Association of prenatal multiple metal exposures with child neurodevelopment at 3 years of age: A prospective birth cohort study.

Prenatal exposures to toxic metals and trace elements have been linked to childhood neurodevelopment. However, existing evidence remains inconclusive, and further research is needed to investigate the mixture effects of multiple metal exposures on childhood neurodevelopment. We aimed to examine the associations between prenatal exposure to specific metals and metal mixtures and neurodevelopment in children. In this prospective cohort study, we used the multivariable linear regressions and the robust modified Poisson regressions to explore the associations of prenatal exposure to 25 specific metals with neurodevelopment among children at 3 years of age in 854 mother-child pairs from the Jiangsu Birth Cohort (JBC) Study. The Bayesian kernel machine regression (BKMR) was employed to assess the joint effects of multiple metals on neurodevelopment. Prenatal manganese (Mn) exposure was negatively associated with the risk of non-optimal cognition development of children, while vanadium (V), copper (Cu), zinc (Zn), antimony (Sb), cerium (Ce) and uranium (U) exposures were positively associated with the risk of non-optimal gross motor development. BKMR identified an interaction effect between Sb and Ce on non-optimal gross motor development. Additionally, an element risk score (ERS), representing the mixture effect of multiple metal exposures including V, Cu, Zn, Sb, Ce and U was constructed based on weights from a Poisson regression model. Children with ERS in the highest tertile had higher probability of non-optimal gross motor development (RR = 2.37, 95 % CI: 1.15, 4.86) versus those at the lowest tertile. Notably, Sb [conditional-posterior inclusion probabilities (cPIP) = 0.511] and U (cPIP = 0.386) mainly contributed to the increased risk of non-optimal gross motor development. The findings highlight the importance of paying attention to the joint effects of multiple metals on children's neurodevelopment. The ERS score may serve as an indicator of comprehensive metal exposure risk for children's neurodevelopment.

Association of Breastfeeding and Neonatal Jaundice With Infant Neurodevelopment.

INTRODUCTION: Exclusive breastfeeding is advantageous for infant neurodevelopment. Nevertheless, insufficient human milk supply in exclusively breastfed infants may elevate the risk of neonatal jaundice, which can potentially result in neurological harm. Whether mothers should adhere to exclusive breastfeeding in infants with neonatal jaundice remains unclear. METHODS: Data comes from the Jiangsu Birth Cohort (JBC), a prospective and longitudinal birth cohort study in China. A total of 2,577 infants born from November 2017 to March 2021 were included in the analysis. Multivariate linear regression models were used to analyze the associations between breastfeeding status, neonatal jaundice, and their interaction with infant neurodevelopment. Analysis was performed in 2022. RESULTS: Compared with "exclusive breastfeeding," fine motor scores of infants were lower for "mixed feeding" (ßadj, -0.16; 95% CI, -0.29 to -0.03; p=0.016) and "no breastfeeding" (ßadj, -0.41; 95% CI, -0.79 to -0.03; p=0.034). Compared with "no neonatal jaundice," infants with "severe neonatal jaundice" had lower scores for cognition (ßadj, -0.44; 95% CI, -0.66 to -0.23; p<0.001) and fine motor (ßadj, -0.19; 95% CI, -0.35 to -0.03; p=0.024). In infants with severe neonatal jaundice, the termination of exclusive breastfeeding before 6 months was associated with worse cognition (ßadj, -0.28; 95% CI, -0.57 to 0.01), while this association was not observed in those without neonatal jaundice (ßadj, 0.09; 95% CI, -0.26 to 0.43). CONCLUSIONS: Exclusive breastfeeding for the first 6 months is beneficial to the neurodevelopment of infants, especially in those with severe neonatal jaundice.

Association between prenatal exposure to trace elements mixture and visual acuity in infants: A prospective birth cohort study.

BACKGROUND: Prenatal environmental factors may affect the development of the offspring and can bring long lasting consequences to the offspring's health. To date, only few studies have reported inconclusive association between prenatal single trace element exposure and visual acuity, and no studies have investigated the association between prenatal exposure to trace elements mixture and visual acuity in infants. METHODS: In the prospective cohort study, grating acuity in infants (12 ± 1 months) was measured by Teller Acuity Cards II. Concentrations of 20 trace elements in maternal urine samples collected in early-trimester were measured by Inductively Coupled Plasma Mass Spectrometry. Elastic net regression (ENET) was applied to select important trace elements. Nonlinear associations of the trace elements levels with abnormal grating were explored using the restricted cubic spline (RCS) method. The associations between selected individual elements and abnormal grating acuity were further appraised using the logistic regression model. Then Bayesian Kernel Machine Regression (BKMR) was used to estimate the joint effects of mixture and interactions between trace elements combining with NLinteraction. RESULTS: Of 932 mother-infant pairs, 70 infants had abnormal grating acuity. The ENET model produced 8 trace elements with non-zero coefficients, including cadmium, manganese, molybdenum, nickel, rubidium, antimony, tin and titanium. RCS analyses identified no nonlinear associations of the 8 elements with abnormal grating acuity. The single-exposure analyses using logistic regression revealed that prenatal molybdenum exposure possessed a significantly positive association with abnormal grating acuity (odds ratio [OR]: 1.44 per IQR increase, 95% confidence interval [CI]: 1.05, 1.96; P = 0.023), while prenatal nickel exposure presented with a significantly inverse association with abnormal grating acuity (OR: 0.64 per IQR increase, 95% CI: 0.45, 0.89; P = 0.009). Similar effects were also observed in BKMR models. Moreover, the BKMR models and NLinteraction method identified potential interaction between molybdenum and nickel. CONCLUSIONS: We established that prenatal exposure to high concentration of molybdenum and low concentration of nickel was associated with the increased risk of abnormal visual acuity. Potential interaction may exist between molybdenum and nickel on abnormal visual acuity.

