Lead poisoning in childhood

Douglas J Lanska MD MS MSPH

Neurotoxicology

Updated 05.20.2024
Released 01.06.1995
Expires For CME 05.20.2027

Lead poisoning in childhood

Author: Douglas J Lanska MD MS MSPH

See Contributor Disclosures

Lead poisoning in childhood

In This Article

Quick Link

Introduction

Overview

Childhood lead poisoning is a growing concern, particularly because new findings have shown that low-level, typical-population lead exposures are associated with the development of cognitive and behavioral deficits. In response to these findings, the United States Centers for Disease Control and Prevention has set a lead level of greater than 5 µg/dl as the minimum value for intervention. The mechanisms of action of lead depend on the time of exposure and the degree of CNS maturation. Early-life lead exposure may lead to disease susceptibility throughout the life course. In this article, the author discusses lead as an environmental risk factor, its effects on health, and its management. He also discusses new trends in research describing how lead leads to epigenetic alterations that may underlie many of the behavioral phenotypes observed in patients exposed to even minimal amounts of lead.

Key points

	• The toxic lead reference level is currently 5 µg/dL as determined by the Centers for Disease Control and Prevention (CDC), which reflects the lead blood levels of children aged 1 to 5 years in the United States who are in the highest 2.5%.
	• Cognitive and behavioral deficits have been linked with population-typical lead exposures.
	• Management is generally aimed at preventing further exposure
	• Chelation therapy is only indicated for very high levels (> 45 µg/dL).
	• Lead influences fetal epigenetic programming that may alter phenotype and disease susceptibility.
	• Maternal bone lead is a marker for adverse fetal outcome.
	• Calcium supplementation during pregnancy and lactation is associated with reduced lead levels.

Historical note and terminology

Widespread commercial use of lead has resulted in the dissemination of the metal in the environment. Recognized since antiquity, the first clinical description of childhood lead poisoning was provided by Australian pediatrician Alfred Jefferis Turner (1861-1947) in 1892.

Australian pediatrician Alfred Jefferis Turner (1861-1947)

Turner provided the first clinical description of childhood lead poisoning in 1892. (Source: Wikimedia Commons. Public domain. Photograph restored by Dr. Douglas J Lanska.)

While a resident at the Children's Hospital in Brisbane, Australia, Turner described four children with ocular neuritis, recurrent emesis, and headache (168). Subsequent patients were also noted to have muscle-wasting, wrist-drop, and footdrop. Although the symptoms were initially attributed to a localized basal meningitis, Turner and his chief, Australian ophthalmologist John Lockhart Gibson (1860-1944), subsequently deduced that these children were suffering from lead poisoning (61; 63; 169; 138), which was found to originate from the powdered residue of deteriorating paint in the children's homes (62). The first account of childhood lead poisoning from paint in the United States followed shortly thereafter, in a child with seizures and coma who had dark blue "lead lines" or Burton lines, on his gum margins (164).

Australian ophthalmologist John Lockhart Gibson (1860–1944)

Gibson was instrumental in recognizing the importance of lead-based paint in the development of childhood lead poisoning from 1897 to 1904. (Source: Gibson JL. A plea for painted railings and painted walls of rooms as the sourc...

Long-term brain dysfunction is often seen in children who survive lead poisoning, and it was first described in relation to lead poisoning in 1943. Refuting conventional wisdom that the symptoms and effects of childhood lead poisoning could be reversed, pediatrician Randolph Kunhart Byers (1896-1988) and child psychologist Elizabeth Evans Lord (1890-1943) at Boston Children's Hospital presented a detailed description of 20 school-aged children who were diagnosed with symptomatic lead poisoning during their early years (24). These children underwent serial psychometric assessment and were found to have deficits in language skills, visual-motor skills, and modulation of behavior.

Lead exposure in children is believed to have reached its height in the late half of the twentieth century. Bans on lead-based paint and the phasing out of leaded gasoline in the 1970s and 1980s have contributed to a steady decline in environmental exposure.

Clinical manifestations

Presentation and course

Most children with elevated blood lead levels appear asymptomatic, or they exhibit a range of mild to severe symptoms. Because children may have no or very mild symptoms, and yet still be at risk of adverse cognitive and neurobehavioral outcomes, the Centers for Disease Control and Prevention advocates periodic screening of blood lead levels in all children between 9 and 36 months (28; 70). Lead poisoning in both children and adults is associated with a wide range of neurologic and nonneurologic symptoms and signs.

Symptoms of lead poisoning

Illustration by Mikael Häggström on June 7, 2015. (Public domain.)

Nonspecific symptoms, erroneously attributed to other causes are temperamental lability, irritability, behavioral changes, sleep disturbance, and decreased play. Some children may experience more pronounced and more worrisome symptoms such as hyperactivity, lassitude, or decreased activity. Some children may exhibit symptoms that are likely to result in diagnostic evaluation, such as delayed language or loss of developmental milestones.

Burton line (lead line). In individuals with chronic lead poisoning, Burton's line (also known as the Burton’s line, Burtonian line, or simply a "lead line") is a very thin, bluish-black line visible along the margin of the gums, at the base of the teeth (23; 129; 79).

Abnormally increased pigmentation of the gums in a child treated with a lead-based folk medicine

Abnormally increased pigmentation of the gums (“lead line” or "Burton line") in a child treated by a traditional Chinese medicine practitioner (Shenzhen, Guangdong, China) with a lead-based folk medicine. (Source: Ying XL, Mark...
Burton line in the upper gum

Burton line indicated by black arrow. (Source: Yang Y, Li S, Wang H, et al. Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature. BMC Gastroenterol 2020;20[1]:335. Creative Common...
Burton line in the lower gum

Burton line indicated by black arrow. (Source: Yang Y, Li S, Wang H, et al. Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature. BMC Gastroenterol 2020;20[1]:335. Creative Common...
Watercolor drawing of the gums and tongue from a case of lead poisoning

Burton's line is evident, and there has been additional lead complex deposited on the lateral margin of the tongue and the buccal mucosa. Illustration by Surgeon and Anatomist Thomas Godart (active 1852-1861). (Source: St. Bart...

Burton line is attributed to a reaction between circulating lead and sulfur ions released by bacterial activity in the mouth, resulting in the deposition of lead sulfide at the junction of the teeth and gums (129). It was originally described by British physician and chemist Henry Burton (1799-1848) in 1840:

“The edges of the gums attached to the necks of two or more teeth of either jaw, were distinctly bordered by a narrow leaden-blue line, about the one-twentieth part of an inch in width, whilst the substance of the gum apparently retained its ordinary colour and condition.”

Although not a sensitive marker of lead poisoning, it should not be overlooked.

Lead encephalopathy. Lead encephalopathy usually results with blood lead levels above 100 µg/dL. Lead encephalopathy presents with headache, altered sensorium, lethargy, seizures, and coma. Cerebral edema due to encephalopathy, which is more common in younger children, can be fatal.

In the past, lead encephalopathy was the typical presentation for a child with lead poisoning. With increased awareness of childhood lead poisoning and availability of screening programs, it is now uncommon for a child in the United States to present with life-threatening neurologic symptoms.

In utero exposure and neurodevelopmental outcomes. Lead exposure in utero adversely affects neurodevelopment independent of postnatal exposure (119; 67). Prenatal lead exposure at low levels is associated with poor intellectual developmental function (144). Blood lead concentrations as low as 6.4 µg/dL are associated with increased risks of behavioral problems such as pervasive developmental problems (104). Maternal lead exposure is also associated with an increased risk of miscarriages, prematurity, low birth weight.

Cognitive impairment. Cognitive impairment due to lead exposure is considered permanent. Even low blood lead levels are known to cause irreversible impaired cognitive function.

Behavioral changes. Hyperactivity and aggressive behavior have been noted in children with high blood lead levels and high bone lead content.

Cranial and peripheral neuropathies. Hearing loss and peripheral neuropathy with decreased nerve conduction velocities can occur at blood lead levels much lower than those that cause CNS toxicity (150). Children do not typically present with peripheral neuropathy, which is commonly seen in adults (154). Lead may produce changes in visual contrast sensitivity (108; 156).

Skeletal abnormalities. Lead accumulates in the metaphyses of growing bones, which are the most metabolically active zones; consequently, x-rays may show bands of increased density at the metaphyses.

Increased linear radiodensity at the distal femoral and proximal tibial and fibular metaphyses in a child treated with a lead-based folk medicine

Anteroposterior radiograph of the knees showing increased linear radiodensity at the distal femoral and proximal tibial and fibular metaphyses in a child treated by a traditional Chinese medicine practitioner (Shenzhen, Guangdo...
Dense metaphyseal lines from lead poisoning

Dense metaphyseal lines indicated by red arrow. (Source: Dr. Abhijit Datir via Wikimedia Commons. Creative Commons Attribution-Share Alike 3.0 Unported License, https://creativecommons.org/licenses/by-sa/3.0/deed.en.)

Although lead toxicity can affect any metaphysis, involvement of the proximal fibula and distal ulnar metaphyses is highly suggestive of lead poisoning. X-rays may also show a "bone-in-bone" appearance (a descriptive term that is applied to bones that appear to have another bone within them). In addition, lead is an osteoclast-poison, so bone density is increased due to unopposed action of osteoblasts.

Blood lead levels are indicative of lead bound to erythrocytes and do not reflect the lead load in the body, as a significant amount of lead can be deposited in the bone. Bone lead is slowly released and is difficult to mobilize, unlike the lead bound to erythrocytes (bone lead has a longer half-life than erythrocyte-bound lead).

Hematologic abnormalities. Lead poisoning causes anemia by inhibiting hemoglobin synthesis and shortening erythrocyte survival.

Postulated model of the regulation of the cellular mechanisms associated with lead poisoning and iron deficiency

Abbreviation: DMT1, divalent metal transporter 1. (Source: *Slota M, Wasik M, Stoltny T, Machon-Grecka A, Kasperczyk S. Effects of environmental and occupational lead toxicity and its association with iron metabolism. Toxicol A...

Usually this is a microcytic hypochromic anemia with basophilic stippling.

Basophilic stippling of erythrocytes in peripheral blood smear of a patient with chronic lead poisoning (2)

Basophilic stippling of erythrocytes indicated by red arrows. (Source: Yang Y, Li S, Wang H, et al. Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature. BMC Gastroenterol 2020;20...
Basophilic stippling of erythrocytes in bone marrow smear of a patient with chronic lead poisoning

Basophilic stippling of erythrocytes indicated by red arrows. (Source: Yang Y, Li S, Wang H, et al. Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature. BMC Gastroenterol 2020;20...
Close-up view of an erythrocyte with basophilic stippling in peripheral blood smear of a patient with chronic lead poisoning (1)

(Source: Yang Y, Li S, Wang H, et al. Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature. BMC Gastroenterol 2020;20[1]:335. Creative Commons Attribution 4.0 International Licens...
Basophilic stippling of erythrocytes in peripheral blood smear of a patient with chronic lead poisoning (3)

Basophilic stippling of erythrocytes indicated by black arrows (objective 1000x, Giemsa stain). (Source: Irawati Y, Kusnoputranto H, Achmadi UF, et al. Blood lead levels and lead toxicity in children aged 1-5 years of Cinangka ...
Basophilic stippling of an erythrocyte in peripheral blood smear of a patient with chronic lead poisoning

Basophilic stippling indicated by black arrow (objective 1000x, Giemsa stain). (Source: Irawati Y, Kusnoputranto H, Achmadi UF, et al. Blood lead levels and lead toxicity in children aged 1-5 years of Cinangka Village, Bogor Re...
Close-up view of an erythrocyte with basophilic stippling in peripheral blood smear of a patient with chronic lead poisoning (2)

(Source: Irawati Y, Kusnoputranto H, Achmadi UF, et al. Blood lead levels and lead toxicity in children aged 1-5 years of Cinangka Village, Bogor Regency. PLoS One 2022;17[2]:e0264209. Creative Commons Attribution License, http...
Basophilic stippling of erythrocytes in peripheral blood smear of a patient with chronic lead poisoning (1)

Basophilic stippling of erythrocytes indicated by black arrows. (Source: Dr. Herbert L Fred and Hendrik A van Dijk via Wikimedia Commons, https://cnx.org/contents/MZa_Ph4e@4/Images-of-Memorable-Cases-Case-81. Accessed October 1...

Hypochromia and microcytosis are typically seen in iron-deficiency anemia, which often coexists with lead toxicity, and they are also seen in alpha-thalassemia. Assessing iron storage status (ferritin) in all cases of lead poisoning is important.

Lead antagonizes the enzymes porphobilinogen synthase and ferrochelatase, inhibiting the synthesis of heme and can ultimately cause elevation of free erythroprotoporphyrin. Lead also impedes the repair of cell membranes, leading to increased erythrocyte fragility. Lead in the blood can cause a range of hematologic abnormalities, ranging from reduction of hemoglobin synthesis to hemolysis (158). Overt anemia that is directly caused by lead poisoning is usually not seen until the blood lead level is over 60 µg/dL.

