Effects of eNOS polymorphisms on nitric oxide formation in healthy pregnancy and in pre-eclampsia

Pre-eclampsia (PE) is associated with decreased nitric oxide (NO) formation. However, no previous study has examined whether genetic variations in the endothelial NO synthase (eNOS) affect this alteration. We hypothesized that PE decreases NO formation depending on eNOS polymorphisms. We examined how three eNOS polymorphisms [T-786C, rs2070744; Glu298Asp, rs1799983; 27 bp variable number of tandem repeats (VNTR) in intron 4] affect plasma nitrite concentrations in 205 pregnant women [107 healthy pregnant (HP) and 98 PE]. Genotypes were determined and eNOS haplotypes were inferred using the PHASE 2.1 program. The plasma nitrite concentrations were determined using an ozone-based chemiluminescence assay. The Glu298Asp polymorphism had no effects on the plasma nitrite concentrations. Higher nitrite levels were found in HP women with the CC versus TT genotype for the T-786C polymorphism (277.9 +/- 19.5 versus 140.6 +/- 8.2 nM; P < 0.05). Lower nitrite levels were found in healthy women with the 4a4a versus 4b4b genotype for the VNTR polymorphism (95.1 +/- 3.3 versus 216.1 +/- 16.8 nM; P < 0.05). No effects of genotypes were found in PE women (all P > 0.05). The `C Glu b` haplotype was more frequent in the HP group than in the PE group (20 versus 5; P = 0.0044). This haplotype was associated with higher nitrite concentrations than the other haplotypes in healthy pregnancies (P < 0.05). No differences in nitrite concentrations were found among PE women with different eNOS haplotypes (P > 0.05). These findings indicate that eNOS polymorphisms affect endogenous NO formation in normal pregnancy, but not in PE, and that the `C Glu b` haplotype may protect against the development of PE by increasing endogenous NO formation.

Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension

Vascular endothelial growth factor (VEGF) is relevant for normal pregnancy, and abnormalities in VEGF functions are associated with hypertensive disorders of pregnancy. Because there are few studies on how VEGF genetic polymorphisms affect susceptibility to pre-eclampsia (PE), and no studies on how they affect susceptibility to gestational hypertension (GH), we compared VEGF genotype and haplotype distributions in normotensive and hypertensive pregnancies. Genotypes and haplotypes for VEGF polymorphisms (C-2578A, G-1154A and G-634C) were determined in 303 pregnant women (108 healthy pregnant, HP; 101 with GH and 94 with PE). When white and non-white pregnant women were considered together, no significant differences were found in the distributions of VEGF genotypes or haplotypes (P > 0.05) in the three groups. However, with only white subjects, significant differences were found in genotypes distributions for two (C-2578A and G-634C) VEGF polymorphisms (both P < 0.05) between the HP and the PE groups. Importantly, the haplotype including the variants C-2578, G-1154 and C-634, which is associated with higher VEGF gene expression, was less common in the PE group compared with the HP group (4% versus 16%; P = 0.0047). However, we found no significant differences in VEGF haplotypes distributions when the HP and GH groups were compared (P > 0.05). These findings suggest a protective effect for the `C-2578, G-1154 and C-634` haplotype against the development of PE, but no major effects of VEGF gene variants on susceptibility to GH.

Perfil de mães adolescentes de São José do Rio Preto/Brasil e cuidados na assistência pré-natal

