Morri E. Markowitz

Low-level lead-induced neurotoxicity in children : an update on central nervous system effects

The neurotoxicity of low-level long-term exposure to lead has a special relevance in children. An extensive database has provided a direct link between low-level lead exposure and deficits in the neurobehavioral-cognitive performance evidenced in childhood through adolescence. Electrophysiological studies showed that neurosensory processing may be affected by lead, with consequent decrease in auditory sensitivity and visuomotor performance. Lead disrupts the main structural components of the blood-brain barrier by primary injury to astrocytes with a secondary damage to the endothelial microvasculature. Within the brain, lead-induced damage occurs preferentially in the prefrontal cerebral cortex, hippocampus and cerebellum. Some characteristic clinical features of lead poisoning may be attributed to this specific anatomical pattern. The cellular, intracellular and molecular mechanisms of lead neurotoxicity are numerous, as lead impacts many biological activities at different levels of control: at the voltage-gated channels and on the first, second and third messenger systems. These effects could be related to leads ability to interfere with the regulatory action of calcium in cell functions. Consequently, it may be assumed that lead acts as a chemical stressor and causes breakdown of the homeostatic cellular mechanisms. This is expressed in both the anatomical site and the neurotransmitter systems which are crucial in modulating emotional response, memory and learning. There is no threshold below which lead remains without effect on the central nervous system; thus, symptoms could simply be a clinical reflection of the brain regions preferentially involved. In integrating these physiological and clinical data, it may be suggested that the different mechanisms of low level lead neurotoxicity have a final common functional pathway.

Effects of iron deficiency on lead excretion in children with moderate lead intoxication.

The effect of iron status on calcium disodium edetate (CaNa2EDTA)-induced lead diuresis was examined in 112 children with moderate lead intoxication. Patients whose blood lead levels were between 25 and 55 micrograms/dl and who had erythrocyte protoporphyrin concentrations greater than or equal to 35 micrograms/dl underwent provocative testing to determine the need for a full course of chelation therapy. A blood sample for lead, erythrocyte protoporphyrin, and serum ferritin determinations was obtained immediately before the intramuscular administration of CaNa2EDTA, 500 mg/m2. Determination of urinary lead level was based on an 8-hour urine collection. Blood lead and ferritin levels were significantly correlated with urinary lead excretion: r = 0.542 and 0.298, respectively, p less than 0.01 for both. Multiple regression models were tested to assess the independent effects of the variables. With blood lead level controlled, ferritin remained significantly associated with urinary lead excretion; for every 1 ng/ml increase in ferritin, urinary lead increased by 2.4 micrograms. This small effect of ferritin on urinary lead was illustrated in a discriminant analysis. Using blood lead level by itself as the independent variable resulted in a 76% correct assignment of provocative test outcomes. Knowing the ferritin level improved this assignment accuracy by only 3%. We conclude that the iron status, as measured by serum ferritin, of children with moderate lead intoxication, has a small but significant effect on CaNa2EDTA-induced lead diuresis. This effect may influence the interpretation of borderline provocative test outcomes. Although chelation therapy should not be withheld pending treatment of iron deficiency, lead stores should be reassessed after iron repletion.

Need for the lead mobilization test in children with lead poisoning.

We evaluated the recommendation of the Centers for Disease Control, that children with moderate lead poisoning undergo the lead mobilization test (LMT) to determine the need for a full course of chelation treatment. Current criteria for selection for this test include a blood Pb concentration (bPb) between 25 and 55 micrograms/dl and an erythrocyte protoporphyrin level greater than 35 micrograms/dl. To determine whether the eligibility criteria could be refined to a smaller group of patients, we compared bPb determinations obtained on the day of the LMT in 198 children with moderate Pb poisoning to the results of the LMT. We found that children with bPb less than 25 micrograms/dl were unlikely to respond to the test dose of calcium disodium ethylenediamine tetraacetate with a Pb diuresis (24/25 patients had low urinary Pb excretion on the LMT). In contrast, 88% of children with bPb greater than or equal to 40 micrograms/dl were likely to excrete sufficient Pb to indicate the need for a full course of chelation. We conclude that the LMT is indicated for children with bPbs between 25 and 40 micrograms/dl. Children with bPb between 40 and 55 micrograms/dl may receive chelation therapy without having an LMT, if the performance of the LMT is not practical. Patients with levels less than 25 micrograms/dl should be followed clinically and removed from further Pb exposure.

