Fibrinogen concentration and factor VIII activity in women with preeclampsia.

OBJECTIVE: To compare fibrinogen concentration and factor VIII activity obtained from pregnant women with preeclampsia with those obtained from women with either normal pregnancies or with complications unrelated to preeclampsia. MATERIALS AND METHODS: Fibrinogen concentration and factor VIII activity were measured in the following groups: normal pregnancy, consisting of women at routine 16- to 28-week antenatal visits or after admission at term for elective cesarean section; women with non-preeclampsia (non-PE) related conditions, including women with threatened abortion, cholestasis, systemic lupus erythematosus (SLE), and previous deep venous thrombosis (DVT); and women with preeclampsia as defined by the Australasion Society for the Study of Hypertension in Pregnancy (ASSHP) criteria. Blood was collected from 44 women in each group. Fibrinogen concentration and factor VIII activity were measured. RESULTS: Fibrinogen concentrations and factor VIII activities were higher in women with preeclampsia compared with those from women with either normal or complicated pregnancies (p < 0.05). It was twice as likely that a woman with preeclampsia would have a raised fibrinogen and factor VIII levels. The ranges for each analyte did, however, show overlap. Women with preeclampsia were more likely to have both a raised fibrinogen concentration and increased factor VIII activity than other pregnant women (p < 0.001). CONCLUSION: This study has shown a novel increase in both fibrinogen concentration and factor VIII activity in pregnant women with preeclampsia compared with values obtained from women with normal or non-preeclampsia complicated pregnancies, with women with preeclampsia twice as likely to have a raised fibrinogen concentration and increased factor VIII activity. These changes may contribute to the hypercoagulability seen in preeclampsia.     

Vascular endothelial growth factor family gene polymorphisms in preeclampsia in Sinhalese women in Sri-Lanka

Objective: To investigate the association of polymorphisms in the vascular endothelial growth factor (VEGF) family genes (VEGFA rs699947, VEGFA rs3025039, PGF rs1042886, KDR rs2071559 and KDR rs2305948) with preeclampsia in Sinhalese women in Sri-Lanka. Methods: We conducted a case-control study where 175 nulliparous Sinhalese women with preeclampsia and 171 normotensive women matched for age, ethnicity, parity and BMI were recruited in tertiary care maternity hospitals in Sri-Lanka. Preeclampsia was diagnosed using international guidelines. DNA extracted from peripheral venous blood and was genotyped using the Sequenom MassARRAY system. χ²-test was used to compare the distribution of allele and genotype frequencies between the cases and the control subjects. Results: The frequency of PGF rs1042886 variant allele (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1–2.1) and dominant genotype model (aOR 1.6, 95% CI 1.0–2.4) were increased in preeclamptic women compared to controls. VEGFA rs699947, VEGFA rs3025039, KDR rs2071559, and KDR rs2305948 polymorphisms were not associated with preeclampsia. Conclusion: Maternal PGF rs1042886 polymorphism is associated with preeclampsia in Sinhalese women in Sri-Lanka.     

Fibrinogen and factor VII levels in patients under estrogen-progestin therapy]

During a 3 month period the Authors have evaluated the possible modification of some coagulation parameters which can be of relevance for thrombophilic state. Fibrinogen and factor VII were measured and following 3 months of oestro-progestinic treatment in 11 women in good general health and without known controindications to contraceptive treatment. No significant difference in some levels of fibrinogen and factor VII were found. We conclude that in the short term fibrinogen and factor VII are not significantly altered but a longer period of follow up is indicated in order to estimate the risk of cardiovascular accidents.     

