Human exposure to currently used pesticides (CUPs) is widespread, with children being especially vulnerable to possible adverse health effects. Assessing exposure and related risks in children is therefore essential. In this study, 6 parent compounds and 9 metabolites of a subset of CUPs were analyzed in 327 urine samples from children (4-12 years) in the ENVIRONAGE cohort, as part of the characterization of their chemical exposome. Among the targeted compounds, 3,5,6-trichloro-2-pyridinol (TCPY), 3-phenoxybenzoic acid (3-PBA) and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (trans-DCCA) were detected in > 50 % of samples, with 3-PBA showing the highest median level (0.33 ng/mL, interquartile range (IQR): 0.18-0.61 ng/mL). These metabolites reflect exposure to chlorpyrifos and pyrethroids, while other biomarkers showed low detection frequencies. The low detection frequencies might partly reflect a limited suitability of included biomarkers rather than absence of exposure. TCPY concentrations (median: 0.16 ng/mL, IQR: 0.07-0.27 ng/mL) were lower than previously reported studies, possibly reflecting the ban on chlorpyrifos in the European Union. Questionnaires on demographics, lifestyle, and dietary habits were used to identify possible exposure determinants. Risk assessment was performed by calculating estimated daily intakes (EDIs), risk characterization ratios (RCRs), and hazard indices (HI) applying a worst-case scenario; assuming metabolites were formed due to exposure to the most toxic parent compound. Time spent cycling was positively associated with levels of 3-PBA and trans-DCCA, while sampling season was identified as a significant variable for trans-DCCA, with the highest concentrations in autumn. Juice consumption was positively associated with TCPY concentrations. All risk characterization ratios for single compounds were below 1, while for two children, the HI for combined exposure to pyrethroids exceeded 1. The current study demonstrates that Belgian children are exposed to chlorpyrifos and pyrethroid pesticides, with most exposures falling within ranges considered safe under the assumed conditions.

Correlation between MBD and age at FFTP. Plots (A and B) show the association of the VBD [in ln (%)] and GLAND [in ln (cm³)] with age at FFTP (in years). Breakpoint is indicated as a red dotted line at 25.7 years.

ABSTRACT:This study evaluated the association between age at first full-term pregnancy (FFTP) and mammographic breast density (MBD) in postmenopausal women. A total of 1,034 women, ages 50 to 69 years, were recruited from the Flemish (Belgium) population–based breast cancer screening program. Participants completed a questionnaire on lifestyle and reproductive factors. From mammography, we assessed the percentage glandular tissue of the total breast volume (GLAND), the volumetric breast density (VBD), and the Breast Imaging Reporting and Data System (BI-RADS) density classification. For statistical analysis, we used the piecewise linear regression model. The average age at FFTP was 26.1 years. Among women with an FFTP > 25.7 years, an each year increase in FFTP age was associated with a 1.17% increase in GLAND [95% confidence interval (CI), 0.20%–2.46%; P = 0.041] and a 1.45% increase in VBD (95% CI, 0.18%–2.75%; P = 0.026). Similarly, the odds of a higher BI-RADS classification increased by 5.0% (95% CI, 0.0%–11.0%; P = 0.059) for each year increase in FFTP age after 25.7 years. For every year delay in age at menarche, a 2.48% higher GLAND (95% CI, 0.43%–4.57%; P = 0.017) and a 2.45% higher VBD (95% CI, 0.38%–4.56%; P ≤ 0.020) were observed. Ever use of oral contraceptive resulted in a 12.24% decrease in GLAND (95% CI, −20.90% to −2.63%; P = 0.014) and a 13.48% decrease in VBD (95% CI, −22.1% to −3.91%; P = 0.007). MBD is significantly higher when FFTP takes place after 25.7 years. Later age at menarche is associated with higher MBD, whereas ever use of oral contraceptive is associated with lower MBD at postmenopause. SIGNIFICANCE:We consider our findings to be highly novel, and to the best of our knowledge, our study is one of the first to investigate associations between age at FFTP and three markers of MBD (GLAND, VBD, and BI-RADS), uncovering that MBD is significantly higher when FFTP occurs after 25.7 years.

