Prothrombin 20210 G-->A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy

Over 50 unselected women with maternal venous thromboembolism were screened for the prothrombin 20210 G→A and MTHFR C677T mutations, in addition to screening for other thrombophilias. The prevalence of thrombophilia in these women was compared with its prevalence in the general population in our area. The prothrombin (OR 4.4; 95% CI 1.2-16) and factor V Leiden (OR 4.5; 95% CI 2.1-14.5) mutations were more common in our patients, compared with the general population, whereas women homozygous for the C677T mutation in the methylene tetrahydrofolate reductase gene (OR 0.45; 95% CI 0.13-1.58) were not. It is recommended that women with a personal or strong family history of venous thromboembolism should be screened for the prothrombin mutation either before or early in pregnancy, in addition to screening for other thrombophilias. Screening for the MTHFR mutation does not appear to identify women at increased risk of maternal venous thrombosis.     

Single inherited thrombophilias and adverse pregnancy outcomes

INTRODUCTION: Inherited thrombophilia is believed to be a multiple gene disease with more than one defect. We aimed to determine the association between single thrombophilic patterns and a variety of pregnancy diseases. METHODS: 284 pregnant women were recruited for the present study and were divided in two groups: A group (176 controls) and B group (108 cases). Patients belonging to the B group had one of the following: severe pre-eclampsia, hemolysis, hepatic enzymes increase, hypertension and low platelet count (HELLP) syndrome, gestational hypertension, fetal growth restriction, intrauterine death, abruptio placentae and disseminated intravascular coagulopathy. To detect methylenetetrahydrofolate reductase (MTHFR) A1298C, MTHFR C677T, factor V Leiden, PAI-1, mutant prothrombin G20210A, an inverse hybridization technology was used. Plasma homocysteine, antithrombin (AT) III and protein S were determined. A modified functional activated protein C resistance was detected. RESULTS: MTHFR C677T and hyperhomocysteinemia were more prevalent than other thrombophilias. Deficiency in AT III was significantly linked with pre-eclampsia (relative risk 0.88; 95% CI 0.83-0.94). Activated protein C resistance (APCR) was significantly related to the abruptio placentae (relative risk 0.71; 95% CI 0.61-0.82). COMMENTS: Apart from the linkage between AT III deficiency and the occurrence of pre-eclampsia, and apart from the increased risk of abruptio placentae in pregnant women with altered APCR, we obtained findings in contrast with some of the published literature. In our case series, no association of pre-eclampsia with factor V Leiden or with prothrombin gene mutation was found.     

Genetic thrombophilias and preeclampsia: a meta-analysis

OBJECTIVE: To assess the relationship between the factor V Leiden (1691 G-A) single nucleotide polymorphism (SNP), the methylene tetrahydrofolate reductase (MTHFR) 677 C-T SNP, and the prothrombin 20210 G-A SNP and the risk of preeclampsia, by conducting a meta-analysis of all case-control studies with data on these polymorphisms and the risk of preeclampsia. DATA SOURCES: MEDLINE (1966 to November 2002), EMBASE (1980 to November 2002). Search terms included "preeclampsia," "thrombophilia," "factor V Leiden," "protein C," "MTHFR," "methylenetetrahydrofolate reductase," "homocysteine," and "prothrombin gene 20210."METHODS OF STUDY SELECTION: Case-control studies of genetic thrombophilias and preeclampsia were included. TABULATION, INTEGRATION, AND RESULTS: We identified 349 titles and reviewed 47 articles for inclusion and exclusion criteria. Thirty-one studies with 7,522 patients were included in the meta-analysis. Data from patients characterized as having severe preeclampsia were extracted and analyzed separately. The pooled odds ratio (OR) for the association of factor V Leiden and all cases of preeclampsia was 1.81 (95% confidence interval [CI] 1.14-2.87) and 2.24 (95% CI 1.28-3.94) for cases of severe preeclampsia. The pooled OR for the MTHFR 677 TT genotype and all preeclampsia was 1.01 (95% CI 0.79-1.29) and 1.38 (95% CI 0.93-2.06) for severe preeclampsia. The OR for the prothrombin 20210 polymorphism and all preeclampsia was 1.37 (95% CI 0.72-2.57) and 1.98 (.94-4.17) for severe preeclampsia. CONCLUSION: This meta-analysis suggests that the factor V Leiden SNP is associated with an increased risk of preeclampsia. Further studies are warranted to determine whether subgroups of high-risk women should be screened for this mutation.     