Association study of IL-10 and IFN-gamma gene polymorphisms in Iranian women with preeclampsia

Preeclampsia (PE) is one of the most serious disorders of human pregnancy and Th1/Th2 imbalance may play a role in its etiology. Considering that cytokine production is under genetic control, in this study we have investigated IFN-gamma+874 (T/A) and three bi-allelic IL-10 promoter polymorphisms in a total of 134 preeclamptic women compared to 164 healthy women. It was shown that the IL-10 -1082 G allele frequency increases significantly in patients compared to the control group (P=0.045). No significant differences were found in any other genotype or allele frequencies of IL-10 and IFN-gamma genes between the two groups. In addition, the frequencies of three common IL-10 haplotypes (GCC, ACC, ATA) did not show any significant difference between the study groups. Since the presence of G nucleotide at position -1082 of IL-10 gene is associated with reduced cytokine production, therefore, the higher frequency of IL-10 -1082 G allele in preeclamptic patients compared to controls may be considered as a genetic susceptibility factor for the development of PE.     

Placental growth factor in the cerebrospinal fluid of women with preeclampsia.

OBJECTIVE: Recent data suggest that excess circulating soluble fms-like tyrosine kinase-1 (sFlt-1) may causally relate to preeclampsia. This study investigates the levels of sFlt-1, VEGF, and PlGF in cerebrospinal fluid (CSF) of patients with preeclampsia and normotensive controls. METHODS: CSF was collected from preeclamptic patients (n=15) and controls (n=7) at the time of spinal anesthesia and assayed for PlGF, sFlt-1, and VEGF (total and free) by specific immunoassays. RESULTS: All sought angiogenic factors were measurable. Levels of free PlGF but not sFlt-1 or VEGF (total or free) were increased in CSF of preeclamptic women. There was no significant difference in the ratios of angiogenic factors in the CSF of women with preeclampsia. There was no correlation between levels of angiogenic factors and CSF cell counts or severity of symptoms. CONCLUSION: Elevated levels of PlGF in CSF preeclamptic women may promote vascular permeability and contribute to the hypertensive encephalopathy seen in such patients.     

Perinatal outcome in women with recurrent preeclampsia compared with women who develop preeclampsia as nulliparas

OBJECTIVE: To compare the rates and perinatal outcome in women who experienced preeclampsia in a previous pregnancy to those in women who developed preeclampsia as nulliparas. STUDY DESIGN: This is a secondary analysis of data from 2 separate multi-center trials of aspirin for prevention of preeclampsia. Women who had preeclampsia in a previous pregnancy (n = 598) were compared with nulliparous women (n = 2934). Outcome variables were rates of preeclampsia, preterm delivery at <37 and <35 weeks of gestation, small-for-gestational-age infant, abruptio placentae, and perinatal death. Data were compared by using chi-square analysis and Wilcoxon rank sum test. RESULTS: The rates of preeclampsia and of severe preeclampsia were significantly higher in the previous preeclamptic group as compared to the nulliparous group (17.9% vs 5.3%, P <.0001, and 7.5% vs. 2.4%, P <.0001, respectively). Women who had recurrent preeclampsia experienced more preterm deliveries before 37 and 35 weeks of gestation than nulliparous women who developed preeclampsia. In addition, among women who developed severe preeclampsia, those with recurrent preeclampsia had higher rates of preterm delivery both before 37 weeks (67% vs 33%, P =.0004) and before 35 weeks of gestation (36% vs 19%, P =.041), and higher rates of abruptio placentae (6.7% vs 1.5%) and fetal death (6.7% vs 1.4%) than did nulliparous women. CONCLUSION: Compared to nulliparous women, women with preeclampsia in a previous pregnancy had significantly higher rates of preeclampsia and adverse perinatal outcomes associated with preterm delivery as a result of preeclampsia.     

