The relationship between prenatal nutrition and offspring autism related outcomes, and its socioeconomic context

Background. Prenatal nutrition may be an aetiological factor in the development of offspring autism. However, findings are inconsistent, possibly because of methodological limitations, such as small sample size and retrospective study design. Additionally, understanding the socioeconomic context of prenatal diet-autism relationships may inform public health. The overall aim was to draw on causally informed approaches to investigate the association between prenatal nutrition and autism and measure the extent to which inequalities in autism may be explain by a ‘healthy’ prenatal dietary pattern (HPDP). Methods. The research problem is introduced in Chapters 1-3, and the research aims were address in Chapters 4-7, which are in journal format. Chapter 4: in a systematic review and meta-analysis, I synthesised evidence on the association between prenatal multivitamin supplements and autism diagnosis and evidence of triangulation. Chapter 5: I measured the association between HPDP and offspring autism diagnosis and autism-associated traits in the Norwegian Mother, Father, and Child Cohort (MoBa). Results related to autismassociated traits were triangulated by replicating the analysis in the Avon Longitudinal Study of Parents and Children (ALSPAC). Chapter 6: Mendelian randomisation was applied to measure the relationship between the genetic instrument for HPDP and autismassociated traits in MoBa. Chapter 7: I measured the controlled direct effects of maternal socioeconomic deprivation on autism diagnosis and autism-associated traits when eliminating the proportion of the total effects which are attributed to HPDP. Results. The probability of autism diagnoses reduced in relation to prenatal multivitamin supplement use compared to no/low use. In MoBa and ALSPAC, the probability of autism diagnosis and autism-associated traits reduced if mothers had a high adherence to HPDP compared to low adherence. Causally informed approaches considered in Chapters 4-7 strengthened the interpretation of results, particularly the cross-context comparison. However, no clear evidence of association emerged from the Mendelian randomisation analysis, though there was insufficient power to detect moderate to large associations. The controlled direct effects analysis demonstrated that a modest proportion of socioeconomic disparities in each outcome were explained by HPDP. Conclusion. This thesis addressed some key limitations of the existing literature and applied causally informed approaches. Although these analyses provide stronger evidence, testing of causation was inconclusive. Future studies should continue to assess whether the associations between HPDP and autism diagnosis and autism-associated traits are causal. If causality were established, HPDP may be a target for intervention to reduce inequalities in the outcomes but when part of a larger strategy

NGC 7789: An Open Cluster Case Study

We have obtained high-resolution spectra of 32 giants in the open cluster NGC 7789 using the Wisconsin-Indiana-Yale-NOAO Hydra spectrograph. We explore differences in atmospheric parameters and elemental abundances caused by the use of the linelist developed for the Gaia-ESO Survey (GES) compared to one based on Arcturus used in our previous work. [Fe/H] values decrease when using the GES linelist instead of the Arcturus-based linelist; these differences are probably driven by systematically lower (~ -0.1 dex) GES surface gravities. Using the GES linelist we determine abundances for 10 elements - Fe, Mg, Si, Ca, Ti, Na, Ni, Zr, Ba, and La. We find the cluster's average metallicity [Fe/H] = 0.03 +/- 0.07 dex, in good agreement with literature values, and a lower [Mg/Fe] abundance than has been reported before for this cluster (0.11 +/- 0.05 dex). We also find the neutron-capture element barium to be highly enhanced - [Ba/Fe] = +0.48 +/- 0.08 - and disparate from cluster measurements of neutron-capture elements La and Zr (-0.08 +/- 0.05 and 0.08 +/- 0.08, respectively). This is in accordance with recent discoveries of supersolar Ba enhancement in young clusters along with more modest enhancement of other neutron-capture elements formed in similar environments.Comment: 15 pages, 9 figures, Table 1 typo fixe

