Giuliane J. Lajos

Brazilian multicentre study on preterm birth (EMIP): prevalence and factors associated with spontaneous preterm birth.

Background Preterm birth rate is increasing and is currently a worldwide concern. The purpose of this study was to estimate the prevalence of preterm birth in a sample of health facilities in Brazil and to identify the main risk factors associated with spontaneous preterm births. Methods and Findings This was a multicentre cross sectional study on preterm births in 20 referral obstetric hospitals with a case-control component to identify factors associated with spontaneous preterm birth. Surveillance was implemented at all centres to identify preterm births. For eligible consenting women, data were collected through a post-delivery questionnaire completed with information from all mother-newborn medical records until death or discharge or at a maximum of 60 days post-delivery, whichever came first. The risk of spontaneous preterm birth was estimated with OR and 95%CI for several predictors. A non-conditional logistic regression analysis was then performed to identify independently associated factors. The overall prevalence of preterm birth was 12.3%. Among them, 64.6% were spontaneous and 35.4% therapeutic. In the case-control component, 2,682 spontaneous preterm births were compared to a sample of 1,146 term births. Multivariate analyses identified the following as risk factors for spontaneous preterm birth among women with at least one previous birth: a previous preterm birth (ORadj = 3.19, 2.30–4.43), multiple pregnancy (ORadj = 29.06, 8.43–100.2), cervical insufficiency (ORadj = 2.93, 1.07–8.05), foetal malformation (ORadj = 2.63, 1.43–4.85), polyhydramnios (ORadj = 2.30, 1.17–4.54), vaginal bleeding (ORadj = 2.16, 1.50–3.11), and previous abortion (ORadj = 1.39, 1.08–1.78). High BMI (ORadj = 0.94, 0.91–0.97) and weight gain during gestation (ORadj = 0.92, 0.89–0.95) were found to be protective factors. Conclusions The preterm birth rate in these health facilities in Brazil is high and spontaneous preterm births account for two thirds of them. A better understanding of the factors associated with spontaneous preterm birth is of utmost importance for planning effective measures to reduce the burden of its increasing rates.

Mother-to-child transmission of human immunodeficiency virus in aten years period

Objectivesto evaluate mother-to-child transmission (MTCT) rates and related factors in HIV-infected pregnant women from a tertiary hospital between 2000 and 2009.Subjects and methodcohort of 452 HIV-infected pregnant women and their newborns. Data was collected from recorded files and undiagnosed children were enrolled for investigation. Statistical analysis: qui-square test, Fisher exact test, Student t test, Mann-Whitney test, ANOVA, risk ratio and confidence intervals.ResultsMTCT occurred in 3.74%. The study population displayed a mean age of 27 years; 86.5% were found to have acquired HIV through sexual contact; 55% were aware of the diagnosis prior to the pregnancy; 62% were not using HAART. Mean CD4 cell-count was 474 cells/ml and 70.3% had undetectable viral loads in the third trimester. HAART included nevirapine in 35% of cases and protease inhibitors in 55%; Zidovudine monotherapy was used in 7.3%. Mean gestational age at delivery was 37.2 weeks and in 92% by caesarian section; 97.2% received intravenous zidovudine. Use of AZT to newborn occurred in 100% of them. Factors identified as associated to MTCT were: low CD4 cell counts, elevated viral loads, maternal AIDS, shorter periods receiving HAART, other conditions (anemia, IUGR (intra uterine growth restriction), oligohydramnium), coinfecctions (CMV and toxoplasmosis) and the occurrence of labor. Use of HAART for longer periods, caesarian and oral zidovudine for the newborns were associated with a decreased risk. Poor adhesion to treatment was present in 13 of the 15 cases of transmission; in 7, coinfecctions were diagnosed (CMV and toxoplasmosis).ConclusionUse of HAART and caesarian delivery are protective factors for mother-to-child transmission of HIV. Maternal coinfecctions and other conditions were risk factors for MTCT.

