Acute toxic exposures in children: analysis of a three year registry managed by a Pediatric poison control Center in Italy.

INTRODUCTION: Acute pediatric poisoning is an emerging health and social problem. The aim of this study is to describe the characteristics of a large pediatric cohort exposed to xenobiotics, through the analysis of a Pediatric Poison Control Center (PPCc) registry. METHODS: This study, conducted in the Pediatric Hospital Bambino Gesù of Rome, a reference National Pediatric Hospital, collected data of children whose parents or caregivers contacted the PPCc by phone (group "P"), or who presented to the Emergency Department (group "ED"), during the three-year period 2014-2016. Data were prospectively and systematically collected in a pre-set electronic registry. Comparisons among age groups were performed and multivariable logistic regression models used to investigate associations with outcomes (hospital referral for "P", and hospital admission for "ED"group). RESULTS: We collected data of 1611 children on group P and 1075 on group ED. Both groups were exposed to both pharmaceutical and non-pharmaceutical agents. Pharmaceutical agent exposure increased with age and the most common route of exposure was oral. Only 10% among P group were symptomatic children, with gastrointestinal symptoms. Among the ED patients, 30% were symptomatic children mostly with gastrointestinal (55.4%) and neurologic symptoms (23.8%). Intentional exposure (abuse substance and suicide attempt), which involved 7.7% of patients, was associated with older age and Hospital admission. CONCLUSIONS: Our study describes the characteristics of xenobiotics exposures in different paediatric age groups, highlighting the impact of both pharmacological and intentional exposure. Furthermore, our study shows the utility of a specific PPCc, either through Phone support or by direct access to ED. PPCc phone counselling could avoid unnecessary access to the ED, a relevant achievement, particularly in the time of a pandemic.

Effects of FTO and PPARγ variants on intrauterine growth restriction in a Brazilian birth cohort.

Intrauterine growth restriction (IUGR) is related to a higher risk of neonatal mortality, minor cognitive deficit, metabolic syndrome, and cardiovascular disease in adulthood. In previous studies, genetic variants in the FTO (fat mass and obesity-associated) and PPARγ (peroxisome proliferator-activated receptor-gamma) genes have been associated with metabolic disease, body mass index, and obesity among other outcomes. We studied the association of selected FTO (rs1421085, rs55682395, rs17817449, rs8043757, rs9926289, and rs9939609) and PPARγ (rs10865710, rs17036263, rs35206526, rs1801282, rs28763894, rs41516544, rs62243567, rs3856806, and rs1805151) single-nucleotide polymorphisms (SNPs) with IUGR, through a case-control study in a cohort of live births that occurred from June 1978 to May 1979 in a Brazilian city. We selected 280 IUGR cases and 256 controls for analysis. Logistic regression was used to jointly analyze the SNPs as well as factors such as maternal smoking, age, and schooling. We found that the PPARγ rs41516544 increased the risk of IUGR for male offspring (OR 27.83, 95%CI 3.65-212.32) as well as for female offspring (OR=8.94, 95%CI: 1.96-40.88). The FTO rs9939609 TA genotype resulted in a reduced susceptibility to IUGR for male offspring only (OR=0.47, 95%CI: 0.26-0.86). In conclusion, we demonstrated that PPARγ SNP had a positive effect and FTO SNP had a negative effect on IUGR occurrence, and these effects were gender-specific.

Is soft drink consumption associated with gestational hypertension? Results from the BRISA cohort.

It is still unknown whether excessive consumption of sugar-sweetened beverages may be linked to gestational hypertensive disorders, other than preeclampsia. This study investigated the association between soft drink consumption and hypertension during pregnancy, analyzing the relationship from the perspective of counterfactual causal theory. Data from pregnant women of the BRISA cohort were analyzed (1,380 in São Luis and 1,370 in Ribeirão Preto, Brazil). The explanatory variable was the frequency of soft drink consumption during pregnancy obtained in a prenatal interview. The outcome was gestational hypertension based on medical diagnosis, at the time of delivery. A theoretical model of the association between soft drink consumption and gestational hypertension was constructed using a directed acyclic graph. Marginal structural models (MSM) weighted by the inverse of the probability of soft drink consumption were also employed. Using Poisson regression analysis, high soft drink consumption (≥7 times/week) was associated with gestational hypertension in São Luís (RR=1.48; 95%CI: 1.03-2.10), in Ribeirão Preto (RR=1.51; 95%CI: 1.13-2.01), and in the two cohorts combined (RR=1.45; 95%CI: 1.16-1.82) compared to lower exposure (<7 times/week). In the MSM, the association between high soft drink consumption and gestational hypertension was observed in Ribeirão Preto (RR=1.63; 95%CI: 1.21-2.19) and in the two cohorts combined (RR=1.51; 95%CI: 1.15-1.97), but not in São Luís (RR=1.26; 95%CI: 0.79-2.00). High soft drink consumption seems to be a risk factor for gestational hypertension, suggesting that it should be discouraged during pregnancy.

