Background: Hypertension during pregnancy is a leading cause of birthing parent mortality and adverse pregnancy outcomes. Since non-metropolitan communities face higher rates of several risk factors for hypertension in pregnancy and shortages in obstetrical services, persons residing in non-metropolitan areas may be at increased risk for adverse outcomes compared to those living in metropolitan areas. Our study objectives were to examine by county of birthing parent residence (1) the prevalence of chronic hypertension (cHTN) and hypertensive disorders of pregnancy (HDP), and (2) the prevalence of adverse birthing parent and neonatal outcomes associated with hypertension. Methods: Using U.S. birth certificate data from 2016 to 2018, we described the prevalence of cHTN and HDP and the association of each with several birthing parent and neonatal outcomes, stratified by non-metropolitan versus metropolitan county of birthing parent residence. Multivariable Poisson regression models were used to calculate adjusted prevalence ratios for birthing parent and neonatal outcomes among individuals with cHTN or HDP who lived in non-metropolitan versus metropolitan U.S. counties. Results: The prevalence of cHTN and HDP for US live births was 2.2% and 7.4%, respectively, among non-metropolitan pregnant individuals and 1.8% and 6.6%, respectively, among metropolitan pregnant individuals. After adjusting for several sociodemographic characteristics among those with HDP, the prevalence ratio for an APGAR score < 7 at 5 minutes (aPR 1.34, 95% CI 1.29-1.38) and neonatal death (aPR 1.36, 95% CI 1.15-1.62) was increased among offspring born to women who resided in non-metropolitan counties. Similar results were seen among those with cHTN. Conclusion: The prevalence of cHTN and HDP is modestly more prevalent in non-metropolitan areas, but most pregnancy outcomes were similar among those residing in non-metropolitan areas compared to metropolitan areas. Further research should investigate the robustness of these findings using alternate definitions of rural and urban areas and the possible link between low APGAR score, low NICU admission, and neonatal death in non-metropolitan counties.

Student Number : 9402058P - M Med Research Report - School of Clinical Medicine - Faculty of Health Sciences / Objective In view of recent suggestions that HIV infection may protect against pre-eclampsia, this study was done to estimate whether untreated HIV positive pregnant women have a lower rate of preeclampsia-eclampsia than HIV negative women. Methods Subjects for this study were pregnant women from Soweto, South Africa, who gave birth from March to December 2002 at midwife-run clinics or at the Chris Hani Baragwanath Hospital, and in whom the HIV status was known. A sample size calculation indicated that 2588 subjects would be required to show statistical significance at P<0.05 with a power of 80% for a reduction in the rate of preeclampsia from 8% to 5% with HIV seropositivity, assuming an HIV seroprevalence rate of 30%. Data collection was by record review from randomly selected patient files and birth registers. Results In the total sample of 2600 women, 1797 gave birth at the hospital and 803 at the midwife-run clinics. The HIV seroprevalence rate was 27.1%. Hypertension was found in 17.3% of women, with 5.3% having preeclampsia-eclampsia. The rates of preeclampsia-eclampsia were 5.2% in HIV negative and 5.7% in HIV positive women (P=0.61). CD4 count results were available for only 13 women (0.5%). Conclusion HIV seropositivity was not associated with any reduction in the risk of developing preeclampsia-eclampsia.

