TY - JOUR
T1 - Association between low fetal fraction in cell-free DNA testing and adverse pregnancy outcome: A systematic review
T2 - A systematic review
AU - Scheffer, Peter G.
AU - Wirjosoekarto, Soetinah A. M.
AU - Becking, Ellis C.
AU - Weiss, Marjan M.
AU - Bax, Caroline J.
AU - Oepkes, Dick
AU - Sistermans, Erik A.
AU - Henneman, Lidewij
AU - Bekker, Mireille N.
N1 - Funding Information: Marjan M. Weiss, Caroline J. Bax, Erik A. Sistermans, Lidewij Henneman, and Mireille N. Bekker are all involved in the TRIDENT‐2 study (Dutch NIPT Consortium) supported by a grant from the Netherlands Organization for Health Research and Development (ZonMw, No. 543002001). Publisher Copyright: © 2021 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85112759611&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/34350596
UR - http://www.scopus.com/inward/record.url?scp=85112759611&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/pd.6028
DO - https://doi.org/10.1002/pd.6028
M3 - Review article
C2 - 34350596
SN - 0197-3851
VL - 41
SP - 1287
EP - 1295
JO - Prenatal diagnosis
JF - Prenatal diagnosis
IS - 10
ER -