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Background The combined influence of early life risk factors on the type 2 diabetes (T2D) development is not well-studied, and it is unclear whether these associations can by modified by genetic risk and healthy lifestyles in later life. Methods We studied 148,621 participants in the UK Biobank. We calculated early-life risk scores (ERS) by summing the cumulative number of three early-life risk factors: low birth weight, maternal smoking during pregnancy, and non-breastfed as a baby. We estimated polygenic risk scores (PRS) for T2D and calculated participants’ modifiable healthy lifestyle score (MHS) during adulthood. Results A total of 7,408 incident T2D were identified. ERS showed a positive dose-response association with T2D risk. Compared with participants with 0 ERS, those with 3 ERS had the highest risk of developing T2D (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.65, 2.26). This association was not modified by T2D-PRS or MHS. In the joint exposure analyses, compared with participants with the lowest risk exposure (i.e., lowest ERS combined with lowest T2D-PRS/healthy lifestyle in later life), we observed highest risk of T2D among individuals with the highest ERS combined with the highest tertile of T2D-PRS (HR = 6.67, 95% CI: 5.43, 8.20) or an unhealthy lifestyle in later life (HR = 4.99, 95% CI: 3.54, 7.02), respectively. Conclusions Early-life risk factors are associated with a higher risk of T2D in a dose-response manner, regardless of genetic risk or later-life healthy lifestyle. Therefore, identifying early-life modifiable risk factors is helpful to develop strategies of T2D prevention.

The effect of saturated fatty acids (SFAs) on incident type 2 diabetes (T2D) is controversial and few have systematically appraised the evidence. We conducted a comprehensive search of prospective studies examining these relationships that were published in PubMed, Web of Science, or EMBASE from 21 February 1989 to 21 February 2019. A total of 19 studies were included for systematic review and 10 for meta-analysis. We estimated the summarized relative risk (RR) and 95% confidence interval (95% CI) using a random (if I2 > 50%) or a fixed effects model (if I2 ≤ 50%). Although the included studies reported inconclusive results, the majority supported a protective effect of odd-chain and an adverse impact of even-chain SFAs. Meta-analysis showed that the per standard deviation (SD) increase in odd-chain SFAs was associated with a reduced risk of incident T2D (C15:0: 0.86, 0.76–0.98; C17:0: 0.76, 0.59–0.97), while a per SD increase in one even-chain SFA was associated with an increased risk of incident T2D (C14:0: 1.13, 1.09–1.18). No associations were found between other SFAs and incident T2D. In conclusion, our findings suggest an overall protective effect of odd-chain SFAs and the inconclusive impact of even- and very-long-chain SFAs on incident T2D.

Assisted reproductive technologies (ART) are increasingly used, however little is known about the long-term health of ART-conceived offspring. Weak selection of comparison groups and poorly characterized mechanisms impede current understanding. In a prospective cohort (Growing Up in Singapore Towards healthy Outcomes; GUSTO; Clinical Trials ID: NCT01174875) including 83 ART-conceived and 1095 spontaneously-conceived singletons, we estimate effects of ART on anthropometry, blood pressure, serum metabolic biomarkers, and cord tissue DNA methylation by emulating a pragmatic trial supported by machine learning-based estimators. We find ART-conceived children to be shorter (−0.5 SD [95% CI: −0.7, −0.2]), lighter (−0.6 SD [−0.9, −0.3]) and have lower skinfold thicknesses (e.g. −14% [−24%, −3%] suprailiac), and blood pressure (−3 mmHg [−6, −0.5] systolic) at 6-6.5 years, with no strong differences in metabolic biomarkers. Differences are not explained by parental anthropometry or comorbidities, polygenic risk score, breastfeeding, or illnesses. Our simulations demonstrate ART is strongly associated with lower NECAB3 DNA methylation, with negative control analyses suggesting these estimates are unbiased. However, methylation changes do not appear to mediate observed differences in child phenotype. Huang and colleagues used machine-learning estimators to analyse a broad range of parameters in a prospective cohort consisting ART and spontaneously conceived children. Small differences in stature and growth could not be explained by parental or perinatal environment factors, nor differences in fetal DNA methylation. No strong differences in metabolic parameters were seen.

