Associations between obesity-related gene expression in maternal and cord blood and newborn adiposity: findings from the Araraquara Cohort study.

BACKGROUND/OBJECTIVES: Genes involved in the regulation of metabolism, adipose tissue deposition, inflammation, and the appetite-satiety axis may play an important role in fetal development, and possibly induce permanent metabolic changes and fat accumulation. In this study we investigated: (1) obesity-related gene expression in maternal and cord blood of overweight/obese and normal-weight pregnant women; (2) associations between obesity-related gene expression in maternal and cord blood; and (3) associations of gene expression in each of maternal and cord blood with newborn adiposity. SUBJECTS/METHODS: Twenty-five overweight/obese and 32 normal-weight pregnant women were selected from the Araraquara Cohort Study according to their pre-pregnancy BMI. Maternal and cord blood gene expression of LEPR, STAT3, PPARG, TLR4, IL-6, IL-10, FTO, MC4R, TNF-α, and NFκB were investigated by relative real-time PCR quantification. The body composition of the newborns was assessed by air displacement plethysmography. Associations between maternal and cord blood gene expression and markers of newborn adiposity (weight, BMI, and fat mass%) were explored by linear regression models controlling for maternal age, pre-pregnancy BMI, maternal gestational weight gain, gestational age, and newborn sex. RESULTS: There was higher TLR4, NFκB, and TNF-a expression, and lower IL-6 expression, in overweight/obese pregnant women and their respective newborns compared with normal-weight women and their newborns (p < 0.001). Maternal PPARG gene expression was associated with both weight and fat mass % of the newborns, and cord blood IL-10 expression was associated with BMI and fat mass %, controlling for confounders. CONCLUSION: To our knowledge, this is the first study to evaluate the relationship of maternal and cord blood gene expression with adiposity markers of the newborn. Our results provide evidence for the contribution of maternal and cord blood gene expression-particularly maternal PPARG and TLR4 expression, and cord blood IL-10 expression-to newborn weight, BMI, and fat mass %.

Mental disorders in pregnancy and 5-8 years after delivery.

BACKGROUND: Even though mental disorders represent a major public health problem for women and respective children, there remains a lack of epidemiological longitudinal studies to assess the psychological status of women throughout pregnancy and later in life. This epidemiological cohort study assessed the relationship between mental disorders of 409 Brazilian women in pregnancy and 5-8 years after delivery. METHODS: The women were followed from 1997 to 2000 at 17 health services, and subsequently from 2004 to 2006 at their homes. Mental disorders were investigated by the Perceived Stress Scale-PSS, General Health Questionnaire-GHQ and State-Trait Anxiety Inventories-STAI. The relationship between scores of the PSS, GHQ and STAI 5-8 years after delivery and in pregnancy was assessed by multivariate linear regression analysis, controlling for the following confounders: maternal age, education, per capita income, family size, work, marital status and body mass index. RESULTS: Scores of the PSS, GHQ and STAI 5-8 years after delivery were positively associated with scores of the PSS, GHQ and STAI in the three trimesters of pregnancy, and inversely associated with maternal age and per capita income (adj. R2 varied from 0.15 to 0.37). PSS, GHQ and STAI scores in the 3rd trimester of pregnancy were positively associated with scores of the PSS, GHQ and STAI in the 1st and 2nd trimesters of pregnancy (adj. R2 varied from 0.31 to 0.65). CONCLUSIONS: The results of this study reinforce the urgency to integrate mental health screening into routine primary care for pregnant and postpartum women.

Association of oxidative stress biomarkers with adiposity and clinical staging in women with breast cancer.

BACKGROUND/OBJECTIVES: Breast cancer is a disease characterised by both oxidative reactions and inflammation. However, few studies have focused on the oxidative and inflammatory biomarkers. The aim of the present study was to evaluate the association between oxidative stress markers and adiposity and clinical staging, as well as the association between the oxidative and the antioxidant biomarkers of women with breast cancer. SUBJECTS/METHODS: A total of 135 cases of breast cancer occurring in 2011 and 2012 were assessed. After exclusions, 101 pre- and post-menopausal women with clinical staging I to IV were eligible to participate in the study. The anthropometric evaluation was performed by collecting data on waist circumference, body mass index and body composition. The socioeconomic and clinical profiles were determined using a standard questionnaire. For the oxidative biomarkers, thiobarbituric acid reactive substances (TBARS), oxidative DNA damage (8-hydroxy-2-deoxyguanosine (8-OHdG)), low-density lipoprotein(-) (LDL(-)), autoantibody anti-LDL(-) and liposoluble antioxidants (α-tocopherol, retinol and ß-carotene) were analysed. The data were analysed using differences in the mean values, correlation tests and multiple linear regression. RESULTS: The antioxidant levels were higher in postmenopausal women with clinical staging I and II and negative lymph nodes. The TBARS level was associated with clinical staging. Adiposity was associated with levels of retinol and 8-OHdG, whereas LDL(-), 8-OHdG and TBARS were correlated with liposoluble antioxidants after adjusting for the confounders. CONCLUSIONS: The adiposity and clinical staging of patients were associated with oxidative stress. The oxidative and antioxidant biomarkers showed a negative correlation in patients with breast cancer.