Determinants of 25(OH)D Sufficiency in Obese Minority Children: Selecting Outcome Measures and Analytic Approaches

OBJECTIVEnTo highlight complexities in defining vitamin D sufficiency in children.nnnSTUDY DESIGNnSerum 25-(OH) vitamin D [25(OH)D] levels from 140 healthy obese children age 6 to 21 years living in the inner city were compared with multiple health outcome measures, including bone biomarkers and cardiovascular risk factors. Several statistical analytic approaches were used, including Pearson correlation, analysis of covariance (ANCOVA), and hockey stick regression modeling.nnnRESULTSnPotential threshold levels for vitamin D sufficiency varied by outcome variable and analytic approach. Only systolic blood pressure (SBP) was significantly correlated with 25(OH)D (r = -0.261; P = .038). ANCOVA revealed that SBP and triglyceride levels were statistically significant in the test groups [25(OH)D <10, <15 and <20 ng/mL] compared with the reference group [25(OH)D >25 ng/mL]. ANCOVA also showed that only children with severe vitamin D deficiency [25(OH)D <10 ng/mL] had significantly higher parathyroid hormone levels (Δ = 15; P = .0334). Hockey stick model regression analyses found evidence of a threshold level in SBP, with a 25(OH)D breakpoint of 27 ng/mL, along with a 25(OH)D breakpoint of 18 ng/mL for triglycerides, but no relationship between 25(OH)D and parathyroid hormone.nnnCONCLUSIONSnDefining vitamin D sufficiency should take into account different vitamin D-related health outcome measures and analytic methodologies.

Vegan Diet and Vitamin A Deficiency

A 6-year-old boy was transferred for tertiary ophthalmic care. He had been hospitalized at an outlying facility with a chief complaint of “swollen, red eyes” and loss of vision. His diagnoses were listed as ocular injury of unknown etiology, electrolyte imbalance, and medical neglect. His parents believed his ocular problem developed 3 months previously, when ocular irritation was discovered after the child’s eyes were splashed with milk at school. They suspected a milk allergy because the child had never been exposed to dairy products, as he was a vegan. An examination at an emergency room soon after revealed edematous eyelids, injected conjunctiva, and “rosy” cheeks. Oral diphenhydramine was prescribed, but the child and his mother left the facility before his medical evaluation was completed. The parents were telephoned and advised to continue treatment with diphenhydramine for 5 days. Advice to follow-up with a primary care physician was not heeded. His parents removed him from kindergarten, because they feared additional exposure to milk products. The child’s symptoms worsened and the parents sought attention from an oriental medical arts practitioner, who prescribed herbal eye drops. Progressive tearing, discomfort, and photophobia developed in the 2 months before admission. The previously active child lost interest in play and became somnolent. In the weeks before admission, he was bed-bound and could not see. The boy had been in good health with no previous visual problems. He was reported to have completed all vaccination series but was not under the regular care of a physician. The family’s diet excluded all dairy and egg products. He had no known drug allergies. On admission to an outlying hospital, his weight of 21 kg fell on the 50th percentile growth curve for age; his height of 112 cm placed him in the 25th percentile. He had apparent central obesity. Notable were his brittle hair; dry, foul-smelling, scaly skin; and poor oral hygiene. He was irritable and had intense blepharospasm. His blood work revealed sodium 127 mEg/L, potassium 2.9 mEg/L, hemoglobin 10.7 g/dL, hematocrit 31 and prealbumin 11 mg/dL (normal range 10–40 mg/dL). A diagnosis of global nutritional deficiency including hypovitaminosis A was considered, but it was assumed that he received adequate vitamin A

Pediatric lead poisoning from folk prescription for treating epilepsy.

BACKGROUNDnA case of lead poisoning resulting from the ingestion of a folk remedy for treating epilepsy is reported.nnnRESULTSnThe initial blood lead concentration of this 6-y-old boy was 63.6μg/dl upon admission. He presented with abdominal pain, constipation, and irritability. The patients liver function tests were significantly increased. Through chelation therapy, the blood lead concentration dropped markedly and clinical symptoms greatly improved. His blood and urine samples were collected for the kinetic analysis of lead elimination.nnnCONCLUSIONSnFolk prescriptions for epilepsy should be considered as potential sources of lead intoxication. Lead poisoning should be taken into consideration for unknown causes of abdominal pain.

Vitamin D and pulmonary function in obese asthmatic children.

Asthma‐related morbidity is higher among children with vitamin D deficiency and obesity, morbidities that frequently co‐exist among minority children. However, the effect of co‐existent obesity and vitamin D deficiency on pulmonary function is poorly understood.