A pré-eclâmpsia afeta 3 a 5% das gestantes em todo o mundo, contribuindo para complicações materno-fetais graves. Sendo a isquemia placentária considerada um dos fatores primordiais para o desenvolvimento da doença. Essa isquemia está associada à alterações de fatores pró e anti angiogênicos, o presente estudo avaliou os fatores pró angiogênicos angiopoetina 1 e 2 (Ang-1 e Ang-2), que atuam na formação e no crescimento de novos vasos durante a placentação. O objetivo do estudo foi avaliar as concentrações plasmática de Ang-1 e Ang-2 na predição de pré-eclâmpsia e verificar a sensibilidade e especificidade dos mesmos por meio da curva ROC. Foram avaliadas 120 gestantes com idade gestacional entre 20 e 25 semanas, que participaram do projeto Coortes BRISA, que contava com um banco de 1400 gestantes, sendo que 30 gestantes com diagnóstico de pré-eclâmpsia (PE) e que realizaram o parto no Hospital das Clínicas de Ribeirão Preto e 90 gestantes saudáveis (GS) que realizaram parto na MATER ( Maternidade do Centro de Referência da saúde da Mulher). As concentrações plasmáticas de Ang-1 e de Ang- 2 foram determinadas utilizando o método ELISA. Para a análise dos dados, foi realizado ANOVA quando comparamos os grupos quanto às variáveis quantitativas. Para as comparações dos níveis pressóricos das gestantes com pré-eclâmpsia grave x pré-eclâmpsia não grave, no momento do recrutamento e com a doença estabelecida, foi utilizado o modelo de regressão linear com efeitos mistos (efeitos aleatórios e fixos). Para as comparações dos dados foi utilizado o pós-teste por contrastes ortogonais. Na comparação das concentrações de Ang-1 entre GS e PE não houve diferença estatística entre os grupos (P= 0,185) o mesmo foi observado para Ang-2 (P= 0,583). Em relação à razão Ang-1/Ang-2, também não observamos diferença estatística (P= 0,107). A capacidade preditiva dos biomarcadores foi avaliada através da curva ROC e a área sobre a curva para Ang-1, Ang-2 e a razão Ang-1/Ang-2 foram 0,47, 0,52 e 0,57 respectivamente. Nosso estudo não encontrou diferença significativa nas concentrações de Ang-1 E Ang-2 e nem na razão entre Ang-1/Ang-2. Ao realizar a curva ROC observamos, que esses biomarcadores não são bons preditores para pré-eclâmpsia. / Preeclampsia affects 3 to 5% of pregnant women worldwide, contributing to severe maternal-fetal complications. As placental ischemia, a set of primordial factors for the development of the disease was proposed. This ischemia is associated with changes in pro and anti-angiogenic functions, the present study is angiography and angiopoietin 1 and 2 (Ang-1 and Ang-2), which act in the formation and growth of new vessels during placentation. The evaluation of the evaluation of Angio-1 and Ang-2 in the prediction of pre-eclampsia and to verify their sensitivity and specificity by means of the ROC curve. There were 20 pregnant women with gestational age between 20 and 25 weeks, who participated in the BRISA Cohorts project, which had a bank of 1400 pregnant women, 30 pregnant women diagnosed with preeclampsia (PE) and who gave birth at Hospital das Clínicas of Ribeirão Preto and 90 healthy pregnant women (GS) who performed part of MATER (Maternity of the Reference Center for Women\'s Health). Plasma Ang-1 and Ang-2 tests were already using the ELISA method. For an analysis of the data, we performed ANOVA when comparing the groups as the quantitative variables. For the comparisons of pressure levels of pregnant women with severe preeclampsia vs. non-severe preeclampsia at the moment of recruitment and with the disease installed, the linear regression model with mixed effects (random and fixed lexus) was used. For the data comparisons, the orthogonal contrasts post-test was used. When comparing the Ang-1 combinations between GS and PE, it was not possible to compare the groups (P = 0.185). The same was observed for Ang-2 (P = 0.583). In relation to the Ang-1 / Ang-2 ratio, we also did not observe the statistical difference (P = 0.107). The ability to distribute the biomarkers was evaluated through the ROC curve and the area over the curve for Ang-1, Ang-2 and the Ang-1 / Ang-2 ratio were 0.47, 0.52 and 0.57 respectively. Our needs were not as significant at Ang-1 and Ang-2 concentrations nor at the Ang-1 / Ang-2 ratio. When performing a ROC curve we observed that these biomarkers are not good predictors of preeclampsia.

