Exposure to a Mixture of Metals and Growth Indicators in 6–11‑Year‑Old Children from the 2013–2016 NHANES

Lead (Pb), mercury (Hg), and fuoride (F) exposure during childhood is of concern owing to their toxicity. Also, evidence suggests that high and low exposure levels to manganese (Mn) and selenium (Se) during this vulnerable period are associated with an increased risk of adverse health efects. A reduced growth is associated with high Pb and F exposure; however, little is known about their impact on children’s body size, and there is a lack of consensus on the efects of Hg, Mn, and Se exposure on children’s anthropometric measures. This is particularly true for childhood metal co-exposures at levels relevant to the general population. We investigated the joint efects of exposure to a metal mixture (Pb, Mn, Hg, and Se in blood and F in plasma) on 6–11-year-old US children’s anthropometry (n=1634). Median F, Pb, Mn, Hg, and Se concentrations were 0.3 µmol/L, 0.5 µg/dL, 10.2 µg/L, 0.3 µg/L, and 178.0 µg/L, respectively. The joint efects of the fve metals were modeled using Bayesian kernel machine and linear regressions. Pb and Mn showed opposite directions of associations with all outcome measured, where Pb was inversely associated with anthropometry. For body mass index and waist circumference, the efect estimates for Pb and Mn appeared stronger at high and low concentrations of the other metals of the mixture, respectively. Our fndings suggest that metal co-exposures may infuence children’s body mass and linear growth indicators, and that such relations may difer by the exposure levels of the components of the metal mixture

Prenatal Exposure to Cigarette Smoke and Anogenital Distance at 4 Years in the INMA-Asturias Cohort

Smoking by women is associated with adverse pregnancy outcomes such as spontaneous abortion, preterm delivery, low birth weight, infertility, and prolonged time to pregnancy. Anogenital distance (AGD) is a sensitive biomarker of prenatal androgen and antiandrogen exposure. We investigated the effect of smoking and passive smoke exposure during pregnancy on anogenital distance in offspring at 4 years in the INMA-Asturias cohort (Spain). Women were interviewed during pregnancy to collect information on tobacco consumption, and anogenital distance was measured in 381 children: Anoscrotal distance in boys and anofourchetal distance in girls. We also measured maternal urinary cotinine levels at 32 weeks of pregnancy. We constructed linear regression models to analyze the association between prenatal smoke exposure and anogenital distance and adjusted the models by relevant covariates. Reported prenatal smoke exposure was associated with statistically significant increased anogenital index (AGI), both at week 12 of pregnancy (β = 0.31, 95% confidence interval: 0.00, 0.63) and at week 32 of pregnancy (β = 0.31, 95% confidence interval: 0.00, 0.63) in male children, suggesting altered androgenic signaling.Funding was provided by CIBERESP (PhD employment contract and fellowship for short stays abroad—2019), FIS-FEDER (grants PI04/2018, PI09/02311, PI13/02429, and PI18/00909), Obra Social Cajastur/Fundación Liberbank, and Universidad de Oviedo

GC gene polymorphism and unbound serum retinol-binding protein 4 are related to the risk of insulin resistance in patients with chronic hepatitis c: A prospective cross-sectional study

Insulin resistance (IR) is found in chronic hepatitis C (CHC) more frequently than in other chronic liver diseases. Prospective cross-sectional study to evaluate a wide multitest panel to identify factors related with IR in CHC and their possible interactions. In 76 patients with CHC we performed a series of routine laboratory analysis as well as specifically designed serum biochemical tests [retinol, retinol-binding protein 4 (RBP4), 25-OH vitamin D, Vitamin E, lipopolysaccharide-binding protein (LBP), interleukin-6 (IL-6), and cystatin C]. The single nucleotide polymorphisms rs7041 and rs4588 GC-DBP (group-specific component-Vitamin D-binding protein), rs738409 PNPLA3 (patatin-like phospholipase domain containing 3), and rs12979860 IL28B (interleukin-28 B) genes were determined. Insulin sensitivity was established with the HOMA-IR and IR was diagnosed when HOMA-IR>3. Fibrosis staging was assessed with liver biopsy or transient elastography. After backward logistic regression analysis, independent variables associated with IR were Gc1s/Gc1s DBP phenotype, that results from the homozygous carriage of the rs7041G/rs4588Chaplotype (P¼0.033); low retinol/RBP4 ratio, reflecting a greater rate of unboundRBP4 (P¼0.005); older age (P¼0.01); high serum tryglicerides (P¼0.026); and advanced (F3–F4) fibrosis stage. The AUROC provided by the multivariate model was 0.950 (95% CI¼0.906–0.993). In addition to previously known ones, the Gc1s/Gc1s phenotype variant of DBP and the unbound fraction of plasma RBP4 may be considered as factors related with the incidence, and possibly the risk, of IR in CHC patients.• Instituto de Salud Carlos III, Fondo de Investigación Sanitari: Ayudas PI12/00241 y PI12/00324 • Junta de Extremadura: Ayuda GR15026 • Fondos FEDERpeerReviewe