Hypocalciuria in women with preeclampsia]

To assess the significance of hypocalciuria in pregnant women, 24-hour urinary calcium excretion and the calcium/creatinine ratio (mg/g) in random urine samples were measured with a Toshiba TDA-30R autoanalyzer in the following 4 groups: 3 mild preeclamptic patients, 5 severe preeclamptic patients, 4 patients with intrauterine growth retardation (IUGR), and 10 healthy pregnant women. The mean 24-hour urinary calcium excretion in the 4 groups was 44.3 +/- 21.3 mg/day, 11.6 +/- 2.7 mg/day, 161.4 +/- 80.4 mg/day and 145.0 +/- 45.0 mg/day, respectively. Calcium excretion was significantly lower in the mild and severe preeclamptic patients than in the women with IUGR and the normal pregnant women. There was also a significant difference between the value in the mild and severe preeclamptic patients. The mean calcium/creatinine ratio in random urine samples was 53 +/- 30 mg/g, 18 +/- 5.6 mg/g, 192 +/- 85 mg/g and 169 +/- 70 mg/g, respectively. Also, such significant as 24-hour urinary calcium excretion were found in the mean calcium/creatinine ratio. From these results we conclude that determination of the 24-hour urinary calcium excretion or the calcium/creatinine ratio in random urine samples is a reliable index of preeclampsia.     

Carriers of thrombophilic factor among women with preeclampsia (preliminary report)

The aim of this study was to determine whether inherited thrombophilia increases the risk of mild preeclampsia. Twenty five women who developed mild preeclampsia and 49 controls--women with previous uneventful pregnancies, were tested for factor V Leiden, C677T gene variant of methylenetetrahydrofolate reductase (MTHFR), polymorphism 4G/5G in plasminogen activator inhibitor 1 (PAI 1), polymorphism A1/A2 in platelet glycoprotein IIb/Illa (GIPrllb/llla A1/A2). The higher but not significant prevalence of C677T gene variant and polymorphism A1/A2 in women with preeclampsia compared with controls was found: 32% and 12.2%, respectively for cases and controls for both factors, with OR: 3.37 (95% CI 0.883-13.2), p > 0.05. The values of OR and RR for these two thrombophilic factors show that platelet integrin polymorphisms (GIPrIIb/llla A1/A2) and C677T gene variant might be have an important role for development of preeclampsia. The carriage of FVL was with a very small prevalence in women with preeclampsia (8%) as compared to controls (6,1%), with OR: 1.333 (CI 95% 0.143-10.864), p > 0.05. The similar results were found for carriage of polymorphism 4G/5G in PAI-1: gene, respectively 24% u 18.4% in women with preeclampsia as compared to controls, OR: 1.404 (95% CI 0.374-5.14), p > 0.05. The results are not significant, because of the small group of selected patients. Larger case-control study should be executed for the evaluation of impact of inherited thrombophilic factors in the development of mild preeclampsia.     

Association between genetic polymorphisms in androgen receptor gene and the risk of preeclampsia in Korean women

Purpose  

To investigate associations between the androgen receptor (AR) polymorphisms as CAG repeats, GGC repeats and c.211G>A polymorphism and the risk of preeclampsia.     

Contribution of TIMP3 polymorphisms to the development of preeclampsia in Han Chinese women

Purpose

The aim of this study was to investigate whether polymorphisms in the tissue inhibitor of metalloproteinase 3 gene (TIMP3) are associated with the risk of preeclampsia (PE) in Han Chinese women.

Methods

Nine single TIMP3 tag-single nucleotide polymorphisms were selected by Haploview and genotyped using the Sequenom method in 181 preeclamptic and 203 healthy pregnant women from eastern China.

Results

The allele frequencies of the tag-single nucleotide polymorphisms were not significantly different between groups (P > 0.05). However, the genotype distribution of rs135025 was shown to differ between the multigravidity PE subgroup (>3) and controls under additive (P = 0.018) and recessive models (P = 0.008), while the genotype distribution of rs80272 differed significantly between the severe PE subgroup and controls under additive (P = 0.014) and dominant models (P = 0.041). Moreover, the H2 haplotype (A-C-G-T-A-A-G-C-G) was found to be associated with the risk of PE (P = 0.035).