Racial inequality in perinatal outcomes in two Brazilian birth cohorts.

This study aimed to estimate and compare racial inequality in low birth weight (LBW), preterm birth (PTB), and intrauterine growth restriction (IUGR) in two Brazilian birth cohorts. This was a cross-sectional study nested within two birth cohorts in Ribeirão Preto (RP) and São Luís (SL), whose mothers were interviewed from January to December 2010. In all, 7430 (RP) and 4995 (SL) mothers were interviewed. The maternal skin color was the exposure variable. Associations were adjusted for socioeconomic and biological covariates: maternal education, per capita family income, family economic classification, household head occupation, maternal age, parity, marital status, prenatal care, type of delivery, maternal pre-pregnancy BMI, hypertension, hypertension during pregnancy, and smoking during pregnancy collected from questionnaires applied at birth. Statistical analysis was done with the chi-squared test and logistic regression. In RP, newborns from mothers with black skin color had a higher risk of LBW and IUGR, even after adjusting for socioeconomic and biological variables (P<0.001). In SL, skin color was not a risk factor for LBW (P=0.859), PTB (P=0.220), and IUGR (P=0.062), before or after adjustment for socioeconomic and biological variables. The detection of racial inequality in these perinatal outcomes only in the RP cohort after adjustment for socioeconomic and biological factors may be reflecting the existence of racial discrimination in the RP society. In contrast, the greater miscegenation present in São Luís may be reflecting less racial discrimination of black and brown women in this city.

Is soft drink consumption associated with gestational hypertension? Results from the BRISA cohort

It is still unknown whether excessive consumption of sugar-sweetened beverages may be linked to gestational hypertensive disorders, other than preeclampsia. This study investigated the association between soft drink consumption and hypertension during pregnancy, analyzing the relationship from the perspective of counterfactual causal theory. Data from pregnant women of the BRISA cohort were analyzed (1,380 in São Luis and 1,370 in Ribeirão Preto, Brazil). The explanatory variable was the frequency of soft drink consumption during pregnancy obtained in a prenatal interview. The outcome was gestational hypertension based on medical diagnosis, at the time of delivery. A theoretical model of the association between soft drink consumption and gestational hypertension was constructed using a directed acyclic graph. Marginal structural models (MSM) weighted by the inverse of the probability of soft drink consumption were also employed. Using Poisson regression analysis, high soft drink consumption (≥7 times/week) was associated with gestational hypertension in São Luís (RR=1.48; 95%CI: 1.03-2.10), in Ribeirão Preto (RR=1.51; 95%CI: 1.13-2.01), and in the two cohorts combined (RR=1.45; 95%CI: 1.16-1.82) compared to lower exposure (<7 times/week). In the MSM, the association between high soft drink consumption and gestational hypertension was observed in Ribeirão Preto (RR=1.63; 95%CI: 1.21-2.19) and in the two cohorts combined (RR=1.51; 95%CI: 1.15-1.97), but not in São Luís (RR=1.26; 95%CI: 0.79-2.00). High soft drink consumption seems to be a risk factor for gestational hypertension, suggesting that it should be discouraged during pregnancy.