Birth weight, rapid weight gain in infancy and markers of overweight and obesity in childhood.

OBJECTIVE: To evaluate the relationship between birth weight and rapid weight gain in infancy and markers of overweight/obesity in childhood, using different cutoff values for rapid weight gain. SUBJECTS/METHODS: Cross-sectional study involving 98 5-year old pre-school Brazilian children. Rapid weight gain was considered as weight gain in standard deviation score (SDS) above +0.67, +1 and +2 in relation to birth weight, at any time during the first 2 years of life. The nutritional status of the children was determined by anthropometry and electrical bioimpedance. Multiple linear regression analysis was used, considering fat mass percentage, body mass index (BMI), waist and neck circumferences as outcomes. RESULTS: Birth weight, rapid weight gain (assessed by different cutoff values) and maternal obesity were positively associated with increased fat mass percentage, BMI, waist and neck circumferences. Different cutoff values of rapid weight gain did not change the positive associations between rapid weight gain and fat mass percentage (>+0.67 SDS, P=0.007; >+1 SDS, P=0.007; >+2 SDS, P=0.01), BMI (>+0.67 SDS, P=0.002; >+1 SDS, P=0.007; >+2 SDS, P<0.001), waist circumference (>+0.67 SDS, P=0.002; >+1 SDS, P=0.002; >+2 SDS, P<0.001) and neck circumference (>+0.67 SDS, P=0.01; >+1 SDS, P=0.03; >+2 SDS, P<0.001). CONCLUSIONS: The use of different cutoff values for the definition of rapid weight gain did not interfere in the associations between birth weight and rapid weight gain with fat mass percentage, BMI, waist and neck circumferences. Children with the highest birth weight, those who undergo rapid weight gain in infancy and whose mothers were obese, seemed to be more at risk for overweight/obesity.

High sensitivity C-reactive protein concentrations, birthweight and cardiovascular risk markers in Brazilian children.

BACKGROUND/OBJECTIVES: High sensitivity C-reactive protein (hs-CRP) and low birthweight have emerged as predictors of cardiovascular diseases (CVDs). In studies involving adults, higher concentrations of hs-CRP have been associated with low birthweight. This study assessed the relationship between hs-CRP and birthweight, and other risk markers for CVDs in childhood. SUBJECTS/METHODS: A total of 459 Brazilian children aged 5-8 years were included in the study. hs-CRP was measured by particle-enhanced immunonephelometry. The nutritional status of the children was assessed by BMI and waist circumference. Total cholesterol and fractions, triglycerides and glucose were measured by enzymatic methods. Insulin sensitivity was determined by the homeostasis model assessment (HOMA) method. Blood pressure was measured by the HDI/Pulse Wave CR-2000 equipment (Hypertension Diagnostics, Eagan, MN, USA). A multivariate linear regression analysis investigated the association between hs-CRP and birthweight, and risk markers for CVDs. RESULTS: There were positive associations between hs-CRP and gender (P=0.001), waist circumference (P<0.001) and systolic blood pressure (SBP) (P=0.03), and negative associations between hs-CRP and age (P<0.001), and high-density lipoprotein cholesterol (HDL-c) (P=0.005) (R²=0.14). Abnormal values of hs-CRP, waist circumference, HDL-c and SBP, respectively, were observed in 27.7, 26.4, 14.4 and 34.7% of the children. CONCLUSIONS: Opposite to studies involving adults, there was no association between hs-CRP and birthweight, implying that time may strengthen the relationship, considering that hs-CRP-concentration-associated metabolic changes increase from childhood to adulthood. The associations between hs-CRP and waist circumference, HDL-c and SBP in very young ages is a matter of concern, especially in females, in view of the large number of children with abnormal values of these measurements.

Maternal stress and distress and child nutritional status.

