Document Detail

An imbalance between angiogenic and anti-angiogenic factors precedes fetal death in a subset of patients: results of a longitudinal study.
MedLine Citation:
PMID:  20459337     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Women with a fetal death at the time of diagnosis have higher maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, than women with a normal pregnancy. An important question is whether these changes are the cause or consequence of fetal death. To address this issue, we conducted a longitudinal study and measured the maternal plasma concentrations of selective angiogenic and anti-angiogenic factors before the diagnosis of a fetal death. The anti-angiogenic factors studied were sVEGFR-1 and soluble endoglin (sEng), and the angiogenic factor, placental growth factor (PlGF).
METHODS: This retrospective longitudinal nested case-control study included 143 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered a term infant with an appropriate weight for gestational age (n=124); and (2) patients who had a fetal death (n=19). Blood samples were collected at each prenatal visit, scheduled at 4-week intervals from the first trimester until delivery. Plasma concentrations of sVEGFR-1, sEng, and PlGF were determined by specific and sensitive ELISA. A linear mixed-effects model was used for analysis.
RESULTS: (1) The average profiles of analyte concentrations as a function of gestational age for sVEGFR-1, sEng and PlGF were different between women destined to have a fetal death and those with a normal pregnancy after adjusting for covariates (p<0.05); (2) Plasma sVEGFR-1 concentrations in patients destined to have a fetal death were significantly lower between 7 and 11 weeks of gestation and became significantly higher than those of women with a normal pregnancy between 20 and 37 weeks of gestation (p<0.05); (3) Similarly, plasma sEng concentrations of women destined to have a fetal death were lower at 7 weeks of gestation (p=0.04) and became higher than those of controls between 20 and 40 weeks of gestation (p<0.05); (4) In contrast, plasma PlGF concentrations were higher among patients destined to develop a fetal death between 7 and 14 weeks of gestation and became significantly lower than those in the control group between 22 and 39 weeks of gestation (p<0.05); (5) The ratio of PlGF/(sVEGFR-1 × sEng) was significantly higher in women destined to have a fetal death between 7 and 13 weeks of gestation (94-781%) and significantly lower (44-75%) than those in normal pregnant women between 20 and 40 weeks of gestation (p<0.05); (6) Similar results were obtained when patients with a fetal death were stratified into those who were diagnosed before or after 37 weeks of gestation.
CONCLUSIONS: Fetal death is characterised by higher maternal plasma concentrations of PlGF during the first trimester compared to normal pregnancy. This profile changes into an anti-angiogenic one during the second and third trimesters.
Roberto Romero; Tinnakorn Chaiworapongsa; Offer Erez; Adi L Tarca; Maria Teresa Gervasi; Juan Pedro Kusanovic; Pooja Mittal; Giovanna Ogge; Edi Vaisbuch; Shali Mazaki-Tovi; Zhong Dong; Sun Kwon Kim; Lami Yeo; Sonia S Hassan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2010-05-12
Journal Detail:
Title:  The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians     Volume:  23     ISSN:  1476-4954     ISO Abbreviation:  J. Matern. Fetal. Neonatal. Med.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-11     Completed Date:  2011-02-17     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101136916     Medline TA:  J Matern Fetal Neonatal Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  1384-99     Citation Subset:  IM    
Perinatology Research Branch, NICHD, NIH, DHHS, Wayne State University/Hutzel Women's Hospital, 3990 John R, Box 4, Detroit, MI 48201, USA.
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MeSH Terms
Antigens, CD / blood*
Fetal Death / blood*
Gestational Age
Longitudinal Studies
Middle Aged
Neovascularization, Physiologic
Pregnancy Proteins / blood*
Receptors, Cell Surface / blood*
Retrospective Studies
Vascular Endothelial Growth Factor Receptor-1 / blood*
Grant Support
Reg. No./Substance:
0/Antigens, CD; 0/ENG protein, human; 0/Pregnancy Proteins; 0/Receptors, Cell Surface; 144589-93-5/placenta growth factor; EC Endothelial Growth Factor Receptor-1

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