Racial inequality in perinatal outcomes in two Brazilian birth cohorts

This study aimed to estimate and compare racial inequality in low birth weight (LBW), preterm birth (PTB), and intrauterine growth restriction (IUGR) in two Brazilian birth cohorts. This was a cross-sectional study nested within two birth cohorts in Ribeirão Preto (RP) and São Luís (SL), whose mothers were interviewed from January to December 2010. In all, 7430 (RP) and 4995 (SL) mothers were interviewed. The maternal skin color was the exposure variable. Associations were adjusted for socioeconomic and biological covariates: maternal education, per capita family income, family economic classification, household head occupation, maternal age, parity, marital status, prenatal care, type of delivery, maternal pre-pregnancy BMI, hypertension, hypertension during pregnancy, and smoking during pregnancy collected from questionnaires applied at birth. Statistical analysis was done with the chi-squared test and logistic regression. In RP, newborns from mothers with black skin color had a higher risk of LBW and IUGR, even after adjusting for socioeconomic and biological variables (P<0.001). In SL, skin color was not a risk factor for LBW (P=0.859), PTB (P=0.220), and IUGR (P=0.062), before or after adjustment for socioeconomic and biological variables. The detection of racial inequality in these perinatal outcomes only in the RP cohort after adjustment for socioeconomic and biological factors may be reflecting the existence of racial discrimination in the RP society. In contrast, the greater miscegenation present in São Luís may be reflecting less racial discrimination of black and brown women in this city.

Effects of FTO and PPARγ variants on intrauterine growth restriction in a Brazilian birth cohort

Intrauterine growth restriction (IUGR) is related to a higher risk of neonatal mortality, minor cognitive deficit, metabolic syndrome, and cardiovascular disease in adulthood. In previous studies, genetic variants in the FTO (fat mass and obesity-associated) and PPARγ (peroxisome proliferator-activated receptor-gamma) genes have been associated with metabolic disease, body mass index, and obesity among other outcomes. We studied the association of selected FTO (rs1421085, rs55682395, rs17817449, rs8043757, rs9926289, and rs9939609) and PPARγ (rs10865710, rs17036263, rs35206526, rs1801282, rs28763894, rs41516544, rs62243567, rs3856806, and rs1805151) single-nucleotide polymorphisms (SNPs) with IUGR, through a case-control study in a cohort of live births that occurred from June 1978 to May 1979 in a Brazilian city. We selected 280 IUGR cases and 256 controls for analysis. Logistic regression was used to jointly analyze the SNPs as well as factors such as maternal smoking, age, and schooling. We found that the PPARγ rs41516544 increased the risk of IUGR for male offspring (OR 27.83, 95%CI 3.65-212.32) as well as for female offspring (OR=8.94, 95%CI: 1.96-40.88). The FTO rs9939609 TA genotype resulted in a reduced susceptibility to IUGR for male offspring only (OR=0.47, 95%CI: 0.26-0.86). In conclusion, we demonstrated that PPARγ SNP had a positive effect and FTO SNP had a negative effect on IUGR occurrence, and these effects were gender-specific.

Uterine vascular resistance and other maternal factors associated with the risk of developing hypertension during pregnancy

Gestational hypertension and pre-eclampsia are important causes of perinatal morbidity. The objective of the present study was to determine the increase in relative risk for developing hypertensive disorders of pregnancy based on the evaluation of pregnant women between 20 and 25 weeks of gestation, and to correlate the findings at this period with the outcome of pregnancy. We conducted a prospective cohort study, with a convenience sample of 1417 patients evaluated at this gestational age, of which 1306 were contacted at childbirth. We detected an increased relative risk of 2.69 (95%CI: 1.86 to 3.89) associated with pulsatility index of the uterine arteries, a 2.8 increase (95%CI: 1.58 to 5.03) in relative risk attributed to maternal age above 35 years, a 1.68 increase (95%CI: 1.17 to 2.40) attributed to parity greater than or equal to 3, and a 5.35 increase (95%CI: 4.18 to 6.85) attributed to chronic hypertension and obesity, with a progressive increase in relative risk according to the degree of overweight, i.e., grades 1, 2, 3, and morbid obesity (2.58, 3.06, 5.84, and 7.28, respectively).