Maternal exposure to metal mixtures during early pregnancy and fetal growth in the Jiangsu Birth Cohort, China.

Previous epidemiological studies have reported that prenatal exposure to metals might have influence on fetal growth. Most studies assessed the effect of individual metals, while the investigation on the relationship between multiple metal exposure and fetal growth is sparse. The objective of the present study is to assess the joint impact of metal mixtures on fetal growth during pregnancy. A total of 1275 maternal-infant pairs from the Jiangsu Birth Cohort (JBC) Study were included to investigate the effect of maternal metal exposure on fetal biometry measures at 22-24, 30-32, and 34-36 weeks of gestation. Lead (Pb), arsenic (As), cadmium (Cd), mercury (Hg), chromium (Cr), vanadium(V), thallium (Tl) and barium (Ba) were measured by inductively coupled plasma mass spectrometry (ICP-MS) in maternal urine samples collected in the first trimester. We used general linear models and restricted cubic splines to test dose-response relationships between single metals and fetal growth. The weighted quantile sum (WQS) models were then applied to evaluate the overall effect of all these metals. We observed inverse associations of exposure to Pb, V and Cr with estimated fetal weight (EFW) at 34-36 weeks of gestation. Notably, maternal exposure to metal mixtures was significantly associated with reduced EFW at 34-36 weeks of gestation after adjusting for some covariates and confounders (aß -0.05 [95% CI: 0.09, -0.01], P = 0.023), and this association was mainly driven by Cr (30.41%), Pb (23.92%), and Tl (15.60%). These findings indicated that prenatal exposure to metal mixtures might impose adverse effects on fetal growth.

The reduction of melatonin levels is associated with the development of preeclampsia: a meta-analysis.

OBJECTIVE: The aim of this analysis was to demonstrate the association between melatonin levels and the development of preeclampsia. METHODS: Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using a random effects model. RESULTS: The pooled SMD between case and control was 1.40 (95% CI: 0.26, 2.55; P = 0.02). And the pooled SMD between mild PE and severe PE was 5.25 (95% CI: 1.5, 9.01; P = 0.006). CONCLUSION: The meta-analysis illustrated that melatonin concentration was significantly lower in women with preeclampsia, and correlated with the severity of the disease.

Mechanisms underlying melatonin-mediated prevention of fenvalerate-induced behavioral and oxidative toxicity in zebrafish.

The neurotoxic effects attributed to the pesticide fenvalerate (FEN) are well-established. The aim of this study was to determine whether melatonin (MLT) was able to protect against FEN-induced behavior, oxidative stress, apoptosis, and neurogenesis using zebrafish (Danio rerio) model. Zebrafish exposed to 100 µg/L FEN for 120 h exhibited decreased swimming activity accompanied by downregulated expression of neurogenesis-related genes (Dlx2, Shha, Ngn1, Elavl3, and Gfap), suggesting that neurogenesis were impaired. In addition, FEN exposure significantly elevated oxidative stress as evidenced by increased malondialdehyde levels, as well as activities of Cu/Zn superoxide dismutase (Cu/Zn SOD), catalase, and glutathione peroxidase. Acridine orange staining demonstrated that embryos treated with FEN for 120 h significantly enhanced apoptosis mainly in the brain. FEN also produced upregulation of the expression of the pro-apoptotic genes (Bax, Fas, caspase 8, caspase 9, and caspase 3) and decreased expression of the anti-apoptotic gene Bcl-2. MLT significantly attenuated the FEN-mediated oxidative stress, modulated apoptotic-regulating genes, and diminished apoptotic responses. Further, MLT blocked the FEN-induced effects on swimming behavior as well as on neurogenesis-related genes. In conclusion, MLT protected against FEN-induced developmental neurotoxicity and apoptosis by inhibiting pesticide-mediated oxidative stress in zebrafish.