Predictiveness of antenatal umbilical artery Doppler for adverse pregnancy outcome in small-for-gestational-age babies according to customised birthweight centiles: population-based study

Objective  To examine the relationship between smallness at birth and the predictive value of umbilical artery Doppler.
Design  Retrospective cohort.
Setting  Tertiary referral university hospital, Barcelona.
Population  A total of 7645 singleton pregnancies delivered between January 2002 and June 2004.
Methods  The associations with adverse outcome were assessed for small-for-gestational-age (SGA) babies according to customised standards who had normal and abnormal umbilical artery Doppler.
Main outcome measures  Neonatal morbidity and perinatal mortality.
Results  Of the 369 SGA fetuses that had been identified antenatally, 70 (19%) had an abnormal umbilical artery Doppler and the babies from these pregnancies had a higher risk for neonatal morbidity when compared with babies with normal birthweight (OR 3.99, 95% CI 1.04–11.03). However, the remaining 299 (81%) fetuses with normal umbilical artery Doppler also had an elevated risk of neonatal morbidity (OR 2.26, 95% CI 1.04–4.39). Overall, many of the instances of adverse outcome associated with smallness for gestational age were attributable to the group with normal Doppler than to the group with abnormal Doppler.
Conclusion  Normal antenatal umbilical artery Doppler cannot be taken as an indicator of low risk in pregnancies where the fetus is SGA according to customised percentiles.     

Dalteparin and Low-Dose Aspirin in the Prevention of Adverse Obstetric Outcomes in Women With Inherited Thrombophilia

ObjectiveTo evaluate the benefit of treatment with dalteparin and low-dose aspirin (ASA) in the prevention of obstetric complications in women with inherited thrombophilia.MethodsA retrospective chart review identified women who had had at least one pregnancy complicated by severe early-onset preeclampsia, placental abruption, fetal growth restriction (FGR), or fetal death. The following inherited thrombophilias were included: deficiencies of antithrombin, protein C, or protein S, and mutations of factor V Leiden (G1691A), factor II (G20210A), or methylenetetrahydrofolate reductase C677T.ResultsThe records of 43 women with 110 pregnancies were included in the study. Anticoagulant prophylaxis was administered using dalteparin in 13 pregnancies, ASA with dalteparin in 26, and ASA alone in 11. Dalteparin alone and ASA alone showed equivalent effects in preventing preeclampsia and FGR. Combined dalteparin and ASA significantly decreased the risk of preeclampsia (odds ratio [OR] 0.80; 95% confidence intervals [CI] 0.70–0.91, P = 0.001) and FGR (OR 0.70; 95% CI 0.60–0.82, P = 0.001).ConclusionData from this retrospective cohort study suggest that combined treatment with dalteparin and ASA decreases the risk of preeclampsia by 20% and the risk of FGR by 30% in women with inherited thrombophilia.     

Evaluation of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase gene mutations in patients with severe pregnancy complications in northern Finland

BACKGROUND: Thrombosis in placenta may lead to severe pregnancy complications. Most important inherited thrombophilias are factor V Leiden mutation, prothrombin mutation, and methylenetetrahydrofolate reductase mutation. The aim of our research was to evaluate the prevalence of inherited thrombophilias in severe pregnancy complications and in normal pregnancies. MATERIAL AND METHODS: The study subjects with severe preeclampsia, intrauterine growth restriction, placental abruption or fetal death were collected during the period 1999-2004 from Oulu University Hospital. We also collected during the same period voluntary parturients with normal pregnancy outcome as the control group. FVL, FII, and MTHFR gene mutations of the patients and controls were analyzed. RESULTS: We found a significant difference in the prevalence of FVL mutation between the groups. There were 9.5% FVL mutations in the study group compared to 1.8% in the control group; the observed difference between prevalences was 7.7% (95% CI 2.0-13.4). No statistical difference was found in the FII or MTHFR mutations between the groups. All FV and FII mutations were heterozygous and all the MTHFR mutations homozygous. CONCLUSION: Women with thrombophilia have a risk for severe pregnancy complications. Randomized controlled trials are needed to assess the influence of low-molecular-weight heparin in pregnant women with thrombophilia.     

Genetic thrombophilias and uterine artery Doppler velocimetry and preeclampsia.

