Maternal urinary metabolic signatures of fetal growth and associated clinical and environmental factors in the INMA study

Background Maternal metabolism during pregnancy is a major determinant of the intra-uterine environment and fetal outcomes. Herein, we characterize the maternal urinary metabolome throughout pregnancy to identify maternal metabolic signatures of fetal growth in two subcohorts and explain potential sources of variation in metabolic profiles based on lifestyle and clinical data. Methods We used 1H nuclear magnetic resonance (NMR) spectroscopy to characterize maternal urine samples collected in the INMA birth cohort at the first (n = 412 and n = 394, respectively, in Gipuzkoa and Sabadell cohorts) and third trimesters of gestation (n = 417 and 469). Metabolic phenotypes that reflected longitudinal intra- and inter-individual variation were used to predict measures of fetal growth and birth weight. Results A metabolic shift between the first and third trimesters of gestation was characterized by 1H NMR signals arising predominantly from steroid by-products. We identified 10 significant and reproducible metabolic associations in the third trimester with estimated fetal, birth, and placental weight in two independent subcohorts. These included branched-chain amino acids; isoleucine, valine, leucine, alanine and 3 hydroxyisobutyrate (metabolite of valine), which were associated with a significant fetal weight increase at week 34 of up to 2.4 % in Gipuzkoa (P < 0.005) and 1 % in Sabadell (P < 0.05). Other metabolites included pregnancy-related hormone by-products of estrogens and progesterone, and the methyl donor choline. We could explain a total of 48–53 % of the total variance in birth weight of which urine metabolites had an independent predictive power of 12 % adjusting for all other lifestyle/clinical factors. First trimester metabolic phenotypes could not predict reproducibly weight at later stages of development. Physical activity, as well as other modifiable lifestyle/clinical factors, such as coffee consumption, vitamin D intake, and smoking, were identified as potential sources of metabolic variation during pregnancy. Conclusions Significant reproducible maternal urinary metabolic signatures of fetal growth and birth weight are identified for the first time and linked to modifiable lifestyle factors. This novel approach to prenatal screening, combining multiple risk factors, present a great opportunity to personalize pregnancy management and reduce newborn disease risk in later life

How to Establish and Follow up a Large Prospective Cohort Study in the 21st Century - Lessons from UK COSMOS.

Large-scale prospective cohort studies are invaluable in epidemiology, but they are increasingly difficult and costly to establish and follow-up. More efficient methods for recruitment, data collection and follow-up are essential if such studies are to remain feasible with limited public and research funds. Here, we discuss how these challenges were addressed in the UK COSMOS cohort study where fixed budget and limited time frame necessitated new approaches to consent and recruitment between 2009-2012. Web-based e-consent and data collection should be considered in large scale observational studies, as they offer a streamlined experience which benefits both participants and researchers and save costs. Commercial providers of register and marketing data, smartphones, apps, email, social media, and the internet offer innovative possibilities for identifying, recruiting and following up cohorts. Using examples from UK COSMOS, this article sets out the dos and don'ts for today's cohort studies and provides a guide on how best to take advantage of new technologies and innovative methods to simplify logistics and minimise costs. Thus a more streamlined experience to the benefit of both research participants and researchers becomes achievable

Impact of mobile phones and wireless devices use on children and adolescents´ mental health: a systematic review

Growing use of mobiles phones (MP) and other wireless devices (WD) has raised concerns about their possible effects on children and adolescents’ wellbeing. Understanding whether these technologies affect children and adolescents’ mental health in positive or detrimental ways has become more urgent following further increase in use since the COVID-19 outbreak. To review the empirical evidence on associations between use of MP/WD and mental health in children and adolescents. A systematic review of literature was carried out on Medline, Embase and PsycINFO for studies published prior to July 15th 2019, PROSPERO ID: CRD42019146750. 25 observational studies published between January 1st 2011 and 2019 were reviewed (ten were cohort studies, 15 were cross-sectional). Overall estimated participant mean age and proportion female were 14.6 years and 47%, respectively. Substantial between-study heterogeneity in design and measurement of MP/WD usage and mental health outcomes limited our ability to infer general conclusions. Observed effects differed depending on time and type of MP/WD usage. We found suggestive but limited evidence that greater use of MP/WD may be associated with poorer mental health in children and adolescents. Risk of bias was rated as ‘high’ for 16 studies, ‘moderate’ for five studies and ‘low’ for four studies. More high-quality longitudinal studies and mechanistic research are needed to clarify the role of sleep and of type of MP/WD use (e.g. social media) on mental health trajectories in children and adolescents

