Juliana Rombaldi Bernardi

Early life stress interacts with the diet deficiency of omega-3 fatty acids during the life course increasing the metabolic vulnerability in adult rats.

Early stress can cause metabolic disorders in adulthood. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) deficiency has also been linked to the development of metabolic disorders. The aim of this study was to assess whether an early stressful event such as maternal separation interacts with the nutritional availability of n-3 PUFAs during the life course on metabolic aspects. Litters were randomized into: maternal separated (MS) and non-handled (NH). The MS group was removed from their dam for 3 hours per day and put in an incubator at 32°C on days 1° to 10° postnatal (PND). On PND 35, males were subdivided into diets that were adequate or deficient in n-3 PUFAs, and this intervention was applied during the subsequent 15 weeks. Animals body weight and food consumption were measured weekly, and at the end of the treatment tissues were collected. MS was associated with increased food intake (p = 0.047) and weight gain (p = 0.012), but no differences were found in the NPY hypothalamic content between the groups. MS rats had also increased deposition of abdominal fat (p<0.001) and plasma triglycerides (p = 0.018) when compared to the NH group. Interactions between early life stress and n-3 PUFAs deficiency were found in plasma insulin (p = 0.033), HOMA index (p = 0.049), leptin (p = 0.010) and liver PEPCK expression (p = 0.050), in which the metabolic vulnerability in the MS group was aggravated by the n-3 PUFAs deficient diet exposure. This was associated with specific alterations in the peripheral fatty acid profile. Variations in the neonatal environment interact with nutritional aspects during the life course, such as n-3 PUFAs diet content, and persistently alter the metabolic vulnerability in adulthood.

Correlation between n-3 polyunsaturated fatty acids consumption and BDNF peripheral levels in adolescents

BackgroundAlthough several studies have reported an association between mental disorders and serum levels of brain-derived neurotrophic factor (BDNF), this association is still poorly understood. The study of factors associated with both BDNF levels and mental disorders, such as n-3 polyunsaturated fatty acids (n-3 PUFAs), may help to elucidate the mechanisms mediating the relationship between the two variables. Therefore, the present study aimed to evaluate whether the intake n-3 PUFAs correlates with serum levels of BDNF.FindingsThis study involved 137 adolescents drawn from a community sample, including a group with high levels of anxiety, assessed using the Screen for Children and Anxiety Related Emotional Disorders. Blood samples were collected and serum BDNF levels were measured. n-3 PUFAs were estimated using a food frequency questionnaire for adolescents. Correlations were performed to assess the association between n-3 PUFAs intake and BDNF levels. Effects of potential confounders (total fat consumption, age, gender and anxiety) were examined using linear regression models. There was a direct correlation between n-3 PUFAs consumption and serum BDNF levels, which remained significant even after accounting for potential confounders.ConclusionsWe were able to detect a correlation between n-3 PUFAs intake and peripheral BDNF levels. Our study was limited by its small sample size, and our external validity may be restricted by the oversampling of anxious adolescents. Our findings may help determine the nature of the association between mental disorders and serum levels of BDNF. However, more studies are needed to elucidate the possible mechanisms by which n-3 PUFAs intake affects BDNF levels, and how this may lead to an increased vulnerability to psychiatric disorders.

Impact of Perinatal Different Intrauterine Environments on Child Growth and Development in the First Six Months of Life--IVAPSA Birth Cohort: rationale, design, and methods.

BackgroundIn the last twenty years, retrospective studies have shown that perinatal events may impact the individual health in the medium and long term. However, only a few prospective studies were designed to address this phenomenon. This study aims to describe the design and methods of the Impact of Perinatal Environmental Variations in the First Six Months of Life - the IVAPSA Birth Cohort.Method/DesignThis is a clinical study and involves the recruitment of a birth cohort from hospitals in Porto Alegre, Rio Grande do Sul, Brazil. Mothers from different clinical backgrounds (hypertensive, diabetics, smokers, having an intrauterine growth restricted child for idiopathic reasons, and controls) will be invited to join the study twenty-four hours after the birth of their child. Data on economic, social, and maternal health care, feeding practices, anthropometric measures, physical activity, and neuropsychological evaluation will be obtained in interviews at postpartum, 7 and 15 days, 1, 3 and 6 months of life.DiscussionTo our knowledge, this is the first thematic cohort focused on the effects of intrauterine growth restriction to prospectively enroll mothers from different clinical backgrounds. The IVAPSA Birth Cohort is a promising research platform that can contribute to the knowledge on the relationship between perinatal events and their consequences on the childrens early life.