OBJECTIVE: The aim of this study was to evaluate the correlation between genetic thrombophilic mutations, uterine artery Doppler at 24 weeks of gestation and preeclampsia. METHODS: In a case control study we performed the genetic analysis for Leiden mutation of factor V gene (FV), G20210A mutation of the prothrombin gene (PT) and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in 103 women that had already attended routine ultrasonography scanner at 20 weeks at our Department. RESULTS: The frequency of heterozygous carriers of the factor V Leiden was 17.4% in the women with preeclampsia and abnormal artery Doppler compared with 3.12% in the patients with normal pregnancies. This difference was statistically significant (P<0.05). The frequency of mutation G20210A of prothrombin gene was 1.5 vs. 4.3% between women with normal pregnancies and with preeclampsia. This difference is not statistically significant. The frequency of homozygous patients for the C677T mutation of MTHFR gene among the patients with preeclampsia was 21.7% and in the control group was 10.3%, but this difference is not statistically significant. No thrombophilic gene variants were found in women with preeclampsia and normal uterine artery Doppler. CONCLUSION: We demonstrated the important association between factor V Leiden mutation, abnormal uterine Doppler at 24 weeks and preeclampsia in our population.     

Inherited thrombophilia screening in Greek women with recurrent fetal loss

OBJECTIVE: The present study was designed to determine the prevalence of factor V Leiden (FVL), prothrombin gene G20210A (PTG) and methylenetetrahydrofolate reductase (MTHFR C677T) mutations in women from South-Western Greece with recurrent fetal loss (RFL) and negative personal thromboembolic history. MATERIALS AND METHODS: 212 women with RFL and 181 women with at least two pregnancies with normal outcome and no history of pregnancy loss were investigated for the commonest thrombophilic mutations (FVL, PTG, MTHFR C677T). Comparisons between groups were performed by Pearson's chi-square test and odd ratios were calculated. RESULTS: An abnormal genotype was detected in 49 women of the study group (23.1%) and in 41 women of the control group (22.6%). CONCLUSION: Inherited thrombophilia screening is not indicated as an initial approach in Greek women with RFL and negative personal thromboembolic history.     

Antiphosphatidyl serine antibodies are more common in normotensive women with small for gestational age pregnancies

BACKGROUND: Small for gestational age (SGA) babies are more common in women with antiphospholipid antibodies but data are limited about the prevalence of antiphospholipid antibodies in women who have delivered SGA babies. AIM: To determine whether elevated levels of anticardiolipin, antiphosphatidyl serine and/or antibeta2 glycoprotein I antibodies are more common in normotensive women who delivered SGA babies compared with women who delivered appropriate for gestational age babies. METHODS: Case-control study. Cases were normotensive women who delivered an SGA baby (birthweight <10th%) without chromosomal or congenital abnormality. Controls were healthy women who delivered a baby at term with birthweight >10th percentage. RESULTS: A total of 137 women with SGA pregnancies and 290 controls had antiphospholipid antibodies measured. The prevalence of anticardiolipin and antibeta2 glycoprotein I antibodies did not differ between SGA cases and controls. Antiphosphatidyl serine IgG antibodies were more common in women with SGA pregnancies than controls seven (5%) versus five (1.7%), relative risk (RR) 1.84 (1.12-3.03). There was no difference in the prevalence of 'any antiphospholipid antibodies' between SGA 10 (7.2%) and controls 16 (5.6%). There was a trend to more abnormal umbilical Doppler studies in SGA pregnancies with positive antiphospholipid antibodies three (50%) versus 19 (24%), RR 2.9 (0.62-13). CONCLUSIONS: Antiphospholipid antibodies were uncommon in this cohort of SGA pregnancies. Further studies are needed in SGA pregnancies with abnormal umbilical Doppler studies to determine if screening for antiphospholipid antibodies is worthwhile in this severe subgroup.     

Frequency of selected thrombophilias in women with placental abruption

OBJECTIVE: There is a growing view that inherited or acquired thrombophilia may predispose a woman towards an adverse pregnancy outcome. The aim of this study was to investigate whether risk factors for placental abruption because of such thrombophilias (such as carriership of factor V Leiden (FVL), prothrombin G20210A gene mutation and homozygous MTHFR C677T) might be used as a predictor for placental abruption. METHODS: A retrospective case-control study conducted at the University Hospital, Palacky University, Olomouc, Czech Republic. One hundred and eighty women with placental abruption out of 20,175 deliveries (0.79%) were compared to 196 unselected gravidae. A detailed medical history was taken with special reference to factors related to hypercoagulation and blood was drawn for polymerase chain reaction analysis. The prevalence of FVL, prothrombin G20210A and MTHFR C677T was related to placental abruption. RESULTS: The heterozygous form of FVL was present in 20of 142 cases (14.1%) in the placental abruption group, compared to ten of 196 (5.1%) in the control group (odds ratio 3.0, 95% confidence interval 1.4-6.7). CONCLUSIONS: We found that factor V Leiden is a significant risk factor for placental abruption.     