While the antioxidative potential of certain vitamins and minerals in cardio-protection has garnered increasing interest, their ability to attenuate associations between air pollution exposure and cardiometabolic diseases (CMDs) remains unexplored. This study examined the associations of air pollution (particulate matter including ultrafine particles (UFP), and nitrogen oxides, including NO2 and NOx) and six dietary antioxidants with incident non-fatal CMDs in 30,519 EPIC-NL study participants. Data on CMD incidence (total cardiovascular disease (CVD), acute myocardial infarction (AMI), coronary heart disease (CHD) and heart failure (HF)) and Type 2 Diabetes Mellitus (T2DM) diagnoses were obtained from medical registries. Annual average ambient concentrations of air pollutants at the participants’ baseline residential addresses were predicted using land use regression models. Dietary intake of antioxidants was assessed via a food frequency questionnaire. Multivariable Cox regression models were used to explore associations. Exposures to NO2 and UFP were associated with elevated HF risk (Hazard Ratio (HR) (95 % CI): 1.24 (1.00, 1.54) and 1.69 (1.04, 2.76), respectively). Higher beta-carotene intake was associated with reduced risk of total CVD and CHD incidence (HR (95 % CI): 0.94 (0.89, 0.99) and 0.92 (0.84, 0.99), respectively), whereas, in general, antioxidant intake was positively associated with incident T2DM. Interaction analyses indicated some variability in CMD risk by antioxidant intake, but none of these interactions remained significant after correcting for multiple comparisons. These findings indicate that the associations of air pollution with incident CMD do not differ by dietary antioxidant intake.

Table S2: Results from the univariate analysis for the volumetric breast density (VBD). For FFTP, we used the proc NLIN procedure, for the others a GLM. Multiplicative estimates provided are calculated according to eβ for the given unit change

BACKGROUND:Individuals with lower socioeconomic status (SES) are at a higher risk of being exposed to adverse environmental factors. Children are more vulnerable to the harmful effects of air pollutants. Therefore, this study examined socioeconomic inequalities in air pollution exposure among children in Flanders, Belgium. METHODS:Data were used from 298 children (age range: 9-12 years), and from their parents who participated in the COGNition and Air pollution in Children study. Socioeconomic status was measured using highest parental education at the individual level and median income at the neighborhood (aggregated) level. Annual average outdoor concentrations of particulate matter with diameters <2.5 μm (PM2.5) and <10.0 μm (PM10), nitrogen dioxide (NO2), and black carbon (BC) in μg/m3 were estimated at the residential address. Mixed regression models were applied to examine the associations. RESULTS:Children from parents with a low education level were exposed to significantly higher levels of PM2.5, PM10, and BC compared to children from parents with a high education level. However, the associations were not significant when tested using regression models. Children who lived in areas with a lower median neighborhood income were exposed to significantly higher levels of air pollution; an interquartile range (IQR; €4505.00) decrease in income was associated with an increase in exposure to PM2.5 of 0.198 μg/m3, PM10 of 0.406 μg/m3, NO2 of 0.740 μg/m3, and BC of 0.063 μg/m3. Children of parents with a low/high education level had a higher exposure to PM2.5, PM10, NO2, and BC when living in a low income neighborhood. Exposure to all air pollutants was the highest for low parental education level and low neighborhood income. CONCLUSIONS:Low neighborhood income was significantly associated with higher levels of air pollution, while parental education level was not significantly associated. Children from parents with a low education and low income were exposed to the highest levels of air pollution.

Telomere length (TL) and mitochondrial DNA content (mtDNAc) are biomarkers of biological ageing that respond to multiple stressors, including air pollution. Despite growing research interest, the association between recent and chronic air pollution and these biomarkers in the general population remains unclear. This study investigated the association between air pollution exposure and TL and mtDNAc using data from the 2018 Belgian Health Examination Survey. Multivariable adjusted generalised linear mixed models were applied to assess the exposure to nitrogen dioxide (NO2), fine particulate matter ≤2.5 μm (PM2.5), and black carbon (BC) over 1-week (recent) and 1-year (chronic) periods prior to participation, estimated with a high-resolution spatiotemporal model. Leucocyte TL and mtDNAc were measured using qPCR. A total of 756 participants (mean age 50.6 years, 49.9 % women) were included in the study. Recent exposure to PM2.5 was associated with a 2.40 % (95 % CI: 0.16, 4.69; p = 0.036) longer TL per IQR increment. Trends of lower mtDNAc were observed for chronic exposure to BC (-3.11, 95 % CI: -6.19, 0.07; p = 0.055) and NO2 (-4.02, 95 % CI: -8.22, 0.36; p = 0.072) per IQR increment. No significant associations were observed between chronic air pollution and TL or recent exposure and mtDNAc. These results suggest an inverse association between chronic air pollution and mtDNAc, and a positive association between recent exposure and TL, providing insight into the time-sensitive and air pollutant effects on ageing biomarkers.

Results from the ordinal logistic regression model for BI-RADS. The model was stratified based on the FFTP results from the GLAND and VBD models: “≤25.7 years” and “>25.7 years.”

Selection process indicating the number of women recruited and excluded during the process of collection and data analysis.

