Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: Prospective cohort study.

BACKGROUND: While systemic inflammation has been implicated in the etiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS), a condition with high case-fatality, is untested. Accordingly, we quantified the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with subsequent ALS occurrence. METHODS: We used data from UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centers between 2006 and 2010. Venous blood was collected at baseline in the full cohort and assayed for CRP, and repeat measurement was made 3-7 years later in a representative subgroup (N = 14,514) enabling correction for regression dilution. ALS was ascertained via national hospitalization and mortality registries until 2021. We computed multivariable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles. RESULTS: In an analytical sample of 400,884 initially ALS-free individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalizations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviors, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalizations (1.20; 1.00, 1.39). There was evidence of dose-response effects across tertiles of CRP for both outcomes (p for trend ≤ 0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalizations (1.37; 1.05, 1.76). CONCLUSIONS: Higher levels of CRP, a blood-based biomarker widely captured in clinical practice, is associated with moderately increased future risk of amyotrophic lateral sclerosis.

Overweight, obesity, and risk of hospitalization for COVID-19: A community-based cohort study of adults in the United Kingdom.

The role of obesity and overweight in occurrence of COVID-19 is unknown. We conducted a large-scale general population study using data from a community-dwelling sample in England (n = 334,329; 56.4 ±8.1 y; 54.5% women) with prospective linkage to national registry on hospitalization for COVID-19. Body mass index (BMI, from measured height and weight) was used as an indicator of overall obesity, and waist-hip ratio for central obesity. Main outcome was cases of COVID-19 serious enough to warrant a hospital admission from 16 March 2020 to 26 April 2020. Around 0.2% (n = 640) of the sample were hospitalized for COVID-19. There was an upward linear trend in the likelihood of COVID-19 hospitalization with increasing BMI, that was evident in the overweight (odds ratio, 1.39; 95% CI 1.13 to 1.71; crude incidence 19.1 per 10,000) and obese stage I (1.70;1.34 to 2.16; 23.3 per 10,000) and stage II (3.38; 2.60 to 4.40; 42.7 per 10,000) compared to normal weight (12.5 per 10,000). This gradient was little affected after adjustment for a wide range of covariates; however, controlling for biomarkers, particularly high-density lipoprotein cholesterol and glycated hemoglobin, led to a greater degree of attenuation. A similar pattern of association emerged for waist-hip ratio. In summary, overall and central obesity are risk factors for COVID-19 hospital admission. Elevated risk was apparent even at modest weight gain. The mechanisms may involve impaired glucose and lipid metabolism.

Explaining Ethnic Differentials in COVID-19 Mortality: A Cohort Study.

Ethnic inequalities in coronavirus disease 2019 (COVID-19) hospitalizations and mortality have been widely reported, but there is scant understanding of how they are embodied. The UK Biobank prospective cohort study comprises approximately half a million people who were aged 40-69 years at study induction, between 2006 and 2010, when information on ethnic background and potential explanatory factors was captured. Study members were prospectively linked to a national mortality registry. In an analytical sample of 448,664 individuals (248,820 women), 705 deaths were ascribed to COVID-19 between March 5, 2020, and January 24, 2021. In age- and sex-adjusted analyses, relative to White participants, Black study members experienced approximately 5 times the risk of COVID-19 mortality (odds ratio (OR) = 4.81, 95% confidence interval (CI): 3.28, 7.05), while there was a doubling in the South Asian group (OR = 2.05, 95% CI: 1.30, 3.25). Controlling for baseline comorbidities, social factors (including socioeconomic circumstances), and lifestyle indices attenuated this risk differential by 34% in Black study members (OR = 2.84, 95% CI: 1.91, 4.23) and 37% in South Asian individuals (OR = 1.57, 95% CI: 0.97, 2.55). The residual risk of COVID-19 deaths in ethnic minority groups may be ascribed to a range of unmeasured characteristics and requires further exploration.

The influence of X chromosome variants on trait neuroticism.