Mid-trimester severe intrauterine growth restriction is associated with a high prevalence of thrombophilia

Objective To investigate the association between severe mid-trimester IUGR, whose causes are unknown in most cases, and maternal thrombophilias.
Design Case–control study.
Setting Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, The Sackler Faculty of Medicine, Tel Aviv University.
Population Twenty-six women with severe mid-trimester (22–26 weeks of gestation) IUGR (birthweight  <3rd centile  ) and 52 matched multiparous women with normal pregnancies (controls).
Methods After excluding pregnancies with vascular maternal disease, chromosomal and structural aberrations and cytomegalovirus infection, 26 women out of 35 with severe mid-trimester IUGR remained and composed the study group. Each was matched for age, ethnicity and smoking status with two healthy women who had normal pregnancies. All the women were tested for genetic and acquired thrombophilias at least eight weeks after delivery.
Main outcome measures Prevalence of maternal thrombophilias.
Results The frequency of thrombophilias was 69% in the study group compared with 14% in the control group [odds ratio (OR) 4.5; 95% confidence interval (CI) 2.3–9, P  < 0.001  ]. The frequencies of factor V Leiden mutation, prothrombin gene mutation and protein S deficiency were significantly increased in the study group compared with the control group. The frequency of multiple thrombophilias was 33% in the study group versus none among the controls. Of the 26 pregnancies with severe mid-trimester IUGR, 13 ended in intrauterine fetal death before 25 weeks of gestation: 10 of these women had thrombophilia.
Conclusion Women with mid-trimester severe IUGR have an increased prevalence of inherited and acquired thrombophilias.     

Interaction between risk factors for fetal growth retardation associated with abnormal umbilical artery Doppler studies

BACKGROUND: The role of antenatal risk factors associated with the occurrence of fetal growth restriction complicated by abnormal umbilical artery Doppler studies has not yet been studied extensively. We evaluated the role and the interactions of antenatal antecedents of fetal growth restriction complicated by abnormal umbilical artery end-diastolic velocities. METHODS: We compared antenatal variables in 183 pregnancies complicated by fetal growth retardation and abnormal umbilical artery Doppler studies and 549 appropriately grown fetuses with normal end-diastolic velocity waveform in the umbilical artery. Logistic regression was used to evaluate the association between antenatal variables and fetal growth retardation and to test for interaction. RESULTS: In logistic models, increasing maternal age [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.01-1.11], nulliparity (OR 2.2, 95% CI 1.37-3.5), smoking during pregnancy (OR 2.56, 95% CI 1.56-4.22), preeclampsia (OR 27.5, 95% CI 15.1-49.9), first-trimester hemorrhage (OR 2.25, 95% CI 1.32-3.82) and low (< 0.2 kg/week) weight gain in pregnancy (OR 3.48, 95% CI 1.71-3.05) were significantly associated with an increased risk of fetal growth restriction complicated by abnormal Doppler studies. These risk factors were also significantly correlated with the occurrence of absent/reversed end-diastolic blood flow in the umbilical artery. Maternal smoking during pregnancy interacted negatively with preeclampsia but positively with a low weight gain in pregnancy. CONCLUSIONS: The results of this study have shown that antenatal risk factors for intrauterine growth retardation (IUGR) complicated by abnormal Doppler studies are similar to those associated with the birth of a small-for-gestational-age infant. Preeclampsia, maternal smoking and low weight gain in pregnancy play a significant causal role in the origin of fetal growth restriction associated with abnormal uteroplacental blood flow.     

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.     

