{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T16:04:11Z","timestamp":1767110651833,"version":"3.48.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypertension, infection, hemorrhage, cardiovascular events, gestational diabetes, anemia, and miscarriage remain the primary cause of maternal mortality and morbidity. Despite advances in maternal health, there remains a gap in the ability to accurately diagnose, or predict the risk of, certain pregnancy-related conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Content<\/jats:title>\n                    <jats:p>Here, we discuss preterm delivery, preeclampsia, ectopic pregnancy, gestational diabetes, and detection of fetal anomalies. These are 5 examples of pregnancy-related conditions for which a significant diagnostic gap still exists. We note that many of the available tests used in this field promote a high negative predictive value (NPV), when tests with high positive predictive value (PPV) are needed to drive treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>To improve the modes of maternal testing, researchers need to establish the performance criteria necessary for the given condition. For low-prevalence conditions with potentially catastrophic outcomes, a single test needs extremely high sensitivity and specificity to achieve the PPV required to identify the small number of affected women who would benefit from intensive intervention. Alternatively, 2-step approaches could be used with a highly sensitive screen followed by a highly specific test. However, the solution to improving maternal morbidity and mortality is 2-fold: both affordable, effective, and rapid modes of testing; and safer, more effective treatments are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/clinchem\/hvaf109","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T11:30:31Z","timestamp":1756207831000},"page":"27-34","source":"Crossref","is-referenced-by-count":0,"title":["From Diagnosis to Delivery: A Look at the Continuing Gap in Maternal Testing"],"prefix":"10.1093","volume":"72","author":[{"given":"Callie","family":"Torres","sequence":"first","affiliation":[{"name":"Department of Pathology & Immunology, Washington University in St. Louis School of Medicine , St. Louis, MO ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeannie","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University in St. Louis School of Medicine , St. Louis, MO ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann M","family":"Gronowski","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology, Washington University in St. Louis School of Medicine , St. Louis, MO ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"2025123010594419300_hvaf109-B1","author":"World Health Organization"},{"key":"2025123010594419300_hvaf109-B2","author":"Tikkanen"},{"key":"2025123010594419300_hvaf109-B3","first-page":"126","article-title":"Amniocentesis for fetal lung maturity: will it become obsolete?","volume":"6","author":"Varner","year":"2013","journal-title":"Rev Obstet Gynecol"},{"key":"2025123010594419300_hvaf109-B4","doi-asserted-by":"crossref","first-page":"e155","DOI":"10.1097\/AOG.0000000000001711","article-title":"Practice Bulletin No. 171: management of preterm labor","volume":"128","author":"ACOG Practice Bulletin","year":"2016","journal-title":"Obstet Gynecol"},{"key":"2025123010594419300_hvaf109-B5","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1097\/AOG.0b013e3181b47217","article-title":"Fetal fibronectin as a short-term predictor of preterm birth in symptomatic patients: a meta-analysis","volume":"114","author":"Sanchez-Ramos","year":"2009","journal-title":"Obstet Gynecol"},{"key":"2025123010594419300_hvaf109-B6","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/uog.19119","article-title":"Prediction of preterm delivery in symptomatic women using PAMG-1, fetal fibronectin and phIGFBP-1 tests: systematic review and meta-analysis","volume":"52","author":"Melchor","year":"2018","journal-title":"Ultrasound Obstet Gynecol"},{"key":"2025123010594419300_hvaf109-B7","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/j.1471-0528.2012.03328.x","article-title":"Prediction of spontaneous preterm delivery in women with threatened preterm labour: a prospective cohort study of multiple proteins in maternal serum","volume":"119","author":"Tsiartas","year":"2012","journal-title":"BJOG"},{"key":"2025123010594419300_hvaf109-B8","doi-asserted-by":"crossref","first-page":"e2444454","DOI":"10.1001\/jamanetworkopen.2024.44454","article-title":"Midpregnancy placental growth factor screening and early preterm birth","volume":"7","author":"Gladstone","year":"2024","journal-title":"JAMA Netw Open"},{"key":"2025123010594419300_hvaf109-B9","doi-asserted-by":"crossref","first-page":"10213","DOI":"10.1038\/s41598-025-92814-y","article-title":"Machine learning prediction of preterm birth in women under 35 using routine biomarkers in a retrospective cohort study","volume":"15","author":"Teng","year":"2025","journal-title":"Sci Rep"},{"key":"2025123010594419300_hvaf109-B10","doi-asserted-by":"crossref","first-page":"e1004571","DOI":"10.1371\/journal.pmed.1004571","article-title":"Genome-wide nucleosome footprints of plasma cfDNA predict preterm birth: a case-control study","volume":"22","author":"Guo","year":"2025","journal-title":"PLoS Med"},{"key":"2025123010594419300_hvaf109-B11","doi-asserted-by":"crossref","first-page":"e237","DOI":"10.1097\/AOG.0000000000003891","article-title":"American College of Obstetricians and Gynecologists (ACOG). Practice Bulletin No. 222: Gestational hypertension and preeclampsia","volume":"135","year":"2020","journal-title":"Obstetrics & Gynecology"},{"key":"2025123010594419300_hvaf109-B12","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/S0140-6736(19)31963-4","article-title":"Planned early delivery or expectant management for late preterm pre-eclampsia (PHOENIX): a randomized controlled trial","volume":"394","author":"Chappell","year":"2019","journal-title":"Lancet"},{"key":"2025123010594419300_hvaf109-B13","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1056\/NEJMoa031884","article-title":"Circulating