Sex-specific associations between cord blood lead and neurodevelopment in early life: The mother-child cohort (Shanghai, China).

The extent to which neurodevelopment is affected by prenatal lead exposure has not been conclusive. In addition, studies on the effects of sex on these relationships are inconsistent. The aim of this study was to investigate the impact of cord blood lead on neurodevelopment in children within sex subgroups. A total of 275 mother-child pairs from the Shanghai mother-child cohort were included. Umbilical cord blood lead was measured using graphite furnace atomic absorption spectrophotometry. The Bayley Scales for Infant Development-III (BSID-III) was used to measure the neurodevelopment of infants at the age of 18 ± 1.5 months. The median and interquartile range of cord blood lead levels in the total participants, male, and female children were 44.0 (24.5) µg/L, 44.0 (24.3) µg/L, and 46.0 (24.0) µg/L, respectively. According to multiple linear regression, cord blood lead concentrations showed a negative association with fine motor scores in all models associated with female children (ß = -1.5; 95%confidence interval: -2.6, -0.4). However, prenatal lead levels were not associated with any of the BSID-III scores in male children. In addition, cord serum DHA was found positively related to fine motor scores in male children. Our findings suggest that prenatal lead exposure could lead to decreased motor function, although this phenomenon was only observed in female children. And DHA may be a protective factor against lead exposure in boys. Thus, further studies are needed to investigate the associations between prenatal lead exposure and neurobehavioral development, as well as the mechanism of sex differences.

Effects of food-borne cholesterol supplementation on lead-induced neurodevelopmental impairments of rats based on BDNF signaling pathway and cholesterol metabolism.

Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-ß levels. Moreover, the MDA content in the lead group was elevated dramatically, whereas the activities of SOD and GSH were significantly inhibited. As for the mechanism, western blot and qRT-PCR experiments were performed, where lead could significantly inhibit the BDNF-TrkB signaling pathway, lowering the protein expression of BDNF and TrkB. Cholesterol metabolism was also affected by lead exposure, in which cholesterol metabolism-related protein expression and gene transcription, including SREBP2, HMGCR, and LDLR, were downregulated. However, cholesterol supplementation efficiently detoxified the negative effects of lead-induced neurotoxicity, reversing the inflammatory response, oxidative stress, inactivation of the BDNF signaling pathway, and imbalance of cholesterol metabolism, thus improving the learning and memory ability of rats. In brief, our study demonstrated that cholesterol supplementation could ameliorate the deficiency of learning and memory induced by lead, which is closely associated with the initiation of the BDNF/TrkB signaling pathway and regulation of cholesterol metabolism.

Prenatal Maternal Occupational Exposure and Postnatal Child Exposure to Elemental Mercury.

OBJECTIVES: Young children are highly vulnerable to elemental mercury toxicity, and elementary mercury exposure in young children in China unfortunately occurs regularly because of the wide use of fluorescent lamps, glass thermometers, and other mercury-contained items. This study aimed to summarize such recent cases in a referral clinic and to make recommendations for postexposure treatment and prevention of future exposure. METHODS: Patients were evaluated between January 2007 and December 2009 in environmental health facilities throughout China and were referred to our clinic. A total of 6 children younger than 4 years with significant elemental mercury exposure were included in this case series analysis. The total mercury content in blood and hair (fetal hair if necessary) and average 24-hour urine mercury concentrations were analyzed. Meso-2,3-dimercaptosuccinic acid or surgery was prescribed for the patient if necessary. RESULTS: Young children were found to be exposed in 3 ways as follows: prenatal exposure through maternal occupational contact in compact fluorescent-lamp factories (2 cases), broken thermometers (3 cases), and other causes of accidental inhalation of mercury vapor during the embryonic and lactation periods (1 case). For 3 cases caused by broken thermometers, x-ray images helped to identify the position of mercury residues. Local excision was used to remove mercury from the floor of the mouth in 1 case. One child was prescribed oral meso-2,3-dimercaptosuccinic acid, and a good response was received. CONCLUSIONS: Substitution of mercury-in-glass thermometers and vigilance to prevent women of childbearing age from occupational mercury exposure were suggested. Treatment selection should vary according to patient situations.

Associations of preterm and early-term birth with suspected developmental coordination disorder: a national retrospective cohort study in children aged 3-10 years.