Screening for pre-eclampsia in a low-risk population at 24 weeks: uterine artery Doppler flow velocimetry and genetic variants of factor V, prothrombin and methylenetetrahydrofolate reductase

AIM: Pre-eclampsia is one of the major causes of maternal and fetal morbidity and mortality. The aim of this study was to evaluate the clinical usefulness of screening of genetic thrombophilic mutations and uterine artery Doppler flow velocimetry at 24 weeks of gestation in the prediction of pre-eclampsia in low risk pregnant women. METHODS: We performed the genetic analysis for Leiden mutation of factor V gene (FV), G20210A mutation of the prothrombin gene (PT) and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene in 103 women that had already attended routine ultrasonography scanner at 24 weeks at our Department. RESULTS: The frequency of heterozygous carriers of the Leiden FV was 17.4% in women with pre-eclampsia and abnormal artery Doppler flow velocimetry compared with 3.12% in patients with normal pregnancies. This difference was statistically significant (P<0.05). The frequency of mutation G20210A of PT gene was 1.5% vs 4.3% between women with normal pregnancies and with pre-eclampsia. This difference is not statistically significant. The frequency of homozygous patients for the C677T mutation of MTHFR gene among patients with pre-eclampsia was 21.7% and in the control group was 10.3%, but this difference is not statistically significant. No thrombophilic genes variants were found in women with pre-eclampsia and normal uterine artery Doppler flow velocimetry. CONCLUSION: We demonstrated the important association between FV Leiden mutation, abnormal uterine artery Doppler flow velocimetry at 24 weeks and pre-eclampsia in our low-risk population.     

Inheritance and perinatal consequences of inherited thrombophilia in Greece.

OBJECTIVE: To investigate the impact of inherited thrombophilic factors on the gestational outcome of unselected pregnant women. METHOD: A total of 392 women with spontaneous pregnancy were investigated for Factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations. Adverse pregnancy outcomes were recorded. RESULTS: Thrombophilic genotypes were significantly higher in women with placental abruption. Heterozygocity for Factor V Leiden increased the risk for placental abruption 9.1 times. The MTHFR T677T genotype increased the risk for placental abruption 4.8 times despite folate supplements, and normal serum folate and B(12) levels. Women with inherited thrombophilia and previous obstetric complications were at significant risk for complications in a subsequent pregnancy (P<0.05). CONCLUSION: Women with placental abruption should be screened for thrombophilic factors and plasma homocysteine should be measured. Subgroups of women with inherited thrombophilia and obstetric complications might benefit from prophylactic anticoagulation in subsequent pregnancies.     

Severe preeclampsia and high frequency of genetic thrombophilic mutations

OBJECTIVE: To determine whether severe preeclampsia is associated with genetic thrombophilic mutations or other types of thrombophilia. METHODS: A case-control study compared 63 consecutive women with severe preeclampsia evaluated at our institution between November 1997 and April 1999 with 126 control women matched for age and ethnicity. All of these women were tested several months after delivery for mutations of factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin gene; for deficiencies of protein C, protein S, and antithrombin-III; and for the presence of anticardiolipin antibodies. RESULTS: Thirty-five study women (56%) had a thrombophilic mutation compared with 24 control women (19%), P <.001. Seven other study women (11%) had other thrombophilias, compared with one control woman (0.8%), P <.01. Within the study group, women with thrombophilia delivered at an earlier gestational age, and their neonates' birth weights were lower compared with those of women without thrombophilia. CONCLUSION: Because thrombophilia was found in 67% of women with severe preeclampsia, we suggest that women who have severe preeclampsia should be tested for thrombophilia.     

Genetic hypofibrinolysis in complicated pregnancies

OBJECTIVE: To assess the hypofibrinolytic 4G/4G mutation of the plasminogen activator inhibitor (PAI-1) gene as a possible factor contributing to severe preeclampsia, abruptio placentae, fetal growth restriction, and stillbirth. METHODS: We compared 94 women from a previous report who had obstetric complications to 95 controls with normal pregnancies matched for ethnic background and age. We collected blood and extracted DNA after delivery. All subjects had been tested for thrombophilic mutations factor V Leiden, C677T mutation in the methylenetetrahydrofolate reductase gene, and the G20210A mutation in the prothrombin gene. In the present study we tested for the hypofibrinolytic 4G/4G mutation in the PAI-1 gene. RESULTS: Women who had obstetric complications were more likely than controls to be 4G/4G homozygotes, 32% (30 of 94) women versus 19% (18 of 95) controls, odds ratio (OR) and 95% confidence intervals (CI) 2.0 (1.02, 3.9). Mutations in the PAI-1 gene were independently associated with obstetric complications (OR 1.56, 95% CI 1.005, 2.43). Heterozygosity for the factor V Leiden mutation was more common in the 30 women who had PAI-1 4G/4G than in the 18 4G/4G controls (33% versus 0%, Fisher P =.008). Seventy-six percent of women had some form of thrombophilia or hypofibrinolysis compared with 37% of controls (Fisher P <.001). CONCLUSIONS: Women with severe preeclampsia, abruptio placentae, fetal growth restriction, and stillbirth had increased incidence of the hypofibrinolytic 4G/4G mutation of the PAI-1 gene that is frequently associated with the thrombophilic factor V Leiden mutation, further predisposing them to thrombosis.     

