showed that absolute rates of fetal chromosomal aberrations ranged between 1% and 2% in women with LFF. A limitation of this review is the potential risk of ascertainment bias because of differences in outcome assessment between pregnancies with LFF and those with normal fetal fraction. Heterogeneity in population characteristics or applied technologies across included studies may not have been fully addressed.
An LFF test result in cfDNA screening is associated with an increased risk of fetal trisomy 13, trisomy 18, monosomy X, and triploidy, but not trisomy 21. Further research is needed to assess the association between LFF and other specific types of fetal chromosomal aberrations.
摘要：
目的：对无细胞DNA（cfDNA）筛查中的低胎儿分数（LFF）和胎儿染色体畸变风险的现有文献进行系统评价和荟萃分析。
方法：我们检索了2010年1月至2021年5月在PubMed和EMBASE数据库中发表的文章。使用QUADAS-2评估偏倚风险。
结果：27项研究符合纳入标准，包括243,700例单胎妊娠的数据。与正常胎儿分数相比，LFF与13三体的高风险相关（OR5.99[3.61-9.95]，I2的异质性=0%，n=22项研究)，18三体(OR4.46[3.07-6.47]，I2=0%，n=22项研究)，X(OR5.88[2.34-14.78]，I2=18%，n=10项研究)，和三倍体（OR36.39[9.83-134.68]，I2=61%，n=6项研究)，但不是21三体(OR1.25[0.76-2.03]，I2=36%，n=23项研究)。LFF还与各种其他类型的胎儿染色体畸变的高风险相关（OR4.00[1.78-9.00]，I2=2%，n=11项研究)。比例的荟萃分析表明，LFF女性胎儿染色体畸变的绝对发生率在1-2％之间。由于LFF妊娠与正常胎儿分数妊娠之间的结局评估存在差异，因此该综述的局限性是确定偏倚的潜在风险。纳入研究的人群特征或应用技术的异质性可能尚未得到充分解决。
结论：cfDNA筛查中的LFF测试结果与胎儿13三体，18三体，X单体的风险增加有关，和三倍体，但不是21三体。需要进一步的研究来评估LFF和其他特定类型的胎儿染色体畸变之间的关联。本文受版权保护。保留所有权利。
方法：我们检索了2010年1月至2021年5月在PubMed和EMBASE数据库中发表的文章。使用QUADAS-2评估偏倚风险。
结果：27项研究符合纳入标准，包括243,700例单胎妊娠的数据。与正常胎儿分数相比，LFF与13三体的高风险相关（OR5.99[3.61-9.95]，I2的异质性=0%，n=22项研究)，18三体(OR4.46[3.07-6.47]，I2=0%，n=22项研究)，X(OR5.88[2.34-14.78]，I2=18%，n=10项研究)，和三倍体（OR36.39[9.83-134.68]，I2=61%，n=6项研究)，但不是21三体(OR1.25[0.76-2.03]，I2=36%，n=23项研究)。LFF还与各种其他类型的胎儿染色体畸变的高风险相关（OR4.00[1.78-9.00]，I2=2%，n=11项研究)。比例的荟萃分析表明，LFF女性胎儿染色体畸变的绝对发生率在1-2％之间。由于LFF妊娠与正常胎儿分数妊娠之间的结局评估存在差异，因此该综述的局限性是确定偏倚的潜在风险。纳入研究的人群特征或应用技术的异质性可能尚未得到充分解决。
结论：cfDNA筛查中的LFF测试结果与胎儿13三体，18三体，X单体的风险增加有关，和三倍体，但不是21三体。需要进一步的研究来评估LFF和其他特定类型的胎儿染色体畸变之间的关联。本文受版权保护。保留所有权利。