Justificativa e objetivo: O manejo hemodinâmico na pré-eclâmpsia grave (PEG) permanece um desafio, especialmente a reposição volêmica durante a cesariana. A sobrecarga de volume pode levar a edema agudo de pulmão, enquanto a restrição hídrica pode exacerbar a falência orgânica, como a injúria renal aguda (IRA). O objetivo do estudo foi a avaliação de IRA pósoperatória em pacientes com pré-eclâmpsia grave submetidas à cesariana, comparando pacientes que receberam estratégia restritiva, com os pacientes que receberam estratégia liberal de hidratação intraoperatória. Métodos: Um total de 46 pacientes foram randomizados em dois grupos de acordo com a hidratação durante a cesariana: liberal (1500 mL de ringer lactato, n = 23); e restritivo (250 mL de ringer lactato, n = 23). Liberada dieta irrestrita 8 horas após a cirurgia. A disfunção renal pós-operatória foi estratificada pelos críterios de Acute Kidney Injury Network (AKIN) modificados. Cistatina C e lipocalina associada à gelatinase de neutrófilos (NGAL) foram avaliadas no período pré-operatório imediato, no primeiro e no segundo dia pós-operatório (PO). Resultados: IRA pós-operatória ocorreu em 43,5% dos pacientes em cada um dos grupos. O débito urinário intraoperatório foi maior no Grupo Liberal do que no Grupo Restritivo (116 mL/h versus 80 mL/h, p = 0,032). Em ambos os grupos, a cistatina C foi significativamente menor no 2º PO do que no 1º PO (p = 0,006). No Grupo Liberal, os níveis de NGAL permaneceram inalterados ao longo do período analisado. No Grupo Restritivo, houve aumento de NGAL no 1º PO em relação ao pré-operatório (p = 0,005), seguida por diminuição no 2º PO em relação ao 1º PO (p = 0,006). Conclusão: A ocorrência de IRA pós-operatória em pacientes com pré-eclâmpsia grave parece não ser dependente da estratégia de hidratação intraoperatória utilizada / Background and objectives: Hemodynamic management in severe preeclampsia remains a challenge, especially for fluid replacement during cesarean section. Volume overload can lead to acute pulmonary edema, whereas volume restriction can lead to acute kidney injury (AKI). The aim of this study was to evaluate postoperative AKI in patients with severe preeclampsia who underwent cesarean section, comparing patients who received restrictive fluid therapy with those who received liberal fluid therapy. Methods A total of 46 patients were randomized into two groups according to fluid therapy during cesarean section: liberal (1500 mL of lactated Ringer\'s, n = 23); and restrictive (250 mL of lactated Ringer\'s, n = 23). Unrestricted diet 8 hours after surgery. Postoperative renal dysfunction was stratified using modified AKI Network classification. Cystatin C and neutrophil gelatinaseassociated lipocalin (NGAL) were evaluated in the immediate preoperative period, postoperative (PO) days 1 and 2. Results: Postoperative AKI occurred in 43.5% of the patients in each of the groups. Intraoperative urine output was higher in the liberal group than in the restrictive group (116 mL/h versus 80 mL/h, p = 0.032). In both groups, serum cystatin C was significantly lower on PO2 than on PO1 (p = 0.006). In the liberal group, NGAL levels remained unchanged throughout the analyzed period. In the restrictive group, NGAL levels were significantly higher on PO1 than in the preoperative period (p = 0.005), although they subsequently dropped, being significantly lower on PO2 than on PO1 (p =0.006). Conclusion: The occurrence of postoperative AKI in patients with severe pre-eclampsia does not appear to be dependent on the type of intraoperative fluid therapy used