Autosomal variants have successfully been associated with trait neuroticism in genome-wide analysis of adequately powered samples. But such studies have so far excluded the X chromosome from analysis. Here, we report genetic association analyses of X chromosome and XY pseudoautosomal single nucleotide polymorphisms (SNPs) and trait neuroticism using UK Biobank samples (N = 405,274). Significant association was found with neuroticism on the X chromosome for 204 markers found within three independent loci (a further 783 were suggestive). Most of the lead neuroticism-related X chromosome variants were located in intergenic regions (n = 397). Involvement of HS6ST2, which has been previously associated with sociability behaviour in the dog, was supported by single SNP and gene-based tests. We found that the amino acid and nucleotide sequences are highly conserved between dogs and humans. From the suggestive X chromosome variants, there were 19 nearby genes which could be linked to gene ontology information. Molecular function was primarily related to binding and catalytic activity; notable biological processes were cellular and metabolic, and nucleic acid binding and transcription factor protein classes were most commonly involved. X-variant heritability of neuroticism was estimated at 0.22% (SE = 0.05) from a full dosage compensation model. A polygenic X-variant score created in an independent sample (maximum N ≈ 7,300) did not predict significant variance in neuroticism, psychological distress, or depressive disorder. We conclude that the X chromosome harbours significant variants influencing neuroticism, and might prove important for other quantitative traits and complex disorders.

Life-course Psychological Distress and Total Mortality by Middle Age: The 1970 Birth Cohort Study.

BACKGROUND: The onset of psychological distress most commonly occurs in adolescence and, in keeping with other exposures, is time-varying across the life course. Most studies of its association with mortality risk are, however, conducted in middle- and older-aged populations with a single baseline assessment. This may lead to an underestimation of the magnitude of distress-mortality relationship. METHODS: We used data from the 1970 British Cohort Study, a prospective cohort study. Psychological distress and covariates were collected at ages 5, 10, and 26. Vital status was ascertained between ages 26 and 44 years. RESULTS: Eighteen years of mortality surveillance of 5,901 individuals (3,221 women) gave rise to 74 deaths. After adjustment for a series of confounding factors which included early life socioeconomic status, birth characteristics, and cognition, relative to the unaffected group, distress in childhood only was associated with around a 50% elevation in mortality risk (hazard ratio = 1.45; 95% confidence interval = 0.84, 2.51), whereas distress in adulthood only was related to a doubling of risk (1.95; 0.90, 4.21). In study members with persistent distress symptoms (childhood and adulthood), there was a tripling of the death rate (3.10; 1.42, 6.74) (P value for trend across these categories: 0.002). CONCLUSION: The suggestion of a strong association between life-course distress and death warrants replication in a study with a greater number of events.

Pre-pandemic cognitive function and COVID-19 vaccine hesitancy: cohort study.

BACKGROUND: Whereas several predictors of COVID-19 vaccine hesitancy have been reported, the role of cognitive function is largely unknown. Accordingly, our objective was to evaluate the association between scores from an array of cognitive function tests and self-reported vaccine hesitancy after the announcement of the successful testing of the first COVID-19 vaccine (Oxford University/AstraZeneca). METHODS: We used individual-level data from a pandemic-focused study ('COVID Survey'), a prospective cohort study nested within United Kingdom Understanding Society ('Main Survey'). In the week immediately following the announcement of successful testing of the first efficacious inoculation (November/December 2020), data on vaccine intentionality were collected in 11,740 individuals (6702 women) aged 16-95 years. Pre-pandemic scores on general cognitive function, ascertained from a battery of six tests, were captured in 2011/12 wave of the Main Survey. Study members self-reported their intention to take up a vaccination in the COVID-19 Survey. RESULTS: Of the study sample, 17.2% (N = 1842) indicated they were hesitant about having the vaccine. After adjustment for age, sex, and ethnicity, study members with a lower baseline cognition score were markedly more likely to be vaccine hesitant (odds ratio per standard deviation lower score in cognition; 95% confidence interval: 1.76; 1.62, 1.90). Adjustment for mental and physical health plus household shielding status had no impact on these results, whereas controlling for educational attainment led to partial attenuation but the probability of hesitancy was still elevated (1.52; 1.37, 1.67). There was a linear association for vaccine hesitancy across the full range of cognition scores (p for trend: p < 0.0001). CONCLUSIONS: Erroneous social media reports might have complicated personal decision-making, leading to people with lower cognitive ability being vaccine-hesitant. With individuals with lower cognition also experiencing higher rates of COVID-19 in studies conducted prior to vaccine distribution, these new findings are suggestive of a potential additional disease burden.