Neighborhood and individual-level trauma-related stressors during pregnancy can increase oxidative stress, potentially altering cellular disease pathway biomarkers such as mitochondrial DNA copy number (mtDNAcn) and telomere length (TL). However, the biological mechanisms linking early-life stressors to long-term health outcomes remain understudied. In a subset of Project Viva participants (n = 415–917), we evaluated associations of neighborhood and individual-level stressors with mean relative mtDNAcn and TL measured in first trimester maternal blood and cord blood. Neighborhood stressors during pregnancy were assessed using the Child Opportunity Index (COI) and Social Vulnerability Index (SVI). Trauma-related stressors were measured using the Personal Safety Questionnaire (PSQ), administered mid-pregnancy, and maternal Adverse Childhood Experiences (ACEs), reported during a mid-life follow-up. In multivariable linear regression analysis, residence in a very high versus very low opportunity neighborhood was associated with lower maternal mtDNAcn ( = − 0.09, 95% confidence interval (CI) − 0.17, − 0.02), while residence in a very high versus very low vulnerability area was associated with higher maternal mtDNAcn ( = 0.06, 95% CI 0.01, 0.12). Additionally, residence in moderate versus very low opportunity neighborhoods was associated with longer cord blood TL ( = 0.39, 95% CI 0.0002, 0.78), but associations were attenuated after cell-type adjustment. Our findings suggest that prenatal neighborhood stressors are associated with increased maternal mtDNAcn and neighborhood opportunity is associated with longer fetal TL, indicating possible links to biological pathways related to oxidative stress and cellular aging.

We investigated body mass index (BMI) trajectories in the first 2 years of life in 1170 children from an Asian mother-offspring cohort in Singapore, and examined their predictors and associations with childhood cardio-metabolic risk measures at 5 years. Latent class growth mixture modelling analyses were performed to identify distinct BMI z-score (BMIz) trajectories. Four trajectories were identified: 73.2%(n = 857) of the children showed a normal BMIz trajectory, 13.2%(n = 155) a stable low-BMIz trajectory, 8.6%(n = 100) a stable high-BMIz trajectory and 5.0%(n = 58) a rapid BMIz gain after 3 months trajectory. Predictors of the stable high-BMIz and rapid BMIz gain trajectories were pre-pregnancy BMI, gestational weight gain, Malay and Indian ethnicity, while predictors of stable low-BMIz trajectory were preterm delivery and Indian ethnicity. At 5 years, children with stable high-BMIz or rapid BMIz gain trajectories had increased waist-to-height ratios [B(95%CI) 0.02(0.01,0.03) and 0.03(0.02,0.04)], sum of skinfolds [0.42(0.19,0.65) and 0.70(0.36,1.03)SD units], fat-mass index [0.97(0.32,1.63)SD units] and risk of obesity [relative risk 3.22(1.73,6.05) and 2.56 (1.19,5.53)], but not higher blood pressure. BMIz trajectories were more predictive of adiposity at 5 years than was BMIz at 2 years. Our findings on BMIz trajectories in the first 2 years suggest important ethnic-specific differences and impacts on later metabolic outcomes.

In Asia, little is known about how maternal feeding practices are associated with dietary intakes and body mass index (BMI) in preschoolers. To assess the relationships between maternal feeding practices with dietary intakes and BMI in preschoolers in Asia using cross-sectional analysis in the GUSTO (Growing Up in Singapore Towards healthy Outcomes) cohort. Mothers (n = 511) who completed the Comprehensive Feeding Practices Questionnaire (CFPQ) and a semi-quantitative Food Frequency Questionnaire (FFQ) when children were 5 years old. Associations between 12 maternal feeding practices (mean scores divided into tertiles) and children's dietary intakes of seven food groups and BMI z-scores were examined using the general linear regression model. Weight and height of the child were measured, and dietary intakes derived from the FFQ. Compared to those in the low tertile, mothers in the high tertile of modelling healthy food intakes had children with higher intakes of vegetables[+20.0g/day (95%CI:11.6,29.5)] and wholegrains[+ 20.9g/day (9.67,31.1)] but lower intakes of sweet snacks[-10.1g/day (-16.3,-4.94)] and fast-foods[-5.84g/day (-10.2,-1.48)]. Conversely, children of mothers in the high tertile for allowing child control (lack of parental control) had lower intake of vegetables[-15.2g/day (-26.6,-5.21)] and wholegrains[-13.6g/day (-22.9,-5.27)], but higher intakes of sweet snacks[+13.7g/day (7.7, 19.8)] and fast-foods[+6.63g/day (3.55,9.72)]. In relation to BMI at 5 years, food restrictions for weight was associated with higher BMI z-scores [0.86SD (0.61,1.21)], while use of pressure was associated with lower BMI z-scores[-0.49SD(-0.78,-0.21)]. Modelling healthy food intakes by mothers was the key feeding practice associated with higher intakes of healthy foods and lower intakes of discretionary foods. The converse was true for allowing child control. Only food restrictions for weight and use of pressure were associated with BMI z-scores.