Protective Role of the Interleukin 33 rs3939286 Gene Polymorphism in the Development of Subclinical Atherosclerosis in Rheumatoid Arthritis Patients

OBJECTIVES: To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US). RESULTS: RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed. CONCLUSIONS: In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA

Association between pre/perinatal exposure to POPs and children's anogenital distance at age 4 years: A study from the INMA-Asturias cohort

Background Prenatal exposure to endocrine-disrupting chemicals may impair genital development and alter reproductive tract anatomy. Anogenital distance (AGD) is a useful biomarker of exposure to chemicals that act as endocrine disruptors. We evaluated associations between prenatal and perinatal exposure to several persistent organic pollutants (POPs) and AGD in 4-year-old children. Methods Data were drawn from the INMA-Asturias cohort. Pediatricians measured the anofourchetal distance in female children and anoscrotal distance in male children. The anogenital index (AGI) was defined as the AGD divided by the child's weight at age of examination. We measured the levels of two hexachlorocyclohexane isomers, hexachlorobenzene, dichlorodiphenyltrichloroethane (DDT) and its metabolites, six polychlorinated biphenyl (PCB) congeners, and six polybrominated diphenyl ether (PBDE) congeners in maternal serum at 12 gestational weeks (n = 155) and in cord blood serum (n = 229). Anthropometric and parental sociodemographic variables were collected via face-to-face interviews. Linear regression models were used to evaluate the relationship between exposure to POPs and AGI, adjusted for confounders and stratified by sex. Results In male children, we found inverse associations between AGI and maternal concentrations of PCB-138 (ß = −0.041, 95% confidence interval [CI]: −0.074, −0.008, second tertile), PCB-153 (ß = −0.052, 95% CI: −0.085, −0.020, second tertile), PCB-180 ß = −0.065, 95% CI: −0.096, −0.035, second tertile; ß = −0.042, 95% CI: −0.073, −0.011, third tertile), PBDE-209 (ß = −0.031, 95% CI: −0.058, −0.006), cord serum concentrations of PCB-153 (ß = −0.029, 95% CI: −0.059, −0.000, second tertile; ß = −0.047, 95% CI: −0.085, −0.008, third tertile), and PCB-180 (ß = −0.041, 95% CI: −0.078, −0.005, third tertile). In female children, AGI was positively associated with maternal serum concentrations of PCB-101 (ß = 0.039, 95% CI: 0.002, 0.076, second tertile), and higher cord serum levels of 4,4′-DDT (ß = 0.032, 95% CI: 0.003, 0.061, third tertile) and 4,4′-DDE (ß = 0.040, 95% CI: 0.011, 0.069, third tertile). Conclusions Our findings provide evidence of associations between specific POPs and AGI in boys and girls aged 4 years, and suggest that pre/perinatal exposure to POPs has a feminizing effect in males and a masculinizing effect in females.The authors would particularly like to thank all the participants for their generous collaboration and the staff from Hospital San Agustin in Aviles for their effort. This study was funded by grants from, CIBERESP (PhD-employment-contract and fellowship for short stays abroad-2019), FIS-FEDER: PI04/2018, PI09/02311, PI13/02429, PI18/00909; Obra Social Cajastur/Fundación Liberbank, and Universidad de Oviedo. We thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript, and Fundación NOE Alimerka.Peer reviewe

Gender influences on physical activity awareness of adolescents and their parents

The imbalances between the actual physical activity (PA) of adolescents and the subjective perception both they and their parents have in this regard can play an important role in perpetuating inactive lifestyles. The aim of this study is to analyse these discrepancies by considering gender as a conditioning factor. The participants in the study were 1697 adolescents, 1244 mothers and 1052 fathers in the educational communities of 26 secondary schools located in urban environments of the Autonomous Community of Galicia (Spain). With regard to actual physical activity, a high prevalence of sedentarism (82.1%) was revealed, this being even more acute in girls (87.8%). However, the perceived levels of activity differed significantly from the actual ones with a clear general overestimation both by the adolescents and their parents. When further exploring the data, gender influences were also detected both in adolescent and parental perceptions, since the high rates of overestimation in sedentary individuals were lower in girls and, on the contrary, the low rates of underestimation in active individuals were higher in girls. Moreover, although the level of agreement between actual and perceived physical activity was low overall, with Cohen’s kappa values ranging from 0.006 to 0.047, the lowest values were observed in the case of girls. In conclusion, both the adolescents and their parents were incapable of correctly assessing the actual physical activity of the former, so it seems that the general population lacks knowledge about the amount of physical activity that adolescents need to do to achieve a healthy lifestyle. Consequently, it would be advisable to implement health education campaigns and awareness-raising interventions directed to young people as well as to their parents and, in doing so, gender must be considered by establishing distinct program designs in terms of this variable

