Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage.

OBJECTIVE: To identify associations or interrelations between carriage of the methylenetetrahydrofolate reductase (MTHFR) C677T, the MTHFR A1298C, the factor V Leiden G1691A, the factor II prothrombin G20210A, the human platelet antigen (HPA) 1 C12548T, and the apolipoprotein (APO) B R3500Q polymorphisms and idiopathic recurrent miscarriage (IRM). DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred forty-five women with a history of three or more consecutive pregnancy losses before 20 weeks gestation and 101 healthy postmenopausal women with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous punctures. MAIN OUTCOME MEASURE(S): Multiplex polymerase chain reaction was performed to identify the different alleles of six candidate genetic risk factors for IRM (MTHFR C677T, MTHFR A1298C, factor V Leiden G1691A, factor II prothrombin G20210A, HPA 1 C12548T, and the APO B R3500Q). RESULT(S): Allele and genotype frequencies of all polymorphisms were not significantly different between the study and the control groups. Also, no significant associations occurred between combinations of polymorphisms and the occurrence of IRM. CONCLUSION(S): Our data fall short of showing any significant association between single polymorphisms of the MTHFR, the Factor V Leiden, the Factor II Prothrombin, the HPA 1 and APO B genes or combinations of these polymorphisms and the occurrence of IRM.

Concentrations of estrogens in patients with preeclampsia.

The role of estrogens in the pathophysiology of preeclampsia remains to be determined. The aim of our study was to compare serum concentrations of 17 beta-estradiol and estriol in women with preeclampsia to normotensive pregnant controls. Serum concentrations of estrogens were measured in women with mild (n = 24) and severe (n = 24) preeclampsia as well as is normotensive pregnant controls (n = 24). Patients were matched for gestational age. Pregnancies complicated by early onset severe preeclampsia are associated with increased rates of maternal and fetal morbidity. Subsequently, we created further subgroups before and after 34 weeks of gestation (34 + 0). Serum estrogen concentrations were determined by standard ELISA technique. Compared to normotensive controls, the differences between the overall median serum concentrations of 17 beta-estradiol in women with mild (3811 v. 3730 pg/ml, P = 0.9) and severe (3811 v. 3630 pg/ml, P = 0.1) preeclampsia were statistically not significant. The differences between the overall median serum concentrations of estroil in controls and in patients with mild (121 v. 76 ng/ml, P = 0.6) and severe (121 v. 79 ng/ml, P = 0.4) preeclampsia were similar. The differences between the median concentrations of 17 beta-estradiol in patient with early onset severe preeclampsia compared to patients with mild preeclampsia (3061 v. 3715 pg/ml, P = 0.004) and controls (3061 v. 3807 pg/ml, P = 0.006) were statistically significant. In addition, the differences between the median concentrations of estriol in women with early onset severe preeclampsia compared to controls were statistically significant (20 v. 92 ng/ml, P = 0.02). The differences between the median concentrations of estrogens in those with late onset severe preeclampsia compared to women with mild preeclampsia were not significant. We found significantly lower concentrations of estrogens in women with early onset severe preeclampsia.

Serum levels of heat shock protein 70 in patients with preeclampsia: a pilot-study.

OBJECTIVE: To evaluate the serum levels of heat shock protein (Hsp) 70 in patients with severe preeclampsia (PE) in comparison to controls. The pathophysiology of PE can be explained, in part, by alterations of endothelial function caused by endothelial cell activation and injury. HSP 70 is essential for cellular recovery, survival and maintenance of homeostasis. STUDY DESIGN: In a matched pair study, serum levels of Hsp 70 were measured in 55 patients with late (group A, n = 24) and early (group B, n = 31) onset of severe PE, and in 55 normotensive controls (group C, n = 24 and group D, n = 31) matched for gestational age. Early onset of severe PE was defined as onset of disease at less than 34 weeks of gestation (34 + 0). Serum levels were determined using a sandwich enzyme-linked immunosorbent assay. RESULTS: The overall median serum levels of Hsp 70 were 2.82 ng/mL (SD +/- 8.33) in preeclamptic women, and 1.01 (SD +/- 1.38) ng/mL in controls (P = 0.08). The median serum levels of Hsp 70 were 0.52 ng/mL (SD +/- 1.14) in group A and 0.86 (SD +/- 1.29) ng/mL in group C (P = 0.15). The median serum levels of Hsp 70 were 4.94 ng/mL (SD +/- 10.46) in group B and 1.33 (SD +/- 2.28) ng/mL (P = 0.04) in group D. The difference between group A and B was also statistically significant (P = 0.01). CONCLUSION: Our study revealed higher serum levels of Hsp 70 in patients with early onset of severe PE. Further studies are recommended in order to elucidate the possible role of Hsp 70 in the pathophysiology of PE.

Basic fibroblast growth factor and hypertensive disorders in pregnancy.

OBJECTIVE: We examined serum concentrations of basic fibroblast growth factor (bFGF) in women with hypertensive disorders in pregnancy and analyzed whether serum concentrations of bFGF can be used as a discriminator between mild and severe preeclampsia. METHODS: One hundred and twenty pregnant women were included in this prospective cohort study. We evaluated serum concentrations of bFGF in pregnant women with chronic hypertension (n=22), mild preeclampsia (n=40), severe preeclampsia (n=31), and healthy pregnant women (n=27). RESULTS: Median serum concentrations of bFGF in healthy pregnant women, women with chronic hypertension, and women with mild or severe preeclampsia were 0.0 (0-37.2), 0.0 (0-3.0), 1.7 (0-97.2), and 0.0 (0-52.0), respectively. Comparison of the median values of serum bFGF concentrations showed a significant difference between healthy pregnant women and women with mild preeclampsia (P=0.02). In a logistic regression model, we found a significant influence of bFGF serum concentrations on the diagnosis of mild preeclampsia (P=0.01), but not on the diagnosis of chronic hypertension (P=0.19) or severe preeclampsia (P=0.41). CONCLUSIONS: Elevated serum concentrations of bFGF are associated with mild preeclampsia, but are not discriminatory for the distinction between mild and severe preeclampsia.