Association between tobacco and/or alcohol consumption during pregnancy and infant development: BRISA Cohort

Fetuses exposed to alcohol and/or tobacco are at risk for perinatal adversities. However, little is currently known about the association of the separate or concomitant use of alcohol and tobacco with infant motor and cognitive development. Thus, the objective of the present study was to investigate the association between maternal consumption of alcohol and/or tobacco during pregnancy and the motor and cognitive development of children starting from the second year of life. The study included 1006 children of a cohort started during the prenatal period (22-25 weeks of pregnancy), evaluated at birth and reevaluated during the second year of life in 2011/2013. The children were divided into four groups according to the alcohol and/or tobacco consumption reported by their mothers at childbirth: no consumption (NC), separate alcohol consumption (AC), separate tobacco consumption (TC), and concomitant use of both (ACTC). The Bayley Scale of Infant and Toddler Development Third Edition screening tool was used for the assessment of motor and cognitive development. Adjusted Poisson regression models were used to determine the association between groups and delayed development. The results indicated that only the ACTC group showed a higher risk of motor delay, specifically regarding fine motor skills, compared to the NC group (RR=2.81; 95%CI: 1.65; 4.77). Separate alcohol or tobacco consumption was not associated with delayed gross motor or cognitive development. However, the concomitant use of the two substances increased the risk of delayed acquisition of fine motor skills.

Psychological distress and mother-child relationship: influence of life context on a population sample (BRISA) through the use of directed acyclic graphs (DAG)

This study aimed to investigate the association between maternal psychological distress and impairment in mother-child relationship in a sample from a Northeast capital city in Brazil with a low Human Development Index, using directed acyclic graphs (DAG). A total of 3,215 women were evaluated for the presence of psychological distress through the Self Reporting Questionnaire instrument and for the mother-child relationship by the first factor of Postpartum Bonding Questionnaire, considered the most appropriate in the literature. Demographic and socioeconomic variables were used to construct a theoretical model and, after this, multivariate logistic regression was performed using variables suggested by Directed Acyclic Graphs (DAG). Psychological distress was present in 22.7% of the women and 12.6% of them presented impaired mother-child relationships. After adjustment, the variable 'maternal mental distress' remained associated with impaired mother-child relationship (RR=3.03), and among the explanatory variables only 'primary school level' (RR=1.48) was associated as a risk factor to this outcome. The results indicated that, in this population, women with psychological distress and lower schooling are more likely to present impaired mother-child relationships.

Socio-environmental determinants of the delay in the first dental visit: results of two population-based cohort studies in Brazil

The objective of this study was to describe the timing of the first dental visit and investigate the association of socioeconomic and behavioral factors with dental visit delay among 10/11-year-old children from two live-birth population cohorts with extremely contrasting socioeconomic profiles. Follow-up data (2004-2005) from cohorts of Ribeirão Preto (RP) (n=790) and São Luís (SL) (n=673) were evaluated. Delay in dental visit was defined as not visiting a dentist before the age of 7. Covariates included family socioeconomic characteristics, mother-related health behavior, and child-related characteristics. Prevalence ratios with robust standard errors were estimated. In both cohorts, less than 5% of children had visited a dentist before the age of two and about 35% of them had not visited a dentist before the age of seven. Lower mother's schooling and lack of private health insurance were associated with the delay in first dental visit for both cohorts. A small number of mother's prenatal care visits and being from a single-father family or a family without parents were only associated in the RP cohort, while having ≥4 siblings and lifetime dental pain were associated in the SL cohort. The association with dental pain probably reveals a preventive care-seeking behavior. Therefore, the percentage of delayed first dental visit of children was very high even among those with the most educated mothers. Further studies are necessary to analyze recent changes and underlying factors related to access to first dental visit after the implementation of the National Oral Health Policy in 2006.

Relative validity of a food frequency questionnaire for adolescents from a capital in the Northeastern region of Brazil

The present study was conducted to evaluate the validity of the Food Frequency Questionnaire (FFQ) used in the RPS Birth Cohort Consortium (Ribeirão Preto, Pelotas, and São Luís) to assess dietary intake of adolescents from São Luís, Maranhão. The research was developed with 152 adolescents aged 18 and 19 years. For the validation of the FFQ, the average of three 24-hour recalls (24HRs) was used as the reference method. The mean and standard deviation of energy and nutrient intake extracted from the surveys were estimated. The paired Student's t-test was used to verify the differences between the instruments. Pearson correlation coefficient, intraclass correlation coefficient (ICC), weighted Kappa, and the Bland-Altman plot were calculated in order to measure the agreement. The study adopted a level of significance <5%. Compared with the three 24HRs, the FFQ overestimated the consumption of most nutrients. Energy-adjusted and de-attenuated concordance Pearson correlation coefficients ranged from 0.06 to 0.43, and correlations were significant for iron, calcium, riboflavin, sodium, saturated fat, niacin, and vitamin C. The energy-adjusted and de-attenuated ICCs ranged from 0.01 to 0.31, and the weighted Kappa ranged from 0.01 to 0.46. The analyses of agreement were significant for vitamin C, fiber, calcium, riboflavin, niacin, sodium, lipids, and iron. In conclusion, the FFQ presented acceptable relative validity for lipids, saturated fatty acids, fiber, calcium, iron, riboflavin, niacin, vitamin C, and sodium. This instrument will be useful in studies about food consumption of adolescents in São Luís, Maranhão.

