Significant Risk Factor For Preeclampsia Research Articles

Assoziationsstudien von Polymorphismen zur Risikoevaluierung in der Schwangerschaft - Literaturübersicht und Metaanalyse

Ein potenziell wirksames Instrument zur Erkennung der individuellen Physiologie und individueller Risikoprofile von Schwangeren stellt die Kenntnis von Polymorphismen dar. Mittlerweile wurden in über 70 Assoziationsstudien die Effekte der Trägerschaft bestimmter Polymorphismen auf die Schwangerschaft und schwangerschaftsassoziierte Erkrankungen wie Präeklampsie und Thrombose untersucht. Eine Metaanalyse von 22, 11 und 10 Studien weist die Trägerschaft des F-V-Leiden G1691A- (OR 1,9; 95 %-KI 1,6 - 2,5), des F II G20210A- (OR 1,8; 95 %-KI 1,1 - 2,9) und des AGT Met235Thr-Polymorphismus (OR 1,6; 95 %-KI 1,4 - 1,8) als signifikante Risikofaktoren für Präeklampsie aus, während die Trägerschaft des MTHFR C677T-Polymorphismus in einer Metaanalyse von 24 Assoziationsstudien nicht mit einem erhöhten Präeklampsierisiko assoziiert ist (OR 1,1; 95 %-KI 0,9 - 1,3).

Hypoxia Favours Necrotic Versus Apoptotic Shedding of Placental Syncytiotrophoblast into the Maternal Circulation

In the third trimester of normal pregnancy, the mother tolerates daily shedding of several grams of dying placental trophoblast into the maternal circulation. The balance between apoptotic and necrotic shedding is presently unknown. Since pre-eclampsia is characterized by an altered placental oxygenation and increased trophoblast shedding, we investigated the role of oxygen on the balance of apoptotic versus necrotic trophoblast shedding in vitro.We studied human trophoblast turnover in explanted villi from late first and third trimester placentas in low oxygen (2 per cent) and higher oxygen tensions (6 per cent and 18 per cent) for up to 72h. Trophoblast turnover including apoptosis and necrosis were assessed by histology, immunolocalization of Mib-1 (proliferation marker), Bcl-2 (apoptosis inhibitor), activated caspase 3 (apoptosis promoter), cytokeratin 18 neo-epitope formation (M30 antibody), TUNEL test (DNA degradation), and 3H-cytidine and3 H-uridine incorporations.Culture in 2 per cent oxygen increased cytotrophoblast proliferation and syncytiotrophoblast shedding by necrosis. The proteins necessary for execution of apoptosis were mostly retained in the cytotrophoblast due to lack of syncytial fusion. Culture in 6 per cent and 18 per cent oxygen reduced cytotrophoblast proliferation. Syncytial fusion occurred and activity of caspase 3 was found in the syncytiotrophoblast; the latter remained intact demonstrating physiologic turnover, including apoptotic shedding.We conclude that severe placental hypoxia favours necrotic rather than apoptotic shedding of syncytial fragments into the maternal circulation. Since uteroplacental ischaemia is a significant risk factor for pre-eclampsia, these findings may explain the link between reduced uteroplacental blood flow and the systemic clinical manifestations of this disease.

Preeclampsia in the parous woman: Who is at risk?

Objective: The purpose of this study was to identify risk factors for preeclampsia in second pregnancies and to determine whether gestational age at delivery in the first pregnancy increases the risk of recurrent preeclampsia. Study Design: We conducted a population-based, case-control study using birth certificate data from the Missouri maternally linked cohort. Data from women delivered of their first 2 singleton pregnancies between 1989 and 1997 (2332 cases with preeclampsia in the second pregnancy and 2370 control cases) were analyzed with logistic regression. Results: Significant risk factors for preeclampsia in a second pregnancy include longer birth interval, previous preterm delivery, previous small-for-gestational-age newborn, renal disease, chronic hypertension, diabetes mellitus, obesity, black race, and inadequate prenatal care. Smoking and same paternity are protective. A history of preeclampsia confers the highest risk for preeclampsia in the second pregnancy; the risk is inversely proportional to gestational age at delivery of the first pregnancy: adjusted odds ratio, 15.0; 95% CI, 6.3-35.4 for 20 to 33 weeks; adjusted odds ratio, 10.2; 95% CI, 6.2-17.0 for 33 to 36 weeks; and adjusted odds ratio, 7.9; 95% CI, 6.3-10.0 for 37 to 45 weeks. Conclusion: The relative risk of recurrent preeclampsia increases with earlier gestational age at delivery of the first pregnancy that was complicated by preeclampsia. (Am J Obstet Gynecol 2002;187:425-9.)

Primipaternity and duration of exposure to sperm antigens as risk factors for pre-eclampsia

Objective: To establish whether primipaternity and duration of unprotected sexual cohabitation is associated with an increased risk of pre-eclampsia. Method: At a tertiary referral center, the study had a case and control group of 60 multigravid women each, as well as a case and control group of 50 primigravid women each. Information was compiled by means of a confidential questionnaire. Result: After multiple logistic regression analysis using age, smoking, hypertension in previous pregnancies, change of paternity and duration of unprotected sexual cohabitation as predictors, the regression coefficients for change of paternity and sexual cohabitation of longer than 6 months in multigravid women were −0.4 ( P=0.15) and −1.4 ( P=0.03), respectively. Conclusion: Multigravid women with a period of unprotected sexual cohabitation of longer than 6 months had a decreased risk of pre-eclampsia. Primipaternity was not a significant risk factor for pre-eclampsia.

METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISMS IN PREECLAMPSIA AND THE HELLP SYNDROME

Objective: To investigate the prevalence of the 677 (C → T) and 1298 (A → C) polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene in our preeclamptic population. For a summary estimation of the risk of the 677 (C → T) polymorphism for preeclampsia, we also performed a meta-analysis on four previously published case-control studies to which our results were added.Methods: Genotypes were analyzed by polymerase chain reaction followed by restriction enzyme analysis. The results of 176 nonpregnant women, previously hospitalized for preeclampsia in a tertiary care center, were compared with 403 Dutch population-based controls.Results were statistically analyzed with a chi-square test.Mean Outcome Measures: The incidence of the 677 (C → T) and 1298 (A → C) polymorphisms in the MTHFR gene.Results: The incidence of both MTHFR missense polymorphisms was not significantly different between cases and controls. We found an odds ratio (OR) of 1.5 [95% confidence interval (CI) 0.8–0.6, p = 0.17] and an OR of 1.0 (95% CI 0.6–1.9, p = 0.23) for the 677 (C → T) and the 1298 (A → C) polymorphism, respectively, in cases comparing the prevalence of the homozygous genotype versus the other two genotypes. The meta-analysis resulted in a significant OR of 2.0 (95% CI 1.4–2.9).Conclusions: In contrast to four previous studies, we were neither able to confirm an increased risk for preeclampsia to the 677 (C → T) polymorphism nor did we find an increased risk for preeclampsia to the 1298 (A → C) polymorphism. From the meta-analysis, however, we conclude that it cannot be ruled out that the homozygous 677TT genotype is a modest but significant risk factor for preeclampsia.