Background The developing kidney is vulnerable to prenatal environmental factors such as metal exposure, potentially altering the risk of later-life kidney dysfunction. This study examines the relationship between prenatal metal exposures, individually and as mixtures, and adolescent kidney function in Project Viva, a prospective longitudinal birth cohort in Massachusetts, USA. Methods We used data on metals measured in blood during pregnancy including 15 in the first trimester and four in the second trimester. We calculated estimated glomerular filtration rate (eGFR) in adolescents (mean: 17.7 years) using cystatin C- (eGFRcys) and creatinine-based (eGFRcreat) equations for children. We used linear regression for single metal analyses, and Bayesian kernel machine regression and quantile-based g-computation for mixture analyses, adjusting for relevant covariates. To account for multiple comparisons in the single metal analyses, we applied the Holm-Bonferroni procedure to control the false discovery rate. Results This study included 371 participants with first trimester metals and adolescent eGFR, and 256 with second trimester metals. Each doubling in first trimester cadmium concentration was associated with lower adolescent eGFRcys (β:-1.51; 95% CI:-2.83, -0.18). Each doubling in first trimester chromium (β:-1.45; 95% CI:-2.71, -0.19), nickel (β:-1.91; 95% CI:-3.65, -0.16), and vanadium (β:-1.69; 95% CI:-3.21, -0.17) was associated with lower adolescent eGFRcreat. After adjusting for multiple comparisons, p-values for associations between adolescent eGFR and chromium, nickel, vanadium and cadmium did not meet the criteria for significance. Metal mixture analyses did not identify statistically significant associations with adolescent eGFR. Conclusions These findings have important implications for future studies investigating the potential mechanisms through which prenatal metal exposures affect long-term kidney health in children.

