Micronutrient Dietary Intake in Latina Pregnant Adolescents and Its Association with Level of Depression, Stress, and Social Support

Adolescent pregnant women are at greater risk for nutritional deficits, stress, and depression than their adult counterparts, and these risk factors for adverse pregnancy outcomes are likely interrelated. This study evaluated the prevalence of nutritional deficits in pregnant teenagers and assessed the associations among micronutrient dietary intake, stress, and depression. One hundred and eight pregnant Latina adolescents completed an Automated Self-Administered 24-hour dietary recall (ASA24) in the 2nd trimester. Stress was measured using the Perceived Stress Scale and the Prenatal Distress Questionnaire. Depressive symptoms were evaluated with the Reynolds Adolescent Depression Scale. Social support satisfaction was measured using the Social Support Questionnaire. More than 50% of pregnant teenagers had an inadequate intake (excluding dietary supplement) of folate, vitamin A, vitamin E, iron, zinc, calcium, magnesium, and phosphorous. Additionally, >20% of participants had an inadequate intake of thiamin, riboflavin, niacin, vitamin B6, vitamin B12, vitamin C, copper, and selenium. Prenatal supplement inclusion improved dietary intake for most micronutrients except for calcium, magnesium, and phosphorous, (>50% below the Estimated Average Requirement (EAR)) and for copper and selenium (>20% below the EAR). Higher depressive symptoms were associated with higher energy, carbohydrates, and fats, and lower magnesium intake. Higher social support satisfaction was positively associated with dietary intake of thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, vitamin C, vitamin E, iron, and zinc. The findings suggest that mood and dietary factors are associated and should be considered together for health interventions during adolescent pregnancy for the young woman and her future child

Mitochondrial Phenotypes in Purified Human Immune Cell Subtypes and Cell Mixtures

Using a high-throughput mitochondrial phenotyping platform to quantify multiple mitochondrial features among molecularly defined immune cell subtypes, we quantify the natural variation in mitochondrial DNA copy number (mtDNAcn), citrate synthase, and respiratory chain enzymatic activities in human neutrophils, monocytes, B cells, and naïve and memory T lymphocyte subtypes. In mixed peripheral blood mononuclear cells (PBMCs) from the same individuals, we show to what extent mitochondrial measures are confounded by both cell type distributions and contaminating platelets. Cell subtype-specific measures among women and men spanning four decades of life indicate potential age- and sex-related differences, including an age-related elevation in mtDNAcn, which are masked or blunted in mixed PBMCs. Finally, a proof-of-concept, repeated-measures study in a single individual validates cell type differences and also reveals week-to-week changes in mitochondrial activities. Larger studies are required to validate and mechanistically extend these findings. These mitochondrial phenotyping data build upon established immunometabolic differences among leukocyte subpopulations, and provide foundational quantitative knowledge to develop interpretable blood-based assays of mitochondrial health

Characterization of mitochondrial DNA quantity and quality in the human aged and Alzheimer’s disease brain

Background Mitochondrial dysfunction is a feature of neurodegenerative diseases, including Alzheimer’s disease (AD). Changes in the mitochondrial DNA copy number (mtDNAcn) and increased mitochondrial DNA mutation burden have both been associated with neurodegenerative diseases and cognitive decline. This study aims to systematically identify which common brain pathologies in the aged human brain are associated with mitochondrial recalibrations and to disentangle the relationship between these pathologies, mtDNAcn, mtDNA heteroplasmy, aging, neuronal loss, and cognitive function. Methods Whole-genome sequencing data from n = 1361 human brain samples from 5 different regions were used to quantify mtDNAcn as well as heteroplasmic mtDNA point mutations and small indels. Brain samples were assessed for 10 common pathologies. Annual cognitive test results were used to assess cognitive function proximal to death. For a subset of samples, neuronal proportions were estimated from RNA-seq profiles, and mass spectrometry was used to quantify the mitochondrial protein content of the tissue. Results mtDNAcn was 7–14% lower in AD relative to control participants. When accounting for all 10 common neuropathologies, only tau was significantly associated with lower mtDNAcn in the dorsolateral prefrontal cortex. In the posterior cingulate cortex, TDP-43 pathology demonstrated a distinct association with mtDNAcn. No changes were observed in the cerebellum, which is affected late by pathologies. Neither age nor gender was associated with mtDNAcn in the studied brain regions when adjusting for pathologies. Mitochondrial content and mtDNAcn independently explained variance in cognitive function unaccounted by pathologies, implicating complex mitochondrial recalibrations in cognitive decline. In contrast, mtDNA heteroplasmy levels increased by 1.5% per year of life in the cortical regions, but displayed no association with any of the pathologies or cognitive function. Conclusions We studied mtDNA quantity and quality in relation to mixed pathologies of aging and showed that tau and not amyloid-β is primarily associated with reduced mtDNAcn. In the posterior cingulate cortex, the association of TDP-43 with low mtDNAcn points to a vulnerability of this region in limbic-predominant age-related TDP-43 encephalopathy. While we found low mtDNAcn in brain regions affected by pathologies, the absence of associations with mtDNA heteroplasmy burden indicates that mtDNA point mutations and small indels are unlikely to be involved in the pathogenesis of late-onset neurodegenerative diseases

