[Prenatal lead exposure related to cord blood brain derived neurotrophic factor (BDNF) levels and impaired neonatal neurobehavioral development].

OBJECTIVE: To explore the relationship between umbilical cord blood brain-derived neurotrophic factor (BDNF) and neonatal neurobehavioral development in lead exposure infants. METHODS: All infants and their mother were randomly selected during 2011 to 2012, subjects were selected according to the umbilical cord blood lead concentrations, which contcentration of lead was higher than 0.48 µmol/L were taken into high lead exposure group, about 60 subjects included. Comparing to the high lead exposure group, according to gender, weight, pregnant week, length and head circumferenece, the level of cord blood lead concentration under 0.48 µmol/L were taken into control group, 60 cases included. Lead content was determined by graphite furnace atomic absorption spectrometry. Neonatal behavioral neurological assessment (NBNA) was used to determine the development of neonatal neuronal behavior. The content of BDNF was detected by ELISA. Comparing the BDNF and the NBNA score between two groups, and linear correlation was given on analysis the correlation between lead concentration in cord blood and BDNF, BDNF and the NBNA score. RESULTS: Lead content in high exposure group was (0.613±0.139) µmol/L, and higher than (0.336±0.142) µmol/L in low exposure group (t=3.21, P<0.001) . NBNA summary score (36.35±1.86), active muscle tension score (6.90±0.27) and general assessment score (5.93±0.32) in high exposure group were lower than those (38.13±0.96, 7.79±0.35, 6.00±0.00) in low exposure group (t values were 8.21, 10.23, 2.32, respectively, P values were <0.001, <0.001 and 0.037) . BDNF content in high exposure group which was (3.538±1.203) ng/ml was higher than low exposure group (2.464±0.918) ng/ml (t=7.60, P<0.001). The correlation analysis found that the cord blood BDNF content was negatively correlated with NBNA summary score, passive muscle tension and active muscle tone score (r was -0.27, -0.29, -0.30, respectively, P values were <0.001, respectively) . CONCLUSION: Prenatal lead exposure results poor neonatal neurobehavioral development and cord blood BDNF was negatively correlated with neonatal neurodevelopment, may serve as a useful biomarker.

Investigation of Childhood Lead Poisoning from Parental Take-Home Exposure from an Electronic Scrap Recycling Facility ­ Ohio, 2012.

Lead affects the developing nervous system of children, and no safe blood lead level (BLL) in children has been identified. Elevated BLLs in childhood are associated with hyperactivity, attention problems, conduct problems, and impairment in cognition. Young children are at higher risk for environmental lead exposure from putting their hands or contaminated objects in their mouth. Although deteriorating lead paint in pre-1979 housing is the most common source of lead exposure in children, data indicate that ≥30% of children with elevated BLLs were exposed through a source other than paint. Take-home contamination occurs when lead dust is transferred from the workplace on employees' skin, clothing, shoes, and other personal items to their car and home. Recycling of used electronics (e-scrap) is a relatively recent source of exposure to developmental neurotoxicants, including lead. In 2010, the Cincinnati Health Department and Cincinnati Children's Hospital Pediatric Environmental Health Specialty Unit (PEHSU) investigated two cases of childhood lead poisoning in a single family. In 2012, CDC's National Institute for Occupational Safety and Health (NIOSH) learned about the lead poisonings during an evaluation of the e-scrap recycling facility where the father of the two children with lead poisoning worked. This report summarizes the case investigation. Pediatricians should ask about parents' occupations and hobbies that might involve lead when evaluating elevated BLLs in children, in routine lead screening questionnaires, and in evaluating children with signs or symptoms of lead exposure.

Encephalopathy from lead poisoning masquerading as a flu-like syndrome in an autistic child.

Acute encephalopathy from childhood lead poisoning is fortunately rare. However, in pediatric patients with developmental disabilities and pica, there is a risk of lead exposure at a dose commensurate with encephalopathy, coupled with a risk of delayed diagnosis because of difficulty in distinguishing between baseline and altered behavior. We report here a 4-year old autistic boy who presented to the pediatrician's office with gastrointestinal symptoms and behavioral changes and was at first thought to have a viral syndrome. He returned 2 days later with a worsening illness; increasing pallor, vomiting, abdominal colic, and changes in consciousness were recognized in the emergency department as lead-induced anemia and encephalopathy, associated with a positive abdominal film for paint chips and a blood lead level equal to 216 microg/dL (10.43 micromol/L) (reference, <10 microg/dL or 0.483 micromol/L). As this case illustrates, prompt recognition is dependent on the skills and suspicions of an astute clinician, especially in the busy emergency department.