Renal artery Doppler investigation of the etiology of oligohydramnios in postterm pregnancy

OBJECTIVE: To investigate the etiology of oligohydramnios in postterm pregnancy using Doppler velocimetry. METHODS: Renal and umbilical artery Doppler velocimetry were performed in women with singleton postterm (287 days' or more gestation) pregnancies. The renal and umbilical artery Doppler resistance index (RI) and end-diastolic velocity were measured. Stepwise logistic regression and the two-tailed t test were used to determine whether the Doppler indices correlated with oligohydramnios (amniotic fluid index less than 5 cm). RESULTS: We studied 147 well-dated, singleton, postterm pregnancies, of which 21 (14.3%) had oligohydramnios. For the study cohort, the mean (+/-standard deviation) gestational age at Doppler was 41.4 +/- 0.45 weeks and at delivery 41.8 +/- 0.47 weeks. Stepwise logistic regression using renal and umbilical artery Doppler indices found the renal RI to be the only significant predictor of oligohydramnios: beta = -10.4186, P <.05 (odds ratio [95% confidence interval (CI)] = 0, 0.88). The renal artery RI was significantly higher in cases with oligohydramnios (RI: mean (+/-standard error) = 0.8843 +/- 0.11 versus 0.8601 +/- 0.05, P 相似文献   

Frequency of factor V, prothrombin and methylenetetrahydrofolate reductase gene variants in preeclampsia

BACKGROUND: The association between thrombophilic variants (Leiden mutation of the factor V gene, G20210A mutation of the prothrombin gene and C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene) with preeclampsia was investigated in a north-eastern Italian population. METHODS: Fifty-eight preeclamptic (PE) women and 74 normal pregnancies were evaluated. Genotypes were determined by polymerase chain reaction. RESULTS: The frequency of heterozygous carriers of the factor V Leiden was similar between PE women (5.2%) compared to the control subjects (4.1%; p 0.76). Also the frequencies of G20210A and C677T mutations were similar between PE and control subjects. CONCLUSIONS: In this population, we found no difference in the prevalence of genetic risk factors for thrombosis in women with preeclampsia compared with control subjects.     

How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review.

OBJECTIVE: To determine whether inherited and acquired thrombophilias are associated with adverse obstetric complications. STUDY DESIGN: A systematic review; studies where women with adverse obstetric complications were tested for one or more acquired and inherited thrombophilias were included. MAIN OUTCOME MEASURES: Prevalence of thrombophilia in women with severe pre-eclampsia/eclampsia, severe placental abruption, intrauterine growth restriction or unexplained stillbirth. RESULTS: Compared with controls, placental abruption was more often associated with homozygous and heterozygous factor V Leiden mutation, heterozygous G20210A prothrombin gene mutation, homocysteinaemia, activated protein C resistance or anticardiolipin IgG antibodies. Women with pre-eclampsia/eclampsia were more likely to have heterozygous factor V Leiden mutation, heterozygous G20210A prothrombin gene mutation, homozygous MTHFR C677T mutation, protein C deficiency, protein S deficiency or activated protein C resistance compared with controls. Unexplained stillbirth, when compared with controls, was more often associated with heterozygous factor V Leiden mutation, protein S deficiency, activated protein C resistance, anticardiolipin IgG antibodies or lupus anticoagulant. Women with intrauterine growth restriction had a higher prevalence of heterozygous G20210A prothrombin gene mutation, homozygous MTHFR C677T gene mutation, protein S deficiency or anticardiolipin IgG antibodies than controls. There was wide heterogeneity in the prevalence of thrombophilia between the studies. CONCLUSIONS: Women with adverse pregnancy outcome are more likely to have a positive thrombophilia screen but studies published so far are too small to adequately assess the true size of this association. Screening for thrombophilia should not become standard practice until clear evidence emerges that thromboprophylaxis during pregnancy improves perinatal outcome. Further research into the link between the observed association, causality and heterogeneity is required.