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Background: Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA., Methods: Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children's Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women's cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders., Results: We studied 4683 mother-child pairings from 103,060 pregnancies included in the Japan Environment and Children's Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children., Conclusion: Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children's growth., (© 2024. The Author(s).)

Background: Prenatal exposure to metallic elements may adversely affect early childhood health. However, more evidence is needed as population-based cohort studies are currently limited., Objectives: We aimed to examine the associations between prenatal metallic (mercury, selenium, and manganese) exposure and the risk of allergic diseases in early childhood until three years of age., Methods: The data from 94,794 mother-infant pairs, who participated in the Japan Environment and Children's study, were used in this study. Prenatal metallic element exposure was measured in maternal blood collected during mid-pregnancy. The incidence of atopic dermatitis, food allergies, asthma, and allergic rhinitis during the first three years of life was prospectively investigated using self-reports of physician-diagnosed allergies. A multivariable modified Poisson regression model was used to estimate the cumulative incidence ratio and their 95% confidence intervals of allergic diseases associated with prenatal exposure to mercury, selenium, and manganese. We further evaluated the interaction between mercury and selenium exposures in this association., Results: We confirmed 26,238 cases of childhood allergic diseases: atopic dermatitis, food allergies, asthma, and allergic rhinitis in 9,715 (10.3%), 10,897 (11.5%), and 9,857 (10.4%), 4,630 (4.9%), respectively. No association was found between prenatal mercury or manganese exposure and the risk of allergic diseases. Prenatal selenium exposure was inversely associated with atopic dermatitis, food allergies, allergic rhinitis, and any allergic diseases, but not with asthma. These inverse associations were more pronounced for lower mercury exposures than for higher exposures., Conclusions: Our findings suggest that prenatal exposure to selenium may be beneficial for reducing the risk of atopic dermatitis, food allergies, allergic rhinitis, and any allergic diseases in early childhood, especially with lower prenatal mercury exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: To our knowledge, the association of maternal exposure to metallic elements with weight trajectory pattern from the neonatal period has not been investigated., Objectives: The goals of this study were to identify infant growth trajectories in weight in the first 3 y of life and to determine the associations of maternal blood levels of lead, cadmium, mercury, selenium, and manganese with growth trajectory., Methods: This longitudinal study, part of the Japan Environment and Children Study, enrolled 103,099 pregnant women at 15 Regional Centres across Japan between 2011 and 2014. Lead, cadmium, mercury, selenium, and manganese levels were measured in blood samples collected in the second (14-27 wk gestational age) or third trimester ( ≥ 28 wk ). Growth trajectory of 99,014 children was followed until age 3 y. Raw weight values were transformed to age- and sex-specific weight standard deviation (SD) scores, and latent-class group-based trajectory models were estimated to determine weight trajectories. Associations between maternal metallic element levels and weight trajectory were examined using multinomial logistic regression models after confounder adjustment., Results: We identified 5 trajectory patterns based on weight SD score: 4.74% of infants were classified in Group I, very small to small; 31.26% in Group II, moderately small; 21.91% in Group III, moderately small to moderately large; 28.06% in Group IV, moderately large to normal; and 14.03% in Group V, moderately large to large. On multinomial logistic regression, higher maternal lead and selenium levels tended to be associated with increased odds ratios (ORs) of poor weight SD score trajectories (Groups I and II), in comparison with Group III. Higher levels of mercury were associated with decreased ORs, whereas higher levels of manganese were associated with increased ORs of "moderately large" trajectories (Groups IV and V)., Discussion: Maternal lead, mercury, selenium, and manganese blood levels affect infant growth trajectory pattern in the first 3 y of life. https://doi.org/10.1289/EHP10321.

Essential micronutrient selenium is excreted into the urine andor expired after being transformed to methylated metabolites. Monomethylated selenium is excreted into the urine in response to a supply within the required to low-toxic range, whereas tri- and dimethylated selenium increase with excessive supply at a toxic dose. Here we show that the major urinary selenium metabolite within the required to low-toxic range is a selenosugar. The structure of 1beta-methylseleno-N-acetyl-d-galactosamine was deduced from the spectroscopic data and confirmed by chemical synthesis. This metabolite was also detected in the liver, and an additional metabolite increased with inhibition of methylation. The latter metabolite was again a selenosugar conjugated with glutathione instead of a methyl group and was assumed to be a precursor for methylation to the former metabolite. A metabolic pathway for the urinary excretion of selenium, i.e., from the glutathione-S-conjugated selenosugar to the methylated one, was proposed. Urinary monomethylated (selenosugar) and trimethylated selenium can be used as specific indices that increase within the required to low-toxic range and with a distinct toxic dose, respectively.

Speciation analysis using high-performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICP MS) is now commonly used to investigate metabolic and toxicological aspects of some metals and metalloids. We have developed a rapid method for simultaneous identification and quantification of metabolites of selenium (Se) compounds using multiple standards labelled with different isotopes. A mixture of the labelled standards was spiked in a selenised garlic extract and the sample was subjected to speciation analysis by HPLC-ICP MS. The selenised garlic contains γ-glutamyl-methylselenocysteine, methylselenocysteine, and selenomethionine and the concentrations of those Se compounds were 723.8, 414.8, and 310.7 ng Se ml−1, respectively. The isotopically labelled standards were also applied to the speciation of Se in rat urine. Selenate, methylselenonic acid, selenosugar, and trimethyselenium ions were found to be excreted by the present speciation procedure. Multiple standards labelled with different stable isotopes enable high-throughput identification and quantitative measurements of Se metabolites. [ABSTRACT FROM AUTHOR]