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.

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.

[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.

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.

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.

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.

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.

Association of maternal and child blood lead and hemoglobin levels with maternal perceptions of parenting their young children.

Biological and psychosocial factors affect child development and behavior. Whereas biological underpinnings behind the neurotoxic effects of lead are studied extensively, the effects of psychosocial factors contributing to poor behavioral outcomes in lead-exposed children are not well understood. Parental attributes and practices may moderate or mediate the effects of lead on children's behavioral outcomes. We investigated the hypothesis that maternal and child lead and hemoglobin levels are associated with maternal perceptions of their parenting. Specifically, we hypothesized that children with higher blood lead (BLL) and lower hemoglobin concentrations would be associated with poorer maternal self-assessments of their parenting skills or the mother-child relationship. Children aged 13-55 months and their mothers (n=109) were recruited from among the participants of a previous lead and anemia screening study and from preschools in Montevideo, Uruguay. The mother-child pair attended two study visits: one to collect biological samples and answer demographic and child questionnaires, including statements regarding parenting; and a second to evaluate maternal IQ, depression and stress, and child development. Of the children, 51.6% had blood lead concentrations (BLLs) ≥ 5 µg/dL, 18.0% had anemia, and 8% had both conditions. Among mothers, 48.4% had BLLs ≥ 5 µg/dL, 16.0% had anemia, and 11% had both. BLLs ≥ 5 µg/dL in mother or child were associated with lower maternal perceptions of being skilled at discipline (p<0.05). Maternal anemia was associated with lower likelihood that mothers would let their children explore and play (p<0.05), whereas child anemia was associated with maternal perception of lower emotional support (p<0.01). In addition to shared environmental exposures, parenting and family interactions need to be considered as potentially contributing factors to poorer outcomes in lead-exposed children.

High prenatal and postnatal lead exposure associated lead encephalopathy in an infant.

An 11-month-old child presented with persistent seizures requiring ventilator support. The child had global developmental delay, was staying in the premises of battery manufacturing unit, had microcytic and hypochromic anemia with basophilic stripling on peripheral smear, lead line on radiograph of the long bones and BLL of 244 µg/dl. The CT scan of the brain revealed cerebral atrophy. The mother also had high BLL and lead line in the radiograph of the long bones. The child was managed with chelation therapy. Given the continuing lead exposure among occupational and general populations in India, this case study highlights the need for prompt environmental preventive actions as well as nutritional and preventive counseling for occupational populations.

Lead poisoning among Burmese refugee children--Indiana, 2009.

Recent routine screening revealed multiple cases of unexplained lead poisoning among children of Burmese refugees living in Fort Wayne, Indiana. A cross-sectional study was conducted to determine (a) the prevalence of elevated blood lead levels (BLLs) among Burmese children and (b) potential sources of lead exposure. A case was defined as an elevated venous BLL (≥10 µg/dL); prevalence was compared with all Indiana children screened during 2008. Environmental and product samples were tested for lead. In all, 14 of 197 (7.1%) children had elevated BLLs (prevalence ratio: 10.7) that ranged from 10.2 to 29.0 µg/dL. Six cases were newly identified; 4 were among US-born children. Laboratory testing identified a traditional ethnic digestive remedy, Daw Tway, containing a median 520 ppm lead. A multilevel linear regression model identified daily use of thanakha, an ethnic cosmetic, and Daw Tway use were related to elevated BLLs (P < .05). Routine monitoring of BLLs among this population should remain a priority.

Practical guidelines for evaluating lead exposure in children with mental health conditions: molecular effects and clinical implications.

Children in the United States are exhibiting extremely high levels of attentional and learning disabilities. Although lead has been eliminated from many industrial products, children continue to come into contact with it, such as in toys and cosmetics. Lead exposure occurs most commonly in poor, urban populations, and can exacerbate psychiatric disorders associated with stress. We present 1) an overview of lead exposure; 2) a detailed summary of current research on the molecular synergy of toxicity caused by lead and stress; 3) a review of human studies that appear to correlate with these molecular findings, including understanding nutrition, environmental enrichment, and caregiving as risk modifiers; and 4) a systematic approach for mental health practitioners in managing children presenting with multiple symptoms and risk factors for mental health conditions. In this article, we review some of the clinical and scientific challenges that relate to the assessment and treatment of children presenting for mental health care who may have potential lead exposure.

A Bland-Altman comparison of the Lead Care® System and inductively coupled plasma mass spectrometry for detecting low-level lead in child whole blood samples.

Chronic childhood lead exposure, yielding blood lead levels consistently below 10 µg/dL, remains a major public health concern. Low neurotoxic effect thresholds have not yet been established. Progress requires accurate, efficient, and cost-effective methods for testing large numbers of children. The LeadCare® System (LCS) may provide one ready option. The comparability of this system to the "gold standard" method of inductively coupled plasma mass spectrometry (ICP-MS) for the purpose of detecting blood lead levels below 10 µg/dL has not yet been examined. Paired blood samples from 177 children ages 5.2-12.8 years were tested with LCS and ICP-MS. Triplicate repeat tests confirmed that LCS and ICP-MS had comparable repeatability. As compared with ICP-MS, LCS had a negative bias of 0.457 µg/dL with an average variability of 1.0 µg/dL. The reproducibility and precision of the LCS is appropriate for the evaluation and monitoring of blood lead levels of individual children in a clinical setting. Recent research however has suggested that increments as small as 0.5 µg/dL may distinguish those at risk of low-level lead-induced neurotoxicity. Thus, we also conclude that the LCS is not useful for research applications attempting to identify neurotoxic effect thresholds for chronic lowest level lead exposure in children. For these types of research applications, a convenient and low-cost device is needed for the precise detection of child blood lead levels below 10 µg/dL.

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.

Brachial plexopathy and nonaccidental injury: role of the neurologist.

Child neurologists must remain vigilant to the possibility of nonaccidental injury. Just as clinicians have become accustomed to considering potential abuse or neglect in children presenting with a head injury or skeletal trauma, physical abuse must also be considered when children present with lesions at other sites of the neuraxis, as illustrated by this child's brachial plexopathy. Key elements from the history can assist clinicians in differentiating accidental events from nonaccidental injuries secondary to abuse or neglect. We report a toddler who presented with a recurrent brachial plexopathy due to nonaccidental injury. Her parents initially denied the occurrence of any significant trauma. Furthermore, her diagnosis was complicated by the identification of concomitant, but unrelated lead toxicity. In this case, the vague and inconsistent parental history, plexopathy recurrence, and identification of a fracture all heightened suspicion of child abuse.