Abstract-Deficient NO formation has been implicated in hypertensive disorders of pregnancy. However, no previous study has compared the circulating nitrite concentrations in healthy pregnant women with those found in hypertensive disorders of pregnancy. Moreover, 2 antiangiogenic factors produced in the placenta (soluble fms-like tyrosine kinase-1 and soluble endogline) may affect NO formation during pregnancy. Here, we hypothesized that lower concentrations of markers of NO formation exist in hypertensive disorders of pregnancy and that inverse relationships exist between these markers and soluble fms-like tyrosine kinase-1 or soluble endogline. In this cross-sectional study, we compared 58 healthy pregnant women with 56 gestational hypertensive subjects and 45 preeclamptic patients. We measured plasma and whole blood nitrite concentrations using an ozone-based chemiluminescence assay and serum soluble fms-like tyrosine kinase-1 and soluble endogline concentrations using enzyme immunoassays. Whole blood nitrite levels were significantly lower in gestational hypertensive subjects and preeclamptic patients (Ϫ36% and Ϫ58%, respectively; both PϽ0.05) compared with healthy pregnant women. The plasma nitrite levels were Ϸ37% lower in both groups with hypertensive disorders of pregnancy compared with the group with normotensive pregnancies (both PϽ0.05). As expected, we found higher circulating soluble fms-like tyrosine kinase-1 and soluble endogline concentrations in preeclampsia compared with gestational hypertensive subjects or with healthy pregnancies (both PϽ0.05). Key Words: NO Ⅲ nitrite Ⅲ whole blood nitrite Ⅲ preeclampsia Ⅲ sEng Ⅲ sFLT-1 N ormal human pregnancy is accompanied by increased blood volume that is accommodated within the cardiovascular system by systemic vasodilatation. 1 This vasodilatation involves increased NO formation, thus decreasing peripheral vascular resistance in healthy pregnant women. 2,3 On the other hand, deficient NO formation has been implicated in hypertensive disorders of pregnancy, such as preeclampsia and gestational hypertension. 4 -7 Indeed, previous studies compared the circulating concentrations of NO metabolites (nitriteϩnitrate) in the plasma from preeclamptic women with those found in healthy pregnant women. 8 -13 Conflicting results were reported, and some studies showed higher, 14 similar, 10,12 or lower 8 nitriteϩnitrate levels in preeclamptic women compared with healthy pregnant women. A possible explanation for these discrepancies is that nitriteϩnitrate may not accurately reflect endogenous NO formation in vivo, and there is mounting evidence that measuring the circulating concentrations of nitrite is an improved alternative to assess endogenously produced NO. [15][16][17][18][19] However, no previous study has compared the circulating nitrite concentrations in healthy pregnant women with those found in women with preeclampsia.The pathophysiology of preeclampsia is not completely known. However, there is evidence that a failure of cytotrophoblast invasion and abse...

Several factors cause urinary tract infection (UTI) to be a relevant complication of the gestational period, aggravating both the maternal and perinatal prognosis. For many years, pregnancy has been considered to be a factor predisposing to all forms of UTI. Today, it is known that pregnancy, as an isolated event, is not responsible for a higher incidence of UTI, but that the anatomical and physiological changes imposed on the urinary tract by pregnancy predispose women with asymptomatic bacteriuria (AB) to become pregnant women with symptomatic UTI. AB affects 2 to 10% of all pregnant women and approximately 30% of these will develop pyelonephritis if not properly treated. However, a difficult-to-understand resistance against the identification of AB during this period is observed among prenatalists. The diagnosis of UTI is microbiological and it is based on two urine cultures presenting more than 10(5) colonies/mL urine of the same germ. Treatment is facilitated by the fact that it is based on an antibiogram, with no scientific foundation for the notion that a pre-established therapeutic scheme is an adequate measure. For the treatment of pyelonephritis, it is not possible to wait for the result of culture and previous knowledge of the resistance profile of the antibacterial agents available for the treatment of pregnant women would be the best measure. Another important variable is the use of an intravenous bactericidal antibiotic during the acute phase, with the possibility of oral administration at home after clinical improvement of the patient. At our hospital, the drug that best satisfies all of these requirements is cefuroxime, administered for 10-14 days. Third-generation cephalosporins do not exist in the oral form, all of them involving the inconvenience of parenteral administration. In view of their side effects, aminoglycosides are considered to be inadequate for administration to pregnant women. The inconsistent insinuation of contraindication of monofluorinated quinolones, if there is an indication, norfloxacin is believed to be a good alternative to cefuroxime. In cases in which UTI prophylaxis is indicated, chemotherapeutic agents are preferred, among them nitrofurantoin, with care taken to avoid its use at the end of pregnancy due to the risk of kernicterus for the neonate.