Association of Neonatal Thyroid Stimulating Hormone Concentration with Intellectual, Psychomotor and Psychosocial Development of Preschool Children

Iodine is necessary for thyroid hormones synthesis which in turn are essential for brain development during fetal and early postnatal life. In these critical periods, severe iodine deficiency can induce irreversible brain damage in the fetus and the infant, resulting in retarded cognitive and/or psychomotor development. Despite the introduction of salt iodization programs such as national measures to control iodine deficiency, some European countries, including Belgium, are still affected by Mild Iodine Deficiency (MID) and MID during pregnancy may affect neurodevelopment of the offspring. Elevated thyroid stimulating hormone (TSH) concentration (>5mU/l) at birth has been used as an indicator of iodine deficiency during late pregnancy and at the population level. This doctoral research aimed to investigate the association between neonatal TSH level, used as a surrogate marker of MID during late pregnancy, and cognitive, psychomotor and psychosocial development of preschool children. It was hypothesized that elevation of TSH at birth is associated with impaired intellectual and psychomotor development and with behavioral problems at 4-5 years. As the use of TSH as an indicator of iodine deficiency has been criticized, we have also set out to assess the potential factors influencing neonatal TSH level measured through neonatal screening using a representative sample of TSH values between 0 and 15 mIU/L. Additionally, we aimed to reevaluate the neonatal TSH cut-off (5mIU/L) used to monitor iodine status in the population. The objective was to evaluate the cut-off point from which we can observe the impairment of children’s neurodevelopment. We hypothesized that this is a good way to establish the best cut-off value for identifying iodine deficiency.The study included 315 Belgian preschool children with a TSH concentration between 0 and 15 mU/L at screening. For each sex and TSH-interval (0-1 mU/L, 1-2 mU/L, 2-3 mU/L, 3-4 mU/L, 4-5 mU/L, 5-6 mU/L, 6-7 mU/L, 7-8 mU/L, 8-9 mU/L, 9-15 mU/L) 19 newborns were randomly selected after excluding infants with congenital hypothyroidism, low birth weight and premature infants. Neonatal TSH was measured in dried blood spots collected by heel stick 3 to 5 days after birth using the Autodelphia method. Cognitive abilities and psychomotor development were assessed using respectively the Wechsler Preschool and Primary Scale of Intelligence-III and the Charlop-Atwell scale of motor coordination. Psychosocial development was measured using the Child Behavior Check List for ages 1½-5 years. In addition, the mothers completed a self-administered questionnaire in order to account for confounding factors. No association between neonatal TSH within the range of 0 to 15 mIU/L - a surrogate marker for mild iodine deficiency during pregnancy and neurocognitive development was present in Belgian preschool children. The current level of iodine deficiency in Belgium is probably not severe enough to affect the neurodevelopment of children. In this study, we were able to identify several maternal and pregnancy related determinants of neonatal TSH levels. Higher TSH levels were associated with a lifetime (up to child birth) smoking behavior in the mother, a lower weight gain during pregnancy, a longer pregnancy duration. Higher TSH levels were found in spring and winter compared to summer and autumn. It is not advised to use elevated neonatal TSH levels at birth as an indicator of iodine deficiency during late pregnancy without taking potential covariates into account. Given the fact that no association was found between TSH and developmental scores in the children, we cannot evaluate the cut-off point from which we can observe the impairment of children’s neurodevelopment.Doctorat en Sciences psychologiques et de l'éducationinfo:eu-repo/semantics/nonPublishe

Association of Neonatal Thyroid Stimulating Hormone Concentration with Intellectual, Psychomotor and Psychosocial Development of Preschool Children