BACKGROUND/OBJECTIVE: To assess the relationship between maternal stress and distress in pregnancy and 5-8 years postpartum and child nutritional status. SUBJECTS/METHODS: Longitudinal cohort study carried out in Jundiai city, Southeast Brazil, involving 409 women followed throughout pregnancy to 5-8 years postpartum, and respective children. Measures of stress and distress were obtained three times in pregnancy (at gestational ages lower than 16 weeks, from 20 to 26 weeks and from 30 to 36 weeks) and 5-8 years postpartum by the Perceived Stress Scale (PSS), General Health Questionnaire (GHQ) and the State-Trait Anxiety Inventories (STAI). The nutritional status of the children was assessed by the World Health Organization body mass index (BMI) z-score for age. The relationship between child BMI z-score for age and scores of the PSS, GHQ and STAI was evaluated by multivariate linear regression, controlling for confounding variables. RESULTS: BMI z-score for age of the children was negatively associated with maternal scores of the PSS 5-8 years postpartum and scores of the GHQ in the second trimester of pregnancy. BMI of the children was positively associated with maternal BMI and birthweight (R(2)=0.13). There was -0.04 (confidence interval -0.07 to -0.9 × 10(-2)) decrease in child BMI per score unit of the PSS increase, and -0.09 (confidence interval -0.18 to -0.6 × 10(-3)) decrease in child BMI per score unit of the GHQ increase. CONCLUSIONS: This study detected a relationship between maternal mental and nutritional status and child nutritional status, implying that if the mother is not physically or mentally well, her capacity for caring for her child may be impaired.

Vitamin-mineral supplement use by low-income Brazilian pregnant adolescents and non-adolescents and the predictors for non-use.

OBJECTIVES: To determine (1) the intake of vitamin-mineral supplements by 855 low-income Brazilian pregnant adolescents and non-adolescents in three interviews (gestational ages < or =16, 20-26 and 30-36 weeks), (2) the relationship between vitamin-mineral supplementation and toxic exposure, and nutritional, psychological, socio-economic, demographic and obstetric characteristics of the women. DESIGN: Longitudinal cohort study. SETTING: Jundiaí city, São Paulo, Brazil. SUBJECTS: A total of 855 pregnant adolescents and non-adolescents who attended antenatal care from September 1997 to August 2000. METHODS: A general questionnaire was utilized three times in pregnancy (gestational ages < or =16, 20-26 and 30-36 weeks) to investigate the vitamin-mineral supplements ingested by the women, their smoking habit and alcohol intake, anthropometric measurements (pre-pregnancy and actual weight, height, mid-upper arm circumference) and psychological (anxiety, stress and distress), socio-economic (per capita income), demographic (education, age, marital status) and obstetric (gravidity) characteristics. The associations between vitamin-mineral supplementation and maternal characteristics were assessed in 12 multiple logistic regression models, stratifying the women by age and per capita income. RESULTS: Iron and vitamin C were the most ingested supplements by adolescents and non-adolescents, in the three interviews. Logistic regression analysis revealed that the maternal predictors for non-use of vitamin-mineral supplementation were acute anxiety and alcohol intake for adolescents, and low education, single without partner, distress (anxiety, depression, etc.) and stress for non-adolescents. CONCLUSIONS: These are important data to identify groups of low-income pregnant women in need of supplementation guidance and nutrition education. Stress/distress was a predictor for non-use of vitamin-mineral supplements for both adolescents and non-adolescents pregnant women.

Haemoglobin variants and anaemia among pre-school/school children in north-east Brazil.

In this study we investigated the presence of haemoglobin (Hb) variants and anaemia among 382 pre-school/school children from Bahia State, Brazil, a state where intermixing involving people from African origin is the highest in the country. Hb variants were investigated by cellulose acetate electrophoresis at alkaline pH. The pattern obtained was confirmed by citrate agar electrophoresis at pH 6.2. From the 382 children investigated, 79 (20.7%) had Hb variants: 47 (59.5%) had HbAS, 28 (35.4%) HbAC, 3 (3.8%) HbSC and 1 (1.3%) HbCC. Two hundred and fourteen children had anaemia. From these, 39 had microcytosis and 14 had low values of ferritin (<12 ng/ml). We cannot exclude thalassaemia among the children with microcytosis and hypochromia because it was not investigated. The majority of the children showed high mean values of ferritin, suggestive of subclinical infection. There was no difference when we compared the prevalence of anaemia among children with Hb variants (65.8%) and those without Hb variants (53.5%) (P = 0.06). These data demonstrate that Hb variants and anaemia are probably important public health problems in north-east Brazil.