A Chemical Abundance Study of 10 Open Clusters Based on WIYN-Hydra Spectroscopy

We present a detailed chemical abundance study of evolved stars in 10 open clusters based on Hydra multi-object echelle spectra obtained with the WIYN 3.5m telescope. From an analysis of both equivalent widths and spectrum synthesis, abundances have been determined for the elements Fe, Na, O, Mg, Si, Ca, Ti, Ni, Zr, and for two of the 10 clusters, Al and Cr. To our knowledge, this is the first detailed abundance analysis for clusters NGC 1245, NGC 2194, NGC 2355 and NGC 2425. These 10 clusters were selected for analysis because they span a Galactocentric distance range Rgc~9-13 kpc, the approximate location of the transition between the inner and outer disk. Combined with cluster samples from our previous work and those of other studies in the literature, we explore abundance trends as a function of cluster Rgc, age, and [Fe/H]. The [Fe/H] distribution appears to decrease with increasing Rgc to a distance of ~12 kpc, and then flattens to a roughly constant value in the outer disk. Cluster average element [X/Fe] ratios appear to be independent of Rgc, although the picture for [O/Fe] is more more complicated by a clear trend of [O/Fe] with [Fe/H] and sample incompleteness. Other than oxygen, no other element [X/Fe] exhibits a clear trend with [Fe/H]; likewise, there does not appear to be any strong correlation between abundance and cluster age. We divided clusters into different age bins to explore temporal variations in the radial element distributions. The radial metallicity gradient appears to have flattened slightly as a function of time, as found by other studies. There is also indication that the transition from the inner disk to the outer disk occurs at different Galactocentric radii for different age bins. (Abridged.)Comment: 35 pages, 12 figures, 18 tables; published in The Astronomical Journal (http://stacks.iop.org/1538-3881/142/59

Healthy prenatal dietary pattern and offspring autism.

Prenatal diet may be causally related to autism; however, findings are inconsistent, with a limited body of research based on small sample sizes and retrospective study designs. To investigate the associations of prenatal dietary patterns with autism diagnosis and autism-associated traits in 2 large prospective cohorts, the Norwegian Mother, Father, and Child Cohort Study (MoBa), and the Avon Longitudinal Study of Parents and Children (ALSPAC). This cohort study used data from MoBa and ALSPAC birth cohort studies conducted across Norway and in the Southwest of England, respectively. Participants were people with singleton pregnancies with self-reported food frequency questionnaire responses. MoBa recruited between 2002 and 2008, and ALSPAC recruited between 1990 and 1992, and children were followed-up until age 8 years or older. Recruitment rates were 41% (95 200 of 277 702 eligible pregnancies) in MoBa and 72% (14 541 of 20 248 eligible pregnancies) in ALSPAC. Data analysis occurred February 1, 2022, to August 1, 2023. A healthy prenatal dietary pattern was derived using factor analysis and modeled as low, medium, and high adherence. In MoBa, the offspring outcomes were autism diagnosis and elevated social communication questionnaire score at ages 3 years and 8 years, with further analysis of the social communication difficulties and restrictive and repetitive behaviors subdomains. In ALSPAC, offspring outcomes were elevated social communication difficulties checklist score at age 8 years. Odds ratios (ORs) were estimated using generalized nonlinear models. MoBa included 84 548 pregnancies (mean [SD] age, 30.2 [4.6] years; 43 277 [51.2%] male offspring) and ALSPAC had 11 760 pregnancies (mean [SD] age, 27.9 [4.7] years; 6034 [51.3%] male offspring). In the final adjusted models, high adherence to a healthy dietary pattern, compared with low adherence, was associated with reduced odds of autism diagnosis (OR, 0.78; 95% CI, 0.66-0.92) and social communication difficulties at age 3 years in MoBa (OR 0.76, 95% CI, 0.70-0.82) and age 8 years in ALSPAC (OR, 0.74; 95% CI, 0.55-0.98). There was no consistent evidence of association with the other outcomes. In this cohort study of mother-child dyads, adherence to a healthy prenatal dietary pattern was associated with a lower odds of autism diagnosis and social communication difficulties but not restrictive and repetitive behaviors

Prenatal vitamins and the risk of offspring autism spectrum disorder: systematic review and meta-analysis

Prenatal nutrition is associated with offspring autism spectrum disorder (herein referred to as autism), yet, it remains unknown if the association is causal. Triangulation may improve causal inference by integrating the results of conventional multivariate regression with several alternative approaches that have unrelated sources of bias. We systematically reviewed the literature on the relationship between prenatal multivitamin supplements and offspring autism, and evidence for the causal approaches applied. Six databases were searched up to 8 June 2020, by which time we had screened 1309 titles/abstracts, and retained 12 articles. Quality assessment was guided using Newcastle–Ottawa in individual studies, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) for the body of evidence. The effect estimates from multivariate regression were meta-analysed in a random effects model and causal approaches were narratively synthesised. The meta-analysis of prenatal multivitamin supplements involved 904,947 children (8159 cases), and in the overall analysis showed no robust association with offspring autism; however, a reduced risk was observed in the subgroup of high-quality observational studies (RR 0.77, 95% CI (0.62, 0.96), I2 = 62.4%), early pregnancy (RR 0.76, 95% CI (0.58; 0.99), I2 = 79.8%) and prospective studies (RR 0.69, 95% CI (0.48, 1.00), I2 = 95.9%). The quality of evidence was very low, and triangulation was of limited utility because alternative methods were used infrequently and often not robustly applied