Interrupted time series analysis of pediatric infectious diseases and the consumption of antibiotics in an Atlantic European region during the SARS-CoV-2 pandemic

The increasing concern about bacterial resistance has made the rational prescription of antibiotics even more urgent. The non-pharmacological measures established to reduce the impact of the SARS-CoV-2 pandemic have modified the epidemiology of pediatric infections and, consequently, the use of antibiotics. Interrupted time series (ITS) analyses are quasi-experimental studies that allow for the estimation of causal effects with observational data in “natural experiments”, such as changes in health policies or pandemics. The effect of the SARS-CoV-2 pandemic on the incidence of infectious diseases and the use of antibiotics between 2018 and 2020 in the Health Area of Vigo (Galicia, Spain) was quantified and analyzed. This paper outlines a real-world data study with administrative records from primary care services provided for the pediatric population. The records were related to episodes classified as infectious by the International Classification of Primary Care (ICPC-2) and oral medication in the therapeutic subgroup J01, corresponding to antibiotics for systemic use, according to the World Health Organization’s Anatomical Therapeutic Chemical (ATC) classification system. The records were classified according to incident episodes, age, dose per inhabitant, and year. Segmented regression models were applied using an algorithm that automatically identifies the number and position of the change points. During the SARS-CoV-2 pandemic, the number of infectious diseases being transmitted between individuals, through the air and through the fecal–oral route, significantly decreased, and a slight decrease in infections transmitted via other mechanisms (urinary tract infections) was also found. In parallel, during the months of the pandemic, there has been a marked and significant reduction in antibacterial agent utilization, mainly of penicillins, cephalosporins, and macrolides.ISCIII Network for Research on Chronicity, Primary Care, and Health Promotion | Ref. RD21/0016/002

Serum concentrations of persistent organic pollutants mixture during pregnancy and anogenital distance in 8-year-old children from the INMA-Asturias cohort

During pregnancy, women are commonly exposed to several endocrine-disrupting chemicals, including persistent organic pollutants (POPs). These compounds can transfer to the fetus through the placenta. Prenatal POP exposure is related to altered fetal genital and reproductive tract development. However, the relationship between exposure to POP mixtures and anogenital distance (AGD) is poorly investigated. This study investigated the association between prenatal exposure to POP mixtures and AGD in 8-year-old children.The authors would particularly like to thank all the participants for their generous collaboration and the staff from Hospital San Agustin in Aviles for their effort. This study was funded by grants from, CIBERESP (PhD-employment-contract and fellowship for short stays abroad-2019), ISCIII: PI04/2018, PI09/02311, PI13/02429, PI18/00909 co-funded by FEDER, “A way to make Europe”/“Investing in your future”, Obra Social Cajastur/Fundación Liberbank, and Universidad de Oviedo. Antonio J. Signes-Pastor is currently funded by CIDEGENT/2020/050. We thank Katherine Thieltges from Edanz (https://www.edanz.com/ac) for editing a draft of this manuscript.Peer reviewe

Exposure to metal mixture and growth indicators at 4-5 years. A study in the INMA-Asturias cohort

Exposure to toxic and non-toxic metals impacts childhood growth and development, but limited data exists on exposure to metal mixtures. Here, we investigated the effects of exposure to individual metals and a mixture of barium, cadmium, cobalt, lead, molybdenum, zinc, and arsenic on growth indicators in children 4-5 years of age.The authors would particularly like to thank the staff from Hospital San Agustin in Aviles for their valuable support and all the participants enrolled in the INMA-Asturias cohort for their generous collaboration. This research was funded by grants from, CIBERESP (PhD-employment-contract and fellowship for short stays abroad-2019), ISCIII: PI04/2018, PI09/02311, PI13/02429, PI18/00909 co-funded by the European Regional Development Fund (FEDER), “A way to make Europe"/"Investing in your future”; Obra Social Cajastur/Fundación Liberbank, and Universidad de Oviedo. A.J.S.P. and M.R.K. are funded by the following projects P01ES022832, RD83544201, R25CA134286, and P42ES007373. A.J.S.P. is also funded by CIDEGENT /2020/050. We thank Katherine Thieltges from Edanz (https://www.edanz.com/ac) for editing a draft of this manuscript.Peer reviewe