Author: Gianpiero Pescarmona
Date: 28/03/2008


The preterm prediction study: elevated cervical ferritin levels at 22 to 24 weeks of gestation are associated with spontaneous preterm delivery in asymptomatic women.2002

Am J Obstet Gynecol. 2008 Jan;198(1):7-22.
Maternal infection and risk of preeclampsia: systematic review and metaanalysis., 2008

There are lingering questions regarding the association between maternal infection and preeclampsia. Systematic review and metaanalysis was conducted of observational studies that examined the relationship between maternal infection and preeclampsia. Forty-nine studies met the inclusion criteria. The risk of preeclampsia was increased in pregnant women with urinary tract infection (pooled odds ratio, 1.57; 95% CI, 1.45-1.70) and periodontal disease (pooled odds ratio, 1.76; 95% CI, 1.43-2.18). There were no associations between preeclampsia and presence of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus, treated and nontreated HIV infection, and malaria. Individual studies did not find a relationship between herpes simplex virus type 2, bacterial vaginosis, and Mycoplasma hominis and preeclampsia. Urinary tract infection and periodontal disease during pregnancy are associated with an increased risk of preeclampsia. More studies are required to verify this as well as to explore whether or not such relationships are causal and, if so, the mechanisms involved.

Clin Exp Obstet Gynecol. 2007;34(2):80-4.
Metabolism of vitamin D3 in the placental tissue of normal and preeclampsia complicated pregnancies and premature births. 2007

The aim of this study was to analyze the hormonal basis for low 1,25(OH)2D3 circulating levels in patients with preeclampsia and/or preterm deliveries. The activity and expression of the 1 alphaOHase, 25-OHase, 24-OHase and VDR in the placental tissue of normal pregnancies, preeclampsia-complicated pregnancies and premature births were investigated. The mRNA of the enzymes was detected in the placental tissue from preeclamptic pregnancies and compared to those of normal placental tissue. Real time PCR analysis showed a significant increased 1 alpha-OHase gene expression in preeclamptic patients, and the gene expression of 24-OHase was significantly decreased. With regard to the 25-OHase the median value of the normal placental tissue was significantly higher than in the placental tissue of preeclamptic patients. The real time analysis of all target genes also showed significant differences in normal placental tissue compared to placental tissue from premature births (VDR: p = 0.041; 1 alpha-OHase: p = 0.013; 24-OHase: p = 0.007; 25-OHase p = 0.027). Our observation of reduced VDR expression on mRNA level in placental tissue indicates a possible dependence of the modulation of VDR expression from proliferation and differentiation processes. It can be speculated whether the down-regulation of VDR in the examined placenta cells was the result of an altered production of calcitriol by these cells. We found a significantly higher 1 alpha-OHase-expression in the placental tissue of pregnant women with preeclampsia or preterm birth compared to healthy pregnant women, whereas the expression of 25-OHase was significantly reduced. These results correlate with other studies and support the significance of the placenta regarding metabolism malfunctions as they were observed in the calcium metabolism for preeclampsia. That a placenta with preeclampsia expresses less 1 alpha-OHase-mRNA and shows less 1 alpha-OHase-activity than in placental samples of inconspicuous placentae, can be granted as a specific alteration in the placental ability to synthesize adequate amounts of 1,25(OH)2D3.

J Biol Chem. 2009 May 29;284(22):14838-48. Epub 2009 Feb 23.
Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface., 2009

Plasma concentrations of biologically active vitamin D (1,25-(OH)(2)D) are tightly controlled via feedback regulation of renal 1alpha-hydroxylase (CYP27B1; positive) and 24-hydroxylase (CYP24A1; catabolic) enzymes. In pregnancy, this regulation is uncoupled, and 1,25-(OH)(2)D levels are significantly elevated, suggesting a role in pregnancy progression. Epigenetic regulation of CYP27B1 and CYP24A1 has previously been described in cell and animal models, and despite emerging evidence for a critical role of epigenetics in placentation generally, little is known about the regulation of enzymes modulating vitamin D homeostasis at the fetomaternal interface. In this study, we investigated the methylation status of genes regulating vitamin D bioavailability and activity in the placenta. No methylation of the VDR (vitamin D receptor) and CYP27B1 genes was found in any placental tissues. In contrast, the CYP24A1 gene is methylated in human placenta, purified cytotrophoblasts, and primary and cultured chorionic villus sampling tissue. No methylation was detected in any somatic human tissue tested. Methylation was also evident in marmoset and mouse placental tissue. All three genes were hypermethylated in choriocarcinoma cell lines, highlighting the role of vitamin D deregulation in this cancer. Gene expression analysis confirmed a reduced capacity for CYP24A1 induction with promoter methylation in primary cells and in vitro reporter analysis demonstrated that promoter methylation directly down-regulates basal promoter activity and abolishes vitamin D-mediated feedback activation. This study strongly suggests that epigenetic decoupling of vitamin D feedback catabolism plays an important role in maximizing active vitamin D bioavailability at the fetomaternal interface.

Prognostic Significance of Serum Uric Acid in Women With Gestational Hypertension. 2011 Hypertension. 2011 Aug 29. [Epub ahead of print]

Aim of our study was to ascertain, prospectively, whether serum uric acid is a suitable predictor of preeclampsia and/or the delivery of small-for-gestational-age infants in women with gestational hypertension. We screened 206 primiparas, with a singleton pregnancy, referred for recent onset of hypertension. At presentation, we measured serum uric acid, creatinine, blood glucose, hemoglobin and platelet level, and 24-hour proteinuria, as well as office and 24-hour blood pressures. We followed the women until 1 month after delivery and recorded pregnancy outcome. After logistic regression analysis, uric acid resulted a significant predictor of preeclampsia, with an unadjusted odds ratio of 9.1 (95% CI: 4.8 to 17.4; P<0.001); after adjustment for age, gestation week, hemoglobin and platelet levels, serum creatinine, office and 24-hour average systolic and diastolic blood pressures, it was 7.1 (95% CI: 3.2 to 15.7; P<0.001). Regarding the association between maternal serum uric acid and the chance of giving birth to a small-for-gestational-age infant, the unadjusted odds ratio was 1.7 (95% CI: 1.4 to 2.2; P<0.001), and it was 1.6 (95% CI: 1.1 to 2.4; P=0.02) after adjustment. Receiver operating characteristic analysis showed that serum uric acid, at a 309-╬╝mol/L cutoff, predicted the development of preeclampsia (area under the curve: 0.955), with 87.7% sensitivity and 93.3% specificity, and the delivery of small-for-gestational-age infants (area under the curve: 0.784) with 83.7% sensitivity and 71.7% specificity. In conclusion, the results of our study show that serum uric acid is a reliable predictor of preeclampsia in women referred for gestational hypertension.

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