Anna Floegel

Supplementary Data from Reproducibility of the Blood and Urine Exposome: A Systematic Literature Review and Meta-Analysis

Endogenous and exogenous metabolite concentrations may be susceptible to variation over time. This variability can lead to misclassification of exposure levels and in turn to biased results. To assess the reproducibility of metabolites, the intraclass correlation coefficient (ICC) is computed. A literature search in three databases from 2000 to May 2021 was conducted to identify studies reporting ICCs for blood and urine metabolites. This review includes 192 studies, of which 31 studies are included in the meta-analyses. The ICCs of 359 single metabolites are reported, and the ICCs of 10 metabolites were meta-analyzed. The reproducibility of the single metabolites ranges from poor to excellent and is highly compound-dependent. The reproducibility of bisphenol A (BPA), mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), methylparaben, and propylparaben is poor to moderate (ICC median: 0.32; range: 0.15–0.49), and for 25-hydroxyvitamin D [25(OH)D], it is excellent (ICC: 0.95; 95% CI, 0.90–0.99). Pharmacokinetics, mainly the half-life of elimination and exposure patterns, can explain reproducibility. This review describes the reproducibility of the blood and urine exposome, provides a vast dataset of ICC estimates, and hence constitutes a valuable resource for future reproducibility and clinical epidemiologic studies.

Supplementary Figure from Reproducibility of the Blood and Urine Exposome: A Systematic Literature Review and Meta-Analysis

Supplementary Data from Reproducibility of the Blood and Urine Exposome: A Systematic Literature Review and Meta-Analysis

Purpose: Understanding factors influencing clinical biomarkers is important for the prevention of chronic disease. This study aimed to estimate transitions of biomarker status from childhood to adolescence and to identify determinants of biomarker status in early life in a prospective children cohort. Subjects and methods: Our sample comprised 1295 children participating in the baseline (2007/08) and second follow-up examination (2013/14) of the multi-center IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS)/I.Family study. Clinical blood biomarkers including glycated hemoglobin A1c (HbA1c), high-density lipoprotein cholesterol (HDL-cholesterol), triglycerides, C-reactive protein (CRP), interleukin 6, ferritin, leptin and insulin-like growth factor 1 (IGF-1) were repeatedly measured in 2007/2008 (age range: 3.0 to <10.0 years) and in 2013/2014. Latent transition analysis was used to estimate biomarker statuses and transition probabilities; determinants of biomarker status were estimated using mixed-effects models. Results: Four distinct biomarker statuses were identified: (1) “normal” (all biomarkers low/medium; except HDL-cholesterol; reference), (2) “low leptin/IGF-1/HbA1c”, (3) “dyslipidemia/high leptin” and (4) “inflammation”. Children classified as “low leptin/IGF-1/HbA1c” at baseline were most likely to stay in this status (89.8%) or to change to the “normal” status (10%) during follow-up. Compared to “normal” children, children classified as “low leptin/IGF-1/HbA1c” were less likely to have a family history of diabetes (0.26 [0.08;0.86]; odds ratio (OR) and 95% confidence interval) or hypertension (0.53 [0.29;0.99]) and the children (0.32 [0.27;0.38]) as well as their mothers (0.93 [0.88;0.98]) had a lower BMI. Children from families with low/medium education had a 55% [9%-119%] higher risk of being in the “dyslipidemia/high leptin” and 49% [1%-121%] higher risk of being in the “inflammation” status as compared to children in the “normal” status. Membership in a sports club reduced the latter risks by 28% [2%-47%] and 40% [17%-56%], respectively. Conclusions: European children showed distinct phenotypes for the investigated biomarkers. Especially parental characteristics like a family history of diabetes or hypertension, a high maternal BMI, or low/medium education were associated with unfavorable biomarker status in children.

Endogenous and exogenous metabolite concentrations may be susceptible to variation over time. This variability can lead to misclassification of exposure levels and in turn to biased results. To assess the reproducibility of metabolites, the intraclass correlation coefficient (ICC) is computed. A literature search in three databases from 2000 to May 2021 was conducted to identify studies reporting ICCs for blood and urine metabolites. This review includes 192 studies, of which 31 studies are included in the meta-analyses. The ICCs of 359 single metabolites are reported, and the ICCs of 10 metabolites were meta-analyzed. The reproducibility of the single metabolites ranges from poor to excellent and is highly compound-dependent. The reproducibility of bisphenol A (BPA), mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-2-ethylhexyl phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), methylparaben, and propylparaben is poor to moderate (ICC median: 0.32; range: 0.15–0.49), and for 25-hydroxyvitamin D [25(OH)D], it is excellent (ICC: 0.95; 95% CI, 0.90–0.99). Pharmacokinetics, mainly the half-life of elimination and exposure patterns, can explain reproducibility. This review describes the reproducibility of the blood and urine exposome, provides a vast dataset of ICC estimates, and hence constitutes a valuable resource for future reproducibility and clinical epidemiologic studies.

While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR_≥4vs.0: 1.74, 95% CI: 1.20–2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR_≥4vs.0: 1.99, 95% CI: 1.06–3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR_≥4vs.0: 1.46, 95% CI: 0.68–3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.

The present study aimed to evaluate two different spectrophotometric assays for detection of vitamin C equivalent antioxidant capacity (VCEAC) of foods. Fifty popular, antioxidant‐rich fruits, vegetables and beverages in the U.S. diet were analyzed for their 2,2′‐azino‐bis‐3‐ethylbenzthiazoline‐6‐sulphonic acid (ABTS) anion radical scavenging activity (ABTS assay) and their ability to reduce 1,1‐diphenyl‐2picrylhydrazyl (DPPH) radical (DPPH assay). The highest VCEAC was detected for strawberry with 520.7 ± 39.3 mg vitamin C equivalent (VCE)/100 g by DPPH assay and for blueberry with 476.6 ± 28.9 mg VCE/100 g by ABTS assay. Although the order differed slightly, both assays identified the same top ten VCEAC food items in the U.S. diet based on fresh weight as blueberry, plum, strawberry, red cabbage, red wine, grape, cherry, green tea, broccoli and apple. VCEAC of 50 food items detected by ABTS assay showed a strong positive relationship with VCEAC measured by DPPH assay (r = 0.886, p Grant Funding Source : Supported by Beginning Grant in Aid (BGIA) No. 0865092E from the American Heart Association and University of Connecticut Faculty Large Grant