Association between low fetal fraction of cell free DNA at the early second-trimester and adverse pregnancy outcomes

Yuan, Xianwen; Zhou, Li-Na; Zhang, Bin; Wang, Huiyan; Yu, Bin; Xu, Jun

doi:10.1016/j.preghy.2020.07.015

Cited by 21 publications

(63 citation statements)

References 29 publications

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“…Women with pre-gestational conditions, such as chronic hypertension and diabetes, were excluded in only two studies. 34,36 36 The 25th percentile of fetal fraction in their cohort corresponded to a fetal fraction of 8.11%, not so different from that of Gerson et al, in which the 25th percentile corresponded to 8.4% fetal fraction. Using these higher cutoff values for LFF could possibly have led to higher rates of adverse events than would have been found if cutoffs had been 4% or one below which a reliable aneuploidy screening result would have been obtained.…”

Section: Discussioncontrasting

confidence: 59%

“…Yuan et al. reported on various cutoff values 36 . The 25th percentile of fetal fraction in their cohort corresponded to a fetal fraction of 8.11%, not so different from that of Gerson et al., in which the 25th percentile corresponded to 8.4% fetal fraction.…”

Section: Discussionmentioning

confidence: 67%

“…However, significant differences were found for the clinically far more relevant birthweight <5th percentile in the study by Clapp et al 33 . and for a birthweight <2500 g in the study by Yuan when using a cutoff for LFF <5th percentile 36 …”

Section: Discussionmentioning

confidence: 79%

“…In 2020, Yuan et al. conducted a historical cohort study of 2191 women with a singleton pregnancy 36 . Outcome measures included PIH, PE, birthweight, GDM, and intrahepatic cholestasis of pregnancy.…”

Section: Resultsmentioning

confidence: 99%

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Association between low fetal fraction in cell‐free DNA testing and adverse pregnancy outcome: A systematic review

et al. 2021

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Objective Low fetal fraction (LFF) in prenatal cell‐free DNA (cfDNA) testing is an important cause of test failure and no‐call results. LFF might reflect early abnormal placentation and therefore be associated with adverse pregnancy outcome. Here, we review the available literature on the relationship between LFF in cfDNA testing and adverse pregnancy outcome. Method A systematic literature search was conducted in MEDLINE and EMBASE up to November 1, 2020. Results Five studies met the criteria for inclusion; all were retrospective observational cohort studies. The cohort sizes ranged from 370 to 6375 pregnancies, with all tests performed in the first trimester or early second trimester. A 4% cutoff for LFF was used in two studies, two studies used the 5th and 25th percentiles, respectively, and one study used a variety of cutoff values for LFF. LFF in prenatal cfDNA testing was observed to be associated with hypertensive disease of pregnancy, small for gestational age neonates, and preterm birth. Conflicting results were found regarding the association between LFF and gestational diabetes mellitus. Conclusions LFF in cfDNA testing is associated with adverse pregnancy outcome,specifically pregnancy‐related hypertensive disorders, preterm birth, and impaired fetal growth related to placental dysfunction. Since the available evidence is limited, a large prospective cohort study on the relationship between fetal fraction and pregnancy outcomes is needed.

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Section: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

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Association between low fetal fraction in cell‐free DNA testing and adverse pregnancy outcome: A systematic review

et al. 2021

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“…Moreover, FF below the 10th percentile was associated with an increased risk of preeclampsia and early preterm birth < 34 weeks (67), and FF greater than or equal to the 95th percentile was also associated with an increased risk of preterm delivery (16). Furthermore, FF below the 5th percentile was associated with an increased risk of low birth weight (67,71). In addition, intrauterine growth restriction under 5th percentile was correlated with low FF (OR = 0.87, IC 95% 0.79-0.96, P = 0.006) (68), and the FF of pregnant women with early-onset growth restriction (2.00 ± 2.23%) was significantly lower than the expected FF (18.97 ± 10.17%) (69).…”

Section: Fetal-placental Characteristicsmentioning

confidence: 99%

Factors Affecting the Fetal Fraction in Noninvasive Prenatal Screening: A Review

Deng

Liu

2022

Front. Pediatr.