Latent subgroups of cognitive performance in lead- and manganese-exposed Uruguayan children: Examining behavioral signatures.

OBJECTIVES: Lead (Pb) and manganese (Mn) are confirmed neurotoxins but it is unclear to what extent low-level exposure produces a unique behavioral signature. The objective of this study was to investigate latent cognitive profiles among children (6-8 years) from Montevideo, Uruguay co-exposed to these metals. METHOD: Among 345 children, blood Pb and hair Mn were measured using atomic absorption spectroscopy and ICP-MS, respectively. Sixteen measures, reflecting multiple domains of cognitive functioning were gathered: (1) three tests from Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-Extra Dimensional Shift (IED), Spatial Span (SSP) and Stockings of Cambridge (SOC), (2) ten tasks from Woodcock-Muñoz Achievement Battery, Revised (WM): Visual-Motor Integration, Verbal Comprehension (Vocabulary, Synonyms, Antonyms, Analogies), Visual-Auditory Comprehension, Concept Formation, Visual Spatial Thinking, Number Inversion and Spatial Relations, (3) Bender Gestalt task, and (4) Weschler block design task. Scores were modeled using latent profile analysis (LPA). Association between blood Pb and hair Mn on performance profiles was assessed using ordinal regression, controlling for confounders. An interaction between Pb and Mn was tested. RESULTS: Mean ± SD of blood Pb was 4.1 ± 2.1 µg/dL and 35% of children had blood Pb ≥ 5 µg/dL. Median [5%, 95%] hair Mn level was 0.8 [0.3, 4.1] ppb. Three latent cognitive performance profiles were identified: high (n = 46, 13%), average (n = 209, 61%) and low (n = 90, 26%). Each one-unit increase in blood Pb was associated with a 28% greater likelihood of belonging to a poorer-performing profile. The association was non-linear, with the effect of Pb on profile membership strongest at lower levels of exposure. There was no meaningful interaction between Pb and Mn. CONCLUSIONS: A behavioral signature for low-level Pb & Mn exposure was not identified, but the likelihood of membership in low-performing profile was higher at lowest levels of blood Pb. There was no effect measure modification between Pb and Mn. Future research should address how complex environments created by chemical exposures and the social context relate to cognitive performance in young children.

The role of modified citrus pectin as an effective chelator of lead in children hospitalized with toxic lead levels.

CONTEXT: Lead toxicity is an ongoing concern worldwide, and children, the most vulnerable to the long-lasting effects of lead exposure, are in urgent need of a safe and effective heavy metal chelating agent to overcome the heavy metals and lead exposure challenges they face day to day. OBJECTIVE: This clinical study was performed to determine if the oral administration of modified citrus pectin (MCP) is effective at lowering lead toxicity in the blood of children between the ages of 5 and 12 years. METHOD: Hospitalized children with a blood serum level greater than 20 microg/dL, as measured by graphite furnace atomic absorption spectrometry (GFAAS), who had not received any form of chelating and/or detoxification medication for 3 months prior were given 15 g of MCP (PectaSol) in 3 divided dosages a day. Blood serum and 24-hour urine excretion collection GFAAS analysis were performed on day 0, day 14, day 21, and day 28. RESULT: This study showed a dramatic decrease in blood serum levels of lead (P = .0016; 161% average change) and a dramatic increase in 24-hour urine collection (P = .0007; 132% average change). CONCLUSION: The need for a gentle, safe heavy metal-chelating agent, especially for children with high environmental chronic exposure, is great. The dramatic results and no observed adverse effects in this pilot study along with previous reports of the safe and effective use of MCP in adults indicate that MCP could be such an agent. Further studies to confirm its benefits are justified.

Lead in a case of encephalopathy.

A 2-year-old boy with a history of pica was admitted with vomiting and treated overnight for viral tonsillitis. A week later, he presented with a prolonged afebrile seizure and required intubation and ventilation. Antibiotics and acyclovir were started. Despite extensive investigations including MRI head, no cause was identified. Four days later, he deteriorated with signs of raised intracranial pressure. On day 5, blood lead concentration in the sample collected at admission was reported as grossly elevated, consistent with a diagnosis of severe lead poisoning from ingesting lead-containing paint at the family home. Chelation therapy was started but, unfortunately, he did not make a neurological recovery, and care was withdrawn. A serious case review identified a lack of awareness of lead poisoning and its relation to pica as a root cause. We report this case to share our experience and the importance of considering lead poisoning in children with pica.