Table S1: Results from the univariate analysis for the glandular tissue (GLAND). For FFTP, we used the proc NLIN procedure, for the others a GLM. Multiplicative estimates provided are calculated according to eβ for the given unit change

Table S3: Results from the univariate ordinal logistic regression model for BI-RADS. The model for FFTP was stratified based on the results from the GLAND and VBD models: ‘≤ 25.7 years’ and ‘> 25.7 years’. Data is presented as Odds Ratio (OR) estimates and 95% Wald confidence intervals

MBD characteristics. Stratification on age at FFTP was made based on the results of the NLIN procedure in SAS.

Results from the PROC NLIN model for the GLAND.

Results from the PROC NLIN model for the VBD.

Prenatal exposure to air pollution has been linked to lower birth weight, yet the role of the placenta in this association is often overlooked. This study investigates whether placental characteristics act as moderators or mediators in the association between prenatal exposure to particulate matter (PM10) and nitrogen dioxide (NO2) and birth weight in twins. The study included 3340 twins (born 2002-2013) from the East Flanders Prospective Twin Survey. Prenatal exposure was estimated using spatial-temporal interpolation for the whole pregnancy and its trimesters. Moderation (interaction) and mediation (direct, indirect, and total effects) of placental weight and umbilical cord insertion were assessed with analyses stratified a priori based on the presence of one or two placentas. Sensitivity analyses included stratification by prematurity. Placental weight acted as both a moderator and mediator. Moderation analysis: in twins with low placental weight, birth weight decreased with -93.18 g per 10 mu g/m(3) PM10 (95% CI: -164.17, -22.19) and -69.28 g per 10 mu g/m(3) NO2 (95% CI: -124.81, -13.76) for the whole pregnancy. Mediation analysis showed positive indirect effects of placental weight indicating an increase of 36.05 g (95% CI: 0.88, 70.61) birth weight per 10 mu g/m(3) PM10 over the whole pregnancy, particularly in twins born <35 weeks. Direct effects were mainly negative, but not significant. For NO2, significant negative indirect effects were observed in the third trimester. Moderation was most pronounced in the second half of pregnancy, while both moderation and mediation were more evident in twins with separate placentas. Positive indirect effects prevailed in the first half of pregnancy, while negative indirect effects were observed in the second half. Umbilical cord insertion was neither a moderator nor a mediator. To conclude, the placenta acts both as moderator and mediator in the association between air pollution and birth weight, highlighting the need to consider these pathways in future research.

Background: Mitochondrial DNA content (mtDNAc) at birth is a sensitive biomarker to environmental exposures that may play an important role in later life health. We investigated sensitive time windows for the association between prenatal ambient temperature exposure and newborn mtDNAc. Methods: In the ENVIRONAGE birth cohort (Belgium), we measured cord blood and placental mtDNAc in 911 participants using a quantitative real-time polymerase chain reaction. We associated newborn mtDNAc with average weekly mean temperature during pregnancy using distributed lag nonlinear models (DLNMs). Doublethreshold DLNMs were used to study the relationships between ambient temperature and mtDNAc below predefined low (5th, 10th, 15th percentile of the temperature distribution) and above predefined high temperature thresholds (95th, 90th, 85th percentile of the temperature distribution). Findings: Prenatal temperature exposure above the used high temperature thresholds was linked to lower cord blood mtDNAc, with the strongest effect in trimester 2 (cumulative estimates ranging from -21.4% to -25.6%). Placental mtDNAc showed positive and negative associations for high temperature exposure depending on the applied high temperature threshold. Negative associations were observed during trimester 1 using the 90th and 95th percentile threshold (-26.1% and -33.2% lower mtDNAc respectively), and a positive association in trimester 3 when applying the most stringent 95th percentile threshold (127.0%). Low temperature exposure was associated with higher mtDNAc for both cord blood and placenta. Cord blood mtDNAc showed a positive association in trimester 2 when using the 10th percentile threshold (11.3%), while placental mtDNAc showed positive associations during the whole gestation and for all applied thresholds (estimates ranging from 80.8% 320.6%). Interpretation: Our study shows that in utero temperature exposure is associated with differences in newborn mtDNAc at birth, with stronger associations observed in the placenta. These findings highlight the impact of prenatal ambient temperature exposure on mtDNAc during pregnancy.

Sociodemographic characteristics. Stratification on age at FFTP was made based on the results of the NLIN procedure in SAS.

