João Luiz Pinto e Silva

Antioxidant Therapy to Prevent Preeclampsia A Randomized Controlled Trial

OBJECTIVE: To study whether antioxidant supplementation will reduce the incidence of preeclampsia among patients at increased risk. METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted at four Brazilian sites. Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomly assigned to daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International Units) or placebo. Analyses were adjusted for clinical site and risk group (prior preeclampsia, chronic hypertension, or both). A sample size of 734 would provide 80% power to detect a 40% reduction in the risk of preeclampsia, assuming a placebo group rate of 21% and &agr;=.05. The &agr; level for the final analysis, adjusted for interim looks, was 0.0458. RESULTS: Outcome data for 707 of 739 randomly assigned patients revealed no significant reduction in the rate of preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of 352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61–1.25]). There were no differences in mean gestational age at delivery or rates of perinatal mortality, abruptio placentae, preterm delivery, and small for gestational age or low birth weight infants. Among patients without chronic hypertension, there was a slightly higher rate of severe preeclampsia in the study group (study drug, 6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio 2.78, 95% confidence interval 0.79–12.62). CONCLUSION: This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of preeclampsia among patients with chronic hypertension and/or prior preeclampsia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.ClinicalTrials.gov, NCT00097110 LEVEL OF EVIDENCE: I

Serum inhibin A and angiogenic factor levels in pregnancies with previous preeclampsia and/or chronic hypertension: are they useful markers for prediction of subsequent preeclampsia?

OBJECTIVE Our objective was to determine whether measurement of placenta growth factor (PLGF), inhibin A, or soluble fms-like tyrosine kinase-1 (sFlt-1) at 2 times during pregnancy would usefully predict subsequent preeclampsia (PE) in women at high risk. STUDY DESIGN We analyzed serum obtained at enrollment (12(0/7) to 19(6/7) weeks) and follow-up (24-28 weeks) from 704 patients with previous PE and/or chronic hypertension (CHTN) enrolled in a randomized trial for the prevention of PE. Logistic regression analysis assessed the association of log-transformed markers with subsequent PE; receiver operating characteristic analysis assessed predictive value. RESULTS One hundred four developed preeclampsia: 27 at 37 weeks or longer and 77 at less than 37 weeks (9 at less than 27 weeks). None of the markers was associated with PE at 37 weeks or longer. Significant associations were observed between PE at less than 37 weeks and reduced PLGF levels at baseline (P = .022) and follow-up (P < .0001) and elevated inhibin A (P < .0001) and sFlt-1 (P = .0002) levels at follow-up; at 75% specificity, sensitivities ranged from 38% to 52%. Using changes in markers from baseline to follow-up, sensitivities were 52-55%. Associations were observed between baseline markers and PE less than 27 weeks (P < or = .0004 for all); sensitivities were 67-89%, but positive predictive values (PPVs) were only 3.4-4.5%. CONCLUSION Inhibin A and circulating angiogenic factors levels obtained at 12(0/7) to 19(6/7) weeks have significant associations with onset of PE at less than 27 weeks, as do levels obtained at 24-28 weeks with onset of PE at less than 37 weeks. However, because the corresponding sensitivities and/or PPVs were low, these markers might not be clinically useful to predict PE in women with previous PE and/or CHTN.

Postpartum dexamethasone for women with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome: a double-blind, placebo-controlled, randomized clinical trial.

OBJECTIVE The purpose of this study was to determine the effectiveness of postpartum dexamethasone in patients with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. STUDY DESIGN A prospective, randomized, double-blind trial was conducted in which 105 women with HELLP syndrome were enrolled and assigned randomly to treatment or placebo groups following delivery. Duration of hospital stay, maternal morbidity, and laboratory and clinical parameters were evaluated. RESULTS There was no difference in maternal morbidity or mortality between the 2 groups. There was also no difference in duration of hospitalization and the need for rescue scheme or the use of blood products between groups. Linear model adjustments showed no significant difference between groups with respect to the pattern of platelet count recovery, aspartate aminotransferase, lactate dehydrogenase, hemoglobin, or diuresis. CONCLUSION These findings do not support the use of dexamethasone in the puerperium for recovery of patients with HELLP syndrome.

Brazilian network for the surveillance of maternal potentially life threatening morbidity and maternal near-miss and a multidimensional evaluation of their long term consequences.

