Maternal serum soluble fms-like tyrosine kinase 1 concentrations are not increased in early pregnancy and decrease more slowly postpartum in women who develop preeclampsia

Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
American Journal of Obstetrics and Gynecology (Impact Factor: 4.7). 08/2005; 193(1):185-91. DOI: 10.1016/j.ajog.2004.11.038
Source: PubMed


We measured maternal serum soluble fms-like tyrosine kinase 1 concentrations across pregnancy and immediately postpartum in women who developed preeclampsia and normal pregnant women.
This was a nested case control study of 113 normal pregnant women and 55 women with preeclampsia.
Serum soluble fms-like tyrosine kinase 1 concentrations increased similarly in early pregnancy in both groups. Mean serum soluble fms-like tyrosine kinase 1 concentrations were increased in women who developed preeclampsia, compared with normal pregnant women, and this increase was most pronounced in severe preeclampsia. However, many women with preeclampsia had soluble fms-like tyrosine kinase 1 concentrations similar to normal pregnant women. Lastly, soluble fms-like tyrosine kinase 1 decreased rapidly after delivery, but this decrease was significantly slower in women with severe preeclampsia.
Increased soluble fms-like tyrosine kinase 1 is not an early-pregnancy event among women who later develop preeclampsia. Increased soluble fms-like tyrosine kinase 1 is more likely to be present in women with severe preeclampsia, but it is not present in all women with preeclampsia. Soluble fms-like tyrosine kinase 1 concentrations decrease more slowly after delivery in women with preeclampsia, consistent with a decreased rate of excretion or continued production.