A pré-eclâmpsia afeta 3 a 5% das gestantes em todo o mundo, contribuindo para complicações materno-fetais graves. Sendo a isquemia placentária considerada um dos fatores primordiais para o desenvolvimento da doença. Essa isquemia está associada à alterações de fatores pró e anti angiogênicos, o presente estudo avaliou os fatores pró angiogênicos angiopoetina 1 e 2 (Ang-1 e Ang-2), que atuam na formação e no crescimento de novos vasos durante a placentação. O objetivo do estudo foi avaliar as concentrações plasmática de Ang-1 e Ang-2 na predição de pré-eclâmpsia e verificar a sensibilidade e especificidade dos mesmos por meio da curva ROC. Foram avaliadas 120 gestantes com idade gestacional entre 20 e 25 semanas, que participaram do projeto Coortes BRISA, que contava com um banco de 1400 gestantes, sendo que 30 gestantes com diagnóstico de pré-eclâmpsia (PE) e que realizaram o parto no Hospital das Clínicas de Ribeirão Preto e 90 gestantes saudáveis (GS) que realizaram parto na MATER ( Maternidade do Centro de Referência da saúde da Mulher). As concentrações plasmáticas de Ang-1 e de Ang- 2 foram determinadas utilizando o método ELISA. Para a análise dos dados, foi realizado ANOVA quando comparamos os grupos quanto às variáveis quantitativas. Para as comparações dos níveis pressóricos das gestantes com pré-eclâmpsia grave x pré-eclâmpsia não grave, no momento do recrutamento e com a doença estabelecida, foi utilizado o modelo de regressão linear com efeitos mistos (efeitos aleatórios e fixos). Para as comparações dos dados foi utilizado o pós-teste por contrastes ortogonais. Na comparação das concentrações de Ang-1 entre GS e PE não houve diferença estatística entre os grupos (P= 0,185) o mesmo foi observado para Ang-2 (P= 0,583). Em relação à razão Ang-1/Ang-2, também não observamos diferença estatística (P= 0,107). A capacidade preditiva dos biomarcadores foi avaliada através da curva ROC e a área sobre a curva para Ang-1, Ang-2 e a razão Ang-1/Ang-2 foram 0,47, 0,52 e 0,57 respectivamente. Nosso estudo não encontrou diferença significativa nas concentrações de Ang-1 E Ang-2 e nem na razão entre Ang-1/Ang-2. Ao realizar a curva ROC observamos, que esses biomarcadores não são bons preditores para pré-eclâmpsia. / Preeclampsia affects 3 to 5% of pregnant women worldwide, contributing to severe maternal-fetal complications. As placental ischemia, a set of primordial factors for the development of the disease was proposed. This ischemia is associated with changes in pro and anti-angiogenic functions, the present study is angiography and angiopoietin 1 and 2 (Ang-1 and Ang-2), which act in the formation and growth of new vessels during placentation. The evaluation of the evaluation of Angio-1 and Ang-2 in the prediction of pre-eclampsia and to verify their sensitivity and specificity by means of the ROC curve. There were 20 pregnant women with gestational age between 20 and 25 weeks, who participated in the BRISA Cohorts project, which had a bank of 1400 pregnant women, 30 pregnant women diagnosed with preeclampsia (PE) and who gave birth at Hospital das Clínicas of Ribeirão Preto and 90 healthy pregnant women (GS) who performed part of MATER (Maternity of the Reference Center for Women\'s Health). Plasma Ang-1 and Ang-2 tests were already using the ELISA method. For an analysis of the data, we performed ANOVA when comparing the groups as the quantitative variables. For the comparisons of pressure levels of pregnant women with severe preeclampsia vs. non-severe preeclampsia at the moment of recruitment and with the disease installed, the linear regression model with mixed effects (random and fixed lexus) was used. For the data comparisons, the orthogonal contrasts post-test was used. When comparing the Ang-1 combinations between GS and PE, it was not possible to compare the groups (P = 0.185). The same was observed for Ang-2 (P = 0.583). In relation to the Ang-1 / Ang-2 ratio, we also did not observe the statistical difference (P = 0.107). The ability to distribute the biomarkers was evaluated through the ROC curve and the area over the curve for Ang-1, Ang-2 and the Ang-1 / Ang-2 ratio were 0.47, 0.52 and 0.57 respectively. Our needs were not as significant at Ang-1 and Ang-2 concentrations nor at the Ang-1 / Ang-2 ratio. When performing a ROC curve we observed that these biomarkers are not good predictors of preeclampsia.

