| 1. |
- Derakhshan, Arash, et al.
(författare)
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Reference ranges and determinants of thyroid function during early pregnancy : the SELMA study
- 2018
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 103:9, s. 3548-3556
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Tidskriftsartikel (refereegranskat)abstract
- Context: Establishing reference ranges as well as identifying and quantifying the determinants of thyroid function during pregnancy is important for proper clinical interpretation and optimizing research efforts. However, such data are sparse, specifically for (F)T3 measurements and most studies do not take into account thyroid antibodies or hCG.Objective: To determine reference ranges and to identify/quantify determinants of TSH, FT4, FT3, TT4 and TT3.Design, Setting and Participants: This study included 2,314 participants of the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study, a population-based prospective pregnancy cohort of mother-child pairs. Reference ranges were calculated by 2.5-97.5th percentiles after excluding TPOAb and/or TgAb positive women.Intervention: None.Main Outcome Measures: TSH, FT4, FT3, TT4 and TT3 in prenatal serum.Results: After exclusion of TPOAb positive women, reference range were: TSH: 0.11-3.48 mU/L, FT4: 11.6-19.4 pmol/L, FT3: 3.72-5.92 pg/mL, TT4: 82.4-166.2 pmol/L and TT3: 1.28-2.92 nmol/L. Additional exclusion of TgAb positive women did not change the reference ranges substantially. Exposure to tobacco smoke, as assessed by questionnaires and serum cotinine, was associated with lower TSH and higher FT3 and TT3. BMI and gestational age were the main determinants of TSH (only for BMI), FT4, FT3, TT4 and TT3.Conclusions: We show that the exclusion of TgAb positive women on top of excluding TPOAb positive women hardly affects clinical reference ranges. We identified various relevant clinical determinants of TSH, FT4, FT3, TT4 and TT3 which could reflect endocrine disrupting effects and/or effects on thyroid hormone transport or deiodination.
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| 2. |
- Levie, Deborah, et al.
(författare)
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The Association of Maternal Iodine Status in Early Pregnancy with Thyroid Function in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy Study
- 2019
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Ingår i: Thyroid. - : Mary Ann Liebert. - 1050-7256 .- 1557-9077. ; 29:11, s. 1660-1668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe maternal iodine deficiency can impact fetal brain development through effects on maternal and/or fetal thyroid hormone availability. The effects of mild-to-moderate iodine deficiency on thyroid function are less clear. The aim was to investigate the association of maternal urinary iodine concentration corrected for creatinine (UI/Creat) with thyroid function and autoantibodies in a mild-to-moderate iodine-deficient pregnant population. Methods: This study was embedded within the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. Clinical reference ranges were determined by the 2.5th and 97.5th population-based percentile cutoffs. The associations of UI/Creat with thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), total T4 (TT4), and total T3 (TT3) were studied using multivariable linear regression in thyroid peroxidase antibody (TPOAb)-negative women. The association of UI/Creat with TPOAb and thyroglobulin antibody (TgAb) positivity was analyzed using multivariable logistic regression. Results: Urinary iodine and thyroid function were measured at a median (95% range) gestational age of 10 (6-14) weeks in 2009 women. The median (95% range) UI/Creat was 85 mu g/g (36-386) and the UI/Creat was below 150 mu g/g in 80.1% of women. Reference ranges did not differ substantially by UI/Creat. A lower UI/Creat was associated with a lower TSH (p = 0.027), a higher TT4 (p = 0.032), and with a corresponding trend toward slightly higher fT4 (p = 0.081), fT3 (p = 0.079), and TT3 (p = 0.10). UI/Creat was not associated with the fT4/fT3 (p = 0.94) or TT4/TT3 ratios (p = 0.63). Women with a UI/Creat of 150-249 mu g/g had the lowest prevalence of TPOAb positivity (6.1%), while women with a UI/Creat of <150 mu g/g had a higher prevalence (11.0%, odds ratio [OR] confidence interval [95% CI] 1.84 [1.07-3.20], p = 0.029). Women with a UI/Creat >= 500 mu g/g showed the highest prevalence and a higher risk of TPOAb positivity, however, only a small proportion of women had such a UI/Creat (12.5%, OR, [95% CI] 2.36 [0.54-10.43], p = 0.26). Conclusions: We could not identify any meaningful differences in thyroid function reference ranges. Lower iodine availability was associated with a slightly lower TSH and a higher TT4. Women with adequate iodine intake had the lowest risk of TPOAb positivity.
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| 3. |
- Cediel Ulloa, Andrea, et al.
(författare)
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Impact of endocrine disrupting chemicals on neurodevelopment : the need for better testing strategies for endocrine disruption-induced developmental neurotoxicity
- 2022
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Ingår i: Expert Review of Endocrinology & Metabolism. - : Taylor & Francis. - 1744-6651 .- 1744-8417. ; 17:2, s. 131-141
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Brain development is highly dependent on hormonal regulation. Exposure to chemicals disrupting endocrine signaling has been associated with neurodevelopmental impairment. This raises concern about exposure to the suspected thousands of endocrine disruptors, and has resulted in efforts to improve regulation of these chemicals. Yet, the causal links between endocrine disruption and developmental neurotoxicity, which would be required for regulatory action, are still largely missing. Areas covered: In this review, we illustrate the importance of two endocrine systems, thyroid hormone and retinoic acid pathways, for neurodevelopment. We place special emphasis on TH and RA synthesis, metabolism, and how endocrine disrupting chemicals known or suspected to affect these systems are associated with developmental neurotoxicity. Expert opinion: While it is clear that neurodevelopment is dependent on proper hormonal functioning, and evidence is increasing for developmental neurotoxicity induced by endocrine disrupting chemicals, this is not grasped by current chemical testing. Thus, there is an urgent need to develop test methods detecting endocrine disruption in the context of neurodevelopment. Key to this development is further mechanistic insights on the involvement of endocrine signaling in neurodevelopment as well as increased support to develop and validate new test methods for the regulatory context.