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    • "Although the majority of the studies suggest a higher level of sFlt-1 concentrations in women destined to develop preeclampsia at term, the elevated levels were not significantly different in most of the studies. Similarly, three studies that did not report the exact levels of sFlt-1 in first trimester reported no significant differences between women with and without preeclampsia [23,28-30]. This is consistent with the conclusions of Levine who found that levels didn't increase until approximately five weeks before the onset of clinical disease [5]. "
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    ABSTRACT: Angiogenic factors are involved in formation of new blood vessels required for placental development and function; and critical for fetal growth and development. Soluble fms-like tyrosine kinase 1(sFlt-1) is an anti-angiogenic protein that inhibits formation of new blood vessels resulting in potential pregnancy complications. The objective of this study was to undertake a systematic review to assess levels of sFlt-1 in early pregnancy and association with adverse pregnancy outcomes. PubMed and Medline databases and reference lists were searched up to July 2010. Inclusion criteria were pregnant women, blood sample taken during first trimester and assessment/reporting of sFlt-1 concentrations and subsequent pregnancy complications. Twelve relevant studies were identified of 71 to 668 women. No pooling of results was undertaken due to variation in sFlt-1 concentrations (range, 166-6,349 pg/ml amongst controls), samples used (serum, plasma), different summary statistics (mean, median, odds ratio) and outcome definitions applied. Levels of sFlt-1 were generally higher among women who developed preeclampsia (11 studies) or gestational hypertension (two studies), but not significantly different to normotensive women in most studies. There was no consistent pattern in association between sFlt-1 concentrations and fetal growth restriction (4 studies); and levels were non-significantly higher for women with postpartum bleeding (1 study) and significantly lower for stillbirths (1 study).This review found no clear evidence of an association between sFlt-1 levels in first trimester and adverse pregnancy outcomes. However, findings were affected by methodological, biological and testing variations between studies; highlighting the need for consistent testing of new biomarkers and reporting of outcome measures.
    Reproductive Biology and Endocrinology 06/2011; 9(1):77. DOI:10.1186/1477-7827-9-77 · 2.23 Impact Factor
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    • "Significant increase in sFlt-1 and decrease in pro-angiogenic factors may be noticed from 2nd trimester onwards [29] [31] and is evident 5–8 weeks prior to onset of the disease [15] [22]. Maternal plasma sFlt-1 concentrations are specifically elevated in severe preeclampsia and early onset preeclampsia [15] [32]. Serum levels of PIGF are decreased in patients who develop preeclampsia as early as 12 weeks of gestational age [33] although by 18–20 weeks of gestational age the decrease is marked [15] [18] [19]. "
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    ABSTRACT: Preeclampsia (PE) is a major contributor to maternal and fetal mortality. The cause of preeclampsia remains unclear, but oxidative stress on the endothelium leading to endothelial dysfunction is said to be the root cause of the disease. The aim of this study was to measure and determine the plasma levels of key angiogenic factors in pregnancy as an indicator for the early onset of preeclampsia in pregnancy. Plasma levels of circulating a soluble fms like tyrosine kinase-1 (sFlt-1), an anti-angiogenic factor, vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), both pro-angiogenic factors were analyzed in normal pregnant Malaysian women (control group, n = 34), women with pregnant induced hypertension (PIH, n = 34) and women with preeclampsia (PE, n = 34) all at three gestational ages, 24-28 weeks (early pregnancy: EP), 32-36 weeks (late pregnancy: LP) and 6 weeks after delivery (postpartum: PN). The plasma levels of angiogenic factors were determined by ELISA. sFlt-1 levels were elevated in PIH and PE patients as compared to controls. PIGF and VEGF were significantly decreased in PIH and PE as compared to the controls. These results suggest that elevated concentration of sFlt-1 and suppressed levels of PIGF and VEGF may contribute to the development of hypertension in pregnancy which precedes preeclampsia.
    Journal of Clinical Biochemistry and Nutrition 11/2010; 47(3):191-7. DOI:10.3164/jcbn.10-27 · 2.19 Impact Factor
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    • "In this study, we report for the first time that levels of sFlt-1 increased at full dilatation compared to pre-labour in pre eclampsia. However, in our study, the rate of decline after placental delivery by 24 hr was not different between normal pregnancy and pre eclampsia in Caesarean section (NP 80%, PE 90%) and labour groups (NP 82%, PE 80%) as reported previously – [36]. In the previous study, plasma sFlt-1 levels were measured at some time in the 48 hours post delivery as the percent change of the serum sFlt1 concentration between delivery and postpartum. "
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    ABSTRACT: Maternal circulating levels of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1), endoglin (sEng) and placental proteins like activin A and inhibin A are increased before the onset of pre-eclampsia. There is evidence for oxidative stress in pre eclampsia. Recently it was shown that placental oxygen concentration is related to sFlt-1 and inhibin A. In addition it is reported that oxidative stress markers are increased in placental tissue delivered after labour. Therefore, the objective of this study is to investigate if these proteins are altered in maternal circulation of labouring pre-eclampsia and normal pregnancies. To assess the effects of labour, samples were taken from 10 normal pregnant (NP) and 10 pre-eclamptic (PE) women pre-labour, full dilation, placental delivery and 24 h. To assess the effects of placental delivery, plasma samples were taken from 10NP and 10PE women undergoing elective Caesarean section, pre-delivery, placental delivery and 10 min, 60 min and 24 h post delivery. SFlt-1 and sEng and activin A and inhibin A were measured using commercial and in house ELISA's respectively. The levels of sFlt-1 and sEng were significantly higher in PE compared to NP women in both groups. In labour, sFlt-1 levels increased significantly at full dilatation in PE women, before declining by 24 hr. However there was no significant rise in sEng levels in labour. Activin A and inhibin A levels declined rapidly with placental delivery in NP and PE pregnancies. There was a significant rise in activin A levels during labour in PE compared to pre labour, but inhibin levels did not increase. Labour in pre-eclamptic women increases the levels of sFlt-1 and activin A. This pilot data suggests that increase in the maternal levels of these factors in labour could predict and/or contribute to the maternal syndrome postpartum.
    PLoS ONE 02/2009; 4(2):e4453. DOI:10.1371/journal.pone.0004453 · 3.23 Impact Factor
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