Associations between maternal urinary iodine assessment, dietary iodine intakes and neurodevelopmental outcomes in the child: A Systematic Review

Abstract Objective Mild to moderate iodine deficiency during pregnancy has been associated with adverse neurodevelopmental outcomes in offspring. Few research studies to date combine assessment of urinary iodine (UIC and/or ICr), biomarkers that best reflect dietary intake, with reported dietary intake of iodine rich foods in their assessment of iodine deficiency. Thus, a systematic review was conducted to incorporate both these important measures. Design Using PRISMA guidelines, a comprehensive search was conducted in three electronic databases (EMBASE®, MedLine® and Web of Science®) from January 1970–March 2021. Quality assessment was undertaken using the Newcastle Ottawa Scale. Eligible studies included reported assessment of iodine status through urinary iodine (UIC and/or ICr) and/or dietary intake measures in pregnancy alongside neurodevelopmental outcomes measured in the children. Data extracted included study author, design, sample size, country, gestational age, child age at testing, cognitive tests, urinary iodine assessment (UIC in μg/L and/or ICr in μg/g), dietary iodine intake assessment and results of associations for the assessed cognitive outcomes. Results Twelve studies were included with nine reporting women as mild-moderately iodine deficient based on World Health Organization (WHO) cut-offs for urinary iodine measurements < 150 μg/l, as the median UIC value in pregnant women. Only four of the nine studies reported a negative association with child cognitive outcomes based on deficient urinary iodine measurements. Five studies reported urinary iodine measurements and dietary intakes with four of these studies reporting a negative association of lower urinary iodine measurements and dietary iodine intakes with adverse offspring neurodevelopment. Milk was identified as the main dietary source of iodine in these studies. Conclusion The majority of studies classified pregnant women to be mild-moderately iodine deficient based on urinary iodine assessment (UIC and/or ICr) and/or dietary intakes, with subsequent offspring neurodevelopment implications identified. Although a considerable number of studies did not report an adverse association with neurodevelopmental outcomes, these findings are still supportive of ensuring adequate dietary iodine intakes and urinary iodine monitoring throughout pregnancy due to the important role iodine plays within foetal neurodevelopment. This review suggests that dietary intake data may indicate a stronger association with cognitive outcomes than urinary iodine measurements alone. The strength of this review distinguishes results based on cognitive outcome per urinary iodine assessment strategy (UIC and/or ICr) with dietary data. Future work is needed respecting the usefulness of urinary iodine assessment (UIC and/or ICr) as an indicator of deficiency whilst also taking account of dietary intakes

Multiparameter Phospho-Flow Analysis of Lymphocytes in Early Rheumatoid Arthritis: Implications for Diagnosis and Monitoring Drug Therapy

The precise mechanisms involved in the initiation and progression of rheumatoid arthritis (RA) are not known. Early stages of RA often have non-specific symptoms, delaying diagnosis and therapy. Additionally, there are currently no established means to predict clinical responsiveness to therapy. Immune cell activation is a critical component therefore we examined the cellular activation of peripheral blood mononuclear cells (PBMCs) in the early stages of RA, in order to develop a novel diagnostic modality.PBMCs were isolated from individuals diagnosed with early RA (ERA) (n = 38), longstanding RA (n = 10), osteoarthritis (OA) (n = 19) and from healthy individuals (n = 10). PBMCs were examined for activation of 15 signaling effectors, using phosphorylation status as a measure of activation in immunophenotyped cells, by flow cytometry (phospho-flow). CD3+CD4+, CD3+CD8+ and CD20+ cells isolated from patients with ERA, RA and OA exhibited activation of multiple phospho-epitopes. ERA patient PBMCs showed a bias towards phosphorylation-activation in the CD4+ and CD20+ compartments compared to OA PBMCs, where phospho-activation was primarily observed in CD8+ cells. The ratio of phospho (p)-AKT/p-p38 was significantly elevated in patients with ERA and may have diagnostic potential. The mean fluorescent intensity (MFI) levels for p-AKT and p-H3 in CD4+, CD8+ and CD20+ T cells correlated directly with physician global assessment scores (MDGA) and DAS (disease activity score). Stratification by medications revealed that patients receiving leflunomide, systemic steroids or anti-TNF therapy had significant reductions in phospho-specific activation compared with patients not receiving these therapies. Correlative trends between medication-associated reductions in the levels of phosphorylation of specific signaling effectors and lower disease activity were observed.Phospho-flow analysis identified phosphorylation-activation of specific signaling effectors in the PB from patients with ERA. Notably, phosphorylation of these signaling effectors did not distinguish ERA from late RA, suggesting that the activation status of discrete cell populations is already established early in disease. However, when the ratio of MFI values for p-AKT and p-p38 is >1.5, there is a high likelihood of having a diagnosis of RA. Our results suggest that longitudinal sampling of patients undergoing therapy may result in phospho-signatures that are predictive of drug responsiveness