Colonização bacteriana do canal cervical em gestantes com trabalho de parto prematuro ou ruptura prematura de membranas

PURPOSE to study cervical colonization in women with preterm labor or premature rupture of membranes. METHODS two hundred and twelve pregnant women with preterm labor or premature rupture of membranes were studied. Two cervical samples from each woman were collected and bacterioscopy and culture were performed. Association of cervical microorganisms and urinary tract infection, chorioamnionitis, fetal stress, antibiotic use, prematurity, neonatal infection, and neonatal death were evaluated. RESULTS the prevalence of endocervical colonization was 14.2% (CI95%=9.5-18.9%), with similar results in preterm labor or premature rupture of membranes. Group B streptococcus was the most prevalent organism (9.4%). Other organisms isolated were Candida sp, Streptococcus sp, Streptococcus pneumoniae, Escherichia coli and Enterococcus sp. The most common findings of bacterioscopy were a reduced number of lactobacilli and a great number of leukocytes. Endocervical colonization was associated with a higher occurrence of urinary tract infection (23.8 versus 5.4%; p<0.01), early-onset neonatal infection (25.0 versus 7.3%; p<0.01) and neonatal mortality (two cases in colonized women; p<0.02) when compared with a negative culture of endocervical mucus. CONCLUSIONS this study showed high prevalence of endocervical colonization despite the use of a nonselective culture media. The main microorganism isolated was group B streptococcus, but other organisms were present in one third of the studied population. More studies are needed to evaluate the influence of endocervical colonization on obstetrical outcome and on neonatal infection and mortality.

The Burden of Provider-Initiated Preterm Birth and Associated Factors: Evidence from the Brazilian Multicenter Study on Preterm Birth (EMIP)

Background About 15 million children are born under 37 weeks of gestation worldwide. Prematurity is the leading cause of neonatal deaths and short/long term morbidities, entailing consequences not only for the individual, but also their family, health agencies, facilities and all community. The provider-initiated preterm birth is currently one of the most important obstetric conditions related to preterm births, particularly in middle and high income countries, thus decreasing the need for therapeutic preterm birth is essential to reduce global prematurity. Therefore detailed knowledge on the factors associated with provider-initiated preterm birth is essential for the efforts to reduce preterm birth rates and its consequences. In this current analysis we aimed to assess the proportion of provider-initiated (pi-PTB) among preterm births in Brazil and identify associated factors. Methods and Findings This is an analysis of a multicenter cross-sectional study with a nested case-control component called Brazilian Multicenter Study on Preterm Birth (EMIP). EMIP was conducted in 20 referral obstetric hospitals located in the three most populated of the five Brazilian regions. We analysed data of women with pi-PTB, defined as childbirth occurring at less than 37 weeks, medically indicated for maternal/fetal compromise or both; and women with term birth, childbirth at or after 37 weeks. Maternal, sociodemographic, obstetric, prenatal care, delivery, and postnatal characteristics were assessed as possible factors associated with pi-PTB, compared to term births. The overall prevalence of preterm births was 12.3%. Of these, approximately one-third of cases were initiated by the provider. Hypertensive disorders, placental abruption, and diabetes were the main maternal conditions leading to pi-PTB. Caesarean section was the most common mode of delivery. Chronic hypertension (OR 7.47; 95%CI 4.02–13.88), preeclampsia/eclampsia/HELLP syndrome (OR 15.35; 6.57–35.88), multiple pregnancy (OR 12.49; 4.86–32.05), and chronic diabetes (OR 5.24; 2.68–10.25) were the most significant factors independently associated with pi-PTB. Conclusions pi-PTB is responsible for about one-third of all preterm births, requiring special attention. The decision-making process relative to the choice of provider-initiated birth is complex, and many factors should be elucidated to improve strategies for its prevention, including evidence-based guidelines on proper management of the corresponding clinical conditions.

