הריון עם MTHFR

שלום רב! בעבר שאלתי אותך את השאלה ואני אשאל שוב עקב דאגות רבות. היום כבר אני נמצאת בשבוע 23 ואני הומוזיגוטית ל- MTHFR C יש רופאים שאמרו לי בעבר שמספיק לי רק חומצה פולית ויש שטוענים שצריך קלקסן. כל הבדיקות נעשו כי בהריון השני שלי היה לי פרוד שלייה בשבוע 30 ואז עשו לי את הבדיקות והתברר שאני הומוזיגוטית ל MTHFR . אתה ענית לי בזמנו שמספיק לי כרגע חומצה פולית. האם עליי לדון בזה שנית? הפחד שלי הוא קריש דם למוח כמו שהיה כתוב באיזה שאלה של בחורה שאמא שלה נפטרה מזה בגיל 28 האם זה אותו המקרה כמו שלי. הרופאים שלי באסף הרופא עדיין טוענים שאין לי צורך בקבלת זריקות והם טוענים שיש מן חוק כזה של חוק זכויות החולה שאני יכולה לבקש זריקות בשיקולי. האם על הפציינט להעמיס כזאת החלטה האם לקחת זריקות או לא ? לי אין מספיק ידע להחליט. אנא תשובתך המהירה. שמחה המודאגת

כמו שכתבתי פעמים רבות, אכן הדעות חלוקות ואין נתונים חד משמעיים שיצביעו לכאן או לכאן - האם הגן עצמו נושא סיכון או שרק העליה ברמת ההומוציסטאין. אין להקיש ממה שתואר בשאלה שהזכרת. אינך יכולה לדעת מה ארע שם ואולי היו אצלה גורמי סיכון נוספים ומשמעותיים יותר. לענ"ד - במצב הידע הנוכחי - אם רמת ההומוציסטאין תקינה אין צורך במתן טיפול נוסף. איני חושב שצריך להעמיס החלטה כזו על הפציינט, בודאי כשאין מידע שיסייע לקבלת ההחלטה. ליקטתי עבורך מספר תקצירים עדכניים בנושא ממדליין: J Obstet Gynaecol Res 2001 Dec;27(6):349-52 The relation between plasma homocysteine concentration and methylenetetrahydrofolate reductase gene polymorphism in pregnant women. Murakami S, Matsubara N, Saitoh M, Miyakaw S, Shoji M, Kubo T. Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. OBJECTIVE: Our purpose was to clarify the influence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism on plasma homocysteine (Hcy) concentrations during early pregnancy. METHODS: Between 1996 and 1998, Hcy concentration and MTHFR gene polymorphism were studied in 840 pregnant women between 6 to 12 weeks' gestation. Hcy concentration was measured by amino acid autoanalyzer (DLC-300, Nihon Denshi), and MTHFR genotypes were determined by the PCR/RFLP methods. Pregnancy outcomes were compared in association with Hcy concentration and MTHFR genotypes. RESULTS: A total of 816 of the 840 women were enrolled into the study because MTHFR genotypes were not available in 24 women. Genotypes of C677T in the MTHFR gene were CC: CT: TT (%) = 280 (34.3): 400 (49.0): 136 (16.7). Plasma Hcy concentration was significantly (p T polymorphism and preeclampsia in two populations. Prasmusinto D, Skrablin S, Hofstaetter C, Fimmers R, van der Ven K. Department of Obstetrics and Gynecology, University of Bonn, Bonn, Germany. OBJECTIVE: The C677T polymorphism of the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene is associated with decreased MTHFR activity and elevated plasma homocysteine levels with the result of an increased risk for vascular disease. Because thrombosis of the maternal spiral arteries can be one of the causative events in the disease, it has been suggested that the C677T polymorphism may also play a role in the pathogenesis of preeclampsia. Our case-control study investigated the prevalence of the 677T allele in two ethnically different populations and the potential association of the 677T allele with preeclampsia. Special attention was paid to the potential contribution of the fetal genotype to disease risk. METHODS: Blood samples were collected from 81 mothers and 61 newborns after preeclampsia and 99 mothers and 61 newborns with normal pregnancies. Genomic DNA was amplified by polymerase chain reaction with locus-specific primers, and presence of the polymorphism was determined by enzymatic digestion with HinfI and visualization on polyacrylamide gels. RESULTS: Genotypes carrying the MTHFR 677T allele were significantly more frequent in German-Croatians than in Indonesians in both patients and controls (P =.0033 in controls). In contrast, the prevalence of genotypes with the 677T allele was not increased among patients with preeclampsia compared with controls in both ethnic groups (P >.5 in all groups). In Germans, the frequency of 677T homozygotes among controls even exceeded that observed in preeclamptic patients (677T/T genotype frequency 0.20 in controls and 0.07 in patients). We did not find an increased prevalence of paternally inherited 677T alleles in preeclamptic fetuses relative to controls or other signs of maternal-fetal transmission distortion. CONCLUSION: In our study, the MTHFR C677T polymorphism was not associated with an increased risk for preeclampsia on the level of the maternal or fetal genotype. However, significant differences of the frequency of genotypes carrying the 677T allele between Middle-Europeans and Indonesians were identified. -------------------------------------------------------------------------------- Hum Reprod 2002 Jun;17(6):1633-7 Prevalence of genetic markers for thrombophilia in recurrent pregnancy loss. Carp H, Salomon O, Seidman D, Dardik R, Rosenberg N, Inbal A. Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer, Israel. [email protected] BACKGROUND: The genetic predispositions to venous thrombosis such as factor V Leiden (FVL) mutation (Arg 506 Gln), prothrombin (FII) gene mutation (G20210A), and mutation of the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) have been reported to be associated with recurrent pregnancy loss. This paper examines the prevalence of markers for genetic thrombophilias in women with recurrent miscarriage. METHODS: The prevalence of FVL, FII G20210A and MTHFR C677T was compared in 108 women with three or more pregnancy losses either exclusively in the first trimester, or mixed first and second trimester losses, with the prevalence found in 82 fertile parous control women without miscarriages. Markers for the thrombophilias were assessed by PCR analysis. RESULTS: Twenty-three of the 108 patients (21.3%), had thrombophilia markers, which was similar to the proportion of patients in the control group (20.7%) with these markers. The prevalences of FVL and FII G20210A were lower in the study group than in the control group (3.7 versus 6.1% for FVL and 4.6 versus 6.1% for FII respectively); however, the difference was not statistically significant. In contrast, the prevalence of MTHFR C677T was higher in the study group than the control population (13 versus 8.5% respectively), but this difference was not statistically significant. There was no statistically significant prevalence of any particular thrombophilia in patients with previous first and second trimester pregnancy losses compared with patients with first trimester losses alone. CONCLUSION: Thrombophilia was not found to be associated with recurrent pregnancy loss. -------------------------------------------------------------------------------- Obstet Gynecol 2002 Apr;99(4):614-9 The C677T polymorphism of the methylenetetrahydrofolate reductase gene and idiopathic recurrent miscarriage. Unfried G, Griesmacher A, Weismuller W, Nagele F, Huber JC, Tempfer CB. Department of Gynecologic Endocrinology and Reproductive Medicine, University of Vienna School of Medicine, Vienna, Austria. OBJECTIVE:To investigate the association between the C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR), serum homocysteine levels, and idiopathic recurrent miscarriage in a Middle-European white population.METHODS:In a case control study, we investigated 133 women with a history of three or more consecutive pregnancy losses before 20 weeks' gestation and 74 healthy controls with at least two live births and no history of pregnancy loss. A DNA extraction and polymerase chain reaction followed by restriction fragment length polymorphism analysis were used to genotype women for the presence of the MTHFR C677T polymorphism. Serum homocysteine levels were assessed by a fluorescence polarization immunoassay.RESULTS:The MTHFR allele frequencies in women with idiopathic recurrent miscarriage and controls were 34.6% and 21.6%, respectively, for the T allele (mutant) and 65.4% and 78.4%, respectively, for the C allele (wild type) (P =.007, odds ratio 1.9, 95% confidence interval 1.2, 3.1). The MTHFR genotype frequencies in women with idiopathic recurrent miscarriage and controls were: 17.3% (T/T), 34.6% (C/T), 48.1% (C/C) and 5.4% (T/T), 32.4% (C/T), 62.2% (C/C), respectively (P =.03, odds ratio 3.7, 95% confidence interval 1.2, 11.8 [T/T versus C/T and C/C]). Serum concentrations of homocysteine were significantly higher in carriers of a MTHFR mutant allele compared with women with no mutant allele (mean 7.4 +/- 2.4 micromol/L [T/T + C/T] versus 6.5 +/- 2.6 micromol/L [C/C], P =.05).CONCLUSION:Carriage of the mutant allele of the MTHFR C677T polymorphism is associated with elevated serum levels of homocysteine and idiopathic recurrent miscarriage. -------------------------------------------------------------------------------- Acta Obstet Gynecol Scand 2002 Mar;81(3):204-7 Management and outcome of pregnancy in women with thrombophylic disorders and past cerebrovascular events. Soriano D, Carp H, Seidman DS, Schiff E, Langevitz P, Mashiach S, Dulitzky M. Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, 52621 Israel. [email protected] OBJECTIVE: To evaluate the maternal and fetal outcome in a cohort of women undergoing a subsequent pregnancy after a previous cerebrovascular event in the presence of thrombophilia. PATIENTS: Fifteen pregnancies were followed up in 12 women with past cerebrovascular events and thrombophilic disorders. The cerebrovascular events occurred during a previous pregnancy in five patients. Six patients had a bad obstetric history including intrauterine fetal death in four cases, early onset of severe preeclampsia in two cases and one infant that was small for gestational age. THE THROMBOPHILIC DISORDERS INCLUDED: anti-phospholipid syndrome, protein C, S or antithrombin III deficiencies, mutations of the methyltetrahydrofolate reductase (MTHFR). All patients received prophylactic treatment with low molecular weight heparin and low dose aspirin. RESULTS: Thromboembolic complications occurred in four pregnancies. Postpartum complications occurred in one patient; deep vein thrombosis and pulmonary emboli after stopping anticoagulation treatment. No patient had long-term neurologic damage. All pregnancies except one resulted in live births. (mean gestational age at delivery 36 +/- 3. 7 weeks, mean birth weight 2656 +/- 811 g). The one remaining pregnancy was electively terminated. There was one neonatal death due to the complications of severe prematurity in a woman with severe HELLP syndrome. CONCLUSION: This preliminary data suggests that women with a history of cerebrovascular events and thrombophilic disorders receiving prophylactic treatment, have a relatively favorable pregnancy outcome; however, they remain at significant risk during pregnancy. Further studies are necessary to determine the optimal prophylactic treatment.