{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T11:49:30Z","timestamp":1766490570675,"version":"3.48.0"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: The antenatal management of Down syndrome (DS) is difficult as it is associated with a high risk for in utero fetal demise (IUFD) with a paucity of literature to guide antenatal surveillance. Avoidance of preterm delivery in the DS fetus, so commonly affected by anomalies, compounds the dichotomy of achieving term delivery while balancing against the risk for IUFD as gestational age advances. Higher-performing tests are needed to predict, and, thus, hopefully prevent, both preterm delivery and fetal mortality. Our study was undertaken to evaluate the performance metrics of current antenatal surveillance parameters that might suggest an increased risk for IUFD. Methods: We studied a retrospective cohort of all continuing pregnancies with a cytogenetically confirmed DS fetus between 2009 and 2019 at a single institution. Cases were investigated for abnormalities in fetal growth, anatomy, UA Doppler, and amniotic fluid volume to analyze their interrelationships and their association with the primary outcome, IUFD. Nonstress testing (NST) and biophysical profile data as available were also reviewed for analysis on each case. Maternal demographic data were also collected. Results: A total of 41 DS pregnancies at &gt;20 weeks gestation were included. Eight (19.5%) resulted in IUFD, while thirty-three (80.5%) resulted in live birth. Between these groups, there was no significant difference in the incidence of fetal structural anomalies. FGR was present in 8\/41 fetuses or 19.5% of all cases. FGR was present in 1 of 8 (12.5%) IUFD cases and 7 of 33 (21.2%) live births (p = 0.50). Thus, notably, 87.5% (7\/8) of the IUFDs occurred in the absence of FGR. Furthermore, 1\/8 (12.5%) FGR cases resulted in IUFD vs. 7\/33 (21.2%) of non-FGR cases (p = 0.50). In DS fetuses after 24 weeks gestation, UA Doppler abnormalities developed in 75% of FGR cases (6\/8) and in 64.5% of normally grown cases (20\/31) (p = 0.33). Abnormal UA Dopplers were noted in 83.3% of IUFD and in 84.8% of liveborn cases (p = 0.34). Eleven of thirty-three live births, however, underwent iatrogenic delivery secondary to worsening fetal surveillance, including ten with worsening UA Doppler indices. There was an increased frequency of abnormal NST in the IUFD group (66.7% vs. 23.8%), although this difference did not reach statistical significance. Polyhydramnios was more frequent in the IUFD group (62.5% vs. 16.1%, p = 0.04). Conclusions: Aside from polyhydramnios, no fetal surveillance parameter demonstrated an association with IUFD that reached statistical significance. A majority of fetuses with DS are normally grown and demonstrate abnormal UA Doppler indices in the absence of FGR. Within our cohort, a substantial number of liveborn deliveries were prompted following worsening UA Dopplers. Both polyhydramnios and UA Doppler indices are worthy of further investigation to inform clinically useful fetal surveillance strategies in DS.<\/jats:p>","DOI":"10.3390\/diagnostics16010039","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T11:30:18Z","timestamp":1766489418000},"page":"39","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Critical Assessment of Antenatal Monitoring for Fetal Well-Being in Down Syndrome Pregnancies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5534-5946","authenticated-orcid":false,"given":"Juliet C.","family":"Bishop","sequence":"first","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Gynecology & Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1792-4029","authenticated-orcid":false,"given":"Angie C.","family":"Jelin","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Gynecology & Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0070-9840","authenticated-orcid":false,"given":"Ahizechukwu C.","family":"Eke","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Gynecology & Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6484-3337","authenticated-orcid":false,"given":"Christine B.","family":"Hertenstein","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Gynecology & Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Gynecology & Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clark T.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Gynecology & Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5419-4934","authenticated-orcid":false,"given":"Karin","family":"Blakemore","sequence":"additional","affiliation":[{"name":"Division of Maternal-Fetal Medicine, Department of Gynecology & Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/bdr2.1589","article-title":"National population-based estimates for major birth defects, 2010\u20132014","volume":"111","author":"Mai","year":"2019","journal-title":"Birth Defects Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1034\/j.1399-0004.2000.570201.x","article-title":"Down syndrome: Genetic recombination and the origin of the extra chromosome 21","volume":"57","author":"Hassold","year":"2000","journal-title":"Clin. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ejhg.2012.94","article-title":"Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: Impact of maternal age and prenatal screening","volume":"21","author":"Loane","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_4","first-page":"45","article-title":"Combined first-trimester screening in northern Finland: Experiences of the first ten years","volume":"30","author":"Merilainen","year":"2014","journal-title":"Clin. Med. Insights Reprod. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/(SICI)1097-0223(199902)19:2<142::AID-PD486>3.0.CO;2-7","article-title":"Fetal loss in Down syndrome pregnancies","volume":"19","author":"Morris","year":"1999","journal-title":"Prenat. Diagn."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/pd.4792","article-title":"Down syndrome: Perinatal mortality risks with each additional week of expectant management","volume":"36","author":"Sparks","year":"2016","journal-title":"Prenat. Diagn."