Plain English summary Many women experience suboptimal cardiovascular health during midlife, increasing their risk of heart disease. Research suggests that exposure to greenspace, such as vegetation and trees, may benefit heart health, but most studies have relied on satellite images rather than street-level views. In this study, we used Google Street View images and artificial intelligence to measure visible greenspace around the homes of 767 women from the Project Viva study in Eastern Massachusetts. We assessed greenspace exposure from trees, grass, and other plants within 500 m of their homes between 2012 and 2016 and examined its association with cardiovascular health scores about five years later, accounting for individual and neighborhood socioeconomic status. We evaluated cardiovascular health scores using the Life’s Essential 8 (LE8) construct, which includes behavioral factors (diet, physical activity, sleep, and smoking) and biomedical factors (body mass index, blood pressure, blood lipids, and blood glucose). Our results showed that women living in areas with more total greenspace—particularly more trees—had higher overall cardiovascular health scores. Living in an area with higher amounts of visible trees was associated with a healthier diet, better sleep, higher physical activity levels, smoking avoidance, and healthier body weight, blood pressure, and blood sugar levels. These findings suggest that increasing trees in neighborhoods could support better cardiovascular health among women in midlife. Policies promoting urban tree planting may be a valuable public health strategy to improve heart health and overall well-being. Background Many women experience suboptimal cardiovascular health (CVH) during midlife. Greenspace exposure has been inversely associated with cardiovascular disease because it may reduce harmful environmental exposures and promote healthy behaviors. Most prior studies used satellite-based rather than ground-level exposures and did not examine overall CVH. Methods We performed a longitudinal analysis of women in the Project Viva cohort based in Eastern Massachusetts. We applied deep learning algorithms to Google Street View images to derive metrics of visible trees, grass, and other greenspace within 500 m of participant’s residential addresses in 2012–2016 (mean age 46 years). About five years later (mean age 51 years), participants completed questionnaires and research measurements including blood collection. We calculated CVH scores using Life’s Essential 8 (LE8) construct (0-100 points, higher = better), which includes four behavioral (diet, physical activity, sleep, and avoidance of smoking) and four biomedical measures (body mass index, blood pressure, blood lipids, and blood glucose). We used linear regression models adjusted for age and both individual- and neighborhood-level socioeconomic status. Results Among 767 participants, 68% were non-Hispanic White, and 74% were college graduates. Mean (SD) CVH score was 72 (13) points. When including three greenspace components in the same model, higher % trees (per SD) was associated with higher overall CVH score (β = 2.4; 95% CI: 1.3, 3.5), as well as higher behavioral (β = 2.8; 95% CI: 1.4, 4.3) and biomedical (β = 2.8; 95% CI: 1.0, 4.7) sub-scores. Additionally, % other greenspace (per SD) was associated with better biomedical CVH scores (β = 2.2; 95% CI: 0.4, 3.9), whereas associations for % grass were non-significant. Higher % trees (per SD) was associated with higher scores for most individual CVH components, including diet (β = 2.1 points; 95% CI: 0.7, 3.4), physical activity (β = 4.0; 95% CI: 1.2, 6.9), sleep (β = 2.6; 95% CI: 0.9, 4.4), BMI (β = 5.8; 95% CI: 2.8, 8.8), and blood glucose (β = 2.2; 95% CI: 0.3, 4.2). Conclusions Greater street-view greenspace exposure, especially visible trees in streetscapes, was associated with better CVH among midlife women. Increasing trees in neighborhoods may be a valuable public health strategy to improve multiple metrics of cardiovascular health. Highlights We examined the associations of street-view greenspace exposure with cardiovascular health among midlife women in the Project Viva cohort. We quantified greenspace exposure using deep learning models applied to Google Street View images, measuring the percentage of trees, grass, and other plants within view in images within 500 m of participants’ homes. We assessed cardiovascular health using the Life’s Essential 8 (LE8) score, which includes behavioral (diet, physical activity, sleep, smoking) and biomedical (BMI, blood pressure, lipids, glucose) components. We found that greater street-view greenspace, particularly trees, was associated with higher overall cardiovascular health scores, including healthier behaviors and biomedical measures. Increasing trees in neighborhoods may be a valuable public health strategy to improve cardiovascular health among midlife women.

Food reward is defined as the momentary value of a food to the individual at the time of ingestion and is characterised by two psychological processes–“liking” and “wanting”. We aimed to validate an age-appropriate food reward task to quantify implicit wanting of children from the GUSTO cohort (n = 430). At age 5 years, child appetitive traits and maternal feeding practices were reported by mothers via questionnaires. At age 6, a write-for-food task based on the child’s preference for food or toy rewards was undertaken in laboratory conditions. Child BMI and skinfold measurements were taken at age 7. Convergent validity of the food reward task was assessed by associating with child appetitive traits, where enjoyment of food/food responsiveness (OR: 1.51; 95% CI: 1.06, 2.15) and emotional overeating (OR: 1.64; 95% CI: 1.09, 2.48) were positively associated with high food reward in children. Criterion validity was tested by associating with child BMI, however no significant relationships were observed. Multivariable logistic regression analysis with maternal feeding practices revealed that children whose mother tend to restrict unhealthy food (OR: 1.37; 95% CI: 1.03, 1.82) and girls whose mothers taught them about nutrition (OR: 2.09; 95% CI: 1.19, 3.67) were more likely to have high food reward. No further significant associations were observed between food reward, other appetitive traits and feeding practices. Despite the lack of association with child weight status, this study demonstrated the value of the write-for-food task to assess food reward in children and presented sex-specific associations with maternal feeding practices.