The health benefits of pedestrian and cyclist commuting: evidence from the Scottish Longitudinal Study

Background: Despite active travel investment increasing, evidence of benefit is often limited to selected health outcomes and a short follow-up period, and cyclists and pedestrians are often analysed together. We aimed to examine prospective associations with multiple health outcomes over 18 years for pedestrians and cyclists separately. Methods: The Scottish Longitudinal Study is based on census data, from which we selected 82 297 individuals aged 16–74 years. Individuals were followed-up between 2001 and 2018 through linkage to hospitalisation, death and prescription records. Cox proportional hazard models were used to compare cyclist and pedestrian commuters with non-active commuters for a range of health outcomes, controlling for pre-existing health conditions, and demographic and socioeconomic characteristics. Results: Compared with non-active commuting, cyclist commuting was associated with lower all-cause mortality risk (HR 0.53, 95% CI 0.38 to 0.73), lower risk of any hospitalisation (HR 0.90, 95% CI 0.84 to 0.97), lower risk of cardiovascular disease (CVD) hospitalisation (HR 0.76, 95% CI 0.64 to 0.91) and of having a CVD prescription (HR 0.70, 95% CI 0.63 to 0.78), lower risk of cancer mortality (HR 0.49, 95% CI 0.30 to 0.82) and cancer hospitalisation (HR 0.76, 95% CI 0.59 to 0.98), and lower risk of having a prescription for mental health problems (HR 0.80, 95% CI 0.73 to 0.89). Pedestrian commuting was associated with lower risk of any hospitalisation (HR 0.91, 95% CI 0.88 to 0.93), lower risk of CVD hospitalisation (HR 0.90, 95% CI 0.84 to 0.96) and of having a CVD prescription (HR 0.90, 95% CI 0.87 to 0.93), and lower risk of a mental health prescription (HR 0.93, 95% CI 0.90 to 0.97). Conclusion: Active commuters were less likely to suffer from a range of negative physical and mental health outcomes than non-active commuters. These findings strengthen the evidence for the health benefits of active commuting

Haemagglutination inhibition and virus microneutralisation serology assays: use of harmonised protocols and biological standards in seasonal influenza serology testing and their impact on inter-laboratory variation and assay correlation: A FLUCOP collaborative study

Introduction: The haemagglutination inhibition assay (HAI) and the virus microneutralisation assay (MN) are long-established methods for quantifying antibodies against influenza viruses. Despite their widespread use, both assays require standardisation to improve inter-laboratory agreement in testing. The FLUCOP consortium aims to develop a toolbox of standardised serology assays for seasonal influenza. Building upon previous collaborative studies to harmonise the HAI, in this study the FLUCOP consortium carried out a head-to-head comparison of harmonised HAI and MN protocols to better understand the relationship between HAI and MN titres, and the impact of assay harmonisation and standardisation on inter-laboratory variability and agreement between these methods. Methods: In this paper, we present two large international collaborative studies testing harmonised HAI and MN protocols across 10 participating laboratories. In the first, we expanded on previously published work, carrying out HAI testing using egg and cell isolated and propagated wild-type (WT) viruses in addition to high-growth reassortants typically used influenza vaccines strains using HAI. In the second we tested two MN protocols: an overnight ELISA-based format and a 3-5 day format, using reassortant viruses and a WT H3N2 cell isolated virus. As serum panels tested in both studies included many overlapping samples, we were able to look at the correlation of HAI and MN titres across different methods and for different influenza subtypes. Results: We showed that the overnight ELISA and 3-5 day MN formats are not comparable, with titre ratios varying across the dynamic range of the assay. However, the ELISA MN and HAI are comparable, and a conversion factor could possibly be calculated. In both studies, the impact of normalising using a study standard was investigated, and we showed that for almost every strain and assay format tested, normalisation significantly reduced inter-laboratory variation, supporting the continued development of antibody standards for seasonal influenza viruses. Normalisation had no impact on the correlation between overnight ELISA and 3-5 day MN formats.publishedVersio