BackgroundIt has been suggested that the study of women who survive life-threatening complications related to pregnancy (maternal near-miss cases) may represent a practical alternative to surveillance of maternal morbidity/mortality since the number of cases is higher and the woman herself is able to provide information on the difficulties she faced and the long-term repercussions of the event. These repercussions, which may include sexual dysfunction, postpartum depression and posttraumatic stress disorder, may persist for prolonged periods of time, affecting womens quality of life and resulting in adverse effects to them and their babies.ObjectiveThe aims of the present study are to create a nationwide network of scientific cooperation to carry out surveillance and estimate the frequency of maternal near-miss cases, to perform a multicenter investigation into the quality of care for women with severe complications of pregnancy, and to carry out a multidimensional evaluation of these women up to six months.Methods/DesignThis project has two components: a multicenter, cross-sectional study to be implemented in 27 referral obstetric units in different geographical regions of Brazil, and a concurrent cohort study of multidimensional analysis. Over 12 months, investigators will perform prospective surveillance to identify all maternal complications. The population of the cross-sectional component will consist of all women surviving potentially life-threatening conditions (severe maternal complications) or life-threatening conditions (the maternal near miss criteria) and maternal deaths according to the new WHO definition and criteria. Data analysis will be performed in case subgroups according to the moment of occurrence and determining cause. Frequencies of near-miss and other severe maternal morbidity and the association between organ dysfunction and maternal death will be estimated. A proportion of cases identified in the cross-sectional study will comprise the cohort of women for the multidimensional analysis. Various aspects of the lives of women surviving severe maternal complications will be evaluated 3 and 6 months after the event and compared to a group of women who suffered no severe complications in pregnancy. Previously validated questionnaires will be used in the interviews to assess reproductive function, posttraumatic stress, functional capacity, quality of life, sexual function, postpartum depression and infant development.

Antioxidant Supplementation and Premature Rupture of the Membranes: A Planned Secondary Analysis

OBJECTIVE The purpose of this study was to determine if antioxidant supplementation during pregnancy reduces the incidence of premature rupture of the membranes (PROM). STUDY DESIGN A placebo-controlled, double-blind trial was conducted. PROM and preterm PROM (PPROM) were planned secondary outcomes of the trial. Women between 12(0/7) and 19(6/7) weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomized to daily treatment with both vitamin C (1000 mg) and E (400 IU) or placebo. RESULTS Outcome data for PROM were available for 697 of 739 patients. The rates of PROM (37/349 [10.6%] vs 19/348 [5.5%]; adjusted risk ratio [RR] 1.89 [95.42% CI, 1.11-3.23]; P = .015), and PPROM (16/349 [4.6%] vs 6/348 [1.7%]; RR 2.68 [1.07-6.71]; P = .025) were increased in the antioxidant group. CONCLUSION Contrary to expectations, vitamins C and E supplementation in this dose combination may be associated with an increased risk of PROM and PPROM.

Exercise and physical activity in the prevention of pre‐eclampsia: systematic review

Exercise and physical activity have been studied and suggested as a way to reduce or minimize the effects of pre‐eclampsia. Our aim was to evaluate the association between exercise and/or physical activity and occurrence of pre‐eclampsia. We conducted electronic searches without year of publication and language limitations. This was a systematic review designed according to PRISMA. Different databases accessed were as follows: PubMed®; Latin‐American and Caribbean Literature in Health Sciences (LILACS); Scientific Electronic Library On‐line (SciELO); Physiotherapy Evidence Database (PEDro); and ISI web of KnowledgeSM. The Medical Subject Headings (MeSH) were as follows: (“exercise” OR “motor activity” OR “physical activity”) AND (“pre‐eclampsia” OR “eclampsia” OR “hypertension, pregnancy‐induced”). Inclusion criteria were studies conducted in adults who were engaged in some physical activity. The selection and methodological evaluation were carried out by two independent reviewers. Risk assessment was made by the odds ratio (OR) and incidence of pre‐eclampsia in the population who performed physical activity/exercise. A total of 231 articles were found, 214 of which were excluded based on title and full‐text, so that 17 remained. Comparison of six case–control studies showed that physical activity had a protective effect on the development of pre‐eclampsia [OR 0.77, 95% confidence interval (CI) 0.64–0.91, p < 0.01]. The 10 prospective cohort studies showed no significant difference (OR 0.99, 95% CI 0.93–1.05, p= 0.81). The only randomized clinical trial showed a protective effect on the development of pre‐eclampsia in the stretching group (OR 6.34, 95% CI 0.72–55.37, p= 0.09). This systematic review indicates a trend toward a protective effect of physical activity in the prevention of pre‐eclampsia.

A amamentação e a alimentação complementar de filhos de mães adolescentes são diferentes das de filhos de mães adultas

OBJECTIVES: to study breastfeeding during the first year of life and the kind of complementary food provided at one year of life to children of adolescent mothers. To compare these data with breastfeeding and complementary food received by children of adult mothers. METHOD: a dual cohort was performed. Children were selected from the files of CAISM/UNICAMP and assessed when they were one year old. This study consisted of 122 children born from adolescent mothers and 123 children born from adult mothers - full-term births, birthweight was 2,500 g or higher. When the children were one year old, the mothers were interviewed at home or at CIPED/UNICAMP. The results were compared using the chi-square test and the Fishers test; a= 5%; the Kaplan-Meier method was used to analyze the duration of breastfeeding and the Wilcoxon test (Breslow) to compare the exclusive, predominant, full and total breastfeeding curves. RESULTS: 94.3% of children of adolescent mothers and 95.9% of children of adult mothers left the maternity hospital being breastfed (p = 0,544). The median exclusive breastfeeding duration for both groups was 90 days. After completing one year, 35.3% and 28.5% of children of adolescent and adult mothers, respectively, continued breastfeeding (p = 0.254): only breastfeeding 11.5% x 8.9% and mixed feeding 23.8% x 19.5% (p = 0.519). Meat intake by children of adolescent mothers was lower than that of children of adult mothers (13.9% x 26.0%; Fishers test: p = 0.031). With regard to egg intake, 11.5% x 19.5% of children of adolescent mothers and adult mothers did not eat egg but the results suggested that the egg intake of children of adolescent mothers was higher (p = 0.082). CONCLUSIONS: duration and pattern of breastfeeding were similar between children of adolescent mothers and of adult mothers. The complementary nutrition was similar, except for a lower intake of meat and a higher intake of eggs among the children of adolescent mothers.