Genetic contributions to two special factors of neuroticism are associated with affluence, higher intelligence, better health, and longer life.

Higher scores on the personality trait of neuroticism, the tendency to experience negative emotions, are associated with worse mental and physical health. Studies examining links between neuroticism and health typically operationalize neuroticism by summing the items from a neuroticism scale. However, neuroticism is made up of multiple heterogeneous facets, each contributing to the effect of neuroticism as a whole. A recent study showed that a 12-item neuroticism scale described one broad trait of general neuroticism and two special factors, one characterizing the extent to which people worry and feel vulnerable, and the other characterizing the extent to which people are anxious and tense. This study also found that, although individuals who were higher on general neuroticism lived shorter lives, individuals whose neuroticism was characterized by worry and vulnerability lived longer lives. Here, we examine the genetic contributions to the two special factors of neuroticism-anxiety/tension and worry/vulnerability-and how they contrast with that of general neuroticism. First, we show that, whereas the polygenic load for neuroticism is associated with the genetic risk of coronary artery disease, lower intelligence, lower socioeconomic status (SES), and poorer self-rated health, the genetic variants associated with high levels of anxiety/tension, and high levels of worry/vulnerability are associated with genetic variants linked to higher SES, higher intelligence, better self-rated health, and longer life. Second, we identify genetic variants that are uniquely associated with these protective aspects of neuroticism. Finally, we show that different neurological pathways are linked to each of these neuroticism phenotypes.

Pre-pandemic cognitive function and COVID-19 mortality: prospective cohort study.

Poorer performance on standard tests of pre-morbid cognitive function is related to an elevated risk of death from lower respiratory tract infections but the link with coronavirus (COVID­19) mortality is untested. Participants in UK Biobank, aged 40 to 69 years at study induction (2006-10), were administered a reaction time test, an indicator of information processing speed, and also had their verbal-numeric reasoning assessed. Between April 1st and September 23rd 2020 there were 388 registry-confirmed deaths (138 women) ascribed to COVID-19 in 494,932 individuals (269,602 women) with a reaction time test result, and 125 such deaths (38 women) in the subgroup of 180,198 people (97,794 women) with data on verbal-numeric reasoning. In analyses adjusted for age, sex, and ethnicity, a one standard deviation slower reaction time was related to a higher rate of death from COVID-19 (hazard ratio; 95% confidence interval: 1.18; 1.09, 1.28), as was a one standard deviation disadvantage on the verbal-numeric reasoning test (1.32; 1.09, 1.59). While there was some attenuation in these relationships after adjustment for additional covariates which included socio-economic status and lifestyle factors, the two pre-pandemic indicators of cognitive function continued to be related to COVID-19 mortality.

Lifestyle risk factors, inflammatory mechanisms, and COVID-19 hospitalization: A community-based cohort study of 387,109 adults in UK.

