{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:54:53Z","timestamp":1791176093544,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Low fetal fraction (LFF) in prenatal cell\u2010free DNA (cfDNA) testing is an important cause of test failure and no\u2010call 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>A systematic literature search was conducted in MEDLINE and EMBASE up to November 1, 2020.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LFF in cfDNA testing is associated with adverse pregnancy outcome,specifically pregnancy\u2010related 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pd.6028","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T20:33:57Z","timestamp":1628109237000},"page":"1287-1295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Association between low fetal fraction in cell\u2010free DNA testing and adverse pregnancy outcome: A systematic review"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9253-5341","authenticated-orcid":false,"given":"Peter G.","family":"Scheffer","sequence":"first","affiliation":[{"name":"Department of Obstetrics Wilhelmina Children's Hospital University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soetinah A. M.","family":"Wirjosoekarto","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Wilhelmina Children's Hospital University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0418-7880","authenticated-orcid":false,"given":"Ellis C.","family":"Becking","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Wilhelmina Children's Hospital University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan M.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Genetics Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline J.","family":"Bax","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Amsterdam UMC University of Amsterdam  Amsterdam The 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