Renal abnormalities. Long-term exposure to lead (typically with blood lead levels higher than 100 µg/dL) leads to proximal renal tubular dysfunction, manifesting as Fanconi syndrome, which results in excess amounts of glucose, bicarbonate, phosphates, uric acid, potassium, and certain amino acids in the urine (105).

Gastrointestinal abnormalities. Gastrointestinal symptoms of lead poisoning usually present as lead colic with anorexia, abdominal pain, vomiting, and constipation. In some there may be x-ray evidence of lead particles in the gastrointestinal tract.

A woman suffering the pain of cholic, illustrated by demons tugging on a rope wound around her stomach

Colored etching by British caricaturist George Cruikshank (1792-1878) in 1819, after an illustration by Royal Navy officer and novelist Captain Frederick Marryat (1792-1848). (Source: Wellcome Collection, London, United Kingdom...
Stool and gas shadows and points of increased density on abdominal x-ray of girl treated with folk medicine containing lead

Abdominal x-ray showing stool and gas shadows as well as points of increased density in an 8-year-old girl who had been treated with a red-colored folk medicine obtained from a traditional Chinese medicine practitioner (Shenzhe...
Abdominal x-ray showing irregular punctate opacities in a 2-year-old with pica residing in a home with leaded paint

Assay of paint chips from the home built in 1960 revealed leaded paint. (Source: Jouhadi Z, Bensabbahia D, Chafiq F, et al. Lead poisoning in children: a case report. Pan Afr Med J 2016;24:316. Creative Commons Attribution Lice...
Abdominal x-ray showing disappearance of metallic opacities 48 hours after a laxative treatment

(Source: Jouhadi Z, Bensabbahia D, Chafiq F, et al. Lead poisoning in children: a case report. Pan Afr Med J 2016;24:316. Creative Commons Attribution License, http://creativecommons.org/licenses/by/2.0.)

Pubertal development and reproductive capacity. Exposure to low levels of lead causes reduced semen volume, abnormal sperm morphology, and reduced sperm motility and viability (82). Delayed pubertal development and decreased height have been reported in girls (151).

Growth. Several studies have demonstrated diminished ponderal and linear growth in children with elevated blood lead levels (14; 149; 152).

Prognosis and complications

Blood lead levels of 5 µg/dL are now the "action level" for intervention designated by the US Centers for Disease Control and Prevention (31). However, the term “blood lead level of concern” is no longer preferred because even low blood lead levels are associated with neurocognitive defects. Movement away from the term “blood lead level of concern” should place greater emphasis on primary prevention rather than action after detection of toxic blood lead levels. The proportion of children with "concerning" blood lead levels in the United States has been declining since at least the late 1990s, whichever threshold is used.

Declining proportion of children with "concerning" blood lead levels, United States 1997-2015

Shown are two different thresholds for "concerning" (based on data from the CDC). Illustration by Morgan Rehnberg on April 19, 2017. (Public domain.)

In Cleveland, a multi-agency integrated data system was used to document the impact of lead exposure on indicators of child and youth development (43). By tracking two cohorts of children from birth to early adulthood and using rigorous matching methods to reduce confounders, marked negative effects were demonstrated on developmental, behavioral, and socioeconomic outcomes due to early childhood lead exposure. The magnitude of disparities between individuals who had elevated blood lead levels (≥5 μg/dL) in early childhood, compared to their matched counterparts, was in the range of 20% to 40%.

Despite progress in reducing lead exposure, substantial neighborhood disparities in lead poisoning persist. A study in Rhode Island linked childhood blood levels (collected from 2006–2019) to census block group rates of poverty and housing built before 1950 (when lead paint was commonly used) (76). Of the 197,384 study children, 12.9% had blood lead levels of 5 μg/dL or greater, and 2.3% had blood lead levels of 10 μg/dL or greater. The proportion of children with blood lead levels of 5 μg/dL or greater increased with increasing poverty and old housing.

Lead exposures also come from drinking water, as exemplified in the lead poisoning fiasco in Flint, Michigan, in 2015. During the period from April 25, 2014, to October 15, 2015, approximately 99,000 residents of Flint, Michigan, were exposed to lead when the drinking water source was switched from the Detroit Water Authority to the Flint Water System.

Childhood lead exposure is also widespread in Chicago, Illinois, where racial inequities are present in both testing rates and exposure levels (142; 89; 101). In a cross-sectional study, a retrospective assessment of lead exposure based on household tests collected from January 2016 to September 2023 was performed (89). Of the 38,385 household lead tests collected, an estimated 68% of children younger than 6 years old were exposed to lead-contaminated water, corresponding to 129,000 children.

Decreased brain volume in adults with childhood lead exposure. In the Cincinnati Lead Study (CLS), an urban, inner-city cohort of individuals was recruited between 1979 and 1984, enrolling pregnant women who lived in neighborhoods with historically high rates of childhood lead poisoning (27). Detailed prenatal and postnatal histories of low-to-moderate lead exposure and behavioral outcomes were monitored over 25 years. Newborns were followed quarterly through 5 years of age, semiannually from ages 5 to 6.5 years, at age 10 years, and between ages 15 and 17 years. One hundred and fifty-seven participants between 19 and 24 years of age underwent brain imaging.

Volumetric analyses of whole brain MRI data revealed significant decreases in brain volume associated with childhood blood lead levels (27).

Regional brain volume loss associated with mean childhood blood lead level for the Cincinnati Lead Study Participants

A composite representation of regions with significant volume loss for male and female participants in the Cincinnati Lead Study (n = 157) associated with mean childhood blood lead level is shown with red and yellow clusters ov...
Inverse correlation of regional brain volume with mean childhood blood lead level for the Cincinnati Lead Study Participants

The relationship of individual brain volume with mean childhood blood lead concentrations within a medial frontal cluster is illustrated by this plot. The model is adjusted for age at time of scanning and birth weight. (Source:...
Structure-function relationship showing areas of cerebral volume loss associated with mean childhood blood lead level for the Cincinnati Lead Study Pa...

A composite representation of regions with significant volume loss for Cincinnati Lead Study Participants associated with blood lead concentration at age 78 months (6.5 years) and adjusted for sex is shown in red and yellow ove...

Approximately 1.2% of the total gray matter was significantly and inversely associated with mean childhood blood lead level. The most affected regions included prefrontal gray matter and the anterior cingulate cortex responsible for executive functions, mood regulation, and decision-making. Areas of lead-associated gray matter volume loss were much larger and more significant in men than women, suggesting that lead-related atrophic changes have a disparate impact across sexes, or that there is a gender-related difference in exposures (eg, because of greater hand-to-mouth behavior at a young age, more active exploration of the environment, etc.).

Brain volume loss associated with lead exposure for males

A composite representation of regions with significant volume loss for Cincinnati Lead Study Participants associated with mean childhood blood lead concentrations is shown in red and yellow overlaid on a standard brain template...
Brain volume loss associated with lead exposure for females

A composite representation of regions with significant volume loss for Cincinnati Lead Study Participants associated with mean childhood blood lead concentrations is shown in red and yellow overlaid upon a standard brain templa...

Adverse cognitive and behavioral outcomes following lead exposure as a child may be related to lead’s effect on brain development producing persistent alterations in structure.

Cognition and IQ scores. According to a study of 488 cases, lead levels below 10 µg/dL result in significantly decreased standardized test scores, thus, affecting subsequent educational attainment (34). During the first 2 years of life, blood lead levels at or above 10 µg/dL are associated with poorer performance on developmental assessment scales (10; 116).

According to a study of 488 cases, lead levels below 10 µg/dL result in significantly decreased standardized test scores, thus, affecting subsequent educational attainment (34). During the first 2 years of life, blood lead levels at or above 10 µg/dL are associated with poorer performance on developmental assessment scales (10; 116).

The blood lead level at age 24 months used to be considered the best predictor of subsequent cognitive abilities and academic performance (116; 12). However, the lead level at 6 years of age is a more accurate predictor of later intellectual abilities (86).

Childhood lead poisoning is associated with lower IQ scores. A median IQ deficit of 6 points was demonstrated on the Wechsler Intelligence Scale for Children-Revised by first and second grade children who had elevated dentine (tooth) lead concentrations (121). This effect amounts to a decline of 3 IQ points for each 10 µg/dL blood level over 10 µg/dL (122). Follow-up studies on older school-aged children demonstrated that these deficits persist and result in ongoing school problems (191; 11).

Intellectual impairment caused by blood levels below 10 µg/dL has also been recognized. Canfield and colleagues showed that IQ declined by 7.4 points as lifetime average blood lead concentrations increased from 1 to 10 µg/dL (25). Children's neurodevelopment is inversely related to their blood lead levels even in the range of less than 10 µg/dL (162).

Children with elevated blood lead levels frequently demonstrate impaired language development, both receptive and expressive. Verbal comprehension, verbal processing, and sentence repetition are some of the skills affected (114). Lead has also been shown to have an adverse effect on auditory processing abilities (51).

Attentional and behavioral problems. Modest levels of lead may compromise a child's attention span, fueling a debate about whether low levels of lead "cause" ADHD. A careful reading of the literature, however, permits a distinction between lead effects and typical ADHD. Whereas teacher rating scales document similar behaviors (170), children exposed to lead have impairment of "focus-execute," the ability to select and respond to critical information, and "shift," the ability to appropriately and adaptively shift focus from one stimulus to another (09). In contrast, children with ADHD make significant errors of omission and commission on continuous performance tests (106), demonstrating impairment of "encode," the ability to process auditory information, or "sustain," the ability to maintain focus over time (ie, vigilance) (118). A study of 43 boys, 8 to 12 years old, with elevated levels of lead by hair analysis demonstrated slower reaction time and impaired flexibility of attention (117).

In a large study, teachers who were blinded to their students' dentine lead levels consistently identified a higher frequency of maladaptive behaviors in those children with elevated lead levels (121). Examples of these behavior problems included hyperactivity, impaired attention span, impulsivity, daydreaming, and inability to follow directions. A clear dose-response relationship was demonstrated by these data, with those children with higher lead levels manifesting a higher frequency of behavioral difficulties (121).

Lead interrupts midbrain dopamine circuitry (41), which is also involved in ADHD (123; 139). Early reports confirmed that lead influences the symptoms of ADHD although typically at levels greater than 10µg/dl (64; 153; 165; 32). However, studies have established a relation between attentional difficulties and low lead exposures (less than 5 µg/dl) that are typical in the United States and Western Europe populations (58; 29; 38; 124; 125; 157). The first study involved 150 children aged 8 to 17 years from a community sample exposed to average lead levels (124). There was a non-ADHD control group and an ADHD group, diagnosed by clinical criteria. The maximum lead level in the sample was 3.4 µg/dl, and the blood lead levels were significantly higher in the ADHD group in comparison with the non-ADHD control group. A subsequent study confirmed the association using a different representative sample of 236 children aged 6 to 17 years (125). The maximum lead level of the sample was 2.2 µg/dl, and the levels were higher in the ADHD group than in the non-ADHD control group. This is the lowest lead level to be associated with ADHD (125). The studies confirm that lead, a neurotoxicant, is a plausible influence on ADHD even at low levels (124; 125).

Motor abilities. Motor coordination may be impaired. Dietrich and colleagues administered a comprehensive neuromotor assessment battery to 245 6-year-old children enrolled in the Cincinnati Lead Study (50). Suspecting that tests of motor coordination may be less influenced by cultural and socioeconomic factors in this predominantly poor, inner-city, African American cohort, the authors found a dose-effect relationship between life-time postnatal lead dose and fine motor coordination. In this cohort, lead levels peaked at 2 years of age and slowly tapered off by the time of neuromotor assessment at 6 years of age. Other studies have demonstrated a significant relationship between postnatal lead levels and standing balance (16) and reaction time (75).

Biological basis

Etiology and pathogenesis

Lead is a metal that has no physiologic function in the human body. Lead exposure starts in utero and continues for life. Lead exists as organic and inorganic compounds. As a divalent ion, lead functions as a surrogate for calcium in most biological systems. Many clinically relevant effects relate to the role of lead as a high potency surrogate in disrupting calcium homeostasis and in interfering with calcium-dependent intracellular functions.

Childhood lead poisoning is caused by inhalation or ingestion of lead particles, which then enter the bloodstream to be distributed throughout the body and permeate bone cells; the lead is then stored long-term within the bone cells. In addition to household dust and paint chips, lead gets into the body through inhalation of vapor (eg, from heat stripping of lead-containing paints).