We conducted the first large-scale general population study on lifestyle risk factors (smoking, physical inactivity, obesity, and excessive alcohol intake) for COVID-19 using prospective cohort data with national registry linkage to hospitalisation. Participants were 387,109 men and women (56.4 ± 8.8 yr; 55.1% women) residing in England from UK Biobank study. Physical activity, smoking, and alcohol intake, were assessed by questionnaire at baseline (2006-2010). Body mass index, from measured height and weight, was used as an indicator of overall obesity. Outcome was cases of COVID-19 serious enough to warrant a hospital admission from 16-March-2020 to 26-April-2020. There were 760 COVID-19 cases. After adjustment for age, sex and mutually for each lifestyle factor, physical inactivity (Relative risk, 1.32, 95% confidence interval, 1.10, 1.58), smoking (1.42;1.12, 1.79) and obesity (2.05 ;1.68, 2.49) but not heavy alcohol consumption (1.12; 0.93, 1.35) were all related to COVID-19. We also found a dose-dependent increase in risk of COVID-19 with less favourable lifestyle scores, such that participants in the most adverse category had 4-fold higher risk (4.41; 2.52-7.71) compared to people with the most optimal lifestyle. C-reactive protein levels were associated with elevated risk of COVID-19 in a dose-dependent manner, and partly (10-16%) explained associations between adverse lifestyle and COVID-19. Based on UK risk factor prevalence estimates, unhealthy behaviours in combination accounted for up to 51% of the population attributable fraction of severe COVID-19. Our findings suggest that an unhealthy lifestyle synonymous with an elevated risk of non-communicable disease is also a risk factor for COVID-19 hospital admission, which might be partly explained by low grade inflammation. Adopting simple lifestyle changes could lower the risk of severe infection.

Ethnic disparities in hospitalisation for COVID-19 in England: The role of socioeconomic factors, mental health, and inflammatory and pro-inflammatory factors in a community-based cohort study.

BACKGROUND: Differentials in COVID-19 hospitalisations and mortality according to ethnicity have been reported but their origin is uncertain. We examined the role of socioeconomic, mental health, and pro-inflammatory factors in a community-based sample. METHODS: We used data on 340,966 men and women (mean age 56.2 years) from the UK Biobank study, a prospective cohort study with linkage to hospitalisation for COVID-19. Logistic regression models were used to estimate associations between ethnicity and hospitalisation for COVID-19. RESULTS: There were 640 COVID-19 cases (571/324,306 White, 31/4,485 Black, 21/5,732 Asian, 17/5,803 Other). Compared to the White study members and after adjusting for age and sex, Black individuals had over a 4-fold increased risk of COVID-19 infection (odds ratio; 95% confidence interval: 4.32; 3.00-6.23), and there was a doubling of risk in the Asian group (2.12; 1.37, 3.28) and the 'other' non-white group (1.84; 1.13, 2.99). After controlling for potential explanatory factors which included neighbourhood deprivation, household crowding, smoking, body size, inflammation, glycated haemoglobin, and mental illness, these effect estimates were attenuated by 33% for Blacks, 52% for Asians and 43% for Other, but remained raised for Blacks (2.66; 1.82, 3.91), Asian (1.43; 0.91, 2.26) and other non-white groups (1.41; 0.87, 2.31). CONCLUSIONS: There were clear ethnic differences in risk of COVID-19 hospitalisation and these do not appear to be fully explained by measured factors. If replicated, our results have implications for health policy, including the targeting of prevention advice and vaccination coverage.

Genetic prediction of male pattern baldness.

Male pattern baldness can have substantial psychosocial effects, and it has been phenotypically linked to adverse health outcomes such as prostate cancer and cardiovascular disease. We explored the genetic architecture of the trait using data from over 52,000 male participants of UK Biobank, aged 40-69 years. We identified over 250 independent genetic loci associated with severe hair loss (P<5x10-8). By splitting the cohort into a discovery sample of 40,000 and target sample of 12,000, we developed a prediction algorithm based entirely on common genetic variants that discriminated (AUC = 0.78, sensitivity = 0.74, specificity = 0.69, PPV = 59%, NPV = 82%) those with no hair loss from those with severe hair loss. The results of this study might help identify those at greatest risk of hair loss, and also potential genetic targets for intervention.

Associations between vascular risk factors and brain MRI indices in UK Biobank.

