Exploring how socioeconomic status affects neighbourhood environments? : effects on obesity risks : a longitudinal study in Singapore

Research on how socioeconomic status interacts with neighbourhood characteristics to influence disparities in obesity outcomes is currently limited by residential segregation-induced structural confounding, a lack of empirical studies outside the U.S. and other 'Western' contexts, and an over-reliance on cross-sectional analyses. This study addresses these challenges by examining how socioeconomic status modifies the effect of accumulated exposures to obesogenic neighbourhood environments on children and mothers' BMI, drawing from a longitudinal mother-child birth cohort study in Singapore, an Asian city-state with relatively little residential segregation. We find that increased access to park connectors was associated with a decrease in BMI outcomes for mothers with higher socioeconomic status, but an increase for those with lower socioeconomic status. We also find that increased access to bus stops was associated with an increase in BMIz of children with lower socioeconomic status, but with a decrease in BMIz of children with higher socioeconomic status, while increased access to rail stations was associated with a decrease in BMIz of children with lower socioeconomic status only. Our results suggest that urban interventions might have heterogeneous effects by socioeconomic status.Peer reviewe

The socioeconomic landscape of the exposome during pregnancy

Background: While socioeconomic position (SEP) is consistently related to pregnancy and birth outcome dis-parities, relevant biological mechanisms are manifold, thus necessitating more comprehensive characterization of SEP-exposome associations during pregnancy. Objectives: We implemented an exposomic approach to systematically characterize the socioeconomic landscape of prenatal exposures in a setting where social segregation was less distinct in a hypotheses-generating manner. Methods: We described the correlation structure of 134 prenatal exogenous and endogenous sources (e.g., micronutrients, hormones, immunomodulatory metabolites, environmental pollutants) collected in a diverse, population-representative, urban, high-income longitudinal mother-offspring cohort (N = 1341; 2009-2011). We examined the associations between maternal, paternal, household, and areal level SEP indicators and 134 ex-posures using multiple regressions adjusted for precision variables, as well as potential effect measure modifi-cation by ethnicity and nativity. Finally, we generated summary SEP indices using Multiple Correspondence Analysis to further explore possible curved relationships. Results: Individual and household SEP were associated with anthropometric/adiposity measures, folate, omega-3 fatty acids, insulin-like growth factor-II, fasting glucose, and neopterin, an inflammatory marker. We observed paternal education was more strongly and consistently related to maternal exposures than maternal education. This was most apparent amongst couples discordant on education. Analyses revealed additional non-linear as-sociations between areal composite SEP and particulate matter. Environmental contaminants (e.g., per-and polyfluoroalkyl substances) and micronutrients (e.g., folate and copper) showed opposing associations by ethnicity and nativity, respectively. Discussion: SEP-exposome relationships are complex, non-linear, and context specific. Our findings reinforce the potential role of paternal contributions and context-specific modifiers of associations, such as between ethnicity and maternal diet-related exposures. Despite weak presumed areal clustering of individual exposures in our context, our approach reinforces subtle non-linearities in areal-level exposures.Peer reviewe

The importance of myo-inositol and D-chiro-inositol to support fertility and reproduction

This review details the physiologic roles of two insulin sensitizers, myo-inositol (MI) and D-chiro-inositol (DCI). In the human ovary, MI is a second messenger of follicle stimulating hormone (FSH) and DCI is an aromatase inhibitor. These activities allow a treatment for polycystic ovary syndrome (PCOS) to be defined based on the combined administration of MI and DCI, where the best MI:DCI ratio is 40:1. In addition, MI plays a pivotal role in the physiology of reproduction, and has beneficial effects on the development of oocytes, spermatozoa, and embryos. By contrast, DCI has little effect on spermatozoa, but high concentrations in the ovary can negatively affect the quality of oocytes and the blastocyst. Overall, the evidence in the literature supports the beneficial effects of MI in both female and male reproduction, warranting clinical use of MI in assisted reproductive treatment (ART).Cette revue détaille les rôles physiologiques de deux sensibilisateurs à l'insuline, le myo-inositol (MI) et le D-chiro-inositol (DCI). Dans l'ovaire humain, le MI est un second messager de l'hormone folliculostimulante (FSH) et le DCI est un inhibiteur de l'aromatase. Ces activités permettent de définir un traitement du syndrome des ovaires polykystiques (SOPK) basé sur l'administration combinée de MI et de DCI, où le meilleur rapport MI:DCI est de 40:1. En outre, le MI joue un rôle essentiel dans la physiologie de la reproduction et a des effets bénéfiques sur le développement des ovocytes, des spermatozoïdes et des embryons. En revanche, le DCI a peu d'effet sur les spermatozoïdes, mais des concentrations élevées dans l'ovaire peuvent avoir un effet négatif sur la qualité des ovocytes et du blastocyste. Dans l'ensemble, les données de la littérature confirment les effets bénéfiques du MI dans la reproduction féminine et masculine, ce qui justifie l'utilisation clinique du MI dans l'assistance médicale à la procréation