In a study of 94 African American women (mean age of 32.7 years) born to women residing where there had been a high incidence of childhood lead poisoning, blood lead concentrations began to rise around 6 months of age and declined at later ages (37). Study participants were obese and had suboptimal vitamin D status [mean 25(OH)D 18.5 ng/ml]. In multivariate regression models, there was no significant association between bone lead concentration at approximately 30 years old and childhood cumulative lead exposure, possibly because a significantly smaller proportion of the lead body burden resides in bone in young children. As the child grows, what lead there was in bone is diluted, and, assuming that there is not ongoing exposure, any remaining signal dwindles. Previous claims that bone lead in older children, adolescents, and adults can recapitulate historical exposure to lead during earlier development are too simplistic because bone lead at later ages may not be an adequate biomarker of childhood lead exposure in some populations.

Sources of lead exposures. There are multiple potential sources of exposure to lead pollution and many resultant potential adverse health effects.

Exposure to lead pollution and possible health effects in humans

(Source: Charkiewicz AE, Backstrand JR. Lead toxicity and pollution in Poland. Int J Environ Res Public Health 2020;17[12]:4385. Adapted from: Wani AL, Ara A, Usmani JA. Lead toxicity: a review. Interdiscip Toxicol 2015;8[2]:55...
Absorption, distribution, and excretion of Pb from the body

Key: thin arrows=absorption pathways; bold arrows=excreting pathways; dashed arrows=movement inside the body. The main locations of Pb in the body (blood, bones, soft tissues).

(Source: Charkiewicz AE, Backstrand ...

Lead paint and other residential exposures. There are multiple residential sources for childhood lead exposure (36).

Possible sources of lead poisoning among children in the home environment

(Source: Charkiewicz AE, Backstrand JR. Lead toxicity and pollution in Poland. Int J Environ Res Public Health 2020;17[12]:4385. Adapted from: Wani AL, Ara A, Usmani JA. Lead toxicity: a review. Interdiscip Toxicol 2015;8[2]:55...

In the United States, the UK, and France, the most common current source of lead in childhood lead poisoning is lead-based paint (45; 128; 91; 180; 181). Peeling or chipping paint from houses built before 1960 can contaminate the dust inside the house and the soil around the outside of the house (40; 178; 45; 180). Lead-based paint was sometimes used after the manufacturing ban in 1978. Improper lead abatement techniques can cause lead poisoning in children in the house being abated or in neighboring houses (39; 111). Remodeling or renovation of older homes may also produce lead dust or spread existing lead dust into the air where it may settle onto contact surfaces. Children living in homes built before the 1978 ban on lead-based residential paint may also be exposed to lead from drinking water service lines made from lead, lead solder, or plumbing materials containing lead (21).

A study of lead exposure pathways in Michigan from 2017 to 2021 studied 429 children in 345 homes; 53 had blood lead levels of 5 ug/dl or greater (180). Blood lead levels were directly predicted by lead in settled (ie, on the floor) house dust, the age of the child, season, and mouthing behavior and indirectly predicted by windowsill and trough dust lead, bare soil lead, proportion of floors with carpets, and exterior building deteriorations. Paint lead was also an indirect predictor of blood lead levels through the soil and settled dust pathways. This study reinforces earlier studies from the 1990s. Before that, the main direct and indirect pathways of lead exposure for most children in older housing remained paint and the contaminated dust and soil it generates.

A retrospective cohort study in England studied cases of lead exposure in children reported to the UK Health Security Agency between 2014 and 2020 via surveillance (45). Inclusion criteria were children under 16 years of age, residing in England, with an elevated blood lead concentration (BLC) level of 0.48 μmol/L (10 µg/dL) or greater and referred for public health management; 266 children met the inclusion criteria. After adjusting for reporting source, housing age, and type, cases residing in housing built before 1976 had a BLC of 0.32 µmols/L higher than cases living in housing built after this time. Housing age and type are a proxy for lead exposure risk through exposure to leaded paint, lead water pipes, and lead-contaminated dust from indoor and outdoor sources.

Lead poisoning cases per Upper Tier Local Authority area and percentage of housing built before 1973 in England

Location of cases, counts per Upper Tier Local Authority (UTLA), UK Health Security Agency (UKHSA) Centre region areas, and percentage of housing built before 1973 per UTLA area (VOA data, 2014). (Source: Crabbe H, Verlander NQ...
Housing characteristics of children with lead exposure, United Kingdom

(Top) Distribution of housing age; percentage of houses built before 1973 for the cases’ local area. Values represent for each case, the percentage of housing built before 1973, for the small area (Lower Super Output Area) wher...

Older infants and toddlers are at risk for ingestion of lead as they engage in developmentally normal oral exploration of their environment. They may crawl on floors covered with dust that contains lead and subsequently put toys in their mouth or suck their thumb. Children at this age are particularly susceptible to the effects of lead poisoning because of rapid brain development. Furthermore, some children exhibit higher rates of hand-to-mouth behaviors than other children, which puts them at higher risk for lead poisoning. Children with pica may eat dirt, paint chips, and other substances that are contaminated with lead (115; 45); however, a history of pica is absent in most children with lead poisoning, so the absence of a history of pica should not dissuade clinicians from testing for lead poisoning.

Windowsill with leaded paint picked off and eaten by a child with lead exposure

(Source: Crabbe H, Verlander NQ, Iqbal N, et al. As safe as houses; the risk of childhood lead exposure from housing in England and implications for public health. BMC Public Health 2022;22[1]:2052. Photography by Rebecca Ingha...

Children may develop lead poisoning following ingestion of lead curtain weights, fishing weights, and bullets (60).

The canned food industry in the United States stopped using lead-soldered cans in 1991. In 1995, the Food and Drug Administration issued a final rule prohibiting the use of lead solder in all food cans, including imported products.

Occupational lead exposures transferred to the home. Lead has been deposited in soil from leaded gasoline and from industrial sources, such as lead smelters or battery recycling facilities, including some units that are operated as in-home occupations (48; 192).

Distribution of children’s blood lead levels around a lead battery factory in China

(Source: Zhang F, Liu Y, Zhang H, et al. Investigation and evaluation of children's blood lead levels around a lead battery factory and influencing factors. Int J Environ Res Public Health 2016;13[6]:541. Creative Commons Attri...

Blood lead levels were markedly higher among children in a Vietnamese battery recycling craft village (48) than among children from Ho Chi Minh City (77).

Distribution of child blood lead levels from a cross-sectional survey in a Vietnamese battery recycling craft village

(n = 109) Blood was collected by fingerstick and analyzed with LeadCare II instrument. Upper limit of detection, 65 𝜇g/dL. (Source: Daniell WE, Van Tung L, Wallace RM, et al. Childhood lead exposure from battery recycli...
Distribution of blood lead levels in a pediatric population in Ho Chi Minh City, Vietnam

(Source: Havens D, Pham MH, Karr CJ, Daniell WE. Blood lead levels and risk factors for lead exposure in a pediatric population in Ho Chi Minh City, Vietnam. Int J Environ Res Public Health 2018;15[1]:93. Creative Commons Attri...

Even the car seats in the family automobiles of workers who work with lead have caused contamination leading to increased lead levels in children and infants (30).

Lactation. Lactation can mobilize maternal lead stores. Cross-sectional studies involving three countries at three separate times have shown that longer duration of breastfeeding is associated with increased lead levels in infants (107).

Air. Lead can be released directly into the air as suspended particles. Historic major sources of lead air emissions were motor vehicles and industrial sources. Motor-vehicle emissions have been reduced by the phasing out of leaded gasoline, but lead is still used in general-aviation gasoline for piston-engine aircraft. Ambient air lead levels are a predictor of blood lead levels greater than 10 µg/dL when controlling for other known contributors (19). Since the late 1970s, elimination of tetraethyl lead in gasoline and lead in paints has dramatically reduced lead pollution in the United States. However, much of the lead that was released from leaded gasoline in the past remains in the environment, especially in the soil near major roadways.

Less common sources. Less common sources of lead include lead pipes or lead solder in copper pipes, lead in crystal and lead-glazed pottery used as food containers, and lead-adulterated food products or ingredients (174).

Birthday cake with icing flowers tinted with primrose petal dust used for cake decorating--Missouri, 2019

In May 2019, Missouri Department of Health and Senior Services identified a cake decorating material referred to as primrose petal dust as a lead hazard during an environmental investigation of an elevated blood lead level (12 ...

Children can also be exposed to lead dust from indoor shooting ranges and from parental activities such as welding, construction, or pottery. In addition, lead continues to be used as a folk remedy in some cultures (eg, China) (07; 189).

Folk medicine obtained from a traditional Chinese medicine practitioner identified as the source of severe lead poisoning in a young boy

A red-colored folk medicine obtained from a traditional Chinese medicine practitioner (Shenzhen, Guangdong, China) identified as the source of severe lead poisoning in a 7-year-old boy. Analysis showed the lead concentration of...

Spices, herbal remedies, ceremonial powders, and imported cookware have also been identified as potential sources of lead (03).

Screening and diagnostic blood lead levels in children exposed to lead-contaminated spices, ceremonial powders, or herbal remedies--North Carolina, 20...

(n = 61) Box plots illustrate the distributions of screening (initial) and diagnostic (confirmatory) blood lead levels. The tops of the boxes represent the 75th percentile and the bottoms the 25th percentile. The middle line of...

Widespread lead contamination has been noted in 60% of imported low-cost jewelry and in cosmetics (177).

Effects on the brain. Biological effects of lead on the CNS are pervasive and complex (41; 59).

Very high blood levels, sufficient to cause seizures and obtundation, are associated with an acute hemorrhagic encephalopathy and cerebral edema. This is related to lead's ability to disrupt the normal capillary function of the endothelial cells in the blood-brain barrier (66) by interfering with calcium's regulatory effect on endothelial cells (17). More importantly, lead may have a greater effect on astrocytes, which surround the microvessels. Astrocytes appear to be more sensitive to the toxic effects of lead at low concentrations (84), sequestering lead within the endoplastic reticulum away from mitochondria (166) to protect neurons from excitotoxic injury and apoptosis (190).

Studies on adrenal chromaffin cells, which are similar to neurons in the central nervous system, showed that lead inhibits the inactivation of voltage-gated calcium channels, removing the cellular "safety switch" and permitting excessive influx of calcium. In calcium-dependent potassium channels, lead prolongs the presynaptic action potential, also permitting calcium influx. Additionally, through its action on phospholipase C (discussed below), lead facilitates the release of calcium from intracellular pools into the cytosol, further compromising cell survival.

Calcium has a critical role in exocytosis and release of neurotransmitters from presynaptic terminals. Because lead is a more potent cation than calcium in this role, it stimulates neurotransmitter release at much lower concentrations, resulting in an increase in basal release of neurotransmitters. At the same time lead effectively competes with calcium released during excitation, resulting in a decrease in evoked release of neurotransmitters. This enhanced basal release and decrement in evoked release creates significant "noise" in neurotransmitter systems. This is particularly relevant during early brain development, when redundant interneuronal pathways are "pruned" in response to the presence or absence of neurotransmitter activity, laying the foundation for the final synaptic network of the adult brain. In a developing brain exposed to lead, there may be a qualitative difference in the normal process of synaptic pruning (22; 66; 94). Permanent damage to the tertiary synaptic structure of the brain during the formative stages is postulated to result from the abnormal synaptic pruning process.

The mechanism for lead's disruptive action in neurotransmitter release is related to its activation of synaptotagmin, a synaptic vesicle protein necessary for exocytosis. This protein has two regulatory domains (C1 and C2) and two catalytic domains (C3 and C4). The C2 regulatory domain has two binding sites for calcium, one of which binds lead at nanomolar (10-9 M) concentrations, whereas calcium typically binds to stimulate neurotransmitter release at micromolar (10-6 M) concentrations (Pevsner, personal communication). This C2 regulatory domain occurs in dozens of proteins, many of which are associated with neurotransmitter release. Prominent among these is phosphokinase C, which, when activated by lead, exacerbates the problem with neurotransmitter release and affects the body's "second messenger system" (112; 18). Animal studies have shown that the vascular adrenergic system and nitric oxide pathway change in short-term and subchronic phases of lead poisoning. An initial increase in blood pressure with decreased levels and nitrates was followed by a reversal of the metabolite levels with blood pressure maintained at high levels (83).

Hematologic effects. Lead binds to enzymes in the heme synthesis pathway. Inhibition of ferrochelatase results in the increased levels of protoporphyrin in the erythrocyte. Protoporphyrin is chelated by lead instead of iron, thus, inhibiting heme formation. Erythrocyte protoporphyrin accumulation results in toxicity independent of lead levels. The rise and fall of erythrocyte protoporphyrin is not related to blood lead levels (103).

Eukaryotic pyrimidine 5'-nucleotidase type 1 (P5N-1) catalyzes dephosphorylation of pyrimidine 5'-mononucleotides. The structure of lead-inhibited P5N-1 revealed that lead binds within the active site and compromises the function of the cationic cavity, which is required for the recognition and binding of the phosphate group of nucleotides. Deficiency of P5N-1 activity in red blood cells results in nonspherocytic hemolytic anemia. The enzyme deficiency is either familial or can be acquired through lead poisoning (15).