Lead Aprons Are a Lead Exposure Hazard

PURPOSEnTo determine whether lead-containing shields have lead dust on the external surface.nnnMETHODSnInstitutional review board approval was obtained for this descriptive study of a convenience sample of 172 shields. Each shield was tested for external lead dust via a qualitative rapid on-site test and a laboratory-based quantitative dust wipe analysis, flame atomic absorption spectrometry (FAAS). The χ2 test was used to test the association with age, type of shield, lead sheet thickness, storage method, and visual and radiographic appearance.nnnRESULTSnSixty-three percent (95% confidence interval [CI]: 56%-70%) of the shields had detectable surface lead by FAAS and 50% (95% CI: 43%-57%) by the qualitative method. Lead dust by FAAS ranged from undetectable to 998 μg/ft2. The quantitative detection of lead was significantly associated with the following: (1) visual appearance of the shield (1xa0= best, 3xa0= worst): 88% of shields that scored 3 had detectable dust lead; (2) type of shield: a greater proportion of the pediatric patient, full-body, and thyroid shields were positive than vests and skirts; (3) use of a hanger for storage: 27% of shields on a hanger were positive versus 67% not on hangers. Radiographic determination of shield intactness, thickness of interior lead sheets, and age of shield were unrelated to presence of surface dust lead.nnnCONCLUSIONSnSixty-three percent of shields had detectable surface lead that was associated with visual appearance, type of shield, and storage method. Lead-containing shields are a newly identified, potentially widespread source of lead exposure in the health industry.

Hormonal contraception and blood lead levels in inner-city adolescent girls.

STUDY OBJECTIVEnPhysiological states of estrogen deficiency can lead to bone demineralization. Lead is stored in bone and may be released into blood during demineralization. The contraceptive injection depomedroxyprogesterone acetate (DMPA) is associated with estrogen deficiency and bone demineralization and, we hypothesized, may be associated with toxic blood lead levels in adolescents at high risk for lead exposure. We sought to compare blood lead levels in inner-city adolescent girls using DMPA with levels in those using oral contraceptive pills (OCP) and those taking no hormones and to examine the influence of lead exposure and reproductive history on blood lead levels in the total sample.nnnDESIGNnCross-sectional survey of a clinical convenience sample.nnnSETTINGnInner-city adolescent clinic in an academic medical center.nnnPARTICIPANTSn174 females aged 13-21 years; 86% minority ethnicity.nnnINTERVENTIONSnNone.nnnMAIN OUTCOME MEASURESnMeasurement of blood lead levels and an 82-item questionnaire examining lead exposure and reproductive history.nnnRESULTSn28 subjects were using DMPA, 25 used OCPs, and 121 used no hormones. Mean blood lead level in the total sample of 174 was 1.6 mug/dL, SD = 1.1. Many subjects had environmental risk factors for lead exposure and 15% reported one or more past pregnancies. Mean blood lead levels for subjects with the various environmental and reproductive risk factors ranged from 1.2 microg/dL to 2.0 microg/dL and were not different from levels for subjects without such risk factors. Mean blood lead levels for subjects in the 3 hormonal groups were significantly different (2.1 vs. 1.2 vs.1.5 microg/dL in DMPA, OCP, and no hormone groups respectively, P = 0.007). We dichotomized the blood lead levels into High > or =4 microg/dL, or Low <4 microg/dL. We found that a significantly higher proportion of girls using DMPA (4/28) than those not using any hormone (2/121) had High levels (P = 0.012).nnnCONCLUSIONSnDespite reported high-risk exposure to lead and the possibility of long-term accumulation of lead in bone, we did not find elevated blood levels in our sample. However, DMPA-treated girls were significantly more likely to have higher mean blood lead levels than OCP users and non-hormone users. In addition, DMPA users were more likely to have blood lead levels more than two standard deviations above the mean for the sample as a whole than untreated girls. Further studies are needed to examine low-level lead poisoning in adolescents and the consequences of contraceptive choices on bone health.

Sources, symptoms and characteristics of childhood lead poisoning: experience from a lead specialty clinic in China

Abstract Objectives: This study explored the sources of lead exposure, identified patients’ geographic distribution and evaluated the symptoms of children with elevated blood lead levels (BLLs) referred to a pediatric lead specialty clinic in China. Material and methods: Data were collected from 515 consecutive outpatients attending the Pediatric Lead Poisoning Clinic in Xinhua Hospital, Shanghai, China, between 2011 and 2016, referred for BLLs ≥5u2009μg/dL. Atomic absorption spectrometry was used to measure venous BLLs. Results: The meanu2009±u2009standard deviation age of the patients was 4.1u2009±u20093.2 years. Their BLLs ranged from 5 to 126u2009μg/dL. The geometric mean and median BLLs were 24 and 26u2009μg/dL, respectively. Two hundred and twenty-two children (43.1%) were exposed to industrial lead pollution—mainly from Zhejiang, Jiangsu, Hunan, Henan and Anhui provinces; whereas, 41.4% (213 cases) were induced by folk medicines used widely throughout China. Other nonindustrial sources of lead exposure included lead-containing tinfoil and tin pots. Household lead paint was a rare source. Most patients exhibited nonspecific symptoms, such as hyperactivity, attention difficulty, aggressiveness, constipation and anorexia. Conclusions: Industrial pollution and folk medicines are important sources of lead exposure in China. Childhood lead poisoning may be difficult to diagnose clinically as symptoms are nonspecific. Thus, blood lead screening may be necessary to identify children at high risk of exposure. Education to raise the awareness of potential sources of exposure resulting in their elimination would be expected to decrease the incidence of children with elevated BLLs.