When one size does not fit all: Reconsidering PCOS etiology, diagnosis, clinical subgroups, and subgroup-specific treatments

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects a large proportion of women. Due to its heterogeneity, the best diagnostic strategy has been a matter of contention. Since 1990 scientific societies in the field of human reproduction have tried to define the pivotal criteria for the diagnosis of PCOS. The consensus Rotterdam diagnostic criteria included the presence of hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology (PCOM), and have now been updated to evidence based diagnostic criteria in the 2018 and 2023 International Guideline diagnostic criteria endorsed by 39 societies internationally. Within the Rotterdam Criteria, at least two out of three of the above-mentioned features are required to be present to diagnose PCOS, resulting in four phenotypes being identified: phenotype A, characterized by the presence of all the features, phenotype B, exhibiting hyperandrogenism and oligo-anovulation, phenotype C, presenting as hyperandrogenism and PCOM and finally the phenotype D that is characterized by oligo-anovulation and PCOM, lacking the hyperandrogenic component. However, it is the hypothesis of the EGOI group that the Rotterdam phenotypes A, B, and C have a different underlying causality to phenotype D. Recent studies have highlighted the strong correlation between insulin resistance and hyperandrogenism, and the pivotal role of these factors in driving ovarian alterations, such as oligo-anovulation and follicular functional cyst formation. This new understanding of PCOS pathogenesis has led the authors to hypothesis that phenotypes A, B, and C are endocrine-metabolic syndromes with a metabolic clinical onset. Conversely, the absence of hyperandrogenism and metabolic disturbances in phenotype D suggests a different origin of this condition, and point towards novel pathophysiological mechanisms; however, these are still not fully understood. Further questions have been raised regarding the suitability of the “phenotypes” described by the Rotterdam Criteria by the publication by recent GWAS studies, which demonstrated that these phenotypes should be considered clinical subtypes as they are not reflected in the genetic picture. Hence, by capturing the heterogeneity of this complex disorder, current diagnostic criteria may benefit from a reassessment and the evaluation of additional parameters such as insulin resistance and endometrial thickness, with the purpose of not only improving their diagnostic accuracy but also of assigning an appropriate and personalized treatment. In this framework, the present overview aims to analyze the diagnostic criteria currently recognized by the scientific community and assess the suitability of their application in clinical practice in light of the newly emerging evidence

The influence of body position on bioelectrical impedance spectroscopy measurements in young children

Bioelectrical impedance techniques are easy to use and portable tools for assessing body composition. While measurements vary according to standing vs supine position in adults, and fasting and bladder voiding have been proposed as additional important influences, these have not been assessed in young children. Therefore, the influence of position, fasting, and voiding on bioimpedance measurements was examined in children. Bioimpedance measurements (ImpediMed SFB7) were made in 50 children (3.5 years). Measurements were made when supine and twice when standing (immediately on standing and after four minutes). Impedance and body composition were compared between positions, and the effect of fasting and voiding was assessed. Impedance varied between positions, but body composition parameters other than fat mass (total body water, intra- and extra-cellular water, fat-free mass) differed by less than 5%. There were no differences according to time of last meal or void. Equations were developed to allow standing measurements of fat mass to be combined with supine measurements. In early childhood, it can be difficult to meet requirements for fasting, voiding, and lying supine prior to measurement. This study provides evidence to enable standing and supine bioimpedance measurements to be combined in cohorts of young children

