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Cited by 287Pregnancy and preeclampsia studiesNeurological Complications and SyndromesReproductive System and Pregnancy

The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age

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Erez, Offer, Romero, Roberto, Espinoza, Jimmy, Fu, Wenjiang, Todem, David, Kusanovic, Juan Pedro, Gotsch, Francesca, Edwin, Samuel +7 more·2008·The Journal of Maternal-Fetal & Neonatal Medicine
DOI 10.1080/14767050802034545PMC PMC2846114
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Abstract

INTRODUCTION: An imbalance between angiogenic and anti-angiogenic factors has been proposed as central to the pathophysiology of preeclampsia (PE). Indeed, patients with PE and those delivering small-for-gestational age (SGA) neonates have higher plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and the soluble form of endoglin (s-Eng), as well as lower plasma concentrations of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) than do patients with normal pregnancies. Of note, this imbalance has been observed before the clinical presentation of PE or the delivery of an SGA neonate. The objective of this study was to determine if changes in the profile of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters are associated with a high risk for the subsequent development of PE and/or delivery of an SGA neonate. METHODS: This longitudinal case-control study included 402 singleton pregnancies in the following groups: (1) normal pregnancies with appropriate for gestational age (AGA) neonates (n = 201); (2) patients who delivered an SGA neonate (n = 145); and (3) patients who developed PE (n = 56). Maternal plasma samples were obtained at the time of each prenatal visit, scheduled at 4-week intervals from the first or early second trimester until delivery. In this study, we included two samples per patient: (1) first sample obtained between 6 and 15 weeks of gestation ('first trimester' sample), and (2) second sample obtained between 20 and 25 weeks of gestation ('second trimester' sample). Plasma concentrations of s-Eng, sVEGFR-1, and PlGF were determined by specific and sensitive immunoassays. Changes in the maternal plasma concentrations of these angiogenesis-related factors were compared among normal patients and those destined to develop PE or deliver an SGA neonate while adjusting for maternal age, nulliparity, and body mass index. General linear models and polytomous logistic regression models were used to relate the analyte concentrations, ratios, and product to the subsequent development of PE and SGA. RESULTS: (1) An increase in the maternal plasma concentration of s-Eng between the first and second trimesters conferred risk for the development of preterm PE and SGA (OR 14.9, 95% CI 4.9-45.0 and OR 2.9, 95% CI 1.5-5.6, respectively). (2) An increase in the maternal plasma concentration of sVEGFR-1 between the first and second trimester conferred risk for the development of preterm PE (OR 3.9, 95% CI 1.2-12.6). (3) A subnormal increase in maternal plasma PlGF concentration between the first and the second trimester was a risk factor for the subsequent development of preterm and term PE (OR 4.3, 95% CI 1.2-15.5 and OR 2.7, 95% CI 1.2-5.9, respectively). (4) In addition, the combination of the three analytes into a pro-angiogenic versus anti-angiogenic ratio (PlGF/(s-Eng x VEGFR-1)) conferred risk for the subsequent development of preterm PE (OR 3.7, 95% CI 1.1-12.1). (5) Importantly, patients with a high change in the s-Eng x sVEGFR-1 product had an OR of 10.4 (95% CI 3.2-33.8) for the development of preterm PE and 1.6 (95% CI 1.0-2.6) for the development of SGA. CONCLUSIONS: Changes in the maternal plasma concentrations of s-Eng, sVEGFR-1, PlGF or their ratios between the first and second trimesters of pregnancy confer an increased risk to deliver an SGA neonate and/or develop PE.

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  1. Richani K, Soto E, Romero R, Espinoza J, Chaiworapongsa T, Nien J, Edwin S, Kim Y, Hong J, Goncalves L, et al. Preeclampsia and SGA differ in the maternal plasma complement split products profile. J Soc Gynecol Investig 2005;12:148a Abstract.
  2. Di Renzo GC. The of the 'anti-angiogenic state' in complica- tions of pregnancy. J Matern Fetal Neonatal Med 2008;21(1): 3-7.
  3. Gonzalez RP, Gomez RM, Castro RS, Nien JK, Merino PO, Etchegaray AB, Carstens MR, Medina LH, Viviani PG, Rojas IT. [A national birth weight distribution curve according to gestational age in chile from 1993 to 2000]. Rev Med Chil 2004;132:1155-1165.

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Authors
Erez, O., Romero, R., Espinoza, J., Fu, W., Todem, D., Kusanovic, J. P., Gotsch, F., Edwin, S., Nien, J. K., Chaiworapongsa, T., Mittal, P., Mazaki-Tovi, S., Than, N. G., Gomez, R., & Hassan, S. S.
Affiliations
  • United States Department of Health and Human Services (US)
  • National Institutes of Health (US)
  • Michigan State University (US)
  • Pontificia Universidad Católica de Chile (CL)
Corresponding author
  • Erez, Offer
  • Romero, Roberto
ORCID
Venue
The Journal of Maternal-Fetal & Neonatal Medicine
Publisher
Informa UK Limited
Published
2008-01
Volume
21
Issue
5
Pages
279-287
ISSN
  • 1476-4954 (ISSN-L)
  • 1476-7058
DOI
10.1080/14767050802034545
PMC
PMC2846114
OpenAlex
W2036421581
Cited by
287
References
59
Citations by year
2026: 5 · 2025: 3 · 2024: 10 · 2023: 8 · 2022: 14 · 2021: 11 · 2020: 8 · 2019: 22 · 2018: 10 · 2017: 16 · 2016: 14 · 2015: 19 · 2014: 22 · 2013: 21 · 2012: 27
FWCI
29.54
Type
journal article
Language
en
Open access
Locations
  • The Journal of Maternal-Fetal & Neonatal Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Health and Human Services
  • National Institutes of Health
  • National Institute of Child Health and Human Development
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (Z01HD002400)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Neurological Complications and Syndromes
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
preeclampsia, small for gestational age, angiogenic factors, anti-angiogenic factors, soluble endoglin, soluble fms-like tyrosine kinase-1, placental growth factor, vascular endothelial growth factor, maternal plasma biomarkers, first and second trimester, risk prediction, pregnancy complications, placental insufficiency, endothelial dysfunction
MeSH terms
Endoglin, Placenta Growth Factor, Adult, Female, Fetal Growth Retardation, Humans, Infant, Newborn, Infant, Small for Gestational Age, Longitudinal Studies, Pre-Eclampsia, Pregnancy, Pregnancy Proteins, Pregnancy Trimester, First, Pregnancy Trimester, Second, Receptors, Cell Surface, Retrospective Studies, Antigens, CD, Linear Models, Risk Assessment, Neovascularization, Physiologic, Vascular Endothelial Growth Factor Receptor-1

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