[Intelligence quotient loss in Mexican pottery artisan's children]. / Pérdida de coeficiente intelectual en hijos de alfareros mexicanos.

BACKGROUND: In Mexico, artisans frequently use lead oxide or greta in order to produce utensils, which are destined to preparation and storage of food and drinks. Additionally, the risk of lead poisoning of artisans and their families is greater than in general population, and within these families, children are the most susceptible to lead poisoning. The aim of this study was to estimate IQ loss in Mexican children from potter families exposed to lead. METHODS: Lead concentrations in soil were determined in 19 potter's homes that functioned as pottery workshops in seven Mexican states between 2009 and 2012. This information was used to estimate blood lead levels through the integrated exposure uptake biokinetic (IEUBK) model. The loss of IQ points was then estimated according to the Lanphear and Schwartz models. RESULTS: The mean lead concentration found in the workshops' soil was 1098.4 ppm. Blood lead levels estimated in children under 8 years old were 26.4 µg/dL and the loss of IQ points comprised from 7.13 to 8.84 points depending on the model. CONCLUSIONS: It is possible that 11 children from families of artisans in Mexico may be losing between 7.13 to 8.84 IQ points, due to lead exposure in their houses-workshops. This loss in IQ points could have important health, economic and social impacts.

Introducción: en México, los alfareros continúan usando frecuentemente el óxido de plomo o greta para producir utensilios, los cuales se destinan a la preparación y almacenamiento de alimentos y bebidas. Adicionalmente, el riesgo de intoxicación por plomo de los alfareros y sus familias es mayor que en la población general, y en tales familias, los niños son los más susceptibles a la intoxicación por plomo. El objetivo del estudio fue estimar la pérdida de puntos de coeficiente intelectual (CI) en hijos de alfareros mexicanos expuestos al plomo. Métodos: durante el periodo de 2009 a 2012 se determinaron las concentraciones de plomo en suelo de 19 casas-talleres de alfareros en siete estados mexicanos. Esta información se utilizó para estimar el nivel de plomo en sangre, por medio del modelo biocinético integrado de absorción por exposición (IEUBK, por sus siglas en inglés). Posteriormente, se calcularon los puntos perdidos de CI según los modelos de Schwartz y Lanphear. Resultados: la concentración promedio de plomo en suelo fue de 1098.4 ppm. Se estimó un nivel de plomo en sangre de 26.4 µg/dL para menores de 8 años. La pérdida de puntos de CI estimada fue 7.13 y 8.84, según el modelo utilizado. Conclusión: es posible que al menos 11 niños de familias alfareras mexicanas estén perdiendo entre 7.13 y 8.84 puntos de CI, debido a la exposición al plomo en sus casas-talleres, lo que supone importantes impactos económicos, sociales y de salud.

The relationship between lead exposure, motor function and behaviour in Inuit preschool children.

The main focus of this study was to determine the role of behaviour in the relationship between postnatal lead exposure and motor function. The sample consisted of 110 preschoolers, of age 5, from Nunavik. Lead concentration was measured at birth and at testing time. Average lead levels were of 4.9 microg/dL (0.24 micromol/L) and 5.3 microg/dL (0.26 micromol/L) for cord and child blood, respectively. Children's balance and fine motor capacities were tested. A modified version of the IBR was used to assess behaviour. Postnatal blood lead concentrations correlated positively with both impulsivity and activity. Neither pre- nor postnatal blood lead concentration correlated with attention level. The children's scores on impulsivity (I) and activity (A) were summed to create the independent variable IA, which was tested as a potential mediator between lead exposure and two dependent variables: the coefficient of covariation in alternating hand movements and transversal sway in tandem position. Mediation was significant only for the latter variable. IA and attention were then tested as potential moderators in the relation between postnatal lead exposure and motor function. No significant interaction between independent variables could be observed. These results do not support the hypothesis that, at low levels of postnatal exposure, lead acts indirectly on motor function via behaviour. However, IA does act as a mediator in the relationship between postnatal blood lead concentration and transversal sway in tandem position.

Environmental and Occupational Lead Exposure Among Children in Cairo, Egypt: A Community-Based Cross-Sectional Study.