BACKGROUND: This study analyzed the motor development and suspected developmental coordination disorder of very and moderately preterm (< 34+0 gestational age), late preterm (34+0-36+6 gestational week), and early-term (37+0-38+6 gestational week) children compared to their full-term peers with a national population-based sample in China. METHODS: A total of 1673 children (799 girls, 874 boys) aged 3-10 years old were individually assessed with the Movement Assessment Battery for Children-second edition (MABC-2). The association between gestational age and motor performance of children was analyzed using a multilevel regression model. RESULTS: The global motor performance [ß = - 5.111, 95% confidence interval (CI) = - 9.200 to - 1.022; P = 0.015] and balance (ß = - 5.182, 95% CI = - 5.055 to - 1.158; P = 0.003) for very and moderately preterm children aged 3-6 years old were significantly lower than their full-term peers when adjusting for confounders. Late preterm and early-term children showed no difference. Moreover, very and moderately preterm children aged 3-6 years had a higher risk of suspected developmental coordination disorder (DCD) (≤ 5 percentile of MABC-2 score) when adjusting for potential confounders [odds ratio (OR) = 2.931, 95% CI = 1.067-8.054; P = 0.038]. Late preterm and early-term children showed no difference in motor performance from their full-term peers (each P > 0.05). CONCLUSIONS: Our findings have important implications for understanding motor impairment in children born at different gestational ages. Very and moderately preterm preschoolers have an increased risk of DCD, and long-term follow-up should be provided for early detection and intervention.

An effective spectral unmixing algorithm for flow cytometry based on GA and least squares.

Spectral unmixing algorithm is one of the key technologies for spectral flow cytometer in biology, chemistry and medicine. The proposed algorithm can separate the overlapping spectra automatically without the premeasured single stained or un-stained samples as the basic pure spectra. Genetic algorithm is adopted to search the optimal positions and peak sharps of the basic spectra derived from the unknown components, and then the concentration of each component can be estimated simultaneously by least squares method. Compared with conventional methods, the proposed algorithm has a wider application scope, such as the multi-stained samples with unknown components or the samples with auto-fluorescence. In the simulation, the convergence rate, accuracy and stability of the proposed algorithm are evaluated under the conditions of completely and partly unknown components. In the experiment, the flow spectra of cyanobacteria are processed, and the results demonstrate the feasibility and effectiveness of the proposed algorithm.

[Exposure level and risk factors of heavy metal in prenatal period among Shanghai infants].

OBJECTIVE: To explore the exposure level and risk factors of heavy metal among Shanghai infants in their prenatal period. METHODS: A total of 1652 pregnant or puerperal women were recruited from 10 midwifery-qualified hospitals in Shanghai since October 2008 to October 2009, by the stratified cluster sampling method. They answered the questionnaire and their umbilical cord blood and serum were collected to detect the content of Pb, Hg, Mn, Cd, As and Tl. The risk factors were analyzed by single and multiple regression methods respectively. RESULTS: The median value of the content of Pb, Hg, Mn, Cd, As and Tl were 41.00, 1.88, 4.10, 0.03, 0.86 and 0.02 µg/L respectively. The Hg concentration of pregnant women who ate fish for 4 - 7 times per week (9.7% (160/1652)) was 2.76 µg/L, which was higher than that of pregnant women who only ate fish for 1-3 times per week (49.3% (814/1652)) and those who seldom ate fish (40.0% (661/1652)); the Hg concentration in the two groups above were 2.41 and 2.03 µg/L separately. The difference had statistical significance (χ(2) = 36.40, P < 0.001). Meanwhile, the concentrations of Pb and Tl in the group of pregnant women whose houses were remodeled by PVC pipe (85.0% (1404/1652)) was higher than the concentrations in group of pregnant women whose houses were remodeled by galvanized pipe (15.0% (248/1652)); the Pb concentration in the two groups above were 45.54 and 40.00 µg/L (Z = 2.54, P < 0.05) and the Tl concentration in the two groups above were 0.021 and 0.018 µg/L (Z = 2.97, P < 0.05). However, the As concentration in the group of PVC pipe remodeled was 4.33 µg/L, which was lower than that in the group of galvanized pipe (9.37 µg/L). The difference had statistical significance (Z = 3.99, P < 0.01). The concentrations of Mn, Cd and Tl in the groups of pregnant women whose house had been remodeled in the last 3 years (38.0% (628/1652)) were 14.78, 0.51 and 0.022 µg/L separately, which were all significantly higher than those in the groups of women whose houses' were not remodeled (62.0% (1024/1652)), whose concentrations were 11.01, 0.29 and 0.02 µg/L respectively. The differences had statistical significance (Mn: Z = 2.46, P < 0.05; Cd: Z = 2.38, P < 0.05; Tl: Z = 2.81, P < 0.01). CONCLUSION: The infants in Shanghai were exposed to heavy metals in their prenatal period. The main sources of the exposure were daily diet and remodeled pollution.