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| 4. |
- Di Criscio, Michela, et al.
(författare)
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A human-relevant mixture of endocrine disrupting chemicals induces changes in hippocampal DNA methylation correlating with hyperactive behavior in male mice
- 2023
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 313
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Tidskriftsartikel (refereegranskat)abstract
- Humans are ubiquitously exposed to endocrine disrupting chemicals (EDCs), substances that interfere with endogenous hormonal signaling. Exposure during early development is of particular concern due to the programming role of hormones during this period. A previous epidemiological study has shown association between prenatal co-exposure to 8 EDCs (Mixture N1) and language delay in children, suggesting an effect of this mixture on neurodevelopment. Furthermore, in utero exposure to Mixture N1 altered gene expression and behavior in adult mice. In this study, we investigated whether epigenetic mechanisms could underlie the long term effects of Mixture N1 on gene expression and behavior. To this end, we analyzed DNA methylation at regulatory regions of genes whose expression was affected by Mixture N1 in the hippocampus of in utero exposed mice using bisulfite-pyrosequencing. We show that Mixture N1 decreases DNA methylation in males at three genes that are part of the hypothalamus-pituitary-adrenal (HPA) axis: Nr3c1, Nr3c2, and Crhr1, coding for the glucocorticoid receptor, the mineralocorticoid receptor, and the corticotropin releasing hormone receptor 1, respectively. Furthermore, we show that the decrease in Nr3c1 methylation correlates with increased gene expression, and that Nr3c1, Nr3c2, and Crhr1 methylation correlates with hyperactivity and reduction in social behavior. These findings indicate that an EDC mixture corresponding to a human exposure scenario induces epigenetic changes, and thus programming effects, on the HPA axis that are reflected in the behavioral phenotypes of the adult male offspring.
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| 5. |
- Barbera, Mariagnese, et al.
(författare)
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A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol
- 2024
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central Ltd. - 1758-9193. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Combining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer’s Disease and emerging evidence of its potential neuro-protective effects (e.g. vascular, metabolic, anti-senescence). MET-FINGER aims to test a FINGER 2.0 multimodal intervention, combining an updated FINGER multidomain lifestyle intervention with metformin, where appropriate, in an APOE ε4-enriched population of older adults (60–79 years) at increased risk of dementia.Methods: MET-FINGER is an international randomised, controlled, parallel-group, phase-IIb proof-of-concept clinical trial, where metformin is included through a trial-within-trial design. 600 participants will be recruited at three sites (UK, Finland, Sweden). Participants at increased risk of dementia based on vascular risk factors and cognitive screening, will be first randomised to the FINGER 2.0 intervention (lifestyle + metformin if eligible; active arm) or to receive regular health advice (control arm). Participants allocated to the FINGER 2.0 intervention group at risk indicators of T2D will be additionally randomised to receive metformin (2000 mg/day or 1000 mg/day) or placebo. The study duration is 2 years. The changes in global cognition (primary outcome, using a Neuropsychological Test Battery), memory, executive function, and processing speed cognitive domains; functional status; lifestyle, vascular, metabolic, and other dementia-related risk factors (secondary outcomes), will be compared between the FINGER 2.0 intervention and the control arm. The feasibility, potential interaction (between-groups differences in healthy lifestyle changes), and disease-modifying effects of the lifestyle-metformin combination will be exploratory outcomes. The lifestyle intervention is adapted from the original FINGER trial (diet, physical activity, cognitive training, monitoring of cardiovascular/metabolic risk factors, social interaction) to be consistently delivered in three countries. Metformin is administered as Glucophage®XR/SR 500, (500 mg oral tablets). The metformin/placebo treatment will be double blinded. Conclusion: MET-FINGER is the first trial combining a multimodal lifestyle intervention with a putative repurposed disease-modifying drug for cognitive impairment prevention. Although preliminary, its findings will provide crucial information for innovative precision prevention strategies and form the basis for a larger phase-III trial design and future research in this field.
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| 6. |
- Galvan-Valencia, Oscar, et al.
(författare)
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Associations of salivary aldosterone levels during pregnancy with maternal blood pressure and birth weight-for-gestational age in a Mexico City birth cohort
- 2024
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Ingår i: Journal of Perinatology. - : Springer Nature. - 0743-8346 .- 1476-5543.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo determine associations of maternal salivary aldosterone with blood pressure (BP) in pregnancy and infant birth weight-for-gestational age (BWGA).MethodsWe measured maternal salivary aldosterone, BP and BWGA z-scores in 471 Mexico City pregnancy cohort participants and performed multivariable linear regression of BP and BWGA on log-aldosterone levels.ResultsLog-aldosterone was positively associated with diastolic BP (beta = 0.12 95% CI: 0.04, 0.21). There were no main effects of log-aldosterone on BWGA. However, we detected an interaction between log-aldosterone and BP in association with BWGA; higher log-aldosterone was associated with lower BWGA in the lowest (beta = -0.12, 95% CI: -0.26, 0.02) and highest (beta = -0.12, 95% CI: -0.29, 0.06) BP tertiles. In contrast, in the middle BP tertile the association was positive (beta = 0.09, 95% CI: -0.02, 0.20), p for interaction = 0.03.ConclusionHigher maternal salivary aldosterone is positively associated with diastolic BP and may affect fetal growth differently depending on concurrent maternal blood pressure.
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