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A paradigm shift in noninvasive prenatal screening has been made with the discovery of cell-free fetal DNA in maternal plasma. Noninvasive prenatal screening is primarily used to screen for fetal aneuploidies, and has been used globally. Fetal fraction, an important parameter in the analysis of noninvasive prenatal screening results, is the proportion of fetal cell-free DNA present in the total maternal plasma cell-free DNA. It combines biological factors and bioinformatics algorithms to interpret noninvasive prenatal screening results and is an integral part of quality control. Maternal and fetal factors may influence fetal fraction. To date, there is no broad consensus on the factors that affect fetal fraction. There are many different approaches to evaluate this parameter, each with its advantages and disadvantages. Different fetal fraction calculation methods may be used in different testing platforms or laboratories. This review includes numerous publications that focused on the understanding of the significance, influencing factors, and interpretation of fetal fraction to provide a deeper understanding of this parameter.

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Association of fetal fraction and cell‐free fetal DNA with adverse pregnancy outcomes: A systematic review

Chen,

Wang,

Wang

et al. 2024

Intl J Gynecology & Obste

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BackgroundAdverse pregnancy outcomes, which can be caused by multiple factors, present a significant threat to the health of mothers and their babies. Cell‐free fetal DNA (cffDNA) from placental trophoblast cells might be able to reflect placental and fetal status. Previous studies have yielded controversial results regarding the association of FF or cffDNA with various adverse pregnancy outcomes. A previous study has attempted to systematically assess the association between low fetal fraction (FF) and adverse pregnancy outcomes, but it failed to perform quantitative analyses due to the few studies included. In the present study, we attempted to quantitatively assess the association of FF (or cffDNA) with adverse pregnancy outcomes and further analyze the causes of heterogeneity.ObjectivesTo investigate the association of high/low FF or cffDNA with adverse pregnancy outcomes.Search StrategyWe searched the databases of PubMed, Embase, Cochrane, and Web of Science from January 1, 1990, to June 15, 2022 in this meta‐analysis.Selection CriteriaStudies on the relationships of adverse pregnancy outcomes in women with FF or cell free DNA were included. Non‐English literature was excluded.Data Collection and AnalysisData about pregnancy outcomes and cell free DNA were extracted and meta‐analyzed. Subgroup analysis was performed by different outcomes.Main ResultsThere were 11 studies included involving 8280 participants. No significant heterogeneity was observed among the studies (I2 = 27%, 25%), and a fixed‐effect model was used for weighted quantitative analysis. The results revealed that the FF or cffDNA during pregnancy was significantly associated with adverse pregnancy outcomes in pregnant women (OR = 1.57, 95% CI [1.24, 1.99], P = 0.233). The overall incidence of the maternal adverse outcomes was 8% (95% CI: 5–13). Subgroup analysis of different outcomes showed an evident association between low FF or cffDNA and hypertensive disorders of pregnancy (HDP) (OR = 1.76, 95% CI [1.36, 2.27], P = 0.581). There was no evidence that the occurrence of spontaneous preterm birth (sPTB) and placental abnormality was associated with FF or cffDNA. No association was observed between low FF or cffDNA during pregnancy and adverse outcomes in fetuses (OR = 1.39, 95% CI [0.99, 1.94], P = 0.242). The overall incidence of adverse outcomes in fetuses was 8% (95% CI: 6–11). There were controversies over the association between high FF or cffDNA and HDP, and sPTB and small for gestational age infant, among different studies.ConclusionsPregnant women with low FF or cffDNA during the first or second trimester of pregnancy have an overall increased risk of adverse pregnancy outcomes, especially HDP. However, the association between FF and various pregnancy outcomes needs to be further explored by more prospective studies.

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Association between low fetal fraction of cell free DNA at the early second-trimester and adverse pregnancy outcomes

Cited by 21 publications

References 29 publications

Association between low fetal fraction in cell‐free DNA testing and adverse pregnancy outcome: A systematic review

Association between low fetal fraction in cell‐free DNA testing and adverse pregnancy outcome: A systematic review

Factors Affecting the Fetal Fraction in Noninvasive Prenatal Screening: A Review

Association of fetal fraction and cell‐free fetal DNA with adverse pregnancy outcomes: A systematic review

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