AIMS: Several factors are known to increase risk for cerebrovascular disease and dementia, but there is limited evidence on associations between multiple vascular risk factors (VRFs) and detailed aspects of brain macrostructure and microstructure in large community-dwelling populations across middle and older age. METHODS AND RESULTS: Associations between VRFs (smoking, hypertension, pulse pressure, diabetes, hypercholesterolaemia, body mass index, and waist-hip ratio) and brain structural and diffusion MRI markers were examined in UK Biobank (N = 9722, age range 44-79 years). A larger number of VRFs was associated with greater brain atrophy, lower grey matter volume, and poorer white matter health. Effect sizes were small (brain structural R2 ≤1.8%). Higher aggregate vascular risk was related to multiple regional MRI hallmarks associated with dementia risk: lower frontal and temporal cortical volumes, lower subcortical volumes, higher white matter hyperintensity volumes, and poorer white matter microstructure in association and thalamic pathways. Smoking pack years, hypertension and diabetes showed the most consistent associations across all brain measures. Hypercholesterolaemia was not uniquely associated with any MRI marker. CONCLUSION: Higher levels of VRFs were associated with poorer brain health across grey and white matter macrostructure and microstructure. Effects are mainly additive, converging upon frontal and temporal cortex, subcortical structures, and specific classes of white matter fibres. Though effect sizes were small, these results emphasize the vulnerability of brain health to vascular factors even in relatively healthy middle and older age, and the potential to partly ameliorate cognitive decline by addressing these malleable risk factors.

Sex Differences in the Adult Human Brain: Evidence from 5216 UK Biobank Participants.

Sex differences in the human brain are of interest for many reasons: for example, there are sex differences in the observed prevalence of psychiatric disorders and in some psychological traits that brain differences might help to explain. We report the largest single-sample study of structural and functional sex differences in the human brain (2750 female, 2466 male participants; mean age 61.7 years, range 44-77 years). Males had higher raw volumes, raw surface areas, and white matter fractional anisotropy; females had higher raw cortical thickness and higher white matter tract complexity. There was considerable distributional overlap between the sexes. Subregional differences were not fully attributable to differences in total volume, total surface area, mean cortical thickness, or height. There was generally greater male variance across the raw structural measures. Functional connectome organization showed stronger connectivity for males in unimodal sensorimotor cortices, and stronger connectivity for females in the default mode network. This large-scale study provides a foundation for attempts to understand the causes and consequences of sex differences in adult brain structure and function.

Cross-sectional associations between personality traits and device-based measures of step count and sedentary behaviour in older age: the Lothian Birth Cohort 1936.

BACKGROUND: While the associations between personality traits and self-reported physical activity are well replicated, few studies have examined the associations between personality and device-based measures of both physical activity and sedentary behaviour. Low levels of physical activity and high levels of sedentary behaviour are known risk factors for poorer health outcomes in older age. METHODS: We used device-based measures of physical activity and sedentary behaviour recorded over 7 days in 271 79-year-old participants of the Lothian Birth Cohort 1936. Linear regression models were used to assess whether personality traits were cross-sectionally associated with step count, sedentary time, and the number of sit-to-stand transitions. Personality traits were entered one at a time, and all-together, controlling for age and sex in Model 1 and additionally for BMI and limiting long-term illness in Model 2. RESULTS: None of the associations between personality traits and measures of physical activity and sedentary behaviours remained significant after controlling for multiple-comparisons using the False Discovery Rate test (all ps > .07). CONCLUSIONS: We found no evidence that personality traits are associated with device-based measures of physical activity or sedentary behaviour in older age. More studies are needed to replicate and examine the nature of these relationships.

Positive and negative well-being and objectively measured sedentary behaviour in older adults: evidence from three cohorts.