Conclusions

Genotypes of rs135025 and rs80272 in TIMP3 may therefore influence susceptibility to PE, and pregnant women carrying the H2 haplotype might be more prone to developing PE.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-015-0529-8) contains supplementary material, which is available to authorized users.     

Factor VII deficiency and its treatment in delivery with recombinant factor VII

The authors present two cases of pregnant women with coagulation disorders--one with inherited deficiency of factor VII and the second with chronic hepatitis. Both cases were successfully treated with recombinant activated factor VII of coagulation (NovoSeven) in delivery. The advantages of using this product are discussed.     

Inhibin-A and superimposed preeclampsia in women with chronic hypertension

OBJECTIVE: To determine if maternal serum inhibin-A can be used as a marker for subsequent development of superimposed preeclampsia in women with chronic hypertension. METHODS: Serum for measurement of inhibin-A was obtained at monthly intervals in women with chronic hypertension requiring antihypertensive medications. Superimposed preeclampsia, the primary outcome of interest, was diagnosed when hypertensive women developed proteinuria (at least 300 mg per 24-hour urine specimen). Serum inhibin-A was considered abnormally elevated when the value exceeded the mean plus two standard deviations of the log for chronically hypertensive women who did not develop preeclampsia. RESULTS: A total of 61 women were enrolled in this study, and 21 (34%) developed superimposed preeclampsia. Inhibin-A levels increased with advancing gestational age. Ten women had abnormally increased inhibin-A levels; eight (80%) developed superimposed preeclampsia, compared with 13 of 51 (26%) women with normal inhibin-A levels (P <.001). Sensitivity and specificity were 38% and 95%, respectively, whereas the positive and negative predictive values were 80% and 75%, respectively. CONCLUSION: Although inhibin-A was abnormally increased an average of 3 weeks before the clinical onset of superimposed preeclampsia, the sensitivity of the test as a screen was too limited to be clinically useful.     

Oxidative stress and immunological alteration in women with preeclampsia

Objectives: To determine plasma concentrations of malondialdehyde (MDA) and of inflammatory markers in women with preeclampsia. Methods: A case–control study was conducted on 50 preeclamptic and 50 healthy pregnant women. The concentrations of MDA were determined by the method of thiobarbituric acid reactive substances. Markers of inflammation were determined by the multiplex method. Results: The concentrations of MDA did not differ between groups (p?>?0.05) and the preeclampsia group had significantly higher IL-6, IL-10, TNF-α and IL-6/IL-10 ratio, compared to those with normal pregnancy. Conclusions: The MDA is a nonspecific marker for oxidative stress in preeclampsia, and the gestantes with preeclampsia have immune dysfunction.     

Recurrent preeclampsia and perinatal outcome: a study of women with recurrent preeclampsia compared with women with preeclampsia who remained normotensive during their prior pregnancies

OBJECTIVE: To evaluate the impact of preeclampsia recurrence on perinatal outcome. MATERIALS AND METHODS: A case-controlled study was performed in multiparous women who developed preeclampsia in index pregnancy (n = 64). Among these, women who had preeclampsia in previous pregnancies (n = 21) were compared to those who remained normotensive during their prior pregnancies (n = 43). Maternal and fetal variables were compared. Multivariate logistic analyses were performed to examine the impact of preeclampsia recurrence on fetal loss, preterm delivery, small for gestational age (SGA) occurrence and respiratory distress syndrome adjusted for confounding variables. RESULTS: No statistical significant difference was observed between the two groups in terms of age, delivery weeks, steroid use and laboratory markers. Fetal loss was higher in women with recurrent preeclampsia (19.0%) than in women with preeclampsia who had a normotensive pregnancy history (4.7%), with adjusted odds ratio (OR) of 5.77 [95% confidence interval (CI) 0.84-39.54]. CONCLUSION: Women with recurrent preeclampsia had a higher rate of perinatal loss compared to women with preeclampsia who were normotensive in their prior pregnancies.