Myo-inositol – a potential prophylaxis against premature onset of labour and preterm birth

The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of myo-inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of myo-inositol as a preventive agent. However, the underlying molecular mechanisms by which myo-inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental myo-inositol in human parturition and explains possible underlying molecular mechanisms by which myo-inositol might modulate the uteroplacental environment and inhibit preterm labour-onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour-onset. A higher uteroplacental inositol level, potentially promoted by maternal myo-inositol supplementation, might affect lipid metabolism, eicosanoid production, and secretion of pro-inflammatory chemocytokines, that overall dampen the pro-labour uteroplacental environment responsible for labour-onset and progress, thus, reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal myo-inositol supplementation and definitively address the efficacy of myo-inositol prophylaxis against PTB

Placental inositol reduced in gestational diabetes as glucose alters inositol transporters and IMPA1 enzyme expression

ContextPerturbed inositol physiology in insulin-resistant conditions has led to proposals of inositol supplementation for gestational diabetes (GDM) prevention, but placental inositol biology is poorly understood.ObjectiveInvestigate associations of maternal glycemia with placental inositol content, determine glucose effects on placental expression of inositol enzymes and transporters, and examine relations with birthweight.Design and ParticipantsCase-control study of placentae from term singleton pregnancies (GDM n = 24, non-GDM n = 26), and culture of another 9 placentae in different concentrations of glucose and myo-inositol for 48 hours.Main Outcome MeasuresPlacental inositol was quantified by the Megazyme assay. Relative expression of enzymes involved in myo-inositol metabolism and plasma membrane inositol transport was determined by quantitative RT-PCR and immunoblotting. Linear regression analyses were adjusted for maternal age, body mass index, ethnicity, gestational age, and sex.ResultsPlacental inositol content was 17% lower in GDM compared with non-GDM. Higher maternal mid-gestation glycemia were associated with lower placental inositol. Increasing fasting glycemia was associated with lower protein levels of the myo-inositol synthesis enzyme, IMPA1, and the inositol transporters, SLC5A11 and SLC2A13, the expression of which also correlated with placental inositol content. In vitro, higher glucose concentrations reduced IMPA1 and SLC5A11 mRNA expression. Increasing fasting glycemia positively associated with customized birthweight percentile as expected in cases with low placental inositol, but this association was attenuated with high placental inositol.ConclusionGlycemia-induced dysregulation of placental inositol synthesis and transport may be implicated in reduced placental inositol content in GDM, and this may in turn be permissive to accelerated fetal growth

Myo-inositol alters C-labelled fatty acid metabolism in human placental explants

We postulate that myo-inositol, a proposed intervention for gestational-diabetes, affects transplacental lipid supply to the fetus. We investigated the effect of myo-inositol on fatty-acid processing in human placental-explants from uncomplicated pregnancies. Explants were incubated with 13C-labeled palmitic-acid, 13C-oleic-acid and 13C-docosahexaenoic-acid across a range of myo-inositol concentrations for 24 h and 48 h. The incorporation of labeled-fatty-acids into individual lipids was quantified by liquid-chromatography-mass-spectrometry. At 24 h, myo-inositol increased the amount of 13C-palmitic-acid and 13C-oleic-acid labeled lipids (median fold-change relative to control=1). Significant effects were seen with 30 µM myo-inositol (physiological) for 13C-palmitic-acid-lysophosphatidylcholines (1.26) and 13C-palmitic-acid-phosphatidylethanolamines (1.17). At 48 h, myo-inositol addition increased 13C-oleic-acid-lipids but decreased 13C-palmitic-acid and 13C-docosahexaenoic-acid lipids. Significant effects were seen with 30 µM myo-inositol for 13C-oleic-acid-phosphatidylcholines (1.25), 13C-oleic-acid-phosphatidylethanolamines (1.37) and 13C-oleic-acid-triacylglycerols (1.32) and with 100 µM myo-inositol for 13C-docosahexaenoic-acid-triacylglycerols (0.78). Lipids labeled with the same 13C-fatty-acid showed similar responses when tested at the same time-point, suggesting myo-inositol alters upstream processes such as fatty-acid uptake or activation. Myo-inositol supplementation may alter placental lipid physiology with unknown clinical consequences