Growth restriction in the prenatal period is a significant public health concern. Metals can negatively affect birth size, and pregnant women may be exposed to metal mixtures. Comprehensive studies analyzing the effects of combined metal exposure with accurate individual blood metal concentrations are limited. The current study investigated the associations between maternal metal exposure and birth size in a large, nationwide Japanese cohort using individual and mixed model approaches. Lead, cadmium, mercury, selenium, and manganese blood concentrations were measured in pregnant women in the Japan Environment and Children's Study (JECS). Measurements of infant birth size-including body weight, body length, and head and chest circumference-were collected. Linear and logistic regressions were used for birth size measurements and the odds of an infant being small in size for gestational age, respectively. Associations between combined metal mixtures and measurements at birth were evaluated using quantile g-computation and Bayesian kernel machine regression (BKMR). Of the 103,060 JECS pregnancies, 93,739 mother-infant pairs were analyzed. The linear regression models showed that lead, selenium, cadmium, and manganese-but not mercury-were associated with body weight. Cadmium was associated with length and chest circumference and mercury was associated with head circumference. Quantile g-computation revealed that manganese increased infant birth weight, length, head circumference, and chest circumference. Lead was the strongest negative factor for infant birth weight, length, head circumference, and chest circumference. The BKMR analysis revealed that the metals had an additive, rather than a synergistic effect. Metal exposure is associated with infant birth size, with lead and manganese playing a more significant role in Japan. The effects of prenatal combined metal exposure at low levels warrant public health attention.

Introduction: Most infants born as small for gestational age (SGA) demonstrate catch up growth by 2–4 years, but some fail to do so. This failure is associated with several health risks, including neuropsychological development issues. However, data on the morphological characteristics of the brains of infants born as SGA without achieving catch up growth are lacking. This study aims to determine the structural aspects of the brains of children born as SGA without catch up growth.Methods: We conducted voxel- and surface-based morphometric analyses of 1.5-T T1-weighted brain images scanned from eight infants born as SGA who could not achieve catch up growth by 3 years and sixteen individuals with idiopathic short stature (ISS) to exclude body size effects. Growth hormone (GH) secretion stimulation tests were used to rule out GH deficiency in all SGA and ISS cases. The magnetic resonance imaging data were assessed using Levene’s test for equality of variances and a two-tailed unpaired t-test for equality of means. The Benjamini–Hochberg procedure was used to apply discovery rate correction for multiple comparisons.Results: Morphometric analyses of both t-statical map and surface-based analyses using general linear multiple analysis determined decreased left insula thickness and volume in SGA without catch up growth compared with ISS.Conclusion: The brain scans of patients with SGA who lack catch up growth indicated distinct morphological disparities when compared to those with ISS. The discernible features of brain morphology observed in patients born as SGA without catch up growth may improve understanding of the association of SGA without catch up growth with both intellectual and psychological outcomes.

Regional anatomical structures of the brain are intimately connected to functions corresponding to specific regions and the temporospatial pattern of genetic expression and their functions from the fetal period to old age. Therefore, quantitative brain morphometry has often been employed in neuroscience investigations, while controlling for the scanner effect of the scanner is a critical issue for ensuring accuracy in brain morphometric studies of rare orphan diseases due to the lack of normal reference values available for multicenter studies. This study aimed to provide across-site normal reference values of global and regional brain volumes for each sex and age group in children and adolescents. We collected magnetic resonance imaging (MRI) examinations of 846 neurotypical participants aged 6.0–17.9 years (339 male and 507 female participants) from 5 institutions comprising healthy volunteers or neurotypical patients without neurological disorders, neuropsychological disorders, or epilepsy. Regional-based analysis using the CIVET 2.1.0. pipeline provided regional brain volumes, and the measurements were across-site combined using ComBat-GAM harmonization. The normal reference values of global and regional brain volumes and lateral indices in our study could be helpful for evaluating the characteristics of the brain morphology of each individual in a clinical setting and investigating the brain morphology of ultra-rare diseases.

Purpose: Central precocious puberty (CPP) is puberty that occurs at an unusually early age with several negative psychological outcomes. There is a paucity of data on the morphological characteristics of the brain in CPP. This study aimed to determine the structural differences in the brain of patients with CPP.Methods: We performed voxel- and surface-based morphometric analyses of 1.5 T T1-weighted brain images scanned from 15 girls with CPP and 13 age-matched non-CPP controls (NC). All patients with CPP were diagnosed by gonadotropin-releasing hormone (GnRH) stimulation test. The magnetic resonance imaging (MRI) data were evaluated using Levene’s test for equality of variances and a two-tailed unpaired t-test for equality of means. False discovery rate correction for multiple comparisons was applied using the Benjamini–Hochberg procedure.Results: Morphometric analyses of the brain scans identified 33 candidate measurements. Subsequently, increased thickness of the right precuneus was identified in the patients with CPP using general linear models and visualizations of cortical thickness with a t-statistical map and a random field theory map.Conclusion: The brain scans of the patients with CPP showed specific morphological differences to those of the control. The features of brain morphology in CPP identified in this study could contribute to further understanding the association between CPP and detrimental psychological outcomes.

Existing evidence on the correlation between maternal vitamin D concentrations and birth outcomes is conflicting. Investigation of these associations requires accurate assessment of vitamin D status, especially in individuals with low 25-hydroxyvitamin D (25(OH)D) concentrations. This study examined the correlations between birth outcomes and the maternal vitamin D metabolite ratio (VMR) 1 (defined as the ratio of 24,25(OH)₂D₃ to 25(OH)D) and VMR2 (defined as the ratio of 3-epi-25(OH)D₃ to 25(OH)D) using data from the Japan Environment and Children’s Study at Chiba Regional Center. A total of 297 mother–neonate pairs were analyzed. Using liquid chromatography–tandem mass spectrometry, we measured 25(OH)D₂, 25(OH)D₃, 24,25(OH)₂D₃, and 3-epi-25(OH)D₃ concentrations in maternal serum samples. These data were analyzed in relation to birth anthropometric data using multivariable linear regression. Of the study participants, 85.2% showed insufficient vitamin D concentrations. VMR1 was strongly correlated with 25(OH)D concentrations, whereas VMR2 showed a weak correlation. Only VMR2 was associated with all anthropometric data. VMR2 in pregnant women with low vitamin D blood concentrations is a useful marker for neonatal anthropometric data and is independent of 25(OH)D. Accurate measurement of vitamin D metabolites could help better understand the effects of vitamin D on birth outcomes.

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.