<p>Impaired placentation and oxidative stress are proposed to play major roles in the pathogenesis of pre-eclampsia (PE). It has recently been pointed out that PE might be more than one disease and may have several different pathogeneses. This thesis describes a new animal model for PE and examines the role of oxidative stress in early respective late onset PE. </p><p>The effects of Suramin injections on day 10 and 11 of pregnancy were investigated in normal and diabetic rats of two strains (U and H), with or without additional vitamin E treatment. Suramin caused placental dysfunction in both rat strains: foetal growth restriction, increased resorption rate, reduced placental blood flow, and decreased maternal blood volume in the placenta. In the U strain Suramin also caused maternal hypertension and reduced renal blood flow. Oxidative stress in the Suramin treated rats was indicated by increased levels of isoprostane 8-iso-PGF_2α in the placenta. Antioxidative treatment with vitamin E partly protected against the effects of Suramin. Streptozotocin-induced diabetes seemed to cause similar placental effects as Suramin, and in the diabetic rats the additional effects of Suramin were only moderate. In conclusion, Suramin-injected pregnant rats constitute a valid animal model for placental dysfunction (U and H rats) and PE (U rats). </p><p>Oxidative stress was estimated in women with early onset (≤ 32 weeks) or late onset (≥ 35 weeks) PE, in normotensive pregnant women of respective gestational length, and in healthy non-pregnant women. The ratio of PAI-1/PAI-2 was measured in serum, and the amount of isoprostane 8-iso-PGF_2α was measured in placenta, serum, and urine. The ratio of PAI-1/PAI-2 and placental isoprostane levels were higher in women with early onset PE compared with all other groups. Serum levels of isoprostane were similar between groups. Urinary levels of isoprostane were similar in all pregnant women, but lower in non-pregnant women. These data indicate that pregnancy increases general oxidative stress, and that early onset, but not late onset PE, causes increased oxidative stress also in placental tissue. The pathogeneses of early and late onset PE are, therefore, not likely to be identical.</p>

Pre-eclampsia is associated with increased risk of cardiovascular disease (CVD) later in life. The ‘gold standard’ for estimating cardiovascular risk - ultrasound assessment of the common carotid artery intima-media thickness (CCA-IMT) - does not convincingly demonstrate this increased risk. The aim of this thesis was to examine whether high-frequency (22 MHz) ultrasound assessment of the individual CCA intima and media layers and calculation of the intima/media (I/M) ratio - can indicate the increased cardiovascular risk after pre-eclampsia. After validation of the method in premenopausal women with systemic lupus erythematosus (SLE) who have a recognized increased risk of CVD, women during and after normal and preeclamptic pregnancies were investigated. Assessment of the individual artery wall layers reliably demonstrated the increased cardiovascular risk in premenopausal women with SLE, while CCA-IMT did not. The artery wall layer dimensions in women with SLE were comparable to those of postmenopausal women without SLE and were 30 years older. Among the women with normal pregnancies negative changes to the artery wall later on in the pregnancy were seen in those with lower serum estradiol, older age, higher body mass index or higher blood pressure early in the pregnancy. About one year postpartum, both the mean intima thickness and the I/M ratio had improved, compared to values during pregnancy. These findings support the theory that normal pregnancy is a stress on the vascular system. Women who developed pre-eclampsia (mean age 31 years) had thicker intima layers, thinner media layers and higher I/M ratios, both at diagnosis and one year postpartum, than women with normal pregnancies, indicating increased cardiovascular risk. Women with a history of severe pre-eclampsia (mean age 44 years; mean 11 years since the last delivery) had thicker intima layers and higher I/M ratios than women with a history of normal pregnancies, indicating long-standing negative vascular effects. Assessment of individual CCA wall layers, but not of CCA-IMT, provided clear evidence of the well-known increased cardiovascular risk in women with SLE or pre-eclampsia. The method has the potential to become an important tool in reducing cardiovascular morbidity and mortality in these women through early diagnosis and intervention.