Vulnerability to dietary n-3 polyunsaturated fatty acid deficiency after exposure to early stress in rats

The exposure to adverse events early in life may affect brain development. Omega-3 polyunsaturated fatty acid (n-3 PUFA) deficiency has been linked to the development of mood and anxiety disorders. The aim of this study was to examine the interaction between variations in the early environment (handling or maternal separation) and the chronic exposure to a nutritional n-3 PUFA deficiency on locomotor activity, sucrose preference, forced swimming test and on serum and hippocampal brain-derived neurotrophic factor (BDNF) levels. Rats were randomized into Non-handled (NH), Neonatal Handled (H) and Maternal Separated (MS) groups. Pups were removed from their dams (incubator at 32°C on postnatal days (PND) 1-10) during 10 min/day (H) or 3h/day (MS). On PND 35, males were subdivided into diets adequate or deficient in n-3 PUFA for 15 weeks. H and MS gained weight differently, and animals receiving the n-3 PUFA deficient diet gained less weight. MS displayed a higher food consumption and higher consumption of sucrose solution during the second hour of exposure to the sucrose preference test. No differences were observed in the swimming test. H group had increased locomotion and showed a higher response to amfepramone. No significant effect was observed on serum BDNF levels. BDNF protein levels were decreased in animals receiving the n-3 PUFA deficient diet. We observed that early life environment and a mild n-3 PUFA deficiency are able to affect several behavioral aspects (food and sucrose consumption and locomotor response), and lead to a differential hippocampal BDNF metabolism in adult life.

Poor infant inhibitory control predicts food fussiness in childhood - A possible protective role of n-3 PUFAs for vulnerable children

Intrauterine growth restriction (IUGR) children are more impulsive towards a sweet reward and have altered feeding behavior in adulthood. We hypothesized that early life inhibitory control predicts feeding behaviors later on in childhood, and the consumption of n-3 PUFAs during infancy may protect IUGR children from developing problematic feeding behaviors. 156 children had information on the Early Childhood Behavior Questionnaire (ECBQ) at 18 months, Food Frequency Questionnaire at 48 months and Children׳s Eating Behavior Questionnaire (CEBQ) at 72 months. There was a significant negative correlation between inhibitory control at 18 months and food fussiness at 72 months. A GLM model predicting food fussiness at 72 months showed significant interaction between n-3 PUFAs, inhibitory control and IUGR, with higher intakes associated with decreased risk for fussiness in IUGR children with poor inhibitory control. Deficits in early inhibitory control predict later food fussiness, and higher intakes of n-3 PUFAs in infancy may protect IUGR children from developing such behavior later.

Neonatal interventions differently affect maternal care quality and have sexually dimorphic developmental effects on corticosterone secretion.

Neonatal handling (H) and maternal separation (MS) both induce changes in maternal care, but the contribution of these changes to the behavioral and neurochemical outcomes of the offspring remains unclear, as studies often find opposite results concerning the frequency of maternal behaviors, particularly in the MS paradigm. In this study, behavior displayed by H, MS and non‐handled (NH) Wistar rat dams were observed during the first 10 days after birth. A tentative assessment of the quality of maternal care was made, using a previously reported score that reflects behavior fragmentation and inconsistency. Central oxytocin levels and hippocampal synaptic plasticity markers were also evaluated in dams, immediately after litter weaning. In adulthood, male and female offspring were subjected to a contextual stress‐induced corticosterone challenge to provide further information on the impact of early interventions on neuroendocrine parameters. We found that while both H and MS interventions induced an increase in the amount of pup‐directed behavior, MS dams displayed a more fragmented and inconsistent pattern of care, reflecting poorer maternal care quality. Interestingly, an increase in oxytocin levels was observed only in H dams. While H offspring did not differ from NH, MS males and females showed marked differences in corticosterone secretion compared to controls. Our results suggest that briefly removing the pups from the nest alters maternal care quantity but not quality and increases central oxytocin, while long separations appear to increase low quality maternal care and change neuroendocrine responses in adult offspring in a sex‐specific manner.

Mitochondrial and Oxidative Stress Aspects in Hippocampus of Rats Submitted to Dietary n-3 Polyunsaturated Fatty Acid Deficiency After Exposure to Early Stress.