BACKGROUND: Sedentary behaviour is related to poorer health independently of time spent in moderate to vigorous physical activity. The aim of this study was to investigate whether wellbeing or symptoms of anxiety or depression predict sedentary behaviour in older adults. METHOD: Participants were drawn from the Lothian Birth Cohort 1936 (LBC1936) (n = 271), and the West of Scotland Twenty-07 1950s (n = 309) and 1930s (n = 118) cohorts. Sedentary outcomes, sedentary time, and number of sit-to-stand transitions, were measured with a three-dimensional accelerometer (activPAL activity monitor) worn for 7 days. In the Twenty-07 cohorts, symptoms of anxiety and depression were assessed in 2008 and sedentary outcomes were assessed ~ 8 years later in 2015 and 2016. In the LBC1936 cohort, wellbeing and symptoms of anxiety and depression were assessed concurrently with sedentary behaviour in 2015 and 2016. We tested for an association between wellbeing, anxiety or depression and the sedentary outcomes using multivariate regression analysis. RESULTS: We observed no association between wellbeing or symptoms of anxiety and the sedentary outcomes. Symptoms of depression were positively associated with sedentary time in the LBC1936 and Twenty-07 1950s cohort, and negatively associated with number of sit-to-stand transitions in the LBC1936. Meta-analytic estimates of the association between depressive symptoms and sedentary time or number of sit-to-stand transitions, adjusted for age, sex, BMI, long-standing illness, and education, were ß = 0.11 (95% CI = 0.03, 0.18) and ß = - 0.11 (95% CI = - 0.19, -0.03) respectively. CONCLUSION: Our findings indicate that depressive symptoms are positively associated with sedentary behavior. Future studies should investigate the causal direction of this association.

Genetic variants linked to education predict longevity.

Educational attainment is associated with many health outcomes, including longevity. It is also known to be substantially heritable. Here, we used data from three large genetic epidemiology cohort studies (Generation Scotland, n = ∼17,000; UK Biobank, n = ∼115,000; and the Estonian Biobank, n = ∼6,000) to test whether education-linked genetic variants can predict lifespan length. We did so by using cohort members' polygenic profile score for education to predict their parents' longevity. Across the three cohorts, meta-analysis showed that a 1 SD higher polygenic education score was associated with ∼2.7% lower mortality risk for both mothers (total ndeaths = 79,702) and ∼2.4% lower risk for fathers (total ndeaths = 97,630). On average, the parents of offspring in the upper third of the polygenic score distribution lived 0.55 y longer compared with those of offspring in the lower third. Overall, these results indicate that the genetic contributions to educational attainment are useful in the prediction of human longevity.

Predicting incident dementia 3-8 years after brief cognitive tests in the UK Biobank prospective study of 500,000 people.

INTRODUCTION: Prospective studies reporting associations between cognitive performance and subsequent incident dementia have been subject to attrition bias. Furthermore, the extent to which established risk factors account for such associations requires further elucidation. METHODS: We used UK Biobank baseline cognitive data (n ≤ 488,130) and electronically linked hospital inpatient and death records during three- to eight-year follow-up, to estimate risk of total dementia (n = 1051), Alzheimer's disease (n = 352), and vascular dementia (n = 169) according to four brief cognitive tasks, with/without adjustment for constitutional and modifiable risk factors. RESULTS: We found associations of cognitive task performance with all-cause and cause-specific dementia (P <  .01); these were not accounted for by established risk factors. Cognitive data added up to 5% to the discriminative accuracy of receiver operating characteristic curve models; areas under the curve ranged from 82% to 86%. DISCUSSION: This study offers robust evidence that brief cognitive testing could be a valuable addition to dementia prediction models.

Maternal and offspring intelligence in relation to BMI across childhood and adolescence.

