Pediatric Neurology 113 (2020) 51e55 Contents lists available at ScienceDirect Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu Topical Review Lead Toxicity in Children: An Unremitting Public Health Problem * Valeria I. Naranjo, MD a, Michael Hendricks, MD b, 1, Kimberly S. Jones, MD c, a Resident Physician, Child Neurology, Department of Neurology, University of Kentucky, Lexington, Kentucky b Medical graduate, College of Medicine, University of Kentucky, Lexington, Kentucky c Associate Professor of Neurology, Department of Neurology, University of Kentucky, Lexington, Kentucky article info abstract Article history: Background: Lead is a pervasive environmental contaminant. Lead accumulates in the body, impairing a Received 27 February 2020 molecular level various cellular processes. Lead exposure during childhood causes adverse and perma- Accepted 6 August 2020 nent neurodevelopmental consequences, sometimes even with “low” blood lead levels. Symptoms are Available online 11 August 2020 frequently silent, making lead exposure an often unrecognized and underestimated threat for pervasive neurocognitive disorders. Keywords: Methods: We identified articles focusing on childhood exposure to lead and neurodevelopment via a Lead search of the electronic database PubMed (National Library of Medicine), including journal articles Lead poisoning Lead toxicity published from 2007 to 2019. These articles were used to evaluate the effect of environmental lead Children exposure and analyze whether control efforts over the past decades have altered the prevalence of Neurotoxicity exposed children. Cognition Conclusions: Children are still being exposed to lead despite evidence of the adverse impact of exposure, Neurodevelopment even for children with blood lead levels below the currently recognized threshold for intervention. Legislative and educational efforts have reduced lead exposure but are not being followed universally. Primary prevention and identification of high-risk populations are the best cost-benefit interventions to fight this public health problem. © 2020 Elsevier Inc. All rights reserved. Background it can persist for years. Lead from lead pipes and solder can also be released into drinking water service lines when the water is acidic.1 Lead is a heavy, bluish-gray metal that is used in several in- Lead and its alloys are still used in automobile batteries, pipes, dustries. It is easily molded and very resistant to corrosion, does not fishing sinkers, ammunition, dyes and paints, ceramic glazes, some degrade to other substances, and accumulates over time. Over the imported toys, and certain cosmetics or traditional remedies. past century lead has contaminated the environment as a result of Occupational or leisure activity exposure may also be a source human activity. In the last several decades it became apparent that through dust and particles settled on clothes and tools. Young both acute and chronic exposure at any level is harmful, with children, who consume more water per unit of body mass than adverse effects on neurodevelopment and cognition. older people and who commonly engage in mouthing behaviors, Chipping and dust from lead-based paint in older housing utits are especially at risk for exposure. Chronic exposure in children constitute an important source, especially in the pediatric popu- younger than six years of age continues to be an environmental and lation. Lead can accumulate in dust, soil, and water sediment, public health problem.2,3 Studies indicate an adverse effect of lead especially near urban areas and mining and industrial sites, where exposure even when the blood lead concentrations are low.4-6 Beginning in the 1970s, efforts were made to control lead con- centrations in the environment, leading to a substantial decline, thanks to regulatory and public education initiatives.2,3 However, Declarations of interest: There are no conflicts of interest to disclose. because lead can never be completely removed from the environ- * Communications should be addressed to: Dr. Jones; Associate Professor of ment, we must continue to monitor diligently. Neurology; Department of Neurology; University of Kentucky; 740 S Limestone Street; Lexington, KY 40536. A notorious incident that drew attention to lead contamination E-mail address: [email protected] (K.S. Jones). occurred when close to 100,000 residents of Flint, Michigan, were 1 Present address: Resident physician at University of Louisville, Child Neurology affected by changes in the drinking water quality after the water Program, 500 South Preston Street, Suite 113, Louisville, KY 40202. https://doi.org/10.1016/j.pediatrneurol.2020.08.005 0887-8994/© 2020 Elsevier Inc. All rights reserved. 