Association of genitourinary infections and cervical length with preterm childbirth

A prospective cohort study was conducted on a convenience sample of 1370 pregnant women with a gestational age of 20 to 25 weeks in the city of Ribeirão Preto. Data on obstetrical history, maternal age, parity, smoking habit, and a history of preterm delivery was collected with the application of a sociodemographic questionnaire. Cervical length was determined by endovaginal ultrasound, and urine and vaginal content samples were obtained to determine urinary tract infection (UTI) and bacterial vaginosis (BV), respectively. The aim of this study was to verify the association of cervical length and genitourinary infections with preterm birth (PTB). Ultrasound showed no association of UTI or BV with short cervical length. PTB rate was 9.63%. Among the women with PTB, 15 showed UTI (RR: 1.55, 95%CI: 0.93-2.58), 19 had BV (RR: 1.22, 95%CI: 0.77-1.94), and one had both UTI and BV (RR: 0.85, 95%CI: 0.13-5.62). Nineteen (14.4%) PTB occurred in women with a cervical length ≤2.5 cm (RR: 2.89, 95%CI: 1.89-4.43). Among the 75 patients with PTB stratified as spontaneous, 10 showed UTI (RR: 2.02, 95%CI: 1.05-3.86) and 14 had a diagnosis of BV (RR: 1.72, 95%CI: 0.97-3.04). A short cervical length between 20 and 25 weeks of pregnancy was associated with PTB, whereas UTI and BV determined at this age were not associated with short cervical length or with PTB, although UTI, even if asymptomatic, was related to spontaneous PTB.

Association of genitourinary infections and cervical length with preterm childbirth.

A prospective cohort study was conducted on a convenience sample of 1370 pregnant women with a gestational age of 20 to 25 weeks in the city of Ribeirão Preto. Data on obstetrical history, maternal age, parity, smoking habit, and a history of preterm delivery was collected with the application of a sociodemographic questionnaire. Cervical length was determined by endovaginal ultrasound, and urine and vaginal content samples were obtained to determine urinary tract infection (UTI) and bacterial vaginosis (BV), respectively. The aim of this study was to verify the association of cervical length and genitourinary infections with preterm birth (PTB). Ultrasound showed no association of UTI or BV with short cervical length. PTB rate was 9.63%. Among the women with PTB, 15 showed UTI (RR: 1.55, 95%CI: 0.93-2.58), 19 had BV (RR: 1.22, 95%CI: 0.77-1.94), and one had both UTI and BV (RR: 0.85, 95%CI: 0.13-5.62). Nineteen (14.4%) PTB occurred in women with a cervical length ≤2.5 cm (RR: 2.89, 95%CI: 1.89-4.43). Among the 75 patients with PTB stratified as spontaneous, 10 showed UTI (RR: 2.02, 95%CI: 1.05-3.86) and 14 had a diagnosis of BV (RR: 1.72, 95%CI: 0.97-3.04). A short cervical length between 20 and 25 weeks of pregnancy was associated with PTB, whereas UTI and BV determined at this age were not associated with short cervical length or with PTB, although UTI, even if asymptomatic, was related to spontaneous PTB.

Association between tobacco and/or alcohol consumption during pregnancy and infant development: BRISA Cohort.