Impaired placentation and oxidative stress are proposed to play major roles in the pathogenesis of pre-eclampsia (PE). It has recently been pointed out that PE might be more than one disease and may have several different pathogeneses. This thesis describes a new animal model for PE and examines the role of oxidative stress in early respective late onset PE. The effects of Suramin injections on day 10 and 11 of pregnancy were investigated in normal and diabetic rats of two strains (U and H), with or without additional vitamin E treatment. Suramin caused placental dysfunction in both rat strains: foetal growth restriction, increased resorption rate, reduced placental blood flow, and decreased maternal blood volume in the placenta. In the U strain Suramin also caused maternal hypertension and reduced renal blood flow. Oxidative stress in the Suramin treated rats was indicated by increased levels of isoprostane 8-iso-PGF2α in the placenta. Antioxidative treatment with vitamin E partly protected against the effects of Suramin. Streptozotocin-induced diabetes seemed to cause similar placental effects as Suramin, and in the diabetic rats the additional effects of Suramin were only moderate. In conclusion, Suramin-injected pregnant rats constitute a valid animal model for placental dysfunction (U and H rats) and PE (U rats). Oxidative stress was estimated in women with early onset (≤ 32 weeks) or late onset (≥ 35 weeks) PE, in normotensive pregnant women of respective gestational length, and in healthy non-pregnant women. The ratio of PAI-1/PAI-2 was measured in serum, and the amount of isoprostane 8-iso-PGF2α was measured in placenta, serum, and urine. The ratio of PAI-1/PAI-2 and placental isoprostane levels were higher in women with early onset PE compared with all other groups. Serum levels of isoprostane were similar between groups. Urinary levels of isoprostane were similar in all pregnant women, but lower in non-pregnant women. These data indicate that pregnancy increases general oxidative stress, and that early onset, but not late onset PE, causes increased oxidative stress also in placental tissue. The pathogeneses of early and late onset PE are, therefore, not likely to be identical.

Preeclampsia results from incomplete trophoblast invasion of the spiral arteries during early pregnancy. Vascular endothelial growth factor (VEGF) and plasminogen activator inhibitor-1 (PAI-1) are critical factors involved in angiogenesis, invasion and hemostasis at the maternal-fetal interface. Both factors are transcriptionally regulated by hypoxia inducible factor (HIF), a heterodimeric complex consisting of HIF-1[beta] and either HIF-1[alpha] or -2[alpha] whose specificity or redundancy in gene regulation is cell-type specific. This study uses siRNA technology to dissect the mechanisms of hypoxia-mediated regulation of PAI-1 and VEGF expression in first trimester trophoblasts. Immortalized first trimester human extravillous trophoblasts (HTR8/SVneo cells) were maintained in serum-free and serum-containing media for 4h (n=3-4), 8h (n=6), 24h (n=5) and 48h (n=5) under normoxic (21% O2) and hypoxic (1-2% O2) conditions to determine a time of maximum induction of both VEGF and PAI-1. Subsequently, cells were maintained for 48h in the presence or absence of siRNA for HIF-1[alpha], HIF-2[alpha], HIF-1[alpha] + -2[alpha], a non-targeting (NT) sequence or Cyclophilin B (CB). Media were then removed, cells lysed, and Western blotting used to assess HIF-[alpha] knockdown. VEGF and PAI-1 levels in the media were quantified by ELISA and results expressed as pg or ng/[micro]g protein. Results from 3 to 8 independent experiments were analyzed using unpaired t-tests. Under hypoxic conditions treatment of cells with HIF-1[alpha], HIF-2[alpha] or HIF -1[alpha] + -2[alpha] siRNA resulted in >90% HIF-Ñ protein knockdown as determined by Western blotting. 