Chronic dietary long-chain polyunsaturated fatty acids (PUFAs) deficiency may lead to changes in cortex and hippocampus neuronal membrane phospholipids, and may be linked to impaired central nervous system function. Particularly docosahexaenoic acid deficiency appears to be involved in neuropsychiatric disorders. On the other hand, adverse events early in life may also profoundly affect brain development, leading to long-lasting effects on neurophysiology, neurobiology and behavior. This research assessed if neonatal stress and a dietary n-3 PUFAs deficiency could interact to produce hippocampal alterations related to mitochondrial functions in adult rats. There were no effects of diet, neonatal intervention or interactions on superoxide dismutase or catalase enzymatic activities, mitochondrial membrane potential and respiratory chain complexes. Rats fed n-3 PUFAs deficient diet displayed higher levels of glutathione peroxidase and catalase activity, higher free radicals production and higher thiol content compared to rats fed n-3 PUFAs adequate diet. There were interactions among diets and neonatal stress, since glutathione peroxidase, free radicals production and thiol content were increased in groups that were subjected to neonatal interventions fed n-3 PUFAs deficient diet. Additionally, reduced mitochondrial potential was observed in handled animals. Total thiol revealed a neonatal stress effect, since animals subjected to neonatal interventions displayed lower thiol content. In conclusion, we observed that a chronic treatment with deficient n-3 PUFAs diet, from the puberty period on, increased free radicals production and imbalanced antioxidant enzymes activities, and these increases were higher in animals subjected to neonatal interventions.

Maternal hypertension and infant growth

The Jornal de Pediatria published, in its 91st volume, a very interesting article entitled: ‘‘Growth of preterm low birth weight infants until 24 months corrected age: effect of maternal hypertension.’’ The authors tackled a very important issue in the context of infant and maternal health worldwide, mainly considering the impact of the gestational period on the offspring’s health and disease pattern during the life course. However, we would like to highlight some points in order to contribute to this subject. According to the Task Force on Hypertension in Pregnancy, the hypertensive disorders in pregnancy are classified into: preeclampsia/eclampsia; chronic hypertension; preeclampsia superimposed on chronic hypertension; and gestational hypertension. In our unpublished systematic review, we analyzed 45 papers (from 2008 to 2015) on the association between hypertensive disorders in pregnancy and offspring’s mediumand long-term health outcomes. We found that the high heterogeneity of results among the studies was mainly caused by different classifications of maternal hypertension, and by the quality of adjustments performed by the authors. Thus, in this article, some methodological questions were raised. Firstly, the authors defined two study groups according to the exposure or not to gestational hypertension syndrome; however, in their study description, it is not clear if women with chronic hypertension were also included in the hypertensive group. It is important to highlight that each hypertensive disorder has a different and complex clinical presentation, with diverse consequences in the offspring. Therefore, it is important that studies address the hypertensive disorders independently (i.e., chronic hypertension vs. gestational hypertension vs. preeclampsia) in their analysis.

Caffeine Intake During Pregnancy in Different Intrauterine Environments and its Association with Infant Anthropometric Measurements at 3 and 6 Months of Age

Objective To investigate the association between maternal caffeine intake during pregnancy and infant anthropometric measurements at age 3 and 6 months. Methods Longitudinal observational study of mother–child pairs stratified into five groups: diabetic women (DM), hypertensive women (HYP), smoking mothers (SMO), mothers of infants small for gestational age (SGA), and controls (CTL). Pairs were recruited from three public hospitals in Porto Alegre, Brazil, from 2011 to 2015, using a convenience sampling strategy. The Food Frequency Questionnaire (FFQ) was administered on postpartum day 7 to evaluate maternal caffeine intake during pregnancy. The anthropometric measurements of interest (weight, length, and skinfold thickness) were assessed at birth and at age 3 and 6 months. Linear regression was used to analyze the interaction between caffeine intake and skinfold thickness. Results Overall, 272 mother–child pairs were investigated (41 DM, 26 HYP, 68 SMO, 25 SGA, and 112 CTL). There were no differences in anthropometric measurements between infants born to mothers who had and had not consumed caffeine during pregnancy (P > 0.05). Children of mothers in the DM group had the highest adjusted average skinfold thicknesses at 3 months. An interaction between maternal caffeine intake during pregnancy and the sum of skinfolds at age 3 months was found in the DM and CTL groups (P < 0.05). However, significant differences were not observed at 6 months. Conclusions Maternal caffeine intake influenced infants skinfold thickness measurements at 3 months of age. This parameter was reduced in infants born to mothers with DM and increased in those born to healthy control mothers.

EP03.02: Measurement of visceral adipose tissue during pregnancy are correlated with birthweight: preliminary results: Electronic Poster Abstracts

evaluated for consistency of measurement and summarised with an intraclass correlation index. Results: In this analysis there was a high level of agreement with an intraclass correlation index of 0.94. No significant differences were seen between the raters with a Pearson Correlation coefficient ranging from 0.7 to 0.92. Conclusions: Our study shows that the measurement of the uterocervical angle is a reproducible and an easily measured variable. We plan to use this as a pilot study to assess uterocervical angle for the prediction and identification of preterm delivery.