{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T17:52:29Z","timestamp":1791741149257,"version":"4.3.4"},"reference-count":26,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Stillbirth remains a major global health challenge, particularly in low- and middle-income countries. Angiogenic imbalance, characterized by elevated soluble fms-like tyrosine kinase-1 (sFlt-1) and reduced placental growth factor (PlGF), is implicated in placental dysfunction, yet few studies have examined the association between the sFlt-1:PlGF ratio and stillbirth.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate the association between maternal circulating sFlt-1:PlGF ratio, using clinically relevant cutoffs, and risk of stillbirth.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This case-control study included participants from 2 health clinics operated by the Dhaka Community Hospital Trust in rural Bangladesh. Pregnant women aged 18 years or older with ultrasonography-confirmed singleton pregnancies were enrolled before or at 16 weeks\u2019 gestation between March 1, 2008, and July 30, 2011. Those delivering stillborn infants (cases) were matched 1:2 with participants in the same cohort who delivered full-term live-born infants (controls). Data were analyzed between September 1, 2025, and January 1, 2026.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Maternal serum sFlt-1:PlGF ratio.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The main outcome was stillbirth, defined as fetal death at 28 weeks\u2019 gestation or more. The association between sFlt-1:PlGF ratio cutoffs of greater than 38 and greater than 85 and stillbirth were estimated using Firth penalized logistic regression, with models adjusted using a propensity score incorporating maternal factors.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The analytic sample included 125 participants (mean [SD] age, 22.3 [3.8] years), of whom 39 were included in the stillbirth group and 86 in the live birth control group. After adjusting for propensity score, an sFlt-1:PlGF ratio greater than 38 was significantly associated with an increased odds of stillbirth (odds ratio [OR], 13.44; 95% CI, 2.03-88.89). Similar results were observed using the cutoff of 85 (OR, 12.95; 95% CI, 1.57-106.64). Elevated sFlt-1:PlGF ratios showed high positive predictive value for stillbirth at the cutoff of 38 (88.9%; 95% CI, 51.8%-99.7%) and 85 (85.7%; 95% CI, 42.1%-99.6%). Negative predictive values were moderate at 73.3% (95% CI, 64.3%-81.1%) and 72.0% (95% CI, 63.0%-79.9%), respectively, indicating that low ratios had a limited ability to rule out stillbirth.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This case-control study found that a high sFlt-1:PlGF ratio using clinically relevant thresholds was associated with stillbirth and corresponded to an estimated 13-fold increased risk. These findings suggest that angiogenic imbalance may contribute to stillbirth and highlight the potential utility of angiogenic markers as indicators of pregnancy complications in low-resource settings.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.7652","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T15:30:37Z","timestamp":1776439837000},"page":"e267652","source":"Crossref","is-referenced-by-count":2,"title":["Maternal Circulating sFlt-1:PlGF Ratio and Stillbirth"],"prefix":"10.1001","volume":"9","author":[{"given":"Mi-Sun S.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki-Do","family":"Eum","sequence":"additional","affiliation":[{"name":"Ariadne Labs, Brigham and Women\u2019s Hospital and Harvard T.H. Chan School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David. C.","family":"Christiani","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard T.H. 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