Serum Metabolic Alterations upon Zika Infection

Zika virus (ZIKV) infection has recently emerged as a major concern worldwide due to its strong association with nervous system malformation (microcephaly) of fetuses in pregnant women infected by the virus. Signs and symptoms of ZIKV infection are often mistaken with other common viral infections. Since transmission may occur through biological fluids exchange and coitus, in addition to mosquito bite, this condition is an important infectious disease. Thus, understanding the mechanism of viral infection has become an important research focus, as well as providing potential targets for assertive clinical diagnosis and quality screening for hemoderivatives. Within this context, the present work analyzed blood plasma from 79 subjects, divided as a control group and a ZIKV-infected group. Samples underwent direct-infusion mass spectrometry and statistical analysis, where eight markers related to the pathophysiological process of ZIKV infection were elected and characterized. Among these, Angiotensin (1-7) and Angiotensin I were upregulated under infection, showing an attempt to induce autophagy of the infected cells. However, this finding is concerning about hypertensive individuals under treatment with inhibitors of the Renin-Angiotensin System (RAS), which could reduce this response against the virus and exacerbate the symptoms of the infection. Moreover, one of the most abundant glycosphingolipids in the nervous tissue, Ganglioside GM2, was also elected in the present study as an infection biomarker. Considered an important pathogen receptor at membranes outer layer, this finding represents the importance of gangliosides for ZIKV infection and its association with brain tropism. Furthermore, a series of phosphatidylinositols were also identified as biomarkers, implying a significant role of the PI3K-AKT-mTOR Pathway in this mechanism. Finally, these pathways may also be understood as potential targets to be considered in pharmacological intervention studies on ZIKV infection management.

Intracluster correlation coefficients for the Brazilian Multicenter Study on Preterm Birth (EMIP): methodological and practical implications

BackgroundCluster-based studies in health research are increasing. An important characteristic of such studies is the presence of intracluster correlation, typically quantified by the intracluster correlation coefficient (ICC), that indicate the proportion of data variability that is explained by the way of clustering. The purpose of this manuscript was to evaluate ICC of variables studied in the Brazilian Multicenter Study on Preterm Birth.MethodsThis was a multicenter cross-sectional study on preterm births involving 20 referral hospitals in different regions of Brazil plus a nested case–control study to assess associated factors with spontaneous preterm births. Estimated prevalence rates or means, ICC with 95% confidence intervals, design effects and mean cluster sizes were presented for more than 250 maternal and newborn variables.ResultsOverall, 5296 cases were included in the study (4,150 preterm births and 1,146 term births). ICC ranged from <0.001 to 0.965, with a median of 0.028. For descriptive characteristics (socio-demographic, obstetric history and perinatal outcomes) the median ICC was 0.014, for newborn outcomes the median ICC was 0.041 and for process variables (clinical management and delivery), it was 0.102. ICC was <0.1 in 78.4% of the variables and <0.3 for approximately 95% of them. Most of ICC >0.3 was found in some clinical management aspects well defined in literature such as use of corticosteroids, indicating there was homogeneity in clusters for these variables.ConclusionsClusters selected for Brazilian Multicenter Study on Preterm Birth had mainly heterogeneous findings and these results can help researchers estimate the required sample size for future studies on maternal and perinatal health.

Methodological issues on planning and running the Brazilian Multicenter Study on Preterm Birth.

Objectives. Assuming that the occurrence of preterm births and their maternal and neonatal associated conditions in Brazil are not completely known, a multicenter study was proposed. The purpose of this paper is to describe the methods used, its processes, achievements, and challenges. Study Design. A multicenter cross-sectional study on preterm births in Brazilian facilities plus a nested case-control study to assess their associated factors. A description of all steps of planning and implementing such a nationwide study, including strategies for dealing with problems arising during the process, is presented. Results. 20 referral hospitals in different regions of Brazil participated in the study. A detailed questionnaire for data collection, an electronic platform for data transcription and monitoring, research materials, and specific monitoring tools were developed; then data management and analyses were performed. Finally, we got information on 4,150 preterm births and 1,146 term births. Conclusions. This study represented the first step of a planned comprehensive assessment of preterm birth in Brazil, with detailed information that will lead to several analyses and further studies, bringing the knowledge to improve screening, diagnosis, and treatment practices in maternal and perinatal health with the final purpose of reducing the burden of this condition in the country.