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These findings suggest a contribution of eNOS haplotypes to the development of hypertensive disorders of pregnancy that is obscured when specific eNOS genotypes alone are considered.

BackgroundPreterm birth is the main cause of morbidity and mortality during the perinatal period. Classical risk factors are held responsible for only 1/3 of preterm births and no current intervention has produced an appreciable reduction of this event. It is necessary to explore new hypotheses and mechanisms of causality by using an integrated approach, collaboration among research groups and less fragmented theoretical-methodological approaches in order to detect new risk factors and to formulate more effective intervention strategies.MethodsThe study will be conducted on a convenience cohort of Brazilian pregnant women recruited at public and private prenatal health services. A total of 1500 pregnant women in São Luís, and 1500 in Ribeirão Preto, will be invited for an interview and for the collection of biological specimens from the 22nd to the 25th week of gestational age (GA). At the time of delivery they will be reinterviewed. GA will be determined using an algorithm based on two criteria: date of last menstruation (DLM) and obstetric ultrasound (OUS) performed at less than 20 weeks of GA. Illicit drug consumption during pregnancy will be determined using a self-applied questionnaire and the following instruments will be used: perceived stress scale, Beck anxiety scale, screening for depression of the Center of Epidemiological Studies (CES-D), experiences of racial discrimination, social network and social support scale of the Medical Outcomes Study and violence (Abuse Assessment Screening and violence questionnaire of the WHO). Bacterial vaginosis, urinary tract infection and periodontal disease will also be identified. Neuroendocrine, immunoinflammatory and medical intervention hypotheses will be tested. The occurrence of elective cesarean section in the absence of labor will be used as a marker of medical intervention.ConclusionPsychosocial, genetic and infectious mechanisms will be selected, since there are indications that they influence preterm birth (PTB). The studies will be conducted in two Brazilian cities with discrepant socioeconomic conditions. The expectation is to identify risk factors for PTB having a greater predictive power than classically studied factors. The final objective is to propose more effective interventions for the reduction of PTB, which, after being tested, might subsidize health policies.Electronic supplementary materialThe online version of this article (doi:10.1186/1742-4755-11-79) contains supplementary material, which is available to authorized users.

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Polycystic ovary syndrome (PCOS) is a multifactorial disorder that arises from interactions between genetic, environmental and intrauterine factors. Small-for-gestational-age (SGA) babies and the daughters of mothers with PCOS represent possible postnatal clinical targets for developmental programming by steroid excess. The presence of excess glucocorticoids and/or androgens during foetal organogenesis and growth might promote changes in gene expression, and these changes might be related to an increase in the risk of PCOS-like reproductive and metabolic disorders in postnatal life, such as rapid growth and weight gain during the first 2 years of life (only in SGA babies), hyperinsulinaemia, adipocyte dysfunction and childhood visceral obesity, premature pubarche and adrenarche (only in SGA babies) and PCOS. In the fourth decade of life, women who have PCOS may be at higher risk for type 2 diabetes mellitus, dyslipidaemia and systemic arterial hypertension, which suggests that these women are also at higher risk for cardiovascular disease during menopause. However, PCOS can also occur in women who were born at appropriate weight for GA or in newborns of women without PCOS, which suggests that genetic variation and environmental factors play important roles in the development and maintenance of PCOS in a population. Genome-wide association studies based on adequate population samples have shown a higher frequency of genetic polymorphisms of the LHCGR, THADA and DENND1A genes in women with PCOS. Genetic studies of PCOS have also included analyses of structural changes in the chromosome based on an assessment of telomere length in single, cross-sectional evaluations, and these studies have produced controversial results. The present narrative review assesses the multifactorial origins of PCOS (including environmental, genetic and intra-uterine factors) and the development of conditions associated with this disorder. It is concluded that although PCOS might originate in the intra-uterine environment through developmental programming by steroid excess, the interaction between genetic and environmental factors is crucial for its appearance. Follow-up studies should be conducted to assess the same populations over their entire lifespans while taking into account different aspects of the pathogenesis of PCOS.Reproduction (2015) 150 R11-R24

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.