Iodine is necessary for thyroid hormones synthesis which in turn are essential for brain development during fetal and early postnatal life. In these critical periods, severe iodine deficiency can induce irreversible brain damage in the fetus and the infant, resulting in retarded cognitive and/or psychomotor development. Despite the introduction of salt iodization programs such as national measures to control iodine deficiency, some European countries, including Belgium, are still affected by Mild Iodine Deficiency (MID) and MID during pregnancy may affect neurodevelopment of the offspring. Elevated thyroid stimulating hormone (TSH) concentration (>5mU/l) at birth has been used as an indicator of iodine deficiency during late pregnancy and at the population level. This doctoral research aimed to investigate the association between neonatal TSH level, used as a surrogate marker of MID during late pregnancy, and cognitive, psychomotor and psychosocial development of preschool children. It was hypothesized that elevation of TSH at birth is associated with impaired intellectual and psychomotor development and with behavioral problems at 4-5 years. As the use of TSH as an indicator of iodine deficiency has been criticized, we have also set out to assess the potential factors influencing neonatal TSH level measured through neonatal screening using a representative sample of TSH values between 0 and 15 mIU/L. Additionally, we aimed to reevaluate the neonatal TSH cut-off (5mIU/L) used to monitor iodine status in the population. The objective was to evaluate the cut-off point from which we can observe the impairment of children’s neurodevelopment. We hypothesized that this is a good way to establish the best cut-off value for identifying iodine deficiency.The study included 315 Belgian preschool children with a TSH concentration between 0 and 15 mU/L at screening. For each sex and TSH-interval (0-1 mU/L, 1-2 mU/L, 2-3 mU/L, 3-4 mU/L, 4-5 mU/L, 5-6 mU/L, 6-7 mU/L, 7-8 mU/L, 8-9 mU/L, 9-15 mU/L) 19 newborns were randomly selected after excluding infants with congenital hypothyroidism, low birth weight and premature infants. Neonatal TSH was measured in dried blood spots collected by heel stick 3 to 5 days after birth using the Autodelphia method. Cognitive abilities and psychomotor development were assessed using respectively the Wechsler Preschool and Primary Scale of Intelligence-III and the Charlop-Atwell scale of motor coordination. Psychosocial development was measured using the Child Behavior Check List for ages 1½-5 years. In addition, the mothers completed a self-administered questionnaire in order to account for confounding factors. No association between neonatal TSH within the range of 0 to 15 mIU/L - a surrogate marker for mild iodine deficiency during pregnancy and neurocognitive development was present in Belgian preschool children. The current level of iodine deficiency in Belgium is probably not severe enough to affect the neurodevelopment of children. In this study, we were able to identify several maternal and pregnancy related determinants of neonatal TSH levels. Higher TSH levels were associated with a lifetime (up to child birth) smoking behavior in the mother, a lower weight gain during pregnancy, a longer pregnancy duration. Higher TSH levels were found in spring and winter compared to summer and autumn. It is not advised to use elevated neonatal TSH levels at birth as an indicator of iodine deficiency during late pregnancy without taking potential covariates into account. Given the fact that no association was found between TSH and developmental scores in the children, we cannot evaluate the cut-off point from which we can observe the impairment of children’s neurodevelopment.Doctorat en Sciences psychologiques et de l'éducationinfo:eu-repo/semantics/nonPublishe

No association between elevated thyroid-stimulating hormone at birth and parent-reported problem behavior at preschool age

Objectives: Mild level of iodine deficiency during pregnancy may reduce maternal thyroid hormone production and supply to the fetus hence affecting brain neurodevelopment. The aim of the present study was to investigate the association between elevated neonatal thyroid-stimulating hormone (TSH) level (<5 mU/L), used as a marker of maternal mild iodine deficiency during late pregnancy, and behavioral development of preschool children.Methods: This retrospective cohort study included 310 Belgian mothers and their children aged 4-5 years old with TSH levels in the range of 0.45-15 mU/L at birth. The TSH level was measured in dried blood spots on filter paper collected by heel stick 3-5 days after birth. Low birth weight, prematurely born children, or children with congenital hypothyroidism were excluded. The degree of behavioral problems was evaluated using the Child Behavior Check List (CBCL) for age 11/2-5 years questionnaire. Relevant socioeconomic, maternal, and child factors were also collected.Results: TSH concentrations and CBCL scores were not associated both in univariate analysis and when adjusting for confounding factors in multivariate analysis.Discussion: Elevated TSH concentrations measured at birth was not associated with behavioral development scores.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Protocol of the PSYCHOTSH study: Association between neonatal thyroid stimulating hormone concentration and intellectual, psychomotor and psychosocial development at 4-5 year of age: A retrospective cohort study