Studies on Children With Developmental Coordination Disorder in the Past 20 Years: A Bibliometric Analysis via CiteSpace.

Children with developmental coordination disorder (DCD) have been commonly observed and drawn an increasing amount of attention over the past decades. The aim of the present study is to evaluate the origin, current hotspots, and research trends on children with DCD using a bibliometric tool. After searching with "children" and "developmental coordination disorder" as the "topic" and "title" words, respectively, 635 original articles with 12,559 references were obtained from the electronic databases, Web of Science Core Collection (WoSCC). CiteSpace V.5.7.R2 was used to perform the analysis. The number of publications in this field was increasing over the past two decades. John Cairney from the Department of Family Medicine, McMaster University, Canada, was found to be the most productive researcher. Meanwhile, McMaster University and Canada were the most productive research institution and country, respectively. Reference and journal co-citation analyses revealed the top landmark articles and clusters in this field. Clumsiness was the most strength burst keyword. Moreover, task, meta-analysis, difficulty, adult, and impact will be the active research hotspots in future. These findings provide the trends and frontiers in the field of children with DCD, and valuable information for clinicians and scientists to identify new perspectives with potential collaborators and cooperative countries.

Increasing prevalence and influencing factors of childhood asthma: a cross-sectional study in Shanghai, China.

BACKGROUND: Asthma has been a global problem, especially in children. We aim to evaluate the contemporary prevalence and influencing factors of asthma among children aged 3-7 years in Shanghai, China. METHODS: A random sample of preschool children was included in this study. The International Study of Asthma and Allergies in Childhood questionnaire was adopted to assess the childhood asthma. Multivariable logistic regression models were used to evaluate the associations between independent variables and childhood asthma. RESULTS: Of 6389 preschool children who were invited to take part in this study, 6163 (response rate: 96.5%) completed the questionnaire and were included in the analysis. The overall prevalence of asthma was 14.6% which increased more than six folds from 2.1% in 1990. Being male, younger age, preterm delivery, being born in spring or autumn, being delivered by elective cesarean section without indication, miscarriage, high socioeconomic status, having allergy history, and exposure to passive smoking, latex paint, and dust were potential risk factors for childhood asthma. Spending more time outdoors (> 30 min/day), having indoor plants, and cleaning rooms more frequently were potential protective factors. CONCLUSIONS: The prevalence of childhood asthma in Shanghai has increased dramatically during the past three decades. The findings about risk and protective factors of childhood asthma could be used to develop appropriate strategies to prevent and control childhood asthma in Shanghai and in other similar metropolitan cities.

Impact of delivery mode on the levels of essential trace elements in breast milk.

Aim: This study investigated whether the parturition mode (vaginal or cesarean [C-] section) affects breast milk concentrations of four essential trace elements (iron, copper, zinc, and manganese).Methods: Women giving birth at seven hospitals in seven different regions of China were enrolled in the study. Each participant provided breast milk, collected on postpartum day 3-5, for determination of iron, copper, zinc, and manganese concentrations. Breast milk concentrations of the subject trace elements were compared between women giving birth vaginally or via C-section.Results: Of the 1243 women enrolled in the study, 617 (49.6%) gave birth via the vaginal route and 626 (50.4%) delivered via C-section. The mean milk concentrations of iron, copper, zinc, and manganese in the milk of women delivering via the vaginal route were higher than those in the milk of women delivering via C-section; only the copper concentration differences were statistically significant, after adjusting for confounding factors (p = .023).Conclusion: Delivery mode impacts breast milk concentrations of essential trace elements, with vaginal delivery being associated with higher essential trace element concentrations than C-sections.

Sex differences in the effects of lead exposure on growth and development in young children.