The relationship between salivary cortisol concentrations and anxiety in adolescent and non-adolescent pregnant women

The main purpose of the present study was to determine the relationship between salivary cortisol concentrations and self-report anxiety in 50 adolescent and 178 non-adolescent women during the last month of pregnancy. The subjects were randomly selected from a previous study involving women who attended antenatal care from September 1997 to August 2000 at 17 health services in Southeast Brazil. Salivary cortisol was measured with an enzyme immunoassay kit, and anxiety was assessed by the State-Trait Anxiety Inventories (STAI) of Spielberger. After saliva collection, the participants completed the STAI. Mean concentrations of cortisol for both pregnant adolescents (14.17 ± 6.78 nmol/l) and non-adolescents (13.81 ± 8.51 nmol/l) were similar (P = 0.89). Forty-three percent of the pregnant adolescents and 30.5 percent of the non-adolescents felt anxious at the time of being questioned (State Anxiety Inventory (SAI) scores >40; P = 0.06). Cortisol concentrations in adolescents were negatively related to the SAI scores (r = -0.39; P = 0.01) which assess a temporary condition of anxiety. There was a statistically significant difference in mean cortisol concentrations between adolescents with low (<=40) and high (>40) SAI scores (P = 0.03, t-test), but no differences for non-adolescents. The negative relationship between salivary cortisol concentrations and anxiety scores in adolescents may be due to puberty-related hormone differences during this period of life. Pregnant adolescents may possess unique biological or psychological characteristics compared to adults and non-pregnant adolescents. Thus, we need to know more about the hypothalamic-pituitary-adrenocortical axis of pregnant adolescents.

The relationship between salivary cortisol concentrations and anxiety in adolescent and non-adolescent pregnant women.

The main purpose of the present study was to determine the relationship between salivary cortisol concentrations and self-report anxiety in 50 adolescent and 178 non-adolescent women during the last month of pregnancy. The subjects were randomly selected from a previous study involving women who attended antenatal care from September 1997 to August 2000 at 17 health services in Southeast Brazil. Salivary cortisol was measured with an enzyme immunoassay kit, and anxiety was assessed by the State-Trait Anxiety Inventories (STAI) of Spielberger. After saliva collection, the participants completed the STAI. Mean concentrations of cortisol for both pregnant adolescents (14.17 +/- 6.78 nmol/l) and non-adolescents (13.81 +/- 8.51 nmol/l) were similar (P = 0.89). Forty-three percent of the pregnant adolescents and 30.5% of the non-adolescents felt anxious at the time of being questioned (State Anxiety Inventory (SAI) scores >40; P = 0.06). Cortisol concentrations in adolescents were negatively related to the SAI scores (r = -0.39; P = 0.01) which assess a temporary condition of anxiety. There was a statistically significant difference in mean cortisol concentrations between adolescents with low (<=40) and high (>40) SAI scores (P = 0.03, t-test), but no differences for non-adolescents. The negative relationship between salivary cortisol concentrations and anxiety scores in adolescents may be due to puberty-related hormone differences during this period of life. Pregnant adolescents may possess unique biological or psychological characteristics compared to adults and non-pregnant adolescents. Thus, we need to know more about the hypothalamic-pituitary-adrenocortical axis of pregnant adolescents.

Maternal psychological stress and distress as predictors of low birth weight, prematurity and intrauterine growth retardation.

OBJECTIVES: To evaluate: (1) the associations between maternal psychological stress, distress and low birth weight (LBW), prematurity and intrauterine growth retardation (IUGR); (2) the interactions between maternal stress, distress and smoking, alcohol and coffee intake; (3) the prevalences of stress and distress in pregnancy. DESIGN: Longitudinal cohort study. SETTING: Jundiaí city, São Paulo state, Brazil. SUBJECTS: A total of 865 pregnant women who attended antenatal care between September 1997 and August 2000. METHODS: Measures of stress and distress were obtained, by interview, three times in pregnancy: at a gestational age (GA) lower than 16 weeks, from 20 to 26 weeks and from 30 to 36 weeks. Stress was investigated by the perceived stress scale, PSS, and distress by both the general health questionnaire, GHQ, and the State Trait Anxiety inventories, STAI. The outcomes were: LBW (birth weight <2500 g), prematurity (gestational age (GA) at birth <37 weeks) and IUGR (birth weight for GA

Vitamin A and neonatal anthropometry.

