Maternal mild thyroid dysfunction and offspring cognitive and motor development from infancy to childhood: the Rhea mother-child cohort study in Crete, Greece.

BACKGROUND: Maternal thyroid hormones' supply is crucial for fetal neurodevelopment; however, the role of maternal mild thyroid dysfunction is not clear. We aimed to assess the association of maternal mild thyroid dysfunction with child neuropsychological development from infancy to early childhood. METHODS: We included 757 mother-child pairs from the prospective 'Rhea' cohort on Crete, Greece. Maternal thyroid functioning was assessed by quantitative analysis of serum thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies and thyroglobulin antibodies at early gestation (mean=14 weeks). Neuropsychological assessment was based on Bayley Scales of Infant Development (18 months of age), McCarthy Scales of Children's Abilities (4 years of age), Raven's Coloured Progressive Matrices, Trail Making Test and Finger Tapping Test (6 years of age). RESULTS: In multivariate adjusted linear regression analyses, maternal hypothyroxinemia was associated with decreased verbal scores at 4 years and reduced motor speed at 6 years of age. Maternal thyroid autoimmunity was associated with decreased child perceptual and motor ability at 4 years of age. Four trajectories of longitudinal non-verbal cognitive development were identified and children exposed to maternal thyroid autoimmunity had increased risk for belonging to an adverse trajectory ('low': adjusted relative risk ratio (RRR) = 2.7 95% CI: (1.4, 5.2), 'high-decreasing': adjusted RRR = 2.2 95% CI: (1.2, 4.0), 'low-increasing': adjusted RRR = 1.8 95% CI: (1.0, 3.2)). CONCLUSION: Maternal hypothyroxinemia is associated with reduced offspring verbal and motor ability. Maternal thyroid autoimmunity is associated with decreased offspring perceptual performance and motor ability and increased risk for adverse non-verbal cognitive development from infancy to childhood.

Association between high levels of inflammatory markers and cognitive outcomes at 4 years of age: The Rhea mother-child cohort study, Crete, Greece.

There is growing evidence associating inflammatory markers in complex, higher order neurological functions, such as cognition and memory. We examined whether high levels of various inflammatory markers are associated with cognitive outcomes at 4 years of age in a mother-child cohort in Crete, Greece (Rhea study). We included 642 children in this cross-sectional study. Levels of several inflammatory markers (IFN-γ, IL-1ß, IL-6, IL-8, IL-17α, IL-10, MIP-1α, TNF-α and the ratios of IL-6 to IL-10 and TNF-α to IL-10) were determined in child serum via immunoassay. Neurodevelopment at 4 years was assessed by means of the McCarthy Scales of Children's Abilities. Multivariate linear regression analyses were used to estimate the associations between the exposures and outcomes of interest after adjustment for various confounders. Our results indicate that children with high TNF-α concentrations (≥90th percentile) in serum demonstrated decreased scores in memory (adjusted ß = -4.0; 95% CI: -7.7, -0.2), working memory (adjusted ß = -4.0; 95% CI: -8.0, -0.1) as well as in memory span scale (adjusted ß = -4.0; 95% CI: -7.9, -0.1). We also found that children with high IFN-γ serum levels showed lower scores in memory span scale (adjusted ß = -3.4; 95% CI: -7.3, -0.4). Children with elevated TNF-α/IL-10 ratio demonstrated decreased quantitative (adjusted ß = -4.3; 95% CI: -8.2, -0.4), motor (adjusted ß = -3.5; 95% CI: -7.5, -0.5), executive function (adjusted ß = -4.8; 95% CI: -8.5, -1.1), general cognitive (adjusted ß = -3.6; 95% CI: -7.3, -0.1), memory (adjusted ß = -3.8; 95% CI: -7.6, -0), working memory (adjusted ß = -3.5; 95% CI: -7.5, -0.5) and memory span scores (adjusted ß = -5.3; 95% CI: -9.1, -1.4) The findings suggest that high levels of TNF-α may contribute to reduced memory performance at preschool age.

Patterns of Early-Life Social and Environmental Exposures and Child Cognitive Development, Rhea Birth Cohort, Crete, Greece.

Early-life exposures are critical for later child cognitive development. McCarthy Scales of Children's Abilities (MSCA) were used to assess cognitive development of 700 preschoolers (Mage  = 4.2 years), derived from the "Rhea" birth cohort, in Greece. Principal component analysis (PCA) was applied on prospectively collected exposure data. Six components were extracted; five of them were associated with child cognition. Higher parental social status, preschool attendance and less TV watching, nonsmoking during pregnancy and breastfeeding, and parental involvement in child life were protective factors of child cognition at 4 years. Increased child birth order was negatively associated with child cognition. Offspring's size at birth was not associated with any cognitive outcome. These findings reveal the importance of early-life exposures to child cognitive development.

Prenatal exposure to persistent organic pollutants in association with offspring neuropsychological development at 4years of age: The Rhea mother-child cohort, Crete, Greece.

BACKGROUND: Persistent Organic Pollutants (POPs) are highly-resistant compounds to environmental degradation and due to fat solubility they bioaccumulate through the food chain. As they cross the placenta, in utero exposure to POPs could disrupt child neurodevelopment as they are considered to be neurotoxic. AIMS: We examined whether in utero exposure to levels of different POPs is associated with offspring cognitive and behavioral outcomes at 4years of age in a mother-child cohort in Crete, Greece (Rhea study). METHODS: We included 689 mother-child pairs. Concentrations of several polychlorinated biphenyls (PCBs) and other organochlorine compounds (dichlorodiphenyl dichloroethene [DDE], hexachlorobenzene [HCB]) were determined in maternal serum collected in the first trimester of pregnancy by triple quadrupole mass spectrometry. Neurodevelopment at 4years was assessed by means of the McCarthy Scales of Children's Abilities. Behavioral difficulties were assessed by Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Linear regression analyses were used to estimate the associations between the exposures and outcomes of interest after adjustment for potential confounders. RESULTS: Children with "high" HCB concentrations (≥90th percentile) in maternal serum, demonstrated decreased scores in perceptual performance (adjusted ß=-6.07; 95% CI: -10.17, -1.97), general cognitive (adjusted ß=-4.97; 95% CI: -8.99, -0.96), executive function (adjusted ß=-6.24; 95% CI: -10.36, -2.11) and working memory (adjusted ß=-4.71; 95% CI: -9.05, -0.36) scales at 4years of age. High exposure to PCBs (≥90th percentile) during pregnancy was associated with a 4.62 points reduction in working memory score at 4years of age (95% CI: -9.10, -0.14). Prenatal exposure to DDE, HCB and PCBs was not associated with child behavioral difficulties. CONCLUSIONS: The findings suggest that prenatal exposure to HCB and PCBs may contribute to reduced cognitive development at preschool age. Our results raise the possibility that exposure to HCB may play a more important role in child cognition than previously considered.