Urinary metabolic profiles in early pregnancy are associated with preterm birth and fetal growth restriction in the Rhea mother-child cohort study

Syftet med studien var att undersöka vilka möjligheter matematikundervisning utomhus kan ge för elevernas utveckling och lärande. Syftet var även att undersöka hur utomhusmatematik kan användas som ett komplement till den traditionella inomhusundervisningen i ämnet matematik. Studien baserades på en kvalitativ forskningsansats där kvalitativa semistrukturerade intervjuer och ostrukturerade observationer användes som metoder för att besvara studiens forskningsfrågor. Sex lärare i F-3 intervjuades och två observationer på två olika skolor genomfördes. Resultatet visar att utomhusmatematiken kompletterar matematikundervisningen inomhus genom ett samspel mellan arbetssätt och miljöer. Resultatet visar även på flera positiva effekter med utomhusmatematik så som verklighetsanknytning, motivation, fysisk aktivitet, hälsa, sinnligt lärande, tillåtande miljö och sociala effekter.  De positiva effekter utomhusmatematiken medföljer för elevernas utveckling och lärande bör uppmärksamma fler lärare om dess möjligheter.

Global metabolic changes induced by plant-derived pyrrolizidine alkaloids following a human poisoning outbreak and in a mouse model

Several hundred cases of Hirmi Valley Liver Disease (HVLD), an often fatal liver injury, occurred from 2001 to 2011 in a cluster of rural villages in Tigray, Ethiopia. HVLD is principally caused by contamination of the food supply with plant derived pyrrolizidine alkaloids (PAs), with high exposure to the pesticide DDT among villagers increasing their susceptibility. In an untargeted global approach we aimed to identify metabolic changes induced by PA exposure through 1H NMR spectroscopic based metabolic profiling. We analysed spectra acquired from urine collected from HVLD cases and controls and a murine model of PA exposure and PA/DDT co-exposure, using multivariate partial least squares discriminant analysis. In the human models we identified changes in urinary concentrations of tyrosine, pyruvate, bile acids, N-acetylglycoproteins, N-methylnicotinamide and formate, hippurate, p-cresol sulphate, p-hydroxybenzoate and 3-(3-hydroxyphenyl) propionic acid. Tyrosine and p-cresol sulphate were associated with both exposure and disease. Similar changes to tyrosine, one-carbon intermediates and microbial associated metabolites were observed in the mouse model, with tyrosine correlated with the extent of liver damage. These results provide mechanistic insight and implicate the gut microflora in the human response to challenge with toxins. Pathways identified here may be useful in translational research and as “exposome” signals

Impacts of air pollution and noise on risk of preterm birth and stillbirth in London

Background Evidence for associations between ambient air pollution and preterm birth and stillbirth is inconsistent. Road traffic produces both air pollutants and noise, but few studies have examined these co-exposures together and none to date with all-cause or cause-specific stillbirths. Objectives To analyse the relationship between long-term exposure to air pollution and noise at address level during pregnancy and risk of preterm birth and stillbirth. Methods The study population comprised 581,774 live and still births in the Greater London area, 2006–2010. Outcomes were preterm birth (<37 completed weeks gestation), all-cause stillbirth and cause-specific stillbirth. Exposures during pregnancy to particulate matter with diameter <2.5 μm (PM2.5) and <10 μm (PM10), ozone (O3), primary traffic air pollutants (nitrogen dioxide, nitrogen oxides, PM2.5 from traffic exhaust and traffic non-exhaust), and road traffic noise were estimated based on maternal address at birth. Results An interquartile range increase in O3 exposure was associated with elevated risk of preterm birth (OR 1.15 95% CI: 1.11, 1.18, for both Trimester 1 and 2), all-cause stillbirth (Trimester 1 OR 1.17 95% CI: 1.07, 1.27; Trimester 2 OR 1.20 95% CI: 1.09, 1.32) and asphyxia-related stillbirth (Trimester 1 OR 1.22 95% CI: 1.01, 1.49). Odds ratios with the other air pollutant exposures examined were null or <1, except for primary traffic non-exhaust related PM2.5, which was associated with 3% increased odds of preterm birth (Trimester 1) and 7% increased odds stillbirth (Trimester 1 and 2) when adjusted for O3. Elevated risk of preterm birth was associated with increasing road traffic noise, but only after adjustment for certain air pollutant exposures. Discussion Our findings suggest that exposure to higher levels of O3 and primary traffic non-exhaust related PM2.5 during pregnancy may increase risk of preterm birth and stillbirth; and a possible relationship between long-term traffic-related noise and risk of preterm birth. These findings extend and strengthen the evidence base for important public health impacts of ambient ozone, particulate matter and noise in early life

Road traffic noise is associated with increased cardiovascular morbidity and mortality and all-cause mortality in London.