Gene expression and protein synthesis. Lead may alter gene expression, and protein synthesis (33).

Developmental lead exposure produces epigenetic effects on DNA methylation mediated at least in part through dysregulation of methyltransferases, even at the lowest levels of exposure (146). Studies of rats exposed to lead demonstrate increased histone acetylation in the hippocampus and increased locomotor activity (109). Even brief postnatal lead exposure produces significant changes in expression of various genes in the hippocampus (145).

In rats, maternal lead exposure can permanently alter the hypothalamic-pituitary-adrenal axis, altering the production of some corticosteroids (173).

Epidemiology

In the United States, the toxic reference blood lead level is currently 5 µg/dL as determined by the Centers for Disease Control and Prevention (CDC). This reference level reflects the lead blood levels of children aged 1 to 5 years in the United States who are in the highest 2.5%. Data regarding childhood blood lead levels in the United States come from the second and third National Health and Nutrition Examination Surveys, conducted by the National Center for Health Statistics/Centers for Disease Control and Prevention. The first blood lead level surveillance occurred during NHANES II (1976 to 1980) and the first part of NHANES III (1988 to 1991) (20). Between these two surveys of mean blood lead level in the overall United States population, there was a 78% decrease, from 12.8 to 2.8 µg/dL. Among children aged 1 to 5 years, the mean blood lead level decreased from 13.7 to 3.2 µg/dL for non-Hispanic white children and from 20.2 to 5.6 µg/dL for black children. Despite this decrease, 8.9% of children 1 to 5 years of age still have blood lead levels greater than 10 µg/dL (132).

The number of children aged less than 5 years with newly confirmed blood lead levels of 70 μg/dL or greater from the U.S. Childhood Blood Lead Surveillance System decreased somewhat from 2009 to 2014 (136).

Number of children younger than 5 years of age with newly confirmed blood lead levels 70 μg/L or greater--Childhood Blood Lead Surveillance System, Un...

The number of reporting jurisdictions varied somewhat from year to year. (Source: Raymond J, Brown MJ. Childhood blood lead levels in children aged <5 years--United States, 2009-2014. MMWR Surveill Summ 2017;66[3]:1-10. [CDC...

Based on data from the U.S. Childhood Blood Lead Surveillance System, the percentage of children aged less than 5 years with blood lead levels from 5 to 9 μg/dL declined over the interval from 2009 to 2014 (136). For children less than 1 year old, the rate of blood lead level 5 to 9 μg/dL declined from 448 per 100,000 children in 2010 to 149 per 100,000 children in 2014. For children 1 to 4 years of age, the rate of blood lead level 5 to 9 μg/dL declined from 806 per 100,000 children in 2010 to 444 per 100,000 children in 2014.

Percentage of children aged younger than 5 years of age with blood lead levels 5 μg/dL or greater, by year and blood lead level

Abbreviation: BLLs = blood lead levels. The number of reporting jurisdictions varied somewhat from year to year. Childhood Blood Lead Surveillance System, United States, 2009-2014. (Source: Raymond J, Brown MJ. Childhood blood ...

Three factors contribute to this decline in mean blood lead levels: (1) removal of tetraethyl lead as an additive to gasoline in the United States between 1976 and 1990, (2) phasing out of lead soldering in food cans by 1991, and (3) a mandate in 1977 by the Consumer Product Safety Commission restricting the allowed amount of lead in paint for household use to less than 0.07% by weight. Although this last action has prevented the use of lead-based paint in newer homes, it did not address the problems of deteriorating paint in older homes, continued use of older stores of leaded interior paint, and use of leaded paint on exterior surfaces such as porches.

Although the overall decline in childhood blood lead levels is a positive trend, children aged 1 to 2 years continue to demonstrate the highest prevalence of elevated blood lead levels. Approximately 450,000 children in the United States are above the 5 µg/dL reference value for blood lead levels and are, therefore, at risk for adverse developmental consequences.

Elevated lead levels are most common among urban rather than rural children, children living in older housing, and low-income children (137). National data are of limited usefulness, however, because local prevalence varies substantially. Norman and colleagues found that children living in rural areas of North Carolina were at significantly higher risk of lead exposure than urban children were (127). Of 114,000 North Carolina children screened over a 2-year period, between 1992 and 1994, more than 20.9% had lead levels greater than 10 µg/dL (126).

A study highlighted the problem of lead toxicity in immigrant refugee populations (29). Malnutrition often compounds the problem. Anemia can enhance lead absorption and, thus, can increase risk for elevated blood lead levels, even in housing with minimal lead exposure hazards. Blood lead levels became elevated after resettlement for nearly 30% of refugee children with two tests, suggesting that lead exposure for these children occurred in the United States. Investigations revealed several risk factors for lead poisoning: living in old homes, the presence of lead hazards, behaviors that could increase the chance of ingesting lead, a lack of awareness of the dangers of lead, and evidence of chronic and acute malnutrition (171).

Lead levels have a seasonal component (188; 73; 96; 99; 134; 135; 136).

Seasonal pattern of elevated blood lead levels among children younger than 5 years of age, United States (2012)

Number of cases of elevated blood lead levels 10 or more micrograms per deciliter among children aged younger than 5 years, by month in 2012 in the United States. (Source: Laidlaw MA, Filippelli GM, Sadler RC, Gonzales CR, Ball...
Percent of children with elevated blood lead levels over time, by age, New York State 1995-1999

From 1994 to 1997, 262,287 children in New York State had blood lead levels drawn within 2 weeks of their first or second birthday. This illustration shows the seasonal and trend components. (Source: Haley VB, Talbot TO. Season...
Declining proportion of children with "concerning" blood lead levels, United States 1997-2015

Shown are two different thresholds for "concerning" (based on data from the CDC). Illustration by Morgan Rehnberg on April 19, 2017. (Public domain.)

The variation of dust lead levels on the floor, windowsills, and carpets are consistent with the variation of blood lead levels, showing the highest levels in the hottest months of the year, June, July, and August (96).

Prevention

In childhood lead poisoning, primary prevention refers to prevention of lead exposure and maintenance of medically acceptable blood lead levels (less than 5 µg/dL). Secondary prevention refers to the identification of a child with an elevated lead level through periodic screening, with subsequent effort to prevent further lead exposure to the child.

Because the major source of lead exposure for children in the United States is lead-based paint, preliminary prevention strategies should focus on housecleaning techniques that will remove lead-contaminated dust (28), or relocating the child, if necessary, during lead abatement. Vacuuming and sweeping both disperse significant amounts of dust, so families are encouraged to use damp-cleaning techniques on all surfaces. A high-phosphate detergent, (eg, powdered automatic dishwasher detergent), should be employed, because the phosphate forms a chemical bond with the lead. A high-efficiency particle accumulator vacuum cleaner (HEPA-VAC) may be used to trap lead-containing dust particles too small to be captured by common household vacuum cleaners.

When a house is abated, the lead paint is permanently removed or encapsulated, thereby rendering the house "lead-free" or "lead-safe." Abatement and renovation should only be carried out by professionals certified to perform lead abatement, and all adults, children, and pets must vacate the premises until the work is complete. Furniture and all of the family's belongings must be stored or protected from dust particles during this time. It is not uncommon for children to suffer acute elevations in blood lead level if they are living in or near a house that is being renovated or abated by untrained persons who have not taken proper precautions (39).

During infant and toddler years, hand-to-mouth behavior is common. Parent education about sources of lead in and around the home and frequent hand washing and fingernail clipping are important preventive measures. In an uncontrolled study, such counseling was effective in reducing mean blood lead level in 78 children from 15 to 8 µg/dL (98). In addition, toys should be washed to remove lead-contaminated dust, and antique toys, often painted with lead-based paint, should not be given to infants and toddlers.

Good nutrition practices are essential to prevent childhood lead poisoning (140). Hand washing effectively removes lead and should be encouraged prior to hand to mouth feeding. Regular feedings are important because gastrointestinal absorption of lead is increased when the stomach is empty. Lead competes with calcium and iron; hence, a diet rich in iron and calcium needs to be promoted. Children with iron deficiency or low calcium stores absorb and retain more lead than those children who are not deficient. Indeed, longitudinal studies demonstrate that iron deficiency is associated with lead poisoning (183).

Diagnostic workup

Targeted blood-lead testing of the populations at high risk for lead poisoning, an approach to secondary prevention, is the current strategy. Children living in or visiting buildings built before 1950 or built before 1978 but renovated in the past 6 months as well as those who have a sibling with lead poisoning are considered at high risk. Risk factors differ by community and no risk questionnaire developed at the national level should be applied across communities to target screening (47). Nevertheless, it is worth addressing the following three questions:

	1. Does your child live in or regularly visit a house that was built before 1950? This question could apply to a facility such as a home day-care center or the home of a babysitter or relative.
	2. Does your child live in or regularly visit a house built before 1978 with recent or ongoing renovations or remodeling (within the last 6 months)?
	3. Does your child have a sibling or playmate who has or had lead poisoning?

Except under particular circumstances (eg, pregnancy, lactation), bone lead stores have low turnover; therefore, (1) it is possible to have significant deposit of lead deposition in bone with meager blood lead levels; and (2) blood lead level may not reflect total lead stores in the body. Regardless of these caveats, the venous blood lead level is currently the best available screening test for lead poisoning.

Clinical testing for lead exposure is necessary to identify those children for whom primary prevention measures have failed (02). Testing will often occur during routine well-child care (as recommended by the American Academy of Family Physicians and the American Academy of Pediatricians).

CDC recommendations for blood lead level include the following:

	• According to state and local guidelines, if available.
	• All non-Medicaid children in the absence of limited local and, therefore, state guidelines.
	• All immigrant, refugee, and internationally adopted children when they arrive in the United States (regardless of age), due to their increased risk, as they may have been exposed to lead in their country of origin.
	• At 12 and 24 months for all Medicaid-enrolled children (unless the state has a CDC and the Centers for Medicare and Medicaid Services [CDC/CMS] waiver indicating that children enrolled in Medicaid are not at higher risk for high blood lead levels than other children).
	• Children less than 72 months of age that missed recommended screening at a younger age should be screened at presentation.
	• Initial and follow-up screening of pregnant and lactating women, as well as for neonates and infants of women with blood lead levels greater than or equal to 5 micrograms per deciliter (µg/dL).

In addition, a blood lead level should also be considered for children with excessive pica or hand-to-mouth activity.

Confirmation of suspected elevation in blood level should be obtained from a venous blood sample because capillary blood samples ("fingersticks") are frequently contaminated by lead dust on the skin and may yield false-positive results (143; 147). Free erythrocyte protoporphyrin is not consistently elevated until the blood lead level is above 40 µg/dL, so it should not be used to screen for lead poisoning (49). At a blood lead level of 35 to 40 µg/dL, only 50% of children will have an elevated free erythrocyte protoporphyrin; when the blood lead level reaches 50 to 55 µg/dL, 95% of children will have an elevated free erythrocyte protoporphyrin. In addition, free erythrocyte protoporphyrin may be elevated by other medical conditions such as iron deficiency. Free erythrocyte protoporphyrin may serve as an indirect indicator of exposure acuity: if the lead level is markedly elevated but free erythrocyte protoporphyrin remains relatively normal, the child most likely has had an acute ingestion; if both lead level and free erythrocyte protoporphyrin are elevated, the child most likely has chronic lead exposure. Free erythrocyte protoporphyrin elevation usually lags slightly behind the blood lead level elevation that causes it.

Radiographs of long bones (hands and knees) may show lead lines in the metaphysis suggestive of long-term lead exposure. Recently ingested paint chips may be seen in plain radiographs of the abdomen. Bone lead stores can be assessed by x-ray fluorescence (85; 87), but this is not done routinely and is only available in research centers.

A lead mobilization test has been used to identify children with lead that may be mobilized by chelation therapy. The test is done by measuring urine lead levels following administration of a single dose of adequacy of iron stores, a chelating agent (eg, calcium sodium EDTA). The test is of limited use and, therefore, is not recommended (113).

Additional blood tests are helpful in evaluating children with lead poisoning, including the following: (1) complete blood count (including hemoglobin, mean corpuscular volume, and red blood cell distribution width; (2) review of the blood smear; (3) serum iron and ferritin; (4) BUN and creatinine. Adequacy of iron stores is important because it is difficult to lower the blood lead level in a child who has chronic iron deficiency anemia. In most cases, concomitant treatment with therapeutic doses of iron will enhance the body's ability to excrete lead.