The adverse effects of lead exposure on children's health have been widely investigated. Physical growth is a central indicator of health in early childhood. However, studies on the associations between lead exposure and the physical growth of young children are still equivocal. This study aimed to investigate the effects of lead exposure on young children's growth. A cross-sectional survey was conducted, and a total of 1678 young children were recruited. Blood lead levels were determined by graphite furnace atomic absorption spectrophotometry and anthropometric measurements were obtained by nurses. The weight-for-age Z-score (WAZ), height-for-age Z-score (HAZ) and BMI for-age Z-score (BMIZ) of the children were calculated according to World Health Organization standards. Multivariable linear models after adjustment for potential confounders were used to evaluate the associations between lead exposure and childhood anthropometric characteristics. Meanwhile, the sex differences in these associations were also examined. The median blood lead levels in total subjects, in boys and in girls were 46.44, 49.00 and 43.27 µg/L, respectively. After adjusting for confounders, a significantly negative association of blood lead levels with WAZ and HAZ was observed. After stratification by sex, the blood lead levels in children were negatively associated with WAZ and HAZ in boys but not in girls. Meanwhile, we further provide evidence that blood lead levels below 50 µg/L may also have adverse effects on young children's HAZ. Our findings suggest that lead exposure may have sex-specific effects on physical growth in young children and that blood lead level in a low levels may also have adverse effects on children's physical growth and development.

Contemporary blood lead levels of children aged 0-84 months in China: A national cross-sectional study.

Despite the global abundance of studies on children's lead (Pb) exposure, the magnitude of Pb exposure among children across China remains unclear, especially for rural areas. In 2000, Pb was removed from petrol, marking a change in the sources of Pb exposure in China. To better understand children's Pb exposure and inform potential approaches to exposure reduction, we conducted a national blood Pb survey of 31,373 children (0-84 months old) from May 2013 to March 2015, using a multi-stage and multi-strata sampling method. Blood lead levels (BLLs) were tested using graphite furnace atomic absorption spectrometry with a detection limit of 1 µg/L. The results show that Chinese children had a contemporary geometric mean (GM) BLL of 26.7 µg/L, with 8.6% of BLLs exceeding 50 µg/L. Boys had higher BLLs (GM 27.2 µg/L) compared to girls (GM: 25.9 µg/L) (p < 0.001). Children at the age of 0-36 months had a lower PbB (GM 25.7 µg/L) level compared with those aged 36-84 months (GM 27.9 µg/L) (p < 0.001). When taking into account sociodemographic factors, a multivariate logistic regression analysis shows that the odds ratios (OR) of having a BLL of 27 µg/dL (i.e., median BLL of this study) or higher were 1.88 (95% CI: 1.76, 2.02) and 1.35 (95% CI: 1.22, 1.49) for homes using coal and biomass fuels, respectively, compared to those using gas or electricity. Meanwhile, children in homes close to roads were more likely to have BLLs exceeding 27 µg/dL (OR: 1.11, 95% CI: 1.03, 1.20). In China, rural children had higher BLLs compared to urban children. As a result of pediatric exposure to Pb, there were approximately 144 million and 36 million IQ points lost for rural children and urban children, respectively, revealing a disparity of Pb exposure between rural and urban areas in China. Cleaner domestic fuels and improved cooking/heating equipment will reduce contemporary Pb exposure in rural areas. In addition, the association between contemporary BLLs and distance away from roads further suggests that resuspension of legacy soil/dust Pb should not be neglected in future remediation programs and household interventions. As a large scale survey, this study provides evidence for revising the reference value of BLL, improving the guideline for clinical and public health management, and implementing interventions to prevent adverse health outcomes associated with low-level Pb exposure in children.

The Impact of Subclinical Hypothyroidism on Adverse Perinatal Outcomes and the Role of Thyroid Screening in Pregnancy.

Subclinical hypothyroidism (SCH) is a mild form of hypothyroidism that is common among women of childbearing age. The impact of SCH on adverse perinatal outcomes is unclear and universal screening for thyroid function before or during pregnancy is also much debated. In the present retrospective cohort study on 7,587 women from Shanghai, we assessed whether SCH was associated with adverse perinatal outcomes. The relationship between the risks of adverse outcomes and the time of screening and LT4 treatment status for SCH were also evaluated. SCH was associated with hypertensive disorders of pregnancy (HDP) [odds ratio (OR): 4.04; 95% confidence interval (CI): 1.85-8.84; P = 0.000]. After classification into four different groups based on the time of screening for thyroid function, the increased likelihood of HDP persisted in those diagnosed with SCH in the first and second trimesters (OR: 9.69; 95% CI: 1.73-54.48; P = 0.01 and OR: 3.66; 95% CI: 1.07-12.57, P = 0.03, respectively). The diagnosis of SCH in the preconception period and the third trimester was not significantly associated with HDP and other adverse perinatal outcomes. Five out of 120 (5/120) treated women (4.17%) vs. 4/45 untreated women (8.89%) developed HDP, 4/5 were treated after conception. The results indicate that during pregnancy, SCH conferred an increased risk of HDP, particularly in women diagnosed with the disorder in the first and second trimesters.