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1002\/pd.5054","article-title":"Antepartum management and obstetric outcomes among pregnancies with Down syndrome from diagnosis to delivery","volume":"37","author":"Guseh","year":"2017","journal-title":"Prenat. Diagn."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e1373","DOI":"10.1542\/peds.2011-3051","article-title":"Predictors of survival in children born with Down syndrome: A registry-based study","volume":"129","author":"Rankin","year":"2012","journal-title":"Pediatrics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1080\/14767058.2018.1511695","article-title":"The role of fetal growth restriction in the association between Down syndrome and perinatal mortality","volume":"33","author":"Yao","year":"2020","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/ajmg.a.10823","article-title":"Poor outcome in Down syndrome fetuses with cardiac anomalies or growth retardation","volume":"116","author":"Wessels","year":"2003","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s13224-011-0092-x","article-title":"Placental insufficiency and fetal growth restriction","volume":"61","author":"Krishna","year":"2011","journal-title":"J. Obstet. Gynaecol. India"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1159\/000357592","article-title":"Update on the diagnosis and classification of fetal growth restriction and proposal of a stage-based management protocol","volume":"36","author":"Figueras","year":"2014","journal-title":"Fetal Diagn. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1097\/OGX.0b013e31826a5c6f","article-title":"Antenatal surveillance of fetal growth restriction","volume":"67","author":"Thompson","year":"2012","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_14","first-page":"67","article-title":"Intrauterine Growth Restriction: Antenatal and Postnatal Aspects","volume":"14","author":"Sharma","year":"2016","journal-title":"Clin. Med. Insights Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1097\/GRF.0b013e318253b318","article-title":"Antepartum evaluation of the fetus and fetal well being","volume":"55","author":"Thorp","year":"2012","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"(2021). Antepartum Fetal Surveillance. ACOG Practice Bulletin Summary, Number 229. Obstet. Gynecol., 137, 1134\u20131136.","DOI":"10.1097\/AOG.0000000000004411"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"American College of Obstetricians and Gynecologists\u2019 Committee on Obstetric Practice, Society for Maternal-Fetal Medicine (2021). Indications for Outpatient Antenatal Fetal Surveillance: ACOG Committee Opinion, Number 828. Obstet. Gynecol., 137, e177\u2013e197.","DOI":"10.1097\/AOG.0000000000004407"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1097\/00003081-199134030-00007","article-title":"Fetal surveillance in the pregnancy complicated by diabetes mellitus","volume":"34","author":"Landon","year":"1991","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1002\/ajmg.a.61586","article-title":"Differences in morbidity and mortality in Down syndrome are related to the type of congenital heart defect","volume":"182","author":"Baban","year":"2020","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.7863\/jum.2011.30.11.1573","article-title":"Amniotic fluid and the clinical relevance of the sonographically estimated amniotic fluid volume: Oligohydramnios","volume":"30","author":"Magann","year":"2011","journal-title":"J. Ultrasound Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1002\/uog.14924","article-title":"Single deepest vertical pocket or amniotic fluid index as evaluation test for predicting adverse pregnancy outcome (SAFE trial): A multicenter, open-label, randomized controlled trial","volume":"47","author":"Kehl","year":"2016","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.bpobgyn.2016.08.004","article-title":"Antenatal fetal surveillance \u201cAssessment of the AFV\u201d","volume":"38","author":"Hughes","year":"2017","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.ajog.2009.10.889","article-title":"Defining normal and abnormal fetal growth: Promises and challenges","volume":"202","author":"Zhang","year":"2010","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s00404-015-3703-4","article-title":"Conflicting umbilical artery Doppler findings in fetuses with trisomy 21","volume":"292","author":"Remig","year":"2015","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1159\/000433431","article-title":"Increased Umbilical Artery Pulsatility Index in Third-Trimester Fetuses with Trisomy 21","volume":"39","author":"Wagner","year":"2016","journal-title":"Fetal Diagn. Ther."},{"key":"ref_26","first-page":"23","article-title":"Introduction to multivariate regression analysis","volume":"14","author":"Alexopoulos","year":"2010","journal-title":"Hippokratia"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"van Smeden, M., de Groot, J.A., Moons, K.G., Collins, G.S., Altman, D.G., Eijkemans, M.J., and Reitsma, J.B. (2016). No rationale for 1 variable per 10 events criterion for binary logistic regression analysis. BMC Med. Res. Methodol., 16.","DOI":"10.1186\/s12874-016-0267-3"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"122","DOI":"10.21315\/mjms2018.25.4.12","article-title":"Sample Size Guidelines for Logistic Regression from Observational Studies with Large Population: Emphasis on the Accuracy Between Statistics and Parameters Based on Real Life Clinical Data","volume":"25","author":"Bujang","year":"2018","journal-title":"Malays. J. Med. Sci."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/1\/39\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T11:45:38Z","timestamp":1766490338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/1\/39"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,22]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["diagnostics16010039"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16010039","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,22]]}}}