52 V.I. Naranjo, M. Hendricks and K.S. Jones / Pediatric Neurology 113 (2020) 51e55 supply source was switched between April 2014 and October 2015. from 2007 to 2010 and 2009 to 2015 showed that approximately The later source lacked necessary corrosion control treatment to 2.6% to 3% of US children younger than six years still had levels prevent lead from being released from pipes into drinking water. 5 mg/dL.11,12 In the United States alone, an estimated loss of 23 An advisory was issued because by-products of disinfectants were million intelligence quotient (IQ) points has been attributed to lead, detected in the water, prompting studies that led to the detection of with 80% of those lost IQ points being in people with BLLs <5 mg/ elevated blood lead levels (BLL) 5 mg/dL in young Flint children. A dL.5 Certain subgroups have been identified to be at higher risk of federal state of emergency was declared in 2016. Flint’s water exposure, including children from low-income families, non- supply was switched back, but the state faced multiple lawsuits Hispanic black children, and children living in older housing related to this public health crisis.7 There also have been recent (built before 1950).12-14 These demographic disparities have per- incidents of products marketed especially for children having high sisted over time. lead concentrations, including jewelry and toys imported from There would be considerable benefit from preventing pervasive other countries. and neurocognitive disorders associated with lead exposure.15 It Before 2012, children were identified as having a blood lead has been estimated that each US dollar invested in controlling lead “level of concern” if the result was above 10 mg/dL. In May 2012, the in paint resulted in a return of $17 to $221 or net savings of $181 to Advisory Committee on Childhood Lead Poisoning Prevention from $269 billion when considering costs of health care, special educa- the Centers for Disease Control and Prevention (CDC) recom- tion, and crime associated with elevated lead exposure.16,17 This mended a population-based reference value to identify children cost-benefit ratio has been compared with that of public health with BLLs greater than 97.5% of children aged one to five years, or interventions such as vaccines.2,11 the highest 2.5% children when tested for lead levels. This reference value, currently set at 5 mg/dL, is not a clinical reference level out- Toxicokinetics lining an acceptable range or a toxicity threshold, but rather a tool to help identify the children in whom prevention efforts need to be Lead can be absorbed via inhalation of lead-containing dust and targeted. This reference value may be decreased further in the paint or through ingestion of contaminated water and food. future.4,8 Gastrointestinal absorption is higher in children. Red blood cells bind most of it, and only 1% to 2% lead can be found in plasma. Lead Methods has a half-life of about 35 days, meaning that blood levels reflect only recent exposure. Lead is then distributed to soft tissues and We reviewed the literature related to lead exposure in child- eventually to bone, where it deposits and can persist for de- hood and its effects on health and the nervous system. This article cades.18,19 BLLs are more reflective of acute exposure, whereas bone reviews the epidemiologic and clinical features of lead toxicity in lead levels better reflect cumulative exposure over time.3 Bone children based on a comprehensive literature review from MED- turnover releases lead back into the bloodstream in pregnancy, LINE electronic database using PubMed, with appropriate key- menopause, and lactation. Lead can also cross the placenta and the words to incorporate recent literature from 2007 or later. Keywords blood brain-barrier in the developing fetus.18 included lead, lead poisoning, lead toxicity, children, neurotoxicity, and neurodevelopment. Other keywords used included neuro- Mechanisms of lead toxicity toxicology and cognition. The included articles were derived pri- marily from human studies and focused on childhood exposure, The exact mechanisms underlying lead toxicity are still unclear, interventions, and indicators of neurodevelopment. In addition, but multiple processes have been described in which lead has an some animal model studies illustrate mechanisms of toxicity and adverse effect. support the neurobehavioral effects of lead exposure. A total of 40 Lead can disturb cellular functions because it substitutes for sources were included, published in peer-reviewed journals and calcium, and to a lesser extent, zinc, and activates processes reliant others available at the official websites from the CDC and the World on calmodulin, a calcium-binding messenger protein.19-21 Lead also Health Organization. We evaluated the effect