Neuroimaging typically does not play a pivotal role in the diagnosis of lead poisoning, except in cases of overt lead encephalopathy. Cerebral edema, presumably a consequence of vascular changes, may be seen in early stages in selected cases (163). With long-standing exposure, calcifications may be seen on CT, appearing patchy, punctate, or linear along the border of cortical and subcortical zones. Calcifications may also be seen on MRI as T2 hypointensities, occasionally surrounded by a hyperintense margin, likely due to an albuminoid matrix into which calcium salts are imbedded (100). Hyperintense lesions may sometimes be seen in periventricular regions (167). MR imaging findings, affecting predominantly the cerebral gray-white matter junction and the subcortical white matter, often resolve after chelation therapy (06).

Management

A fundamental principle of lead poisoning management is the removal of the source of lead exposure, without which chelation will have only transient ameliorative effects.

Childhood lead poisoning is currently classified by a system outlined in 1991 by Centers for Disease Control and Prevention. The venous blood lead level determines the recommended interventions. A blood lead level less than or equal to 5 µg/dL whole blood is considered medically acceptable (13). The complete classification system is as follows:

Class	Blood lead level (µg/dL)	Action
I	less than 5	Rescreen more than once per year with regular monitoring for developmental and behavioral problems
IIA	5 to 14	Confirmatory venous lead level within 1 month
IIB	15 to 19	Confirmatory venous lead level within 1 month; assess sources of lead; educate parents; environmental investigation and lead abatement if elevated levels persist
III	20 to 44	Repeat blood lead levels in 1 week to 1month, depending on the blood lead levels. Chelation therapy is not advised. Complete medical evaluation; identify and eliminate environmental sources
IV	45 to 69	Repeat blood lead levels in 48 hours. Begin medical treatment, environmental assessment and remediation within 48 hours
V	greater than 70	Repeat blood lead levels immediately to confirm the levels. Begin medical treatment, environmental assessment and remediation immediately.

Venous blood lead levels of 45 µg/dL or more require chelation therapy. Chelation is the process by which a metal is chemically bound in a form that is easily excreted by the human body. In 1991 meso 2,3-dimercaptosuccinic acid (succimer) was approved for use in children. This water-soluble oral chelating agent is an analogue of British anti-lewisite but is more selective for lead, less toxic, and does not mobilize essential trace elements. Succimer, which can be used on an inpatient basis or in a "lead-safe" outpatient environment, is usually given for a period of 19 to 28 days. It is the preferred treatment regimen for children with blood lead levels between 45 and 70 µg/dL, although it is contraindicated in children with G6PD deficiency. The impact of treatment with succimer on developmental outcome of children with moderately elevated blood lead levels (20 to 44 µg/dL) has not yet been established. Chelation therapy with concomitant use of a cathartic removes the lead present in the intestine and prevents further absorption.

Another commonly used chelating agent for children with blood lead levels between 45 and 70 µg/dL is calcium disodium versenate, which is given intramuscularly twice a day for 5 days. This medication can be used for the small number of children who are unresponsive to succimer or who are allergic to sulfa drugs. It is less metal-specific, and will also chelate zinc, copper, and iron from the body (39). The 5-day course may be repeated after a 3-day rest period during which supplementation of the other chelated metals can be given.

Lead levels above 70 µg/dL are considered medical emergencies, whether neurologic symptoms are present or not (28); children with such levels require therapy with two chelating agents for more than one course. At these levels the risk of developing acute encephalopathy is high, especially if the child is already neurologically compromised or the blood lead level is rising quickly. Among those children with blood lead levels higher than 70 µg/dL and no evidence of encephalopathy calcium sodium EDTA combined with dimercaptosuccinic acid or British anti-Lewisite may be used, whereas those with evidence of encephalopathy require a combination of calcium sodium EDTA and British anti-Lewisite. British anti-Lewisite and penicillamine are associated with neutropenia. In a child with symptomatic lead poisoning, chelation will shorten the period of morbidity and can be lifesaving. Fluid intake must be closely monitored to ensure adequate urine flow without overhydration. A benzodiazepine is recommended for the initial treatment of seizures in this setting (131).

Dimercaptosuccinic acid	350 mg/m2 per dose (not 10 mg/kg) every 8 hours, by mouth, for 5 days; then every 12 hours for 14 days
Calcium sodium EDTA	1000 to 1500 mg/m2 per 24 hour for 5 days; IV infusion, continuous or intermittent; IM in divided doses every 6 or 12 hours for 5 days.
British anti-Lewisite, also known as Dimercaprol	300 to 500 mg/m2 per 24 hours; IM only, in divided doses every 4 hours, for 3 to 5 days. Only for blood lead level greater than or equal to 70 µg/dL.
Penicillamine	10 mg/kg per 24 hours for 2 weeks, increasing to 25 to 40 mg/kg per 24 hours; oral, in divided doses every 12 hours, for 12 to 20 weeks

Any child receiving chelation therapy must be under close medical surveillance and should undergo frequent monitoring for renal, hepatic, and hematologic side effects (65), as all the above chelation agents utilize renal excretion. British anti-lewisite utilizes some hepatic excretion.

Among divalent cations, the ionophore monensin shows high activity and selectivity for the transport of lead ions (Pb2+) across phospholipid membranes. On co-administration to rats that were receiving meso-dimercaptosuccinate for treatment of lead intoxication, monensin significantly increased the amount of lead removed from femur, brain, and heart. Monensin may act by co-transporting lead and hydroxide ions out of cells, in exchange for external sodium ions. The net effect would be to shuttle intracellular lead to extracellular dimercaptosuccinic acid thereby enhancing its effectiveness. Thus, monensin may be useful for the treatment of lead intoxication when applied in combination with hydrophilic lead chelators (74).

Children with elevated blood levels of lead are at risk for poor nutrition and should ideally receive a diet consistent with the 2010 dietary guidelines recommended by the U.S. Food and Drug Administration (46). Given similar structural properties between lead and calcium, children at risk for lead poisoning should receive adequate amounts of calcium in their diet.

Special considerations

Pregnancy

Lead can cross the placenta and deposit in fetal tissues. Though mobilization of bone lead stores has been reported during pregnancy the maternal blood lead levels tend to remain relatively constant over the duration of the pregnancy, provided there is no increase in maternal lead exposure or ingestion (10; 26). Maternal blood lead levels may rise during later trimesters in pregnancy (110). Because the central nervous system develops rapidly throughout fetal life, it may be especially vulnerable to toxins. The lowest fetal blood lead threshold for adverse effects has not been established (26) and probably does not exist, meaning that any lead exposure will convey some adverse effect of fetal development. Infant neurodevelopment is adversely affected by exposure to lead independent of postnatal blood lead levels.

Lead also interacts with other metals to influence neurocognitive development. For example, there is a dose-dependent interaction between lead and cadmium exposure at 6 months of age (97). Cadmium levels below the median maternal blood level are antagonistic to lead during early pregnancy. At median levels of cadmium, the interaction with lead is minimal. However, levels of cadmium above the median result in a synergistic modification of effect between prenatal cadmium and lead exposures, to the detriment of neurocognitive development.

Although blood lead is a marker for recent exposure, bone lead is an indicator of chronic exposure. Bone lead is both a depot for cumulative lead and a source of exposure with bone turnover. Bone lead is mobilized during pregnancy and lactation, (160; 72). During pregnancy, maternal bone lead increases blood lead from 9% to 65% (71). Chronic exposure produces reactive oxygen species (01; 04), which interfere with DNA methylation (172). There is an inverse relationship between maternal bone lead and DNA methylation of umbilical cord samples (130), which suggests that the maternal lead influences the epigenome of the developing fetus, producing disease vulnerability throughout the lifetime. In addition, blood lead affects homocysteine levels, which have been linked to decreases in DNA methylation (187), likely from suppression of DNA methyltransferases (44; 92).

Maternal bone lead is associated with adverse birth outcomes (68) and neurodevelopmental consequences (67). Maternal lead exposure can cause spontaneous abortions and stillbirths, and lead was used as an abortifacient prior to the 20th century (148; 120). Fetal death and premature birth have been associated with maternal occupational lead exposure; consequently, this has led to occupational hygiene measures as well as laws that excluded pregnant women from lead-related work (120). No clear pattern of congenital anomalies associated with fetal lead exposure has been reported, although available studies are limited (148).

Prenatal lead exposure is associated with neurodevelopmental deficits in young children (10; 88; 102; 69). Measurement of cord blood levels, monoamine concentrations, and neurodevelopmental outcome in 244 newborns in Paris demonstrated a negative correlation between both 5-HIAA concentration and sociability at age 9 months, leading to speculation that variance of serotonergic activity may mediate some behavioral consequences of elevated levels of lead (159).

DNA methylation, which regulates gene expression by suppression of transposons (179), is susceptible to environmental modification (54). In animals, environmental exposures during early life may influence DNA methylation, causing phenotype changes that produce a lifetime of disease vulnerability (176; 52; 53; 185). In addition, transgenerational inheritance of the phenotype is possible through environmental alterations on the germline of the epigenome (05; 35; 93). Investigations about early-life lead exposures using rodents and monkey models have demonstrated effects in the regulation of the amyloid precursor protein, reduction in the DNA methyltransferase activity, and susceptibility to Alzheimer disease in later life (08; 184).

Lead has affinity for calcium-binding sites (141), and calcium deficiency promotes intestinal lead absorption (78) and retention (155). In pregnancy and lactation, when there is an increased calcium demand (133), maternal bone lead is mobilized into the circulation (72; 110; 161). Increased milk consumption during pregnancy is associated with lower maternal and umbilical cord lead levels in postpartum women (81). In the United States, the recommended dietary intake of calcium for pregnant and lactating women is 1,000 mg to 1300 mg/day (90). Studies have shown that lactating women who had a daily intake of 1,200 mg of calcium had a reduced maternal blood lead by 15% to 20% (80) and breast milk lead by 5% to 10% (56) throughout the course of lactation. In pregnancy, 1,200 mg of daily calcium supplementation was associated with an average reduction of 11% in blood lead level relative to placebo (55). Dietary calcium supplementation is a cost-effective means to lower lead exposure of the developing fetus and the breastfeeding infant.