OBJECTIVE: The present study tested the association between both mothers' and offspring's intelligence and offspring's body mass index (BMI) in youth. METHOD: Participants were members of the National Longitudinal Survey of Youth 1979 (NLSY-79) Children and Young Adults cohort (n = 11,512) and their biological mothers who were members of the NLSY-79 (n = 4932). Offspring's IQ was measured with the Peabody Individual Achievement Test (PIAT). Mothers' IQ was measured with the Armed Forces Qualification Test (AFQT). A series of regression analyses tested the association between IQ and offspring's BMI by age group, while adjusting for pre-pregnancy BMI and family SES. The analyses were stratified by sex and ethnicity (non-Black and non-Hispanic, Black, and Hispanic). RESULTS: The following associations were observed in the fully adjusted analyses. For the non-Blacks and non-Hispanics, a SD increment in mothers' IQ was negatively associated with daughters' BMI across all age-groups, ranging from ß = -0.12 (95% CI -0.22 to -0.02, p = 0.021) in late childhood, to ß = -0.17 (95% C.I. -0.27 to -0.07, p = 0001), in early adolescence and a SD increment in boys' IQ was positively associated with their BMI in early adolescence ß = 0.09 (95% CI 0.01-0.18, p = 0.031). For Blacks, there was a non-linear relationship between mothers' IQ and daughters' BMI across childhood and between girls' IQ and BMI across adolescence. There was a positive association between mothers' IQ and sons' BMI in early adolescence (ß = 0.17, 95% CI 0.02-0.32, p = 0.030). For Hispanic boys, there was a positive IQ-BMI association in late childhood (ß = 0.19, 95% CI 0.05-0.33, p = 0.008) and early adolescence (ß = 0.17, 95% CI 0.04-0.31, p = 0.014). CONCLUSION: Mothers' IQ and offspring's IQ were associated with offspring's BMI. The relationships varied in direction and strength across ethnicity, age group and sex. Obesity interventions may benefit from acknowledging the heterogeneous influence that intelligence has on childhood BMI.

Preconception Maternal Iodine Status Is Positively Associated with IQ but Not with Measures of Executive Function in Childhood.

Background: Adverse effects of severe maternal iodine deficiency in pregnancy on fetal brain development are well-established, but the effects of milder deficiency are uncertain. Most studies examine iodine status in pregnancy; less is known about iodine nutrition before conception. Objective: We examined relations between maternal preconception iodine status and offspring cognitive function, within a prospective mother-offspring cohort. Methods: Maternal iodine status was assessed through the use of the ratio of iodine:creatinine concentrations (I/Cr) in spot urine samples [median (IQR) period before conception 3.3 y (2.2-4.7 y)]. Childhood cognitive function was assessed at age 6-7 y. Full-scale IQ was assessed via the Wechsler Abbreviated Scale of Intelligence, and executive function through the use of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Analyses (n = 654 mother-child dyads) were adjusted for potential confounders including maternal intelligence, education, and breastfeeding duration. Results: The median (IQR) urinary iodine concentration was 108.4 µg/L (62.2-167.8 µg/L) and the I/Cr ratio 114 µg/g (76-164 µg/g). The preconception I/Cr ratio was positively associated with child IQ, before and after adjustment for potential confounding influences [ß = 0.13 (95% CI: 0.04, 0.21)/SD, P = 0.003]. 8.9% of women had a preconception urinary I/Cr ratio <50 µg/g; compared with those with an I/Cr ratio ≥150 µg/g, the IQ of their offspring was 0.49 (95% CI: 0.79, 0.18) SD lower. There were no associations with the executive function outcomes assessed via CANTAB, before or after adjustment for confounders. Conclusion: The positive association between iodine status before conception and child IQ provides some support for demonstrated links between low maternal iodine status in pregnancy and poorer cognitive function reported in other studies. However, given the negative effects on school performance previously observed in children born to iodine-deficient mothers, the lack of associations with measures of executive function in the present study was unexpected. Further data are needed to establish the public health importance of low preconception iodine status.

Arachidonic acid and DHA status in pregnant women is not associated with cognitive performance of their children at 4 or 6-7 years.

Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6-7 years in 724 mother-child pairs from the Southampton Women's Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (ß=0·36, P<0·001). DHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (ß=0·46, P<0·001). Children's cognitive function at the age of 4 years was assessed by the Wechsler Preschool and Primary Scale of Intelligence and at the age of 6-7 years by the Wechsler Abbreviated Scale of Intelligence. Executive function at the age of 6-7 years was assessed using elements of the Cambridge Neuropsychological Test Automated Battery. Neither DHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6-7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.