Low levels of vitamin A have a major impact on growth, development, and immunity. The aim of this study was to determine the relationship between cord concentrations of vitamin A and neonatal anthropometry in 711 babies born at term in Brazil. Gestational age of the babies was evaluated by the Capurro method. Vitamin A was measured by high performance liquid chromatography. Concentrations of vitamin A in cord blood correlated significantly (p < 0.001) with birthweight (r = 0.24), length (r = 0.20), chest circumference (r = 0.24), mid-upper arm circumference (r = 0.23), triceps skinfold thickness (r = 0.26), and head circumference (r = 0.12) of the babies. The anthropometric measurements of the babies were sorted by the vitamin A concentrations (means and standard deviations) and divided into quartiles. Differences between the quartiles were tested by analysis of variance. Babies in the bottom length, head circumference and triceps skinfold thickness quartiles had lower mean vitamin A concentrations than those of quartiles two, three and four. Babies in the bottom birthweight, chest and mid-upper arm circumferences quartiles had lower mean vitamin A concentrations than those of quartiles three and four (p < 0.003). These data shows that smaller/shorter babies had lower concentrations of vitamin A than heavier/longer babies, probably reflecting the important role of this micronutrient on growth.

[Parameters for the assessment of iron status]. / Parâmetros para avaliação do estado nutricional de ferro.

The assessment of iron status at individual and populational levels has been the target of many studies because some issues still need to be defined. A Medline, Lilacs and Dedalus literature review was carried out for the period of 1972 to 1998 and scientific publications in both English and Portuguese relating hematological and biochemical parameters were used in the assessment of iron status. The parameters reflect the three different stages of iron storage deficiency, which occur in a gradual and progressive way leading to the development of anaemia. In general, when used alone, these parameters are neither sensitive nor specific for detecting iron deficiency anaemia. Moreover, some advantages and limitations should be taken into consideration for the choice of the appropriate parameter. To improve both sensitivity and specificity, different parameters have been used in association and their specific contribution is determined according to the characteristics of the study population, methodological issues and the costs involved in the process.

Folate and intrauterine growth retardation.

The objectives of this case-control study were to compare the levels of folate in cord and maternal blood of 315 mothers who had intrauterine growth-retarded (IUGR) babies and 321 mothers who had appropriate-for-gestational-age (AGA) babies, to evaluate the correlation between cord and maternal folate and to assess the prevalence of folate deficiency. Mothers were recruited from the four largest hospitals in Campinas city, south-east Brazil. The gestational ages of the newborns were evaluated by the Capurro method. They were classified as being IUGR according to the Lubchenco birthweight-for-gestational-age standard. Red blood cell (RBC) folate was measured by radio-immunoassay. Slightly more IUGR (25.7%) than AGA babies (19.9%) had cord folate levels < or = 226.5 nmol/l (100 ng/ml) (p = 0.05) and similar percentages of IUGR (32.1%) and AGA (29.9%) mothers had folate levels < or = 226.5 nmol/l. Mean cord folate levels in IUGR and AGA babies were 10% higher than mean folate levels in the two groups of mothers (p < 0.001). There were weak correlations between maternal and cord folate in IUGR (r = 0.31) and AGA (r = 0.35) (p < 0.001) mother/baby groups. In this population, 35% of mothers were folate-deficient although it was not associated with IUGR. Nevertheless, it would be important to give Brazilian women folate tablets during pregnancy and to investigate the effect on concentrations of homocysteine and on the prevalence of birth defects.

Maternal and neonatal anthropometry.

Anthropometric measurements were assessed in 434 Brazilian mother-baby pairs (263 appropriate-for-gestational-age [AGA] and 171 intrauterine growth-retarded [IUGR]) to compare their distribution and to evaluate associations in AGA and IUGR pairs. Mothers who delivered IUGR babies were thinner and shorter than mothers of AGA babies; the cut-off points of risk for delivering an IUGR baby were 50 kg for weight (OR = 3.8, p < 0.001) and 150 cm for height (OR = 3.6, p < 0.001). IUGR mothers also tended to gain less weight in pregnancy than AGA mothers, presenting a risk 6.1 times higher for weight gain < or = 7 kg (p < 0.001). There were weak though statistically significant correlations between AGA mother-baby pairs, and a few weak correlations between IUGR mother-baby pairs. The larger number of statistically significant correlations between anthropometric measurements in AGA mother-baby pairs than in IUGR pairs shows that in this region of the country, where maternal malnutrition has a low prevalence, probably other factors are associated with IUGR. It seems that the influence of maternal nutrition on a baby's size at birth is more important in populations with moderate-to-severe malnutrition. In Brazil, as in some other developing countries, overweight is becoming an important issue and the prevalence of malnutrition has decreased. In this study, there were few mothers (n = 17) with a body mass index (BMI) < or = 20. On the other hand, there were many (n = 209) overweight (BMI 25-30) and obese (BMI > 30) mothers. We advise further large epidemiological studies to assess the diet of pregnant women and its relationship to maternal weight, weight gain and low birthweight (particularly IUGR) in countries with a considerable prevalence of maternal undernutrition and maternal overweight/obesity.