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Cited by 3,720Pregnancy and preeclampsia studiesNeurological Complications and SyndromesAngiogenesis and VEGF in Cancer

The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.

Circulating Angiogenic Factors and the Risk of Preeclampsia

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Levine, Richard J., Maynard, Sharon E., Qian, Cong, Lim, Kee-Hak, England, Lucinda J., Yu, Kai F., Schisterman, Enrique F., Thadhani, Ravi, Sachs, Benjamin P., Epstein, Franklin H., Sibai, Baha M., Sukhatme, Vikas P., Karumanchi, S. Ananth·2004·New England Journal of Medicine
DOI 10.1056/nejmoa031884
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Abstract

BACKGROUND: The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PlGF) and vascular endothelial growth factor (VEGF), may have a pathogenic role. METHODS: We performed a nested case-control study within the Calcium for Preeclampsia Prevention trial, which involved healthy nulliparous women. Each woman with preeclampsia was matched to one normotensive control. A total of 120 pairs of women were randomly chosen. Serum concentrations of angiogenic factors (total sFlt-1, free PlGF, and free VEGF) were measured throughout pregnancy; there were a total of 655 serum specimens. The data were analyzed cross-sectionally within intervals of gestational age and according to the time before the onset of preeclampsia. RESULTS: During the last two months of pregnancy in the normotensive controls, the level of sFlt-1 increased and the level of PlGF decreased. These changes occurred earlier and were more pronounced in the women in whom preeclampsia later developed. The sFlt-1 level increased beginning approximately five weeks before the onset of preeclampsia. At the onset of clinical disease, the mean serum level in the women with preeclampsia was 4382 pg per milliliter, as compared with 1643 pg per milliliter in controls with fetuses of similar gestational age (P<0.001). The PlGF levels were significantly lower in the women who later had preeclampsia than in the controls beginning at 13 to 16 weeks of gestation (mean, 90 pg per milliliter vs. 142 pg per milliliter, P=0.01), with the greatest difference occurring during the weeks before the onset of preeclampsia, coincident with the increase in the sFlt-1 level. Alterations in the levels of sFlt-1 and free PlGF were greater in women with an earlier onset of preeclampsia and in women in whom preeclampsia was associated with a small-for-gestational-age infant. CONCLUSIONS: Increased levels of sFlt-1 and reduced levels of PlGF predict the subsequent development of preeclampsia.

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Authors
Levine, R. J., Maynard, S. E., Qian, C., Lim, K.-H., England, L. J., Yu, K. F., Schisterman, E. F., Thadhani, R., Sachs, B. P., Epstein, F. H., Sibai, B. M., Sukhatme, V. P., & Karumanchi, S. A.
Affiliations
  • National Institutes of Health (US)
  • Beth Israel Deaconess Medical Center (US)
  • Allied Technology (United States) (US)
  • Harvard University (US)
  • University of Cincinnati (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2004-02-12
Volume
350
Issue
7
Pages
672-683
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa031884
OpenAlex
W2081255404
Cited by
3,720
References
24
Citations by year
2026: 148 · 2025: 165 · 2024: 142 · 2023: 152 · 2022: 207 · 2021: 180 · 2020: 170 · 2019: 182 · 2018: 185 · 2017: 229 · 2016: 201 · 2015: 171 · 2014: 193 · 2013: 199 · 2012: 185
FWCI
122.15
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Clinical Neurology › Neurological Complications and Syndromes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
preeclampsia, soluble fms-like tyrosine kinase-1, placental growth factor, vascular endothelial growth factor, angiogenic factors, serum biomarkers, preeclampsia risk prediction, small for gestational age, nulliparous women
MeSH terms
Placenta Growth Factor, Adult, Cross-Sectional Studies, Female, Gestational Age, Humans, Pre-Eclampsia, Pregnancy, Pregnancy Proteins, Risk Factors, Biomarkers, Body Mass Index, Logistic Models, Odds Ratio, Case-Control Studies, Statistics, Nonparametric, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor A

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