Objetivos: Identificar o perfil sócio-demográfico; características da vida sexual e reprodutiva; característicasdo pré-natal, intercorrências e tipo de parto; tipo de orientações recebidas no pré-natal; freqüência de baixopeso, prematuridade e Apgar. Método: Estudo descritivo, de 84 mães adolescentes com parto entre 01/10/2004 a 01/12/2004. Resultados: Das adolescentes estudadas, 96,4% tinham entre 15 a 19 anos; 73,8% viviamcom o companheiro; 65% recebiam até três salários mínimos; 79,3% nunca tinham trabalhado; 52,4%freqüentavam a escola quando engravidaram. A média de idade da primeira relação sexual foi de 15 anos;64,3% faziam uso de contraceptivo; apenas 9,5% usavam-no quando engravidaram; 100% das adolescentesfizeram pré-natal; 58,5% iniciaram no primeiro trimestre de gravidez; 84,6% fizeram de seis a doze consultas;83,3% eram primíparas e 83,3% não planejaram a gravidez. As complicações maternas foram: 44% anemia;35,7% infecção urinária; 14,3% sangramento vaginal; 14,2% pressão alta; 2,4% diabetes gestacional e 1,2%eclampsia. Parto cesárea foi feito em 61,9%. Receberam orientação para não fazer uso de medicação semordem médica 85,7% das adolescentes; para não usar drogas 73,8%; quanto aos prejuízos do fumo e bebidaalcoólica 72,6%; em relação ao tipo de alimentação na gestação 70,2%; sobre os cuidados com os dentes54,8%; sobre os sinais do início do trabalho de parto 72,6%; quanto aos tipos de parto 60,7%; sobre aimportância do aleitamento materno 76,2%; quanto ao banho do bebê 17,9% e 18,3% sobre o curativo doumbigo. Encontrou-se 6% de recém-nascidos de baixo peso e prematuros; o Apgar foi superior a 8 em 86,9%dos casos no primeiro minuto e 95,1 % no quinto minuto. Neste grupo de adolescentes, a assistência pré-natal adequada (início no primeiro trimestre e número mínimo de seis consultas) permitiu bons resultados,apesar da idade das mães estar associada com gravidezes de risco.

Obstetric Outcome in Pregnant Women on Long-term Dialysis: A Case Series

Background: Although still uncommon, pregnancy frequency in women on maintenance hemodialysis therapy has increased in the past 20 years. Most published reports suggest that intensified hemodialysis regimens result in better pregnancy outcomes. The small number of patients investigated in all reported series is the main limitation of the available studies. Study Design: Retrospective case series. Setting & Participants: Data for all pregnancies that occurred in 1988-2008 in women undergoing maintenance hemodialysis (52 pregnancies) at the Sao Paulo University Medical School (Sao Paulo, Brazil). Outcomes & Measurements: We analyzed maternal and fetal outcomes of 52 pregnancies, as well as their relationship with various clinical, laboratory, and hemodialysis parameters, such as pre-eclampsia, pregnancy before or after dialysis therapy, hemodialysis dose, polyhydramnios, anemia, and predialysis serum urea level. In addition, logistic regression models for a composite adverse fetal outcome (perinatal death or extremely premature delivery) and linear regression models for birth weight were built. Results: 87% overall rate of successful delivery, with a mean gestational age of 32.7 +/- 3.1 weeks. Pre-eclampsia was associated with a poor prognosis compared with pregnancies without pre-eclampsia: a successful delivery rate of 60% versus 92.9% (P = 0.02), extremely premature delivery rate of 77.8% versus 3.3% (P = 0.001), lower gestational age (P = 0.001), and birth weight (P = 0.001). Patients with an adverse composite fetal outcome had a higher frequency of pre-eclampsia (P = 0.001), lower frequency of polyhydramnios (P = 0.03), lower third-trimester hematocrit (P = 0.03), and higher predialysis serum urea level (P = 0.03). The same results were seen for birth weight. Limitations: Retrospective data analysis. The absence of creatinine clearance measurements did not allow evaluation of the impact of residual renal function on fetal outcome. Conclusions: Outcomes of pregnancy in women undergoing hemodialysis often are good. Preeclampsia, third-trimester hematocrit, polyhydramnios, and predialysis serum urea level are important variables associated with fetal outcome and birth weight. Am J Kidney Dis 56:77-85. (C) 2010 by the National Kidney Foundation, Inc.Inc