Fetuses exposed to alcohol and/or tobacco are at risk for perinatal adversities. However, little is currently known about the association of the separate or concomitant use of alcohol and tobacco with infant motor and cognitive development. Thus, the objective of the present study was to investigate the association between maternal consumption of alcohol and/or tobacco during pregnancy and the motor and cognitive development of children starting from the second year of life. The study included 1006 children of a cohort started during the prenatal period (22-25 weeks of pregnancy), evaluated at birth and reevaluated during the second year of life in 2011/2013. The children were divided into four groups according to the alcohol and/or tobacco consumption reported by their mothers at childbirth: no consumption (NC), separate alcohol consumption (AC), separate tobacco consumption (TC), and concomitant use of both (ACTC). The Bayley Scale of Infant and Toddler Development Third Edition screening tool was used for the assessment of motor and cognitive development. Adjusted Poisson regression models were used to determine the association between groups and delayed development. The results indicated that only the ACTC group showed a higher risk of motor delay, specifically regarding fine motor skills, compared to the NC group (RR=2.81; 95%CI: 1.65; 4.77). Separate alcohol or tobacco consumption was not associated with delayed gross motor or cognitive development. However, the concomitant use of the two substances increased the risk of delayed acquisition of fine motor skills.

Relative validity of a food frequency questionnaire for adolescents from a capital in the Northeastern region of Brazil.

The present study was conducted to evaluate the validity of the Food Frequency Questionnaire (FFQ) used in the RPS Birth Cohort Consortium (Ribeirão Preto, Pelotas, and São Luís) to assess dietary intake of adolescents from São Luís, Maranhão. The research was developed with 152 adolescents aged 18 and 19 years. For the validation of the FFQ, the average of three 24-hour recalls (24HRs) was used as the reference method. The mean and standard deviation of energy and nutrient intake extracted from the surveys were estimated. The paired Student's t-test was used to verify the differences between the instruments. Pearson correlation coefficient, intraclass correlation coefficient (ICC), weighted Kappa, and the Bland-Altman plot were calculated in order to measure the agreement. The study adopted a level of significance <5%. Compared with the three 24HRs, the FFQ overestimated the consumption of most nutrients. Energy-adjusted and de-attenuated concordance Pearson correlation coefficients ranged from 0.06 to 0.43, and correlations were significant for iron, calcium, riboflavin, sodium, saturated fat, niacin, and vitamin C. The energy-adjusted and de-attenuated ICCs ranged from 0.01 to 0.31, and the weighted Kappa ranged from 0.01 to 0.46. The analyses of agreement were significant for vitamin C, fiber, calcium, riboflavin, niacin, sodium, lipids, and iron. In conclusion, the FFQ presented acceptable relative validity for lipids, saturated fatty acids, fiber, calcium, iron, riboflavin, niacin, vitamin C, and sodium. This instrument will be useful in studies about food consumption of adolescents in São Luís, Maranhão.

Socio-environmental determinants of the delay in the first dental visit: results of two population-based cohort studies in Brazil.

The objective of this study was to describe the timing of the first dental visit and investigate the association of socioeconomic and behavioral factors with dental visit delay among 10/11-year-old children from two live-birth population cohorts with extremely contrasting socioeconomic profiles. Follow-up data (2004-2005) from cohorts of Ribeirão Preto (RP) (n=790) and São Luís (SL) (n=673) were evaluated. Delay in dental visit was defined as not visiting a dentist before the age of 7. Covariates included family socioeconomic characteristics, mother-related health behavior, and child-related characteristics. Prevalence ratios with robust standard errors were estimated. In both cohorts, less than 5% of children had visited a dentist before the age of two and about 35% of them had not visited a dentist before the age of seven. Lower mother's schooling and lack of private health insurance were associated with the delay in first dental visit for both cohorts. A small number of mother's prenatal care visits and being from a single-father family or a family without parents were only associated in the RP cohort, while having ≥4 siblings and lifetime dental pain were associated in the SL cohort. The association with dental pain probably reveals a preventive care-seeking behavior. Therefore, the percentage of delayed first dental visit of children was very high even among those with the most educated mothers. Further studies are necessary to analyze recent changes and underlying factors related to access to first dental visit after the implementation of the National Oral Health Policy in 2006.

Psychological distress and mother-child relationship: influence of life context on a population sample (BRISA) through the use of directed acyclic graphs (DAG).