Effects of lead, mercury, aluminium and manganese co-exposure on the serum BDNF concentration of pre-school children in Taizhou, China.

Previous studies have shown that toxic metal exposure can have adverse effects on the nervous system of children, but the toxicology of metal co-exposure on neurodevelopment remains to be clarified. Brain derived neurotrophic factor (BDNF) plays an important role in nervous system development, but the possible effects of metal co-exposure on the serum BDNF concentrations of children remain unknown. A total of 561 children living in Taizhou City, China were recruited to participate in our cross-sectional multicenter survey. We measured their blood Pb, Hg, Al and Mn levels and serum BDNF concentrations as well as determined their associations in the total and within sex subgroups. The geometric means of the blood Pb, Hg, Al and Mn levels in all the participants were 67.18 µg/L, 1.01 µg/L, 52.03 µg/L and 18.26 µg/L, respectively. The serum BDNF concentration in children was 19.45 ng/mL. After adjusting for confounders, the blood Pb levels were significantly negatively associated with the serum BDNF concentrations in all the subjects and boys but not in girls. In addition, a significantly negative interaction between blood Pb and blood Hg and a positive interaction between blood Pb and blood Al on serum BDNF concentrations were also observed in boys but not in girls. Our findings highlight the toxic effects of metal co-exposure on serum BDNF levels in pre-school children and indicate that these effects might differ by gender, which suggest that special attention should be paid to the sex-specific effects of metal exposure.

Lead exposure induces Alzheimers's disease (AD)-like pathology and disturbes cholesterol metabolism in the young rat brain.

Lead exposure has been evidenced as a risk factor for Alzheimer's disease (AD), mainly affecting the ageing. However, the early manifestation and mechanisms of AD-like pathology induced by lead exposure remains to be elucidated. Considering the fact that impaired cholesterol metabolism is associated with many neurodegenerative disorders including AD, in this study we focused on the role of cholesterol metabolism in lead induced premature AD-like pathology. We treated weaning rats with lead at different concentrations for 4 weeks. We found that developmental lead exposure increased amyloid-beta (Aß) accumulation and amyloid plaque deposition in the cortex and hippocampus. Lead exposure increased amyloid precursor protein (APP) expression and activated the sterol regulatory element binding protein 2 (SREBP2)-beta secretase (BACE1) pathway. In addition, we found that lead exposure decreased cholesterol levels by upregulating the expression of liver X receptor-a (LXR-a) and ATP-binding cassette transporter protein family member A1 (ABCA1) and decreasing the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR) and low density lipoprotein receptor (LDL-R) in young rat brain tissues. Taken together, our data demonstrated that developmental lead exposure induced early manifestation of AD-like pathology and disturbed cholesterol metabolism in young rat brains.

Body burden of Hg in different bio-samples of mothers in Shenyang city, China.

Hg is an accumulative and neuro-toxic heavy metal which has a wide range of adverse effects in human health. However, few studies are available on body burden of Hg level in different bio-samples of pregnant women in Chinese population. Therefore, this study evaluated Hg levels in different maternal bio-samples in Shenyang city, China and investigated the correlation of Hg levels in different bio-samples. From October to December 2008, 200 pregnant women about to deliver their babies at ShengJing Hospital (Shenyang city, northeast of China) participated in this study. The geometric mean (GM) of Hg levels in cord blood, maternal venous blood, breast milk, and maternal urine were 2.18 µg/L, 1.17 µg/L, 1.14 µg/L, and 0.73 µg/L, respectively, and the GM of maternal hair Hg level was 404.45 µg/kg. There was a strong correlation between cord blood and maternal blood total Hg level (r = 0.713, P<0.001). Frequency of fish consumption more than or equal to 3 times per week during pregnancy was suggested as a significant risk factor of prenatal Hg exposure (unadjusted OR 3.5, adjusted OR 2.94, P<0.05). This study provides evidence about Hg burden of mothers and the risk factors of prenatal Hg exposure in Shenyang city, China.