Tocolysis among Women with Preterm Birth: Associated Factors and Outcomes from a Multicenter Study in Brazil

OBJECTIVE  To evaluate the use of tocolysis in cases of preterm birth due to spontaneous preterm labor in a Brazilian sample. METHODS  A sample of 1,491 women with preterm birth due to spontaneous preterm labor were assessed, considering treatment with tocolysis or expectant management, according to gestational age at birth (< 34 weeks and 34 to 36 + 6 weeks) and drugs prescribed. The study took place in 20 Brazilian hospitals from April 2011 to July 2012. Bivariate analyses were conducted to evaluate associations with sociodemographic and obstetric characteristics and odds ratios with their respective 95% confidence intervals were estimated for maternal and neonatal outcomes. RESULTS  A total of 1,491 cases of preterm birth were considered. Tocolysis was performed in 342 cases (23%), 233 of which (68.1%) were delivered before 34 weeks. Within the expectant management group, 73% was late preterm and with more advanced labor at the time of admission. The most used drugs were calcium channel blockers (62.3%), followed by betamimetics (33%). Among the subjects in the tocolysis group, there were more neonatal and maternal complications (majority non-severe) and an occurrence of corticosteroid use that was 29 higher than in the expectant management group. CONCLUSION  Tocolysis is favored in cases of earlier labor and also among those with less than 34 weeks of gestation, using preferably calcium channel blockers, with success in achieving increased corticosteroid use. Tocolysis, in general, was related to higher maternal and neonatal complication rates, which may be due to the baseline difference between cases at admission. However, these results should raise awareness to tocolysis use.

P5.01 Antiretroviral therapy during pregnancy and maternal and neonatal side effects in an hiv-infected pregnant women cohort attended at obstetrician service of school of medical sciences at university of campinas (CAISM/UNICAMP), brazil between 2000 and 2016

Introduction Significant progress of ART in HIV infection has led to a remarkable decline in mother-to-child transmission (MTCT) of HIV. However, the use of complex regimens can cause side effects to women and exposed children.The objective of this study was to evaluate side effects in pregnant women and their neonates exposed to ART at an universitary hospital in Brazil between 2000 and 2016. Methods Cohort study of 793 pregnant women and 787 newborns selected from clinical records and epidemiologic surveillance system. Analysis was performed through proportions and medians. The specific effect of different ART regimens was analysed through risk ratios (RR), qui-square test, Fisher’s exact test, student t test, Mann-Whitney test, 95% confidence interval and level of significance of 0.05. Results MTCT rate was 2.3%. Mean age was 28 years, more than 60% were White and diagnosed before pregnancy. HAART use: 17.4% with nevirapine (NVP), 16.9% with nelfinavir (NFV), 53.2% with lopinavir/ritonavir (LPV/R), 4.3% with other PI (26 with atazanavir/ritonavir). Only 1.9% women did not use ART by late diagnosis. There were: 56% cases of maternal anaemia,14.1% of thrombocytopenia, 54.5% of hepatic abnormalities, 2.7% of allergic reactions, 82% of dyslipidemia, 6.2% of diabetes. NVP use was associated to hepatotoxicity, allergic reactions and anaemia. NFV was associated to hepatic impairment and allergic reaction, ATV/R use was associated to bilirrubin increase, and LPV/R to dyslipidemia.Prematurity rate was 21.7% and low birth weight rate 22.5%. In the newborns: 25.7% of anaemia, 3.6% of thrombocytopenia, 36% of hepatic impairment. Congenital anomalies were presented in 10%. NVP use associated to anaemia and hepatic impairment. NFV was associated to hepatic abnormalities. ATV/R was associated to thrombocytopenia. Conclusion Although growing evidence indicates that antiretroviral treatment in pregnancy has overall a very favourable risk-benefit profile, it is important to maintain monitoring of the safety and efficacy of drug classes in order to optimise treatment recommendations.

Evaluation of prenatal corticosteroid use in spontaneous preterm labor in the Brazilian Multicenter Study on Preterm Birth (EMIP)

To evaluate prenatal corticosteroid use in women experiencing spontaneous preterm labor and preterm delivery.