angiogenic factors and the risk of preeclampsia","volume":"350","author":"Levine","year":"2004","journal-title":"N Engl J Med"},{"key":"2025123010594419300_hvaf109-B14","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1414838","article-title":"Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia","volume":"374","author":"Zeisler","year":"2016","journal-title":"N Engl J Med"},{"key":"2025123010594419300_hvaf109-B15","doi-asserted-by":"crossref","first-page":"EVIDoa2200161","DOI":"10.1056\/EVIDoa2200161","article-title":"Circulating angiogenic factor levels in hypertensive disorders of pregnancy","volume":"1","author":"Thadhani","year":"2022","journal-title":"NEJM Evid"},{"key":"2025123010594419300_hvaf109-B16","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.1097\/AOG.0000000000005576","article-title":"American College of Obstetricians and Gynecologists (ACOG). ACOG Clinical Practice Update: Biomarker prediction of preeclampsia with severe features","volume":"143","year":"2024","journal-title":"Obstet Gynecol"},{"issue":"2S","key":"2025123010594419300_hvaf109-B17","doi-asserted-by":"crossref","first-page":"S1222","DOI":"10.1016\/j.ajog.2020.08.018","article-title":"Guidelines-similarities and dissimilarities: a systematic review of international clinical practice guidelines for pregnancy hypertension","volume":"226","author":"Scott","year":"2022","journal-title":"Am J Obstet Gynecol"},{"key":"2025123010594419300_hvaf109-B18","doi-asserted-by":"crossref","first-page":"eadd8752","DOI":"10.1126\/sciadv.adi4777","article-title":"Adrenomedullin has a pivotal role in trophoblast differentiation: a promising nanotechnology-based therapeutic target for early-onset preeclampsia","volume":"9","author":"Zhang","year":"2023","journal-title":"Sci Adv"},{"key":"2025123010594419300_hvaf109-B19","doi-asserted-by":"crossref","first-page":"e020302","DOI":"10.1161\/JAHA.120.020302","article-title":"Circulating growth differentiation factor 15 is increased preceding preeclampsia diagnosis: implications as a disease biomarker","volume":"10","author":"Cruickshank","year":"2021","journal-title":"J Am Heart Assoc"},{"key":"2025123010594419300_hvaf109-B20","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/ajh.2011.99","article-title":"Endothelin: key mediator of hypertension in preeclampsia","volume":"24","author":"George","year":"2011","journal-title":"Am J Hypertens"},{"key":"2025123010594419300_hvaf109-B21","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1080\/14737159.2021.1997593","article-title":"Cell-free DNA as a potential biomarker for preeclampsia","volume":"21","author":"Palei","year":"2021","journal-title":"Expert Rev Mol Diagn"},{"key":"2025123010594419300_hvaf109-B22","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1038\/s41591-023-02510-5","article-title":"Cell-free DNA methylome analysis for early preeclampsia prediction","volume":"29","author":"De Borre","year":"2023","journal-title":"Nat Med"},{"key":"2025123010594419300_hvaf109-B23","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1038\/s41591-025-03509-w","article-title":"Preeclampsia risk prediction from prenatal cell-free DNA screening","volume":"31","author":"Adil","year":"2025","journal-title":"Nat Med"},{"key":"2025123010594419300_hvaf109-B24","doi-asserted-by":"crossref","first-page":"e91","DOI":"10.1097\/AOG.0000000000002560","article-title":"ACOG Practice Bulletin No. 193: tubal ectopic pregnancy","volume":"131","author":"American College of Obstetricians and Gynecologists\u2019 Committee on Practice Bulletins\u2014Gynecology","year":"2018","journal-title":"Obstet Gynecol"},{"key":"2025123010594419300_hvaf109-B25","first-page":"45","article-title":"Overview of ectopic pregnancy diagnosis, management, and innovation","volume":"67","author":"Mullany","year":"2023","journal-title":"Woman\u2019s Health"},{"key":"2025123010594419300_hvaf109-B26","first-page":"45","article-title":"Activin A and pathologies of pregnancy: a review","volume":"57","author":"Barber","year":"2023","journal-title":"Placenta"},{"key":"2025123010594419300_hvaf109-B27","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1373\/clinchem.2006.067587","article-title":"Presence of cell-free fetal DNA in plasma of women with ectopic pregnancies","volume":"52","author":"L\u00e1z\u00e1r","year":"2006","journal-title":"Clin Chem"},{"key":"2025123010594419300_hvaf109-B28","doi-asserted-by":"crossref","first-page":"e49","DOI":"10.1097\/AOG.0000000000002501","article-title":"American College of Obstetricians and Gynecologists Committee on Practice Bulletins\u2014Obstetrics. 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Practice Bulletin No. 226: Screening for fetal chromosomal abnormalities","volume":"136","year":"2020","journal-title":"Obstet Gynecol"},{"key":"2025123010594419300_hvaf109-B39","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3399\/bjgp17X691625","article-title":"Non-invasive prenatal testing: use of cell-free fetal DNA in Down syndrome screening","volume":"67","author":"Rafi","year":"2017","journal-title":"Br J Gen Pract"},{"key":"2025123010594419300_hvaf109-B40","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ajog.2024.08.017","article-title":"The use of free DNA for fetal RHD genotyping in the Rh negative pregnant patient-the time has come","volume":"232","author":"Moise","year":"2025","journal-title":"Am J Obstet Gynecol"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/clinchem\/article-pdf\/72\/1\/27\/66163261\/hvaf109.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/clinchem\/article-pdf\/72\/1\/27\/66163261\/hvaf109.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T15:59:55Z","timestamp":1767110395000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/72\/1\/27\/8407345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,30]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12,30]]},"published-print":{"date-parts":[[2025,12,30]]}},"URL":"https:\/\/doi.org\/10.1093\/clinchem\/hvaf109","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,12,30]]}}}