Media

References

01: Adonaylo VN, Oteiza PI. Lead intoxication: antioxidant defenses and oxidative damage in rat brain. Toxicology 1999;135(2-3):77-85. PMID 10463764
02: Advisory Committee on Childhood Lead Poisoning Prevention of the Centers for Disease Control and Prevention. Low Level Lead Exposure Harms Children: A Renewed Call for Primary Prevention. January 4, 2012. https://www.cdc.gov/nceh/lead/docs/final_document_030712.pdf. Accessed October 11, 2022.
03: Angelon-Gaetz KA, Klaus C, Chaudhry EA, Bean DK. Lead in spices, herbal remedies, and ceremonial powders sampled from home investigations for children with elevated blood lead levels--North Carolina, 2011-2018. MMWR Morb Mortal Wkly Rep 2018;67(46):1290-4. PMID 30462630
04: Antonio-Garcia MT, Masso-Gonzalez EL. Toxic effects of perinatal lead exposure on the brain of rats: involvement of oxidative stress and the beneficial role of antioxidants. Food Chem Toxicol 2008;46(6):2089-95. PMID 18417264
05: Anway MD, Leathers C, Skinner MK. Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. Endocrinology 2006;147(12):5515-23. PMID 16973726
06: Atre AL, Shinde PR, Shinde SN, et al. Pre- and post-treatment MR imaging findings in lead encephalopathy. Am J Neuroradiol 2006;27(4):902-3. PMID 16611788
07: Baer RD, Garcia de Alba J, Cueto LM, Ackerman A, Davison S. Lead based remedies for empacho: patterns and consequences. Soc Sci Med 1989;29:1373-9. PMID 2629119
08: Basha MR, Wei W, Bakheet SA, et al. The fetal basis of amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and beta-amyloid in the aging brain. J Neurosci 2005;25(4):823-9. PMID 15673661
09: Bellinger D, Hu H, Titlebaum L, Needleman HL. Attentional correlates of dentin and bone lead levels in adolescents. Arch Environ Health 1994;49:98-105. PMID 8161248
10: Bellinger D, Leviton A, Waternaux C, Needleman H, Rabinowitz M. Longitudinal analyses of prenatal and postnatal lead exposure and early cognitive development. N Engl J Med 1987;316:1037-43. PMID 3561456
11: Bellinger D, Needleman H, Bromfield R, Mintz M. A followup study of the academic attainment and classroom behavior of children with elevated dentine lead levels. Biol Trace Elem Res 1984;6:207-23. PMID 24264021
12: Bellinger DC, Stiles KM, Needleman HL. Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study. Pediatrics 1992;90:855-61. PMID 1437425
13: Binns HJ, Campbell C, Brown MJ. Interpreting and managing blood lead levels of less than 10 microg/dL in children and reducing childhood exposure to lead: recommendations of the Centers for Disease Control and Prevention Advisory Committee on Childhood Lead Poisoning Prevention. Pediatrics 2007;120(5):e1285-98. PMID 17974722
14: Bithoney WG. Elevated lead levels in children with nonorganic failure to thrive. Pediatrics 1986;78:891-5. PMID 2429250
15: Bitto E, Bingman CA, Wesenberg GE, Mc Coy JG, Phillips GN Jr. Structure of pyrimidine 5'-nucleotidase type 1.Insight into mechanism of action and inhibition during lead poisoning. J Biol Chem 2006;281(29):20521-9. PMID 16672222
16: Bhattacharya A, Shukla R, Bornschein RL, Dietrich KN, Keith R. Lead effects on postural balance of children. Environ Health Perspect 1990;89:35-42. PMID 2088753
17: Bressler JP, Goldstein GW. Mechanisms of lead neurotoxicity. Biochem Pharmacol 1991;41(4):479-84. PMID 1671748
18: Bressler J, Kim KA, Chakraborti T, Goldstein G. Molecular mechanisms of lead neurotoxicity. Neurochem Res 1999;24:595-600. PMID 10227691
19: Brink L, Talbott E, Sharma R, et al. Do US ambient air lead levels have a significant impact on childhood blood lead levels: results of a national study. J Environ Public Health 2013;2013:278042. PMID 23983719
20: Brody DJ, Pirkle JL, Kramer RA, et al. Blood lead levels in the US population. JAMA 1994;272:277-83. PMID 8028140
21: Brown MJ, Margolis S. Lead in drinking water and human blood levels in the United States. MMWR Surveill Summ 2012;61 Suppl:1-9. PMID 22874873
22: Bull RJ, McCauley PT, Taylor DH, Croften KM. The effects of lead on the developing nervous system of the rat. Neurotoxicology 1983;4:1-18. PMID 6308527
23: Burton H. On a remarkable effect on the human gums, produced by the absorption of lead. Med Chir Trans 1840;23:63-79. PMID 20895719
24: Byers RK, Lord EE. Late effects of lead poisoning on mental development. Am J Dis Child 1943;66:471-94.
25: Canfield RL, Henderson CR Jr, Cory-Sletchta DA, Cox C, Jusko TA, Lanphear BP. Intellectual impairment in children with blood lead concentrations below 10 microg per deciliter. N Engl J Med 2003;348(16):1517-26. PMID 12700371
26: Carrington CD, Sheehan DM, Bolger PM. Hazard assessment of lead. Food Addit Contam 1993;10:325-35. PMID 8359314
27: Cecil KM, Brubaker CJ, Adler CM, et al. Decreased brain volume in adults with childhood lead exposure. PLoS Med 2008;5(5):e112. PMID 18507499
28: Centers for Disease Control and Prevention. Preventing lead poisoning in young children. Georgia: US Department of Health and Human Services/Public Health Service/Centers for Disease Control and Prevention, 1991:1-105.
29: Centers for Disease Control and Prevention. Elevated blood lead levels in refugee children -- New Hampshire, 2003-2004. MMWR Morb and Mortal Wkly Rep 2005;54(2):42-6. PMID 15660019
30: Centers for Disease Control and Prevention. Childhood lead poisoning associated with lead dust contamination of family vehicles and child safety seats - Maine 2008. MMWR Morb Mortal Wkly Rep 2009;58(32):890-3. PMID 19696718
31: Centers for Disease Control and Prevention. Response to Advisory Committee on Childhood Lead Poisoning Prevention Recommendations in “Low Level Lead Exposure Harms Children: A Renewed Call of Primary Prevention." 2012. https://www.cdc.gov/nceh/lead/acclppdocs/cdc_response_lead_exposure_recs.pdf. Accessed October 2022a.
32: Centers for Disease Control and Prevention. Third national report on human exposure to environmental chemicals. Atlanta, Georgia: National Center for Environmental Health, 2005. Available at:Publication No. 05-0570. Accessed October 2022b.
33: Chakraborti T, Kim KA, Goldstein GG, Bressler JP. Increased AP-1 DNA binding activity in PC12 cells treated with lead. J Neurochem 1999;73:187-94. PMID 10386970
34: Chandramouli K, Steer CD, Ellis M, Emond AM. Effects of early childhood lead exposure on academic performance and behaviour of school age children. Arch Dis Child 2009;94(11):844-8. PMID 19770197
35: Chang HS, Anway MD, Rekow SS, Skinner MK. Transgenerational epigenetic imprinting of the male germline by endocrine disruptor exposure during gonadal sex determination. Endocrinology 2006;147(12):5524-41. PMID 16973722
36: Charkiewicz AE, Backstrand JR. Lead toxicity and pollution in poland. Int J Environ Res Public Health 2020;17(12):4385. PMID 32570851
37: Chettle DR, Dietrich KN, Bhattacharya A, et al. Early childhood lead exposure is not reflected in adult bone lead: results of a sub-cohort of African American women in the Cincinnati lead study. Environ Res 2023;231(Pt 1):115956. PMID 37105282
38: Chiodo LM, Covington C, Sokol RJ, et al. Blood lead levels and specific attention effects in young children. Neurotoxicol Teratol 2007;29:538-46. PMID 17553667
39: Chisolm JJ. Evaluation of the potential role of chelation therapy in treatment of low to moderate lead exposures. Environ Health Perspect 1990;89:67-74. PMID 1965166
40: Chisolm JJ, Mellits ED, Quaskey SA. The relationship between the level of lead absorption in children and the age, type, and condition of housing. Environ Res 1985;38:31-45. PMID 4076109
41: Cory-Slechta DA. Relationships between lead-induced learning impairments and changes in dopaminergic, cholinergic and glutamatergic neurotransmitter system functions. Ann Rev Pharmacol Toxicol 1995;35:391-415. PMID 7598500
42: Cory-Slechta DA, Pounds JG. Lead neurotoxicity. In: Chang LW, Dyer RW, editors. New York: Marcel Dekker, 1995:61-89.
43: Coulton C, Richter FG, Cho Y, Park J, Jeon J, Fischer RL. Making the case for lead safe housing: downstream effects of lead exposure on outcomes for children and youth. Health Place 2023;84:103118. PMID 37839260
44: Cox R, Prescott C, Irving CC. The effect of S-adenosyl-homocysteine on DNA methylation in isolated rat liver nuclei. Biochim Biophys Acta 1977;474(4):493-9. PMID 836843
45: Crabbe H, Verlander NQ, Iqbal N, et al. As safe as houses; the risk of childhood lead exposure from housing in England and implications for public health. BMC Public Health 2022;22(1):2052. PMID 36352379
46: Cunningham E. What role does nutrition play in the prevention or treatment of childhood lead poisoning? J Acad Nutr Diet 2012;112(11):1916. PMID 23102188
47: Dalton MA, Sargent JD, Stukel TA. Utility of a risk assessment questionnaire in identifying children with lead exposure. Arch Pediatr Adolesc Med 1996;150(2):197-202. PMID 8556126
48: Daniell WE, Van Tung L, et al. Childhood lead exposure from battery recycling in Vietnam. Biomed Res Int 2015;2015:193715. PMID 26587532
49: DeBaun MR, Sox HC. Setting the optimal erythrocyte protoporphyrin screening decision threshold for lead poisoning: a decision analytic approach. Pediatrics 1991;88:121-31. PMID 2057248
50: Dietrich KN, Berger OG, Succop PA. Lead exposure and the motor developmental status of urban six-year-old children in the Cincinnati Prospective Study. Pediatrics 1993;91:301-7. PMID 7678702
51: Dietrich KN, Succop PA, Berger OG, Keith RW. Lead exposure and the central auditory processing abilities and cognitive development of urban children: the Cincinnati lead study cohort at age 5 years. Neurotoxicol Teratol 1992;14:51-6. PMID 1593979
52: Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect 2006;114:567-72. PMID 16581547
53: Dolinoy DC, Huang D, Jirtle RL. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci U S A 2007a;104(32):13056-61. PMID 17670942
54: Dolinoy DC, Weidman JR, Jirtle RL. Epigenetic gene regulation: linking early developmental environment to adult disease. Reprod Toxicol 2007b;23(3):297-307. PMID 17046196
55: Ettinger AS, Lamadrid-Figueroa H, Tellez-Rojo MM, et al. Effect of calcium supplementation on blood lead levels in pregnancy: a randomized placebo-controlled trial. Environ Health Perspect 2009;117(1):26-31. PMID 19165383
56: Ettinger AS, Téllez-Rojo MM, Amarasiriwardena C, et al. Influence of maternal bone lead burden and calcium intake on levels of lead in breast milk over the course of lactation. Am J Epidemiol 2006;163(1):48-56. PMID 16282237
57: Farfel MR, Chisolm JJ. Health and environmental outcomes of traditional and modified practices for abatement of residential lead-based paint. Am J Public Health 1990;80:1240-5. PMID 2136329
58: Fewtrell LJ, Prüss-Ustün A, Landrigan P, Ayuso-Mateos JL. Estimating the global burden of disease of mild mental retardation and cardiovascular diseases from environmental lead exposure. Environ Res 2004;94:120-33. PMID 14757375
59: Finkelstein Y, Markowitz ME, Rosen JF. Low-level lead-induced neurotoxicity in children: an update on central nervous system effects. Brain Res Brain Res Rev 1998;27:168-76. PMID 9622620
60: Gellert GA. Risk of pediatric lead poisoning from nonenvironmental exposures: gun ownership. Am J Dis Child 1993;147:720-2. PMID 8322739
61: Gibson JL. Ocular neuritis, simulating basal meningitis-plumbism. Australasian Medical Gazette 1897;16:479-82.
62: Gibson JL. A plea for painted railings and painted walls of rooms as the source of lead poisoning amongst Queensland children. Australasian Medical Gazette 1904;23:149-53.
63: Gibson JL. A plea for painted railings and painted walls of rooms as the source of lead poisoning amongst Queensland children. 1904. Public Health Rep 2005;120(3):301-4. PMID 16134572
64: Gittelman R, Eskenazi B. Lead and hyperactivity revisited: an investigation of nondisadvantaged children. Arch Gen Psychiatry 1983;40:827-33. PMID 6683492
65: Glotzer DE. Management of childhood lead poisoning: strategies for chelation. Pediatr Ann 1994;23:606-15. PMID 7838613
66: Goldstein GW. Neurologic concepts of lead poisoning in children. Pediatr Ann 1992;21:384-8. PMID 1620563
67: Gomaa A, Hu H, Bellinger D, et al. Maternal bone lead as an independent risk factor for fetal neurotoxicity: a prospective study. Pediatrics 2002;110(1 pt 1):110-8. PMID 12093955
68: Gonzalez-Cossio T, Peterson KE, Sanin LH, et al. Decrease in birth weight in relation to maternal bone-lead burden. Pediatrics 1997;100(5):856-62. PMID 9346987
69: Goyer RA. Results of lead research: prenatal exposure and neurological consequences. Environ Health Perspect 1996;104:1050-4. PMID 8930545
70: Green M. Bright futures: guidelines for health supervision of infants, children, and adolescents. Arlington, VA: National Center for Education in Maternal and Child Health, 1994.
71: Gulson BL, Jameson CW, Mahaffey KR, Mizon KJ, Korsch MJ, Vimpani G. Pregnancy increases mobilization of lead from maternal skeleton. J Lab Clin Med 1997;130(1):51-62. PMID 9242366
72: Gulson BL, Mizon KJ, Korsch MJ, Palmer JM, Donnelly JB. Mobilization of lead from human bone tissue during pregnancy and lactation--a summary of long-term research. Sci Total Environ 2003;303(1-2):79-104. PMID 12568766
73: Haley VB, Talbot TO. Seasonality and trend in blood lead levels of New York State children. BMC Pediatr 2004;4:8. PMID 15180903
74: Hamidinia SA, Erdahi WL, Chapman CJ, Steinbaugh GE, Taylor RW, Pfeiffer DR. Monensin improves the effectiveness of meso-dimercaptosuccinate when used to treat lead intoxication in rats. Environ Health Perspect 2006;114(4):484-93. PMID 16581534
75: Hammond PB, Dietrich KN. Lead exposure in early life: health consequences. Rev Environ Contam Toxicol 1990;115:91-124. PMID 2189166
76: Hauptman M, Rogers ML, Scarpaci M, Morin B, Vivier PM. Neighborhood disparities and the burden of lead poisoning. Pediatr Res 2023;94(2):826-36. PMID 36899126
77: Havens D, Pham MH, Karr CJ, Daniell WE. Blood lead levels and risk factors for lead exposure in a pediatric population in Ho Chi Minh City, Vietnam. Int J Environ Res Public Health 2018;15(1):93. PMID 29316694
78: Heard MJ, Chamberlain AC. Effect of minerals and food on uptake of lead from the gastrointestinal tract in humans. Hum Toxicol 1982;1(4):411-5. PMID 7173926
79: Helmich F, Lock G. Burton's line from chronic lead intoxication. N Engl J Med 2018;379(19):e35. PMID 30403939
80: Hernández-Avila M, Gonzalez-Cossío T, Hernández-Avila JE, et al. Dietary calcium supplements to lower blood lead levels in lactating women: a randomized placebo-controlled trial. Epidemiology 2003;14(2):206-12. PMID 12606887
81: Hernández-Avila M, Sanin LH, Romieu I, et al. Higher milk intake during pregnancy is associated with lower maternal and umbilical cord lead levels in postpartum women. Environ Res 1997;74(2):116-121. PMID 9339224
82: Hernandez-Ochoa I, Garcia-Vargas G, Lopez-Carrillo L. Low lead environmental exposure alters semen quality and sperm chromatin condensation in northern Mexico. Reprod Toxicol 2005;20(2):221-8. PMID 15907657
83: Heydari A, Norouzzadeh A, Khoshbaten A, et al. Effects of short-term and subchronic lead poisoning on nitric oxide metabolites and vascular responsiveness in rat. Toxicol Lett 2006;166(1):88-94. PMID 16860498
84: Holtzman D, Olson JE, DeVries C, Bensch K. Lead toxicity in primary cultured cerebral astrocytes and cerebellar granular neurons. Toxicol Appl Pharmacol 1987;89:211-25. PMID 3603558
85: Hoppin JA, Aro A, Hu H, Ryan PB. In vivo bone lead measurement in suburban teenagers. Pediatrics 1997;100(3 Pt 1):365-70. PMID 9282707
86: Hornung RW, Lanphear BP, Dietrich KN. Age of greatest susceptibility to childhood lead exposure: a new statistical approach. Environ Health Perspect 2009;117(8):1309-12. PMID 19672413
87: Hu H. Bone lead as a new biologic marker of lead dose: recent findings and implications for public health. Environ Health Perspect 1998;106(Suppl 4):961-7. PMID 9703479
88: Huel G, Tubert P, Frery N, Moreau T, Dreyfus J. Joint effect of gestational age and maternal lead exposure on psychomotor development of the child at six years. Neurotoxicology 1992;13:249-54. PMID 1508426
89: Huynh BQ, Chin ET, Kiang MV. Estimated childhood lead exposure from drinking water in Chicago. JAMA Pediatr 2024;178(5):473-9. PMID 38497944
90: Institute of Medicine. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D and fluoride. Washington, DC: National Academy Press, 1997.
91: Jacobs DE, Brown MJ. Childhood lead poisoning 1970-2022: charting progress and needed reforms. J Public Health Manag Pract 2023;29(2):230-40. PMID 36442070
92: James SJ, Melnyk S, Pogribna M, Pogribny IP, Caudill MA. Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology. J Nutr 2002;132(8 suppl):2361S–6S. PMID 12163693
93: Jirtle RL, Skinner MK. Environmental epigenomics and disease susceptibility. Nat Rev Genet 2007;8(4):253-62. PMID 17363974
94: Johnston MV, Goldstein GW. Selective vulnerability of the developing brain to lead. Curr Opin Neurol 1998;11:689-93. PMID 9870138
95: Jouhadi Z, Bensabbahia D, Chafiq F, et al. Lead poisoning in children: a case report. Pan Afr Med J 2016;24:316. PMID 28154671
96: Kemp FW, Neti PV, Howell RW, Wenger P, Louria DB, Bogden JD. Elevated blood lead concentrations and vitamin D deficiency in winter and summer in young urban children. Environ Health Perspect 2007;115(4):630-5. PMID 17450235