The aim of this study was to assess childhood lead exposure in a representative sample of Cairo, and to investigate the possible risk factors and sources of exposure. This cross-sectional study was conducted from November 2014 through April 2015. The target population was children aged 6 to 18 years, recruited into 4 groups, garbage city, moderate-living standard area, urban and suburban schools, and workshops in the city of Cairo. Blood lead levels (BLLs) and hemoglobin (Hb) concentrations were measured. Also, potential local environmental sources were assessed for hazardous lead contamination. Analysis on 400 participants has been carried out. A total of 113 children had BLLs in the range 10 to 20 µg/dL. Smoking fathers, housing conditions, playing outdoors, and exposure to lead in residential areas were significantly correlated with high BLLs. The mean values of hemoglobin were inversely correlated with BLLs. Children involved in pottery workshops had the highest BLLs and the lowest Hb values with a mean of (43.3 µg/dL and 8.6 g/dL, respectively). The mean value of environmental lead in workshop areas exceeded the recommended levels. Also, those values measured in dust and paint samples of garbage city were significantly high. Moreover, the mean lead levels in the soil samples were significantly higher in urban schools (P = 0.03) than the suburban ones. Childhood lead poisoning accounts for a substantial burden in Egypt, which could be preventable. Development of national prevention programs including universal screening program should be designed to reduce incidence of lead toxicity among children.

Physician barriers to lead testing of Medicaid-enrolled children.

BACKGROUND: The rate of blood lead testing among Medicaid-enrolled children is low. OBJECTIVE: To determine barriers to lead testing perceived by pediatricians to develop future interventions to improve the rate of appropriate blood lead testing. METHODS: We developed a mail survey based on findings from 6 focus groups of primary-care providers in Michigan. We then surveyed a random sample of 520 primary-care pediatricians in Michigan. Pediatricians who did not accept Medicaid were excluded from the analysis. RESULTS: The overall response rate was 65% (257 of 396 potentially eligible respondents). Most (68%) reported that they routinely test 1-year-old Medicaid-enrolled children. Practices with onsite blood testing were more likely to report routine testing of 1-year-old children (79% vs 62%; P < .01). Most (76%) who do not routinely test were aware of the Medicaid requirements for testing. The most common reason (70%) for not testing Medicaid-enrolled children was physicians' belief that they practice in a low-risk area. However, 35% of those who do not test because they practice in a low-risk area actually have their main practice site in a high-risk area. CONCLUSIONS: To improve the rate of blood lead testing, the public health department should provide pediatricians with data regarding the local risk of lead poisoning. The public health department should also consider working with practices to facilitate onsite blood collection for lead testing.

Systemic Lead Toxicity.

A 4-year-old girl with slow mentation had increasing knee tenderness and limping gait.

Relationship among maternal blood lead, ALAD gene polymorphism and neonatal neurobehavioral development.

Lead is a widely used heavy metal that can affect children's nervous system development. ALAD gene polymorphism is associated with lead neurotoxicity. This study aimed to clarify the relationship among maternal blood lead, ALAD gene polymorphism, and neonatal neurobehavioral development through detecting maternal blood lead and ALAD gene polymorphism. 198 maternal and neonatal were selected as the research object. Graphite furnace atomic absorption method was applied to detect the maternal blood lead concentration. PCR-RFLP was used to detect ALAD genotype distribution. Neonatal NANB score was treated as effect indicator. SPSS was used for statistical analysis. The ALAD genotype was 181 cases (91.4%) for ALAD11 and 17 cases (8.6%) for ALAD12. ALAD allele frequency distribution accords with genetics Hardy-Weinberg balance (P > 0.05). Blood lead level in maternal with ALAD12 genotype was significantly higher than with ALAD11 genotype (P < 0.01). NANB score in high blood lead neonatal group was obviously lower than the low blood lead group (P < 0.05). Newborn's NANB score from the maternal with ALAD11 genotype was lower than from the maternal with ALAD12 genotype (P < 0.01). After ruling out the confounding factors influence by multiple linear regressions, ALAD gene polymorphisms had no significant correlation with neonatal NANB score (P > 0.05). ALAD gene polymorphism is associated with the blood lead level. Low level lead exposure in utero may cause newborn early neurobehavioral maldevelopment. Maternal ALAD gene polymorphism can affect early neonatal neurobehavioral development by influencing the blood lead level.

Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society.

Autism is a common disorder of childhood, affecting 1 in 500 children. Yet, it often remains unrecognized and undiagnosed until or after late preschool age because appropriate tools for routine developmental screening and screening specifically for autism have not been available. Early identification of children with autism and intensive, early intervention during the toddler and preschool years improves outcome for most young children with autism. This practice parameter reviews the available empirical evidence and gives specific recommendations for the identification of children with autism. This approach requires a dual process: 1) routine developmental surveillance and screening specifically for autism to be performed on all children to first identify those at risk for any type of atypical development, and to identify those specifically at risk for autism; and 2) to diagnose and evaluate autism, to differentiate autism from other developmental disorders.