AIMS: Road traffic noise has been associated with hypertension but evidence for the long-term effects on hospital admissions and mortality is limited. We examined the effects of long-term exposure to road traffic noise on hospital admissions and mortality in the general population. METHODS AND RESULTS: The study population consisted of 8.6 million inhabitants of London, one of Europe's largest cities. We assessed small-area-level associations of day- (7:00-22:59) and nighttime (23:00-06:59) road traffic noise with cardiovascular hospital admissions and all-cause and cardiovascular mortality in all adults (≥25 years) and elderly (≥75 years) through Poisson regression models. We adjusted models for age, sex, area-level socioeconomic deprivation, ethnicity, smoking, air pollution, and neighbourhood spatial structure. Median daytime exposure to road traffic noise was 55.6 dB. Daytime road traffic noise increased the risk of hospital admission for stroke with relative risk (RR) 1.05 [95% confidence interval (CI): 1.02-1.09] in adults, and 1.09 (95% CI: 1.04-1.14) in the elderly in areas >60 vs. 60 vs. <55 dB]. Positive but non-significant associations were seen with mortality for cardiovascular and ischaemic heart disease, and stroke. Results were similar for the elderly. CONCLUSIONS: Long-term exposure to road traffic noise was associated with small increased risks of all-cause mortality and cardiovascular mortality and morbidity in the general population, particularly for stroke in the elderly

Modulatory effects of SES and multilinguistic experience on cognitive development: a longitudinal data analysis of multilingual and monolingual adolescents from the SCAMP cohort

Previous research has shown that cognitive development is sensitive to socio-economic status (SES) and multilinguistic experiences. However, these effects are difficult to disentangle and SES may modulate the effects of multilingualism. The present study used data from a large cohort of pupils who took part in the Study of Cognition, Adolescents and Mobile Phones (SCAMP) at ages 11–12 (T1) and 13–15 years old (T2). Cognitive measures were derived from tasks of cognitive flexibility, verbal, spatial and visuo-spatial working memory, speech processing and non-verbal reasoning. Using SES information collected through questionnaires (school type, level of deprivation, parental education and occupation), the sample was clustered into high/medium/low SES groups. Comparisons focused on 517 monolingual and 329 multilingual pupils in the high/low SES groups. Having controlled for multiple comparisons, the results indicated a significant beneficial effect of bilingualism in measures of working memory, visuo-spatial processing and non-verbal reasoning. These effects were present in both high and low SES individuals and sustained at both times of development, with a particularly significant improvement of working memory abilities in low SES bilinguals at T2 as compared to monolingual peers. Theoretical and practical implications of these findings are considered and guidance for educators is discussed

Long-term effect of mobile phone use on sleep quality: results from the cohort study of mobile phone use and health (COSMOS)

BACKGROUND: Effects of radiofrequency electromagnetic field exposure (RF-EMF) from mobile phone use on sleep quality has mainly been investigated in cross-sectional studies. The few previous prospective cohort studies found no or inconsistent associations, but had limited statistical power and short follow-up. In this large prospective cohort study, our aim was to estimate the effect of RF-EMF from mobile phone use on different sleep outcomes. MATERIALS AND METHODS: The study included Swedish (n = 21,049) and Finnish (n = 3120) participants enrolled in the Cohort Study of Mobile Phone Use and Health (COSMOS) with information about operator-recorded mobile phone use at baseline and sleep outcomes both at baseline and at the 4-year follow-up. Sleep disturbance, sleep adequacy, daytime somnolence, sleep latency, and insomnia were assessed using the Medical Outcome Study (MOS) sleep questionnaire. RESULTS: Operator-recorded mobile phone use at baseline was not associated with most of the sleep outcomes. For insomnia, an odds ratio (OR) of 1.24, 95% CI 1.03-1.51 was observed in the highest decile of mobile phone call-time (>258 min/week). With weights assigned to call-time to account for the lower RF-EMF exposure from Universal Mobile Telecommunications Service (UMTS, 3G) than from Global System for Mobile Communications (GSM, 2G) the OR was 1.09 (95% CI 0.89-1.33) in the highest call-time decile. CONCLUSION: Insomnia was slightly more common among mobile phone users in the highest call-time category, but adjustment for the considerably lower RF-EMF exposure from the UMTS than the GSM network suggests that this association is likely due to other factors associated with mobile phone use than RF-EMF. No association was observed for other sleep outcomes. In conclusion, findings from this study do not support the hypothesis that RF-EMF from mobile phone use has long-term effects on sleep quality