Effect of a physical exercise program during pregnancy on uteroplacental and fetal blood flow and fetal growth: a randomized controlled trial.

OBJECTIVE: To estimate the effect of supervised physical exercise on maternal physical fitness, fetoplacental blood flow, and fetal growth. METHODS: This was a randomized controlled trial comparing three groups of pregnant women. Groups were as follows: exercise initiated at 13 weeks (group A); exercise initiated at 20 weeks (group B); and a control group (no supervised exercise; group C). The women in groups A and B walked at moderate intensity three times weekly. Physical fitness level was evaluated at weeks 13, 20, and 28. Fetal growth and uteroplacental blood flow were evaluated monthly. Birth weight was registered. Analysis of variance for repeat measures was used for outcomes evaluated throughout pregnancy. Risk ratio was used as a measure of the relative risk of preeclampsia, fetal growth restriction, macrosomia, small-for-gestational-age newborns, and large-for-gestational-age newborns. RESULTS: All the women analyzed completed more than 85% of the program. According to the evaluation conducted at week 28, physical fitness improved, with mean maximal oxygen consumptions (VO2max) of 27.3±4.3 (group A), 28±3.3 (group B), and 25.5±3.8 (group C; P=.03). Mean birth weights were 3,279±453 g (group A), 3,285±477 g (group B), and 3,378±593 g (group C; P=.53), with no difference in the frequency of large for gestational age or small for gestational age. No association was found between the practice of physical activity and the variables investigated (preeclampsia, fetal weight, blood pressure, and pulsatility index of the uterine, umbilical, and middle cerebral arteries). CONCLUSION: Moderate-intensity walking improved the physical fitness level of healthy, pregnant, previously sedentary women without affecting fetoplacental blood flow or fetal growth. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00641550. LEVEL OF EVIDENCE: II

From planning to practice : building the national network for the surveillance of severe maternal morbidity

BackgroundImproving maternal health is one of the Millennium Development Goals for 2015. Recently some progress has been achieved in reducing mortality. On the other hand, in developed regions, maternal death is a relatively rare event compared to the number of cases of morbidity; hence studying maternal morbidity has become more relevant. Electronic surveillance systems may improve research by facilitating complete data reporting and reducing the time required for data collection and analysis. Therefore the purpose of this study was to describe the methods used in elaborating and implementing the National Network for the Surveillance of Severe Maternal Morbidity in Brazil.MethodsThe project consisted of a multicenter, cross-sectional study for the surveillance of severe maternal morbidity including near-miss, in Brazil.ResultsFollowing the development of a conceptual framework, centers were selected for inclusion in the network, consensus meetings were held among the centers, an electronic data collection system was identified, specific software and hardware tools were developed, research material was prepared, and the implementation process was initiated and analyzed.ConclusionThe conceptual framework developed for this network was based on the experience acquired in various studies carried out in the area over recent years and encompasses maternal and perinatal health. It is innovative especially in the context of a developing country. The implementation of the project represents the first step towards this planned management. The system online elaborated for this surveillance network may be used in further studies in reproductive and perinatal health.

Prevalência de dores nas costas na gestação

OBJECTIVES: To evaluate the prevalence of back pains, identify their location and the association between age, time of pregnancy, nervous injury and the presence of pain prior to pregnancy. METHODS: Back pain was identified by means of a descriptive study. From January to December of 2001, using a questionnaire structured by the authors, 203 pregnant women arriving for Pre-natal care were interviewed after selection in the waiting rooms of the Primary Health care Units of the city of Paulinia (state of Sao Paulo). RESULTS: Prevalence of back pain was of 79.8%; of these location in the lumbar region was reported by 80.8% and in the sacroiliac by 49.1% of the pregnant women. Pain was more frequent among younger women. Prevalence of back pain did not increase with progress of pregnancy. Symptoms of nervous injury not related to the site of the back pain were reported by 47.7% of those pregnant. CONCLUSION: Almost 80% of the pregnant women reported back pain at some time during pregnancy. The most often reported sites were the lumbar and sacroiliac. Pain was more frequent among the younger women. Half of the pregnant women reported symptoms of nervous injury.