BACKGROUND:Green space exposure has been linked to improved cognitive functioning over the life course. We examined whether newborn insulin-like growth factor 1 (IGF1) plays a part in this. METHODS:We measured cord blood plasma IGF1 in 317 mother-child pairs from the ENVIRONAGE birth cohort. Prenatal green space exposure was assessed within several radii (50-1000 m) around the maternal residence. Multivariable linear regression models were used to associate IGF1 levels with green space exposure. Cognitive functioning was assessed at follow-up at 4 to 6 years of age, using the Cambridge Neuropsychological Test Automated Battery (CANTAB), and converted to components by principal component analysis. Mediation analysis was conducted to examine the relationship between green space exposure and cognitive functioning, with IGF1 as a mediator. FINDINGS:Prenatal short vegetation (< 3 m in height) exposure associated with newborn IGF1 within 50, 100 and 1000 m (P ≤ 0.05), and newborn IGF1 significantly predicted the neurocognitive domain of attention/psychomotor speed during childhood (P < 0.01). Newborn IGF1 significantly mediated the association between prenatal short vegetation exposure and the latencies of the Motor Screening task and the Big/Little Circle task: Per IQR increase in short vegetation within 50 m, the latencies decreased by 0.45 % (95 % CI: -0.986 to -0.047, P = 0.014) and 0.48 % (95 % CI: -1.164 to -0.016, P = 0.044) via IGF1. INTERPRETATION:Residential surrounding green space during pregnancy may be associated with long-lasting cognitive benefits for the child, mediated through higher cord blood IGF1 protein levels at birth.

BACKGROUND:Appetite hormones are considered a promising target in fighting obesity as impaired appetite hormone levels have already been associated with obesity. However, further insights in the drivers of appetite hormone levels are needed. OBJECTIVES:In this study, we investigated the associations of fasting appetite hormone levels with lifestyle and environmental exposures in children and adolescents. METHODS:A total of 534 fasting blood samples were collected from children and adolescents (4-16y,50% boys) and appetite hormone levels (glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide (PP), leptin and ghrelin) were measured. Exposures included dietary quality (fiber-rich food intake, sugar propensity, fat propensity), psychosocial stress (happiness, negative emotions, negative life events and emotional problems), sleep duration, physical activity and environmental quality (long term black carbon (BC), particulate matter <2.5 μM (PM2.5), nitrogen dioxide (NO2) exposure, and green space in a 100 m and 2000 m radius around the residence). A multi-exposure score was calculated to combine all the exposures at study in one measure. Associations of individual exposures and multi-exposure score with appetite hormone levels were evaluated using linear mixed regression models adjusting for sex, age, socioeconomic status, waist-to-height ratio and multiple testing. RESULTS:GLP-1 was associated with air pollution exposure (NO2 β* = -0.13, BC β* = -0.15, PM2.5 β* = -0.16, all p < 0.001). Leptin was associated with green space in a 100 m radius around the residence (β* = -0.11; p = 0.002). Ghrelin was associated with negative emotions (active ghrelin β* = -0.16; p = 0.04, total ghrelin β* = -0.23; p = 0.0051) and happiness (active ghrelin β* = 0.25; p < 0.001, total ghrelin β* = 0.26; p < 0.001). Furthermore, total ghrelin levels were associated with the multi-exposure score, reflecting unhealthy exposures and lifestyle (β* = -0.22; p = 0.036). DISCUSSION:Our findings provide new insights into the associations of exposures with appetite hormone levels, which are of high interest for preventive obesity research. Further research is crucial to reveal the underlying mechanisms of the observed associations.

INTRODUCTION:Twin pregnancies are associated with an increased risk of perinatal morbidity and mortality. Pregnancy complications related to twins, such as fetal growth restriction, and twin-to-twin transfusion syndrome (TTTS), are associated with hemodynamic changes in the fetal heart. Two-dimensional speckle tracking echocardiography (2D STE) is a tool to evaluate fetal cardiac function. This paper aims to review the literature regarding global longitudinal strain (rate) and peak systolic strain (rate) assessed with 2D STE in twin pregnancies. Feasibility, frame rate, and angle of the fetal heart at the time of measurement were selected as secondary outcomes. METHODS:The databases Medline, Embase, Scopus, and Web of Science were searched. RESULTS:Seven articles met the inclusion criteria and selected all monochorionic diamniotic (MCDA) twins with TTTS as the study population. The global longitudinal strain in the right and left ventricle and the peak systolic strain in the right ventricle of the recipient MCDA twin are significantly decreased compared to the donor MCDA twin. 2D STE assessment was shown feasible and reproducible in MCDA pregnancies. Large heterogeneity in technical characteristics between the articles induces inconsistent results. CONCLUSION:Although feasible, the knowledge of 2D STE is very limited in twin pregnancy. Prospective studies are needed to evaluate the 2D STE assessment in uncomplicated twin pregnancies considering its possible additive value in the diagnostics of pregnancy-related pathologies.