Impaired neuropsychological functioning in lead-exposed children.

Neuropsychological functions were assessed in 174 children participating in a longitudinal study of low-level lead exposure. At age 5 1/2 years, children were administered the Working Memory and Planning Battery of the Cambridge Neuropsychological Testing Automated Battery. Measures of sociodemographic characteristics of the family, prenatal and perinatal risk, quality of caregiving and crowding in the home, and maternal and child intelligence were used as covariates to test the hypothesis that children with higher lifetime average blood lead concentrations would perform more poorly on tests of working memory, attentional flexibility, and planning and problem solving. The lifetime average blood lead level in this sample was 7.2 micrograms per deciliter (mug/dL; range: 0-20 mug/dL). Children with greater exposure performed more poorly on tests of executive processes. In both bivariate and multivariate analyses, children with higher lifetime average blood lead concentrations showed impaired performance on the tests of spatial working memory, spatial memory span, intradimensional and extradimensional shifts, and an analog of the Tower of London task. Many of the significant associations remained after controlling for children's intelligence test scores, in addition to the other covariates. These findings indicate that the effects of pediatric lead exposure are not restricted to global indexes of general intellectual functioning, and executive processes may be at particular risk of lead-induced neurotoxicity.

Distortion product oto-acoustic emissions in Andean children and adults with chronic lead intoxication.

Neuroauditory disorders and sensory-neural hearing loss have been suggested as possible etiologic factors in the neurodevelopmental learning disabilities attributed to lead (Pb) intoxication. However, studies relating hearing loss to Pb poisoning have presented disparate results, suggesting that auditory sensitivity may not be a reliable marker of Pb intoxication. Oto-acoustic emissions, sounds that can be recorded non-invasively from the ear canal and are preneural responses of the outer hair cells of the inner ear, have been found to be diminished in ears exposed to some toxic agents. In the current study, distortion product oto-acoustic emissions (DPOAEs) were obtained from 28 ears of 14 children and 10 ears of 5 adults living in a highly Pb-contaminated environment in remote villages in the Andes Mountains of Ecuador. Blood lead (PbB) levels for the children (ages: 5-14 years) ranged from 33.4 to 118.2 microg/dl (mean: 51.5; SD: 22.9 microg/dl), or 3-12 times higher than the U.S. Centers for Disease Control and Prevention's toxic level of 10 microg/dl. The PbB levels for the adults ranged from 19.2 to 55.7 microg/dl. Despite the high PbB levels, the children had normal hearing thresholds, and DPOAEs were present for the children at the following f2 frequencies: 1187, 1500, 1906, 2406, 3031, 3812, 4812 and 6031 Hz. Although there was a tendency for the children to have diminished DPOAEs, no consistent correlation of DPOAEs with PbB level was found. The adults had diminished DPOAEs that were consistent with their observed, probably noise-related hearing loss. Contrary to some reports in the literature, the current results show no unequivocal clinical or subclinical evidence that high PbB levels have a toxic effect on the cochlea.

[Effects of low-level lead exposure on neurobehaviour development in 1-3 year-old children and the intervention guideline].

In order to study the effects of low-level lead exposure on neurobehaviour development, the neurobehaviour functions in eighty-five 1-3 year-old children were assessed by Neurobehaviour Psychological Test (recommended by the Institute of Psychology, Chinese Academy of Sciences). The results showed that the increase of blood lead (BPb) level in each 100 micrograms/L was associated with an average loss of 3-4 points of Development Quotient (DQ) in these subjects. Age, hand-mouth habits and environmental lead pollution are the main risk factors. It is concluded that even in a low-level lead exposure, DQ in young children may be affected. Certain intervention steps based on the levels of lead exposure were recommended.

Role of chelation in the treatment of lead poisoning: discussion of the Treatment of Lead-Exposed Children Trial (TLC).

Lead exposure in children is one component leading to cognitive impairment. The Treatment of Lead-Exposed Children Trial (1994-2004) studied the effect of succimer in treating low levels of lead exposure (20-44 mcg/dL) in children 12 to 33 months old. While succimer was effective in reducing blood lead concentrations in the short term, treatment of blood lead levels did not result in any detectable improvement in a wide variety of measurements of cognitive or behavioral function. Furthermore, blood lead concentrations were not distinguishable between chelated and non-chelated individuals at 1 year. The most important treatment strategy is identification and termination of major sources of lead exposure.