This study aimed to investigate the association between maternal psychological distress and impairment in mother-child relationship in a sample from a Northeast capital city in Brazil with a low Human Development Index, using directed acyclic graphs (DAG). A total of 3,215 women were evaluated for the presence of psychological distress through the Self Reporting Questionnaire instrument and for the mother-child relationship by the first factor of Postpartum Bonding Questionnaire, considered the most appropriate in the literature. Demographic and socioeconomic variables were used to construct a theoretical model and, after this, multivariate logistic regression was performed using variables suggested by Directed Acyclic Graphs (DAG). Psychological distress was present in 22.7% of the women and 12.6% of them presented impaired mother-child relationships. After adjustment, the variable 'maternal mental distress' remained associated with impaired mother-child relationship (RR=3.03), and among the explanatory variables only 'primary school level' (RR=1.48) was associated as a risk factor to this outcome. The results indicated that, in this population, women with psychological distress and lower schooling are more likely to present impaired mother-child relationships.

Uterine vascular resistance and other maternal factors associated with the risk of developing hypertension during pregnancy.

Gestational hypertension and pre-eclampsia are important causes of perinatal morbidity. The objective of the present study was to determine the increase in relative risk for developing hypertensive disorders of pregnancy based on the evaluation of pregnant women between 20 and 25 weeks of gestation, and to correlate the findings at this period with the outcome of pregnancy. We conducted a prospective cohort study, with a convenience sample of 1417 patients evaluated at this gestational age, of which 1306 were contacted at childbirth. We detected an increased relative risk of 2.69 (95%CI: 1.86 to 3.89) associated with pulsatility index of the uterine arteries, a 2.8 increase (95%CI: 1.58 to 5.03) in relative risk attributed to maternal age above 35 years, a 1.68 increase (95%CI: 1.17 to 2.40) attributed to parity greater than or equal to 3, and a 5.35 increase (95%CI: 4.18 to 6.85) attributed to chronic hypertension and obesity, with a progressive increase in relative risk according to the degree of overweight, i.e., grades 1, 2, 3, and morbid obesity (2.58, 3.06, 5.84, and 7.28, respectively).

Role of RIN1 on telomerase activity driven by EGF-Ras mediated signaling in breast cancer.

Epidermal growth factor (EGF)-receptor regulates several downstream signaling pathways upon EGF stimulation that involves cell proliferation, migration and invasion. Internalized EGF-receptor is either recycled or degraded, which fate is regulated in part by Ras interference 1 (RIN1). In this study, we tested the hypothesis that RIN1, a Ras effector protein and Rab5 guanine nucleotide exchange factor, controls several signaling molecules leading to the modulation of the telomerase activity; thus, allowing proper cell proliferation. We report that expression of RIN1 completely blocked proliferation of MCF-12 A and MCF-7 cells, while partially inhibited proliferation of MDA-MB-231 cells upon EGF stimulation. Furthermore, expression of the C-terminal region of RIN1 selectively plays a critical role in the inhibition of the proliferation of MDA-MB-231 cells. However, this inhibitory effect was specifically affected by the independent expression of RIN1:Vsp9 and RIN1:RA domains. Additionally, endogenous level of expression of RIN1 was decreased in metastatic MDA-MB-231 cells as compared with non-tumorigenic MCF-12 A cells. We observed that expression of RIN1:R94A mutant blocked the proliferation of MDA-MB-231 cells, while expression of RIN1:Y561F and RIN1:R629A mutants completely reversed the inhibitory effect of RIN1:WT. Consistent with our observations, we found that expression of RIN1:WT in MDA-MB-231 cells diminished both protein kinase B (AKT) and extracellular-signal-regulated kinase 1/2 (ERK1/2) activities while p38 mitogen-activated protein kinases (p38 MAPK) and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) were unaffected, but it produced downregulation of cellular-myelocytomatosis (c-Myc), erythroblast transformation specific (Ets2) and signal transducer and activator of transcription 3 (Stat3) activities. Inversely, expression of high-mobility group box 1 (HMBG1) was inhibited whereas expression of forkhead box transcription factor 1 (FOXO1) was increased in cells expressing RIN1. Interestingly, expression of RIN1 blocked telomerase activity and human telomerase reverse transcriptase (hTERT) expression, which correlated with the downregulations of c-Myc, Ets-2 and Stat3 activation. Taken together these findings indicate that RIN1 is a critical player in the modulation of the telomerase activity as well as hTERT expression in MDA-MB-231 cells upon EGF stimulation.