97: Kim Y, Ha EH, Park H, et al. Prenatal lead and cadmium co-exposure and infant neurodevelopment at 6 months of age: The Mothers and Children's Environmental Health (MOCEH) study. Neurotoxicology 2013;35:15-22. PMID 23220728
98: Kimbrough R, LeVois M, Webb D. Management of children with slightly elevated blood lead levels. Pediatrics 1994;93:188-91. PMID 8121729
99: Laidlaw MA, Filippelli GM, Sadler RC, Gonzales CR, Ball AS, Mielke HW. Children's blood lead seasonality in Flint, Michigan (USA), and soil-sourced lead hazard risks. Int J Environ Res Public Health 2016;13(4):358. PMID 27023578
100: Lang CJ. The use of neuroimaging techniques for clinical detection of neurotoxicity: a review. Neurotoxicology 2000;21:847-56. PMID 11130290
101: Lee J, Hu M. Effect of environmental and socioeconomic factors on increased early childhood blood lead levels: a case study in Chicago. Int J Environ Res Public Health 2024;21(4):383. PMID 38673296
102: Lewis M, Worobey J, Ramsay DS, McCormack MK. Prenatal exposure to heavy metals: effect on childhood cognitive skills and health status. Pediatrics 1992;89:1010-5. PMID 1594339
103: Lidsky TI, Schneider JS. Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain 2003;126(Pt 1):5-19. PMID 12477693
104: Liu J, Liu X, Wang W, et al. Blood lead concentrations and children’s behavioral and emotional problems: a cohort study. JAMA Pediatr 2014;168(8):737-45. PMID 25090293
105: Loghman-Adham M. Aminoaciduria and glycosuria following severe childhood lead poisoning. Pediatr Nephrol 1998;12(3):218-21. PMID 9630041
106: Losier BJ, McGrath PJ, Klein RM. Error patterns on the continuous performance test in non-medicated and medicated sample of children with and without ADHD: a meta-analytic review. J Child Psychol Psychiatry 1996;37:971-87. PMID 9119944
107: Lozoff B, Jimenez E, Wolf A, et al. Higher infant blood lead levels with longer duration of breastfeeding. J Pediatr 2009;155(5):663-7. PMID 19595371
108: Lucchini R, Albini E, Cortesi I, et al. Assessment of neurobehavioral performance as a function of current and cumulative occupational lead exposure. Neurotoxicology 2000;21:805-12. PMID 11130286
109: Luo M, Xu Y, Cai R, et al. Epigenetic histone modification regulates developmental lead exposure induced hyperactivity in rats. Toxicol Lett 2014;225(1):78-85. PMID 24291742
110: Manton WI, Angle CR, Stanek KL, Kuntzelman D, Reese YR, Kuehnemann TJ. Release of lead from bone in pregnancy and lactation. Environ Res 2003;92(2):139-51. PMID 12854694
111: Marino PE, Landrigan PJ, Graef J, et al. A case report of lead paint poisoning during renovation of a Victorian farmhouse. Am J Public Health 1990;80:1183-5. PMID 2119148
112: Markovac J, Goldstein GW. Picomolar concentrations of lead stimulate brain protein kinase C. Nature 1988;334:71-3. PMID 3386747
113: Markowitz ME, Rosen JF. Need for the lead mobilization test in children with lead poisoning. J Pediatr 1991;119(2):305-10. PMID 1907320
114: Mayfield SA. Language and speech behaviors of children with undue lead absorption: a review of the literature. J Speech Hear Res 1983;26:362-8. PMID 6645459
115: McElvaine MD, DeUngria EG, Matte TD, Copley CG, Binder S. Prevalence of radiographic evidence of paint chip ingestion among children with moderate to severe lead poisoning, St Louis, Missouri, 1989 through 1990. Pediatrics 1992;89:740-2. PMID 1557271
116: McMichael AJ, Baghurst PA, Wigg NR, Vimpani GV, Robertson EF, Roberts RJ. Port Pirie cohort study: environmental exposure to lead and children's abilities at the age of four years. N Engl J Med 1988;319:468-75. PMID 3405253
117: Minder B, Das-Smaal EA, Brand EF, Orlebeke JF. Exposure to lead and specific attentional problems in schoolchildren. J Learn Disabil 1994;27:393-9. PMID 7519655
118: Mirsky A, Anthony B, Duncan C, Ahearn M, Kellam S. Analysis of the elements of attention: a neuropsychological approach. Neuropsychol Rev 1991;2:109-46. PMID 1844706
119: Morgan RE, Garavan H, Smith EG, Driscoll LL, Levitsky DA, Strupp BJ. Early lead exposure produces lasting changes in sustained attention, response initiation, and reactivity to errors. Neurotoxicol Teratol 2001;23(6):519-31. PMID 11792522
120: National Research Council. Introduction. In: Measuring lead exposure in infants, children, and other sensitive populations. Washington DC: National Academy Press, 1993:24.
121: Needleman HL, Gunnow C, Leviton A, et al. Deficits in psychologic and classroom performance of children with elevated dentine lead levels. N Engl J Med 1979;300:689-95. PMID 763299
122: Needleman HL, Schell A, Bellinger D, Leviton A, Alred EN. The long-term effects of exposure to low doses of lead in childhood. N Engl J Med 1990;322:83-8. PMID 2294437
123: Nigg JT, Casey BJ. An integrative theory of attention-deficit/hyperactivity disorder based on the cognitive and affective neurosciences. Dev Psychopathol 2005;17:785-806. PMID 16262992
124: Nigg JT, Knottnerus GM, Martel MM, et al. Low blood lead levels associated with clinically diagnosed attention-deficit/hyperactivity disorder and mediated by weak cognitive control. Biol Psychiatry 2008;63(3):325. PMID 17868654
125: Nigg JT, Nikolas M, Knottnerus GM, Cavanagh K, Friderici K. Confirmation and extension of association of blood lead with attention-deficit/hyperactivity disorder (ADHD) and ADHD symptom domains at population-typical exposure levels. J Child Psychol Psychiatry 2010;51(1):58-65. PMID 19941632
126: Norman EH, Bordley WC. Lead toxicity intervention in children. J R Soc Med 1995;88:121-4. PMID 7752152
127: Norman E, Bordley W, Hertz-Picciotto I, Newton D. Rural-urban blood lead differences in North Carolina children. Pediatrics 1994;94:59-64. PMID 8008539
128: Oleko A, Pecheux M, Saoudi A, et al. Estimation of blood lead levels in the French population using two complementary approaches: Esteban (2014-2016) as part of the human biomonitoring program and the national surveillance system for childhood lead poisoning (2015-2018). Environ Res 2022;213:113630. PMID 35679905
129: Pearce JM. Burton's line in lead poisoning. Eur Neurol 2007;57(2):118-9. PMID 17179719
130: Pilsner JR, Hu H, Ettinger A, et al. Influence of prenatal lead exposure on genomic methylation of cord blood DNA. Environ Health Perspect 2009;117(9):1466-71. PMID 19750115
131: Piomelli S, Rosen JF, Chisolm JJ, Graef JW. Management of childhood lead poisoning. J Pediatr 1984;105:523-32. PMID 6481529
132: Pirkle JL, Brody DJ, Gunter EW, et al. The decline in blood lead levels in the United States. JAMA 1994;272:284-91. PMID 8028141
133: Prentice A. Calcium in pregnancy and lactation. Annu Rev Nutr 2000;20:249-72. PMID 10940334
134: Raymond J, Brown MJ. Summary of Notifiable Noninfectious Conditions and Disease Outbreaks: Childhood Blood Lead Levels - United States, 2007-2012. MMWR Morb Mortal Wkly Rep 2015;62(54):76-80. Erratum in: MMWR Morb Mortal Wkly Rep 2015;64(45):1277. PMID 26505220
135: Raymond J, Brown MJ. Blood lead levels in children aged <5 years - United States, 2007-2013. MMWR Morb Mortal Wkly Rep 2016;63(55):66-72. PMID 27736835
136: Raymond J, Brown MJ. Childhood Blood Lead Levels in Children Aged <5 Years - United States, 2009-2014. MMWR Surveill Summ 2017;66(3):1-10. PMID 28103215
137: Raymond J, Wheeler W, Brown MJ. Lead Screening and prevalence of blood lead levels in children aged 1-2 years--Child Blood Lead Surveillance System, United States, 2002-2010 and National Health and Nutrition Examination Survey, United States, 1999-2010. MMWR Surveill Summ 2014;63 Suppl 2:36-42. PMID 25208256
138: Rosner D, Markowitz G, Lanphear B. J. Lockhart Gibson and the discovery of the impact of lead pigments on children's health: a review of a century of knowledge. Public Health Rep 2005;120(3):296-300. PMID 16134571
139: Sagvolden T, Johansen EB, Aase H, Russell VA. A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes. Behav Brain Sci 2005;28:397-419. PMID 16209748
140: Sargent JD. The role of nutrition in the prevention of lead poisoning in children. Pediatr Ann 1994;23:636-42. PMID 7838616
141: Sauk JJ, Somerman MJ. Physiology of bone: mineral compartment proteins as candidates for environmental perturbation by lead. Environ Health Perspect 1991;91:9-16. PMID 2040255
142: Schachner JN, Wodtke GT. Environmental inequality and disparities in school readiness: the role of neurotoxic lead. Child Dev 2023;94(6):e308-27. PMID 37307305
143: Schlenker TL, Fritz CJ, Mark D, et al. Screening for pediatric lead poisoning. JAMA 1994;271:1346-8. PMID 8158820
144: Schnaas L, Rothenberg SJ, Flores MF, et al. Reduced intellectual development in children with prenatal lead exposure. Environ Health Perspect 2006;114(5):791-7. PMID 16675439
145: Schneider JS, Anderson DW, Sonnenahalli H, Vadigepalli R. Sex-based differences in gene expression in hippocampus following postnatal lead exposure. Toxicol Appl Pharmacol 2011;256(2):179-90. PMID 21864555
146: Schneider JS, Kidd S, Anderson DW. Influence of developmental lead exposure on expression of DNA methyltransferases and methyl cytosine-binding proteins in hippocampus. Toxicol Lett 2013;217(1):75-81. PMID 23246732
147: Schonfeld DJ, Cullen MR, Rainey PM, et al. Screening for lead poisoning in an urban pediatric clinic using samples obtained by fingerstick. Pediatrics 1994;94:174-9. PMID 8036069
148: Schwartz J. Low level health effects of lead: growth, developmental, and neurological disturbances. In: Needleman HL, editor. Human lead exposure. Florida: CRC Press, 1992:237-8.
149: Schwartz J, Angle C, Pitcher H. Relationship between childhood blood lead levels and stature. Pediatrics 1986;77:281-8. PMID 3951909
150: Schwartz J, Landrigan PJ, Feldman RG, Silbergeld EK, Baker EL Jr, von Lindern IH. Threshold effect in lead-induced peripheral neuropathy. J Pediatr 1988;112:12-7. PMID 2826742
151: Selevan SG, Rice DC, Hogan KA, Euling SY. Blood lead concentration and delayed puberty in girls. N England J Med 2003;348(16):1527-36. PMID 12700372
152: Shukla R, Dietrich KN, Bornschein RL, Berger O, Hammond PB. Lead exposure and growth in the early preschool child: a follow-up report from the Cincinnati lead study. Pediatrics 1991;88:886-92. PMID 1945627
153: Silva PA, Hughes P, Williams S, Faed JM. Blood lead, intelligence, reading attainment, and behaviour in eleven year old children in Dunedin, New Zealand. J Child Psychol Psychiatry 1988;29:43-52. PMID 3350882
154: Singhal RL, Thomas JA. Lead toxicity. Baltimore-Munich: Urban and Schwarzenberg, 1980.
155: Six KM, Goyer RA. Experimental enhancement of lead toxicity by low dietary calcium. J Lab Clin Med 1970;76(6):933-42. PMID 5485382
156: Skalik IJ, Otto DA, Hudnell K, Bahbouh R, Maleckova L. Neurobehavioral and visual assessment of Prague school children living in district with varying traffic density: gender differences and lead effects. Neurotoxicology 2000;21:903-4.
157: Strömberg U, Lundh T, Skerfving S. Yearly measurements of blood lead in Swedish children since 1978: the declining trend continues in the petrol-lead-free period 1995–2007. Environ Res 2008;107:332-5. PMID 18466895
158: Suwalsky M, Villena F, Norris B, Cuevas YF, Sotomayor CP, Zatta P. Effects of lead on the human erythrocyte membrane and molecular models. J Inorg Biochem 2003;97(3):308-13. PMID 14511893
159: Tang HW, Huel G, Campagna D, Hellier G, Boissinot, Blot P. Neurodevelopmental evaluation of 9-month-old infants exposed to low levels of lead in utero: involvement of monoamine neurotransmitters. J Appl Toxicol 1999;19:167-72. PMID 10362267
160: Téllez-Rojo MM, Hernández-Avila M, Gonzalez-Cossio T, et al. Impact of breastfeeding on the mobilization of lead from bone. Am J Epidemiol 2002;155(5):420-8. PMID 11867353
161: Téllez-Rojo MM, Hernández-Avila M, Lamadrid-Figueroa H, et al. Impact of bone lead and bone resorption on plasma and whole blood lead levels during pregnancy. Am J Epidemiol 2004;160(7):668-78. PMID 15383411
162: Téllez-Rojo MM, Bellinger DC, Arroyo-Quiroz C, et al. Longitudinal associations between blood lead concentrations lower than 10 microg/dL and neurobehavioral development in environmentally exposed children in Mexico City. Pediatrics 2006;118(2):e323-30. PMID 16882776
163: Teo JG, Goh KH, Ahujy A, Hg HK, Poon WS. Intracranial vascular calcifications, glioblastoma multiforme, and lead poisoning. Am J Neuroradiol 1997;18:576-9. PMID 9090426
164: Thomas HM, Blackfan KD. Recurrent meningitis, due to lead, in a child of five years. Am J Dis Child 1914;8:377-80.
165: Thomson GO, Raab GM, Hepburn WS, Hunter R, Fulton M, Laxen DP. Blood-lead levels and children’s behavior results from the Edinburg Lead Study. J Child Psychol Psychiatry 1989;30:515-28. PMID 2768355
166: Tiffany-Castiglioni E, Sierra EM, Wu J, Rowles TK. Lead toxicity in neuroglia. Neurotoxicology 1989;10:417-44. PMID 2696897
167: Trope I, Lopez-Villegas D, Lenkinski RE. Magnetic resonance imaging and spectroscopy of regional brain structure in a 10-year-old boy with elevated blood lead levels. Pediatrics 1998;101:E7. PMID 9606249
168: Turner AJ. A form of cerebral disease characterized by definite symptoms, probably a localized basal meningitis. Transcript of the Intercolonial Medical Congress of Australasia 1892:98-100.
169: Turner AJ. Lead poisoning among Queensland children. Australasian Medical Gazette 1897;16:475-9.
170: Tuthill RW. Hair lead levels related to children's classroom attention-deficit behavior. Arch Environ Health 1996;51:214-20. PMID 8687242
171: United Nations Standing Committee on Nutrition. Nutrition information in crisis situations; May 2004. Report no. 2. Available at http://www.unsystem.org. Accessed April 2006.
172: Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC. Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2) Nucleic Acids Res. 2004;32(14):4100-8. PMID 15302911
173: Virgolini MB, Bauter MR, Weston DD, Cory-Slechta DA. Permanent alterations in stress responsivity in female offspring subjected to combined maternal lead exposure and/or stress. Neurotoxicology 2006;27(1):11-21. PMID 16140384
174: Viveiros B, Caron G, Barkley J, et al. Cake decorating luster dust associated with toxic metal poisonings - Rhode Island and Missouri, 2018-2019. MMWR Morb Mortal Wkly Rep 2021;70(43):1501-4. PMID 34710080
175: Wani AL, Ara A, Usmani JA. Lead toxicity: a review. Interdiscip Toxicol 2015;8(2):55-64. PMID 27486361
176: Waterland RA, Jirtle RL. Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 2003;23(15):5293-300. PMID 12861015
177: Weidenhamer JD, Clement ML. Widespread lead contamination of imported low-cost jewelry in the US. Chemosphere 2007;67(5):961-5. PMID 17166553
178: Weitzman M, Aschengrau A, Bellinger D, Jones R, Hamlin JS, Beiser A. Lead-contaminated soil abatement and urban children's blood lead levels. JAMA 1993;269:1647-54. PMID 8455298
179: Wilson AS, Power BE, Molloy PL. DNA hypomethylation and human diseases. Biochim Biophys Acta 2007;1775(1):138-62. PMID 17045745
180: Wilson J, Dixon SL, Wisinski C, et al. Pathways and sources of lead exposure: Michigan Children's Lead Determination (the MI CHILD study). Environ Res 2022;215(Pt 2):114204. PMID 36075478
181: Wilson NJ, Friedman E, Kennedy K, et al. Using exterior housing conditions to predict elevated pediatric blood lead levels. Environ Res 2023;218:114944. PMID 35473524
182: Winneke G, Kraemer U. Neuropsychological effects of lead in children: interactions with social background variables. Neuropsychobiology 1984;11:195-202. PMID 6472605
183: Wright RO, Tsaih SW, Schwartz J, Wright RJ, Hu H. Association between iron deficiency and blood lead level in a longitudinal analysis of children followed in an urban primary care clinic. J Pediatr 2003;142(1):9-14. PMID 12520247
184: Wu J, Basha MR, Brock B, et al. Alzheimer’s disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (Pb): evidence for a developmental origin and environmental link for AD. J Neurosci 2008;28(1):3-9. PMID 18171917
185: Xie Y, Liu J, Benbrahim-Tallaa L, et al. Aberrant DNA methylation and gene expression in livers of newborn mice transplacentally exposed to a hepatocarcinogenic dose of inorganic arsenic. Toxicology 2007;236(1-2):7-15. PMID 17451858
186: Yang Y, Li S, Wang H, et al. Chronic lead poisoning induced abdominal pain and anemia: a case report and review of the literature. BMC Gastroenterol 2020;20(1):335. PMID 33054779
187: Yi P, Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ. Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem 2000;275(38):29318-23. PMID 10884384
188: Yiin LM, Rhoads GG, Lioy PJ. Seasonal influences on childhood lead exposure. Environ Health Perspect 2000;108(2):177-82. PMID 10656860
189: Ying XL, Markowitz M, Yan CH. Folk prescription for treating rhinitis as a rare cause of childhood lead poisoning: a case series. BMC Pediatr 2018;18(1):219. PMID 29980188
190: Yu Z, Luo H, Fu W, Mattson M. The endoplasmic reticulum stress-responsive protein GRP78 protects against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis. Exp Neurol 1999;155:303-14. PMID 10072306
191: Yule Q, Lansdown R, Millar I, Urbanowicz M. The relationship between blood lead concentrations, intelligence and attainment in a school population: a pilot study. Dev Med Child Neurol 1981;23:567-76. PMID 7286450
192: Zhang F, Liu Y, Zhang H, et al. Investigation and evaluation of children's blood lead levels around a lead battery factory and influencing factors. Int J Environ Res Public Health 2016;13(6):541. PMID 27240393

