Midgestation Maternal Serum 25-Hydroxyvitamin D Level and Soluble Fms-Like Tyrosine Kinase 1/Placental Growth Factor Ratio as Predictors of Severe Preeclampsia

Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, 3010 Old Clinic Building, CB#7516, Chapel Hill, NC 27599-7516, USA.
Hypertension (Impact Factor: 6.48). 12/2011; 58(6):1120-5. DOI: 10.1161/HYPERTENSIONAHA.111.179069
Source: PubMed


Recent studies have shown that low serum 25-hydroxyvitamin D (25[OH]D) level is a risk factor for preeclampsia. The clinical significance of in vitro findings that vitamin D regulates vascular endothelial growth factor production is unclear. We sought to determine whether there is an association between midgestation serum 25(OH)D levels and angiogenic factor activity and to compare their predictive value for the development of severe preeclampsia. We conducted a nested case-control study of women with severe preeclampsia (n=41) versus women with uncomplicated term birth (n=123) who had second trimester genetic screening (15-20 weeks). Using banked frozen serum, we measured levels of 25(OH)D, vascular endothelial growth factor, soluble fms-like tyrosine kinase 1, and placental growth factor and compared their correlations and predictive values. We found no correlation between serum 25(OH)D and angiogenic factors levels. 25(OH)D alone was comparable to vascular endothelial growth factor and soluble fms-like tyrosine kinase 1/placental growth factor ratio as a predictive marker for severe preeclampsia. A composite of both 25(OH)D level and soluble fms-like tyrosine kinase 1/placental growth factor ratio was more predictive than either alone (area under curve: 0.83 versus 0.74 and 0.67, respectively). In conclusion, combining midpregnancy 25(OH)D level with soluble fms-like tyrosine kinase 1/placental growth factor ratio provides a better prediction for the development of severe preeclampsia.

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Available from: Carlos A Camargo, Jan 01, 2016
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    • "Similarly, mineralisation of fetal bones occurs relatively late in pregnancy, while the induction of VDR and CYP27B1 in both maternal and fetal placental tissues occurs early in gestation, and thus alternative actions for intracrine 1,25(OH) 2 D have to be taken into consideration now (Evans et al. 2004). These include possible effects on fetal development through homeobox gene expression (Du et al. 2005) and placental vascularisation (Woodham et al. 2011). Studies by ourselves and others have supported an immunomodulatory function for vitamin D within the placenta and the specific role of maternal decidua in this process becomes the major focus of the current review. "
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    ABSTRACT: During pregnancy, immune activity is tightly regulated so that antimicrobial protection of the mother and fetus is balanced with the need for immune tolerance to prevent fetal rejection. In this setting, the maternal-fetal interface, in the form of the uterine decidua, provides a heterogeneous immune cell population with the potential to mediate diverse activities throughout pregnancy. Recent studies have suggested that vitamin D may be a key regulator of immune function during pregnancy, with the fetal-maternal interface representing a prominent target. Among its non-classical actions are potent immunomodulatory effects, including induction of antibacterial responses and modulation of T-lymphocytes to suppress inflammation and promote tolerogenesis. Thus, vitamin D may play a pivotal role in normal decidual immune function by promoting innate responses to infection, while simultaneously preventing an over-elaboration of inflammatory adaptive immunity. Research to date has focused upon the potential role of vitamin D in preventing infectious diseases such as tuberculosis, as well as possibly suppressing of autoimmune disease. Nevertheless, vitamin D may also influence facets of immune function not immediately associated with primary innate responses. This review summarises our current understanding of decidual immune function with respect to the vitamin D metabolism and signalling, and as to how this may be affected by variations in maternal vitamin D status. There has recently been much interest in vitamin D supplementation of pregnant women, but our knowledge of how this may influence the function of decidua remains limited. Further insight into the immunomodulatory actions of vitamin D during pregnancy will help shed light upon this. © 2015 Society for Endocrinology.
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    ABSTRACT: Preeclampsia is a heterogeneous syndrome affecting 3% to 5% of all pregnancies. An imbalance of the antiangiogenic and proangiogenic factors, soluble receptor fms-like tyrosine kinase 1 and placental growth factor (PGF), is thought to contribute to the pathophysiology of preeclampsia. Maternal plasma PGF and soluble receptor fms-like tyrosine kinase 1 were quantified by specific immunoassays in cross-sectional samples from 130 preeclamptic subjects and 342 normotensive controls at delivery and longitudinally in samples from 50 women who developed preeclampsia and 250 normotensive controls. Among women who developed preeclampsia, 46% (n=23) evidenced a pattern of consistently low maternal PGF across pregnancy below the lower 95% CI of controls from 15 weeks' gestation to term. In contrast, the remaining 54% (n=27) of women who developed preeclampsia had maternal PGF concentrations similar to or above (n=7) those of normotensive controls. Subjects with low PGF across pregnancy who developed preeclampsia evidenced significantly higher blood pressure in early pregnancy (P<0.05) and, after diagnosis, earlier gestational age at delivery (P<0.05) and more preterm birth (P<0.05) compared with preeclamptic patients with high PGF. A significant subset of women who develop preeclampsia show evidence of consistently low PGF across pregnancy. Low PGF with preeclampsia was associated with preterm delivery compared with preeclamptic patients with high PGF. Identifying women with consistently low plasma PGF during pregnancy may provide a greater understanding of preeclampsia pathophysiology and may provide more focused research and clinical activities.
    Preview · Article · May 2012 · Hypertension
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    ABSTRACT: Decreased maternal 25-hydroxy vitamin D (25-OH-D) and placenta growth factor (PlGF) have both been associated with the diagnosis of early-onset severe preeclampsia (EOSPE). Prior investigations have identified these biomarkers to be decreased at the time of diagnosis of preeclampsia and prior to the onset of clinical diagnosis of preeclampsia. This investigation aimed to define the association of these biomarkers with EOSPE. This will yield information concerning possible potential for these biomarkers to be used in diagnosis of preeclampsia. Patients with EOSPE and healthy controls were recruited and demographics, outcomes, and plasma were collected at matched gestational age. 25-OH-D was assessed by radioimmunoassay and reported in ng/mL. PlGF was assessed by ELISA and reported in pg/mL. Receiver operator curves were constructed for each regression model and sensitivity and specificity were reported for each biomarker. In EOSPE, both 25-OH-D and PlGF were decreased significantly compared to controls. The combination of age, race, and PlGF or 25-OH-D performed well in discrimination of EOSPE and controls. The logistic regression model using both PlGF and 25-OH-D is shown below: PlGF and 25-OH-D are sensitive and specific markers for diagnosis of EOSPE. However, PlGF provided a higher sensitivity and specificity for EOSPE diagnosis. Copyright © 2012. Published by Elsevier B.V.
    No preview · Article · Aug 2012 · American Journal of Perinatology
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