48h of hypoxic treatment caused a statistically significant increase in PAI-1 levels (p<0.01) and VEGF levels (p<0.001) compared to normoxic controls. Under hypoxic conditions, PAI-1 levels were 4.75 [plus-minus] 0.46 ng/[micro]g protein and VEGF levels were 7.27 [plus-minus] 1.08 pg/[micro]g protein. Treatment with siRNA to HIF-1[alpha], HIF-2[alpha] and HIF-1[alpha] + -2[alpha] significantly reduced PAI-1 levels to 3.3 [plus-minus] 0.35 (p<0.02), 3.1 [plus-minus] 0.38 (p<0.03) and 2.4 [plus-minus] 0.19 (p<0.003), respectively. No significant difference in PAI-1 reduction was noted between the three HIF siRNA conditions. Under hypoxic conditions, levels of VEGF in cells treated with siRNA to HIF-1[alpha] (5.79 [plus-minus] 0.55), HIF-2[alpha] (5.50 [plus-minus] 1.24) and HIF-1[alpha] + -2[alpha] (4.24 [plus-minus] 0.93) were reduced compared to the hypoxic control (7.27 [plus-minus] 1.08), yet these effects did not reach statistical significance. However, when compared with the levels observed in cells treated with NT siRNA (9.90 [plus-minus] .98), all HIF siRNA treatments promoted a significant reduction in VEGF expression (p<0.003, p<0.02 and p<0.003 for HIF-1[alpha], HIF-2[alpha] and HIF-1[alpha]+ -2[alpha], respectively). In conclusion, these results indicate that hypoxia-mediated changes in PAI-1 and VEGF expression in trophoblasts are regulated similarly by both HIF-1[alpha] and HIF-2[alpha]. This provides important insight into the molecular mechanisms regulating hemostasis and trophoblast invasion as well as their potential dysfunction in pregnancies complicated by preeclampsia

Made available in DSpace on 2015-07-22T20:50:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-04-29 / Objetivo: avaliar a possível relação entre polimorfismos dos genes codificadores de receptor 1 de interleucina (IL) 1 (IL-1R1) (PstI, rs2234650), IL-12 (+1188, rs3212227), IL-18 (-137, rs187238), IL-18 (-607, rs1946519), receptor tipo Toll (TLR) 2 (TLR-2) (+2258, rs5743708) e TLR-4 (+896, rs4986790) e a pré-eclâmpsia (PE). Pacientes e métodos: Este estudo de caráter caso-controle incluiu 109 pacientes com PE e 174 gestantes sem patologia sistêmica ou obstétrica, e com história de duas ou mais gestações sem intercorrências, como controles. O DNA genômico foi extraído de sangue periférico por método de DTAB/CTAB, e os polimorfismos foram genotipados por técnicas de PCR-RFLP ou PCR-ARMS. Para a análise dos resultados, foram utilizados os testes t de Student e exato de Fischer, tendo sido adotado o nível de significância de p<0,05. Resultados: As freqüências genotípicas do polimorfismo do gene IL-1R1 foram 20,9% CC, 59% CT e 20,1% TT em casos de PE; e 24,7% CC, 56,2% CT e 19,1% TT em controles (p=0,82). As freqüências do polimorfismo do gene IL-12 foram 54,7% AA, 32,9% AC e 12,4% CC em casos de PE; e 55,4% AA, 33,8% AC e 10,8% CC em controles (p=0,93). As freqüências genotípicas de IL-18 (-137) foram 5,2% CC, 42,7% CG e 52,1% GG em casos de PE; e 7,6% CC, 43% CG e 49,4% GG em controles (p=0,74). As freqüências genotípicas de IL-18 (-607) foram 41% CC, 52,7% CA e 6,3% AA em pacientes com PE; e 32,2% CC, 56,2% CA e 11,6% AA no grupo controle (p=0,22). As freqüências do polimorfismo do gene TLR-2 foram 84,6% GG e 15,4% GA em casos de PE; e 84,8% GG e 15,2% GA em controles (p=0,97). As freqüências do polimorfismo do gene TLR-4 foram 93,6% AA e 6,4% AG em casos de PE; e 87,6% AA, 11,7% AG e 0,7% GG em controles (p=0,23). Não houve diferenças significantes entre os grupos, quanto às freqüências genotípicas e alélicas. Conclusões: Não foi observada associação entre polimorfismos de genes codificadores de IL- 1R1, IL-12, IL-18, TLR-2 e TLR-4 e a ocorrência de pré-eclâmpsia. / Problem: Intense maternal inflammatory response is a central event in the pathogenesis of preeclampsia (PE) Our aim was to assess a possible relation between pro-inflammatory mediators: IL-1R1, IL-12, IL-18, IL-18, TLR-2 and TLR-4 gene polymorphisms and PE. Method of Study: This case-control study included 109 patients with PE and 174 healthy women (controls). Genotyping were performed by PCR-ARMS or PCR-RFLP techniques. Data were analyzed by Student´s t or Fischer´s exact tests, and significance was set at p<0.05. Results: Genotypic and allelic distribution for all six polymorphisms was similar between the study and control groups (p=0.82 for IL-1R1, p=0.93 for IL-12, p=0.74 for IL-18 -137, p=0.22 for IL-18 -607, p=0.97 for TLR-2 and p=0.23 for TLR-4 gene polymorphisms). Conclusions: Our findings suggest that the analyzed pro-inflammatory gene polymorphisms are not associated with the occurrence of PE. Further studies have to be done to confirm these results. / TEDE / BV UNIFESP: Teses e dissertações