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Douglas J Lanska MD MS MSPH

Dr. Lanska of the University of Wisconsin School of Medicine and Public Health and the Medical College of Wisconsin has no relevant financial relationships to disclose.
See Profile

Former Authors

Cecilia Davoli MD
David A Griesemer MD
Anantha Harijith MD
Michael Vincent S Mendoza MD
Kathleen M Bonifacio MD
Bhagwan Moorjani MD
Jose Porras BS
Brandon Root MD
Robert J Singer MD
Bernard L Maria MD

Patient Profile

Age range of presentation: 0 month to 18 years
Sex preponderance: male=female
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: Abatement/demolition/renovation workers

Automobile factory workers

Automobile repair workers

Battery production workers

Bridge construction workers

Bridge painters

Cable production workers

Ceramic pottery production workers

Lead paint manufacturing workers

Lead smelters

Metal manufacture workers

Printers

Ship construction workers

Ship painters

Stained/leaded glass workers

Typesetters

ICD & OMIM codes

ICD-10: Lead poisoning: T56.0
ICD-11: Harmful effects of or exposure to noxious substances, chiefly nonmedicinal as to source, not elsewhere classified: NE61

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Lead poisoning in childhood

Associated Disorders

Attention deficit hyperactivity disorder
Communication disorder
Developmental delay
Hyperactivity
Iron deficiency
- Iron deficiency anemia
- Language disorder
- Learning disabilities
- Mental retardation
- Pica

Differential Diagnosis

developmental delay
learning disabilities
visual-motor incoordination
auditory deficits
autism
- language disorders
- speech problems
- mental retardation
- encephalopathy
- seizures
- coma
- bacterial meningitis
- viral encephalitis
- obstructive hydrocephalus
- pseudotumor cerebri
- ischemic stroke
- hemorrhagic stroke
- brain tumors
- status epilepticus
- nonaccidental trauma
- closed head injuries
- colicky pain
- anorexia
- constipation
- failure-to-thrive

Also Relevant

British anti-Lewisite
Chelation therapy
Chemical and drug poisoning in children
Lead neuropathy
Metal neurotoxicity
- Toxic peripheral neuropathies

Lead poisoning in childhood

Lead poisoning in childhood

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Special considerations

Pregnancy

Media

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Acute cerebellar ataxia in children

Zika virus: neurologic complications

Cerebral edema in childhood

CNS germinoma

Vein of Galen malformations

Patent foramen ovale

Migraine in childhood

Neonatal opioid withdrawal syndrome

Lead poisoning in childhood

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Special considerations

Pregnancy

Media

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Acute cerebellar ataxia in children

Zika virus: neurologic complications

Cerebral edema in childhood

CNS germinoma

Vein of Galen malformations

Patent foramen ovale

Migraine in childhood

Neonatal opioid withdrawal syndrome

This is an article preview.
Start a Free Account
to access the full version.