Background: Several European countries, including Belgium, still suffer from mild iodine deficiency. Thyroid stimulating hormone (TSH) concentration in whole blood measured at birth has been proposed as an indicator of maternal iodine status during the last trimester of pregnancy. It has been shown that mild iodine deficiency during pregnancy may affect the neurodevelopment of the offspring. In several studies, elevated TSH levels at birth were associated with suboptimal cognitive and psychomotor outcomes among young children. This paper describes the protocol of the PSYCHOTSH study aiming to assess the association between neonatal TSH levels and intellectual, psychomotor and psychosocial development of 4-5 year old children. The results could lead to a reassessment of the recommended cut-offlevels of 5 > mU/L used for monitoring iodine status of the population. Methods: In total, 380 Belgian 4-5 year old preschool children from Brussels and Wallonia with a neonatal blood spot TSH concentration between 0 and 15 mU/L are included in the study. For each sex and TSH-interval (0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8, 8-9 and 9-15 mU/L), 19 newborns were randomly selected from all newborns screened by the neonatal screening centre in Brussels in 2008-2009. Infants with congenital hypothyroidism, low birth weight and prematurity were excluded from the study. Neonatal TSH concentration was measured by the Autodelphia method in dried blood spots, collected by heel stick on filter paper 3 to 5 days after birth. Cognitive abilities and psychomotor development are assessed using the Wechsler Preschool and Primary Scale of Intelligence - third edition - and the Charlop-Atwell Scale of Motor coordination. Psychosocial development is measured using the Child Behaviour Check List for age 1 1/2 to 5 years old. In addition, several socioeconomic, parental and child confounding factors are assessed. Conclusions: This study aims to clarify the effect of mild iodine deficiency during pregnancy on the neurodevelopment of the offspring. Therefore, the results may have important implications for future public health recommendations, policies and practices in food supplementation. In addition, the results may have implications for the use of neonatal TSH screening results for monitoring the population iodine status and may lead to the definition of new TSH cut-offs for determination of the severity of iodine status and for practical use in data reporting by neonatal screening centres.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Neonatal thyroid-stimulating hormone level is influenced by neonatal, maternal, and pregnancy factors

The percentage of newborns with a neonatal whole blood thyroid-stimulating hormone (TSH) greater than 5 mIU/L has been used as an indicator of iodine deficiency at the population level. However, TSH levels in newborns may be influenced by many factors other than iodine status. The objective of this study was to identify neonatal, maternal, and pregnancy-related determinants of neonatal TSH levels in a retrospective cohort study. The study sample included 313 Belgian mothers and their 4-to 5-year-old children. The children had a neonatal TSH concentration between 0 and 15 mIU/L at neonatal screening, and blood samples were collected 3 to 5 days after birth. Children with suspected congenital hypothyroidism (neonatal TSH level >15 mIU/L), prematurely born (ie, <37 weeks), or with a low birth weight (ie, <2500 g) were excluded. Information about maternal and birth-related determinants was collected from the neonatal screening center via a self-administered questionnaire filled in by the mother together with the child's health booklet. Higher TSH levels were found in spring and winter compared to summer and autumn (P = .011). Higher TSH levels were associated with lifetime smoking behavior (up to child birth) in the mother (P = .005), lower weight gain during pregnancy (P = .014), and longer pregnancies (P = .003). This study showed that several neonatal, maternal, and pregnancy-related determinants are influencing neonatal TSH level.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Stress and circulating cell-free mitochondrial DNA : A systematic review of human studies, physiological considerations, and technical recommendations

Cell-free mitochondrial DNA (cf-mtDNA) is a marker of inflammatory disease and a predictor of mortality, but little is known about cf-mtDNA in relation to psychobiology. A systematic review of the literature reveals that blood cf-mtDNA varies in response to common real-world stressors including psychopathology, acute psychological stress, and exercise. Moreover, cf-mtDNA is inducible within minutes and exhibits high intra-individual day-to-day variation, highlighting the dynamic regulation of cf-mtDNA levels. We discuss current knowledge on the mechanisms of cf-mtDNA release, its forms of transport (“cell-free” does not mean “membrane-free”), potential physiological functions, putative cellular and neuroendocrine triggers, and factors that may contribute to cf-mtDNA removal from the circulation. A review of in vitro, pre-clinical, and clinical studies shows conflicting results around the dogma that physiological forms of cf-mtDNA are pro-inflammatory, opening the possibility of other physiological functions, including the cell-to-cell transfer of whole mitochondria. Finally, to enhance the reproducibility and biological interpretation of human cf-mtDNA research, we propose guidelines for blood collection, cf-mtDNA isolation, quantification, and reporting standards, which can promote concerted advances by the community. Defining the mechanistic basis for cf-mtDNA signaling is an opportunity to elucidate the role of mitochondria in brain-body interactions and psychopathology