Lead is a known neurotoxin, able to produce metabolic and infrastructural perturbations at the molecular and cellular levels of the developing nervous system.¹⁵ Children are much more susceptible to the adverse neurodevelopmental effects of lead than are adults, due to the vulnerability of their nervous system, the postnatal continuation of nervous system maturation, and the increased permeability of neuronal structures to lead’s entry.¹⁵ Numerous studies have confirmed adverse neurodevelopmental, neurobehavioral, and cognitive effects of prenatal and postnatal lead exposure.^16,17 Prospective longitudinal studies have demonstrated the long-lasting sequelae of lead exposure on intellectual and academic achievement later in childhood even after apparently low-level exposures with BLL less than 10 μg/dL.^18-20 Neurological outcomes include cognitive damage, hearing loss, visual effects, delayed speech acquisition, learning disabilities, lower reading and arithmetic skills, poor attention, deficits of other aspects of executive function, and other educational, behavioral, and emotional problems, which can persist into adolescence and adulthood.^19,21-29

Symptoms of ASD share some similar characteristics to the symptoms of lead neurotoxicity noted above.⁷ For example, DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) criteria for ASD, as detailed by the American Psychiatric Association, includes persistent deficits in social-emotional reciprocity and nonverbal communicative behaviors.³⁰ Significant language delay and coexisting intellectual disability are notable in many children with ASD.³¹ In addition to neurologic and behavioral symptoms, both childhood lead poisoning and ASD are often associated with poor appetite, restricted food choices, and gastrointestinal symptoms, such as constipation or abdominal discomfort.

These similarities may prompt parents and clinicians to wonder whether lead poisoning in a child can cause ASD, and if there might, therefore, be a treatable cause of their child’s ASD. However, current scientific evidence does not support this hypothesis. Instead, any association of ASD and lead poisoning is more likely secondary to pica habits, the compulsive chewing and eating of nonfood items, seen commonly in children with ASD. This behavior puts them at high risk for exposure to lead-containing dust and other lead-contaminated objects. The association between such pica behaviors and a higher risk of lead poisoning was described as early as 1976 by Cohen et al.⁵ Another study confirmed that children with ASD are more likely to be re-exposed to sources of lead contamination than children without ASD.⁶ Unfortunately, the normal hand-mouth behaviors and oral exploratory habits of infancy, which usually extinguish within the preschool years, can persist in children with ASD well into later childhood and beyond such that their risk for lead contamination continues. While these pica behaviors continue, these children also continue to grow taller and stronger, allowing them access to new surfaces and areas of households that may contain lead hazards not previously accessible to them at a younger age. A study that investigated epidemiologic characteristics of severe lead poisoning in New York City found a trend toward severe lead poisoning occurring at older ages in children with ASD compared with the cases without ASD (5.99 years vs 3.69 years, respectively).³²

Despite some overlapping symptoms, there is no convincing evidence that childhood lead poisoning causes ASD; however, rare cases of misdiagnosis can occur. For example, a case was reported in which a child misdiagnosed with severe autism was found, instead, to suffer from chronic lead poisoning. His hearing improved, with accompanying advancement in neurodevelopmental status (receptive and expressive language), after his very severe lead poisoning was treated successfully with chelation.⁵ The risk of lead poisoning in genetic disorders similar to autism, such as Landau-Kleffner syndrome, has also been reported.³³

Lead poisoning may manifest in a number of different ways in a child with ASD. Although potentially asymptomatic, a child may also become more irritable secondary to abdominal colic from lead. While becoming quiet and more withdrawn may seem like an improvement in the behavior of a child with autism and attention-deficit/hyperactivity disorder, this may actually be the unrecognized beginning of lead-induced encephalopathy, a medical emergency.³⁴ Clinicians should maintain a high level of suspicion for lead poisoning in children with ASD when such symptoms arise.

Pica behaviors predispose children with ASD to unrecognized foreign body ingestion, which poses an additional risk if the foreign body contains lead-leaching materials. Pica also predisposes children to ingestion of other nonfood items that may be contaminated with lead such as dirt, house dust, and paint chips. Because of their restricted diets and related nutritional deficiencies, children with ASD may be iron deficient, a known comorbidity of lead poisoning.³⁵ As evidenced by mouse studies, the presence of iron deficiency may enhance gastrointestinal uptake of lead, predisposing those with lead exposure to elevated blood lead levels.³⁶

Providers should be aware of the recommended universal or targeted lead screening guidelines in their locality and, at a minimum, adhere to these guidelines. Most children with ASD will require enhanced and extended monitoring for lead poisoning. Table 1 offers some recommendations to clinicians regarding screening and diagnosis of lead poisoning in children with ASD.

Some parents take their children to alternative health care providers for assessment of their ASD. These providers may send hair and/or urine for analysis of metals. Hair is a complex medium that is technically difficult to assay with precision. The interpretation of levels of metals found to be elevated in such an analysis has been challenged.³⁷ Hair analyses have been shown to be unreliable when performed in commercial laboratories.^38,39 Children with reports of elevated hair lead levels often have very low BLLs, no evidence of exposure to environmental lead, and no need for medical management. In such cases a venous BLL can be obtained to determine the child’s actual lead burden.

Children with lead poisoning require close medical monitoring with frequent office visits and even occasional emergency department referrals. Table 3 gives recommendations for clinicians in office practice managing children with both ASD and an elevated BLL.

Children with ASD and lead poisoning may need to be hospitalized for a number of reasons. If they have a BLL ≥70 μg/dL and/or have evidence of lead encephalopathy, then hospitalization, often triaged to a critical care unit, is the safest course of management. Admittedly, recognizing lead encephalopathy can be difficult in children with ASD who have baseline behavioral problems, though parents are often able to note any changes in their child’s mental status. Children with lower BLLs, such as those with BLL 45 to 69 μg/dL, may also require hospitalization for chelation if compliance with oral medication-taking is questionable and/or a lead-safe home environment cannot be assured.

Hospitalization can be a very difficult time for both the patient and their family, especially in a child with ASD. Table 4 lists some recommendations for clinicians to consider when hospitalizing a patient with ASD for inpatient management of severe lead poisoning.

Table 5 addresses chelation in children with ASD whose lead poisoning is severe enough to consider use of these medications to lower the body’s burden of lead. Details of specific chelants have been reviewed elsewhere.⁴¹ All of the chelants used to treat lead poisoning can have serious adverse effects, such as bone marrow suppression, nephrotoxicity, chemical hepatitis, allergic rashes, and gastrointestinal disturbances. Administration of iron supplementation or foods with milk, zinc, or iron may decrease the absorption of d-penicillamine.⁴² The clinician contemplating use of such medications should review these potential adverse effects with the parents/guardians in obtaining their consent for treatment.

Treating a child with ASD with a parenteral medication like CaNa₂EDTA requires insertion of an intravenous catheter, which in our experience is likely to be pulled out, interfering with the necessary continuous therapy. Nurses are challenged with protecting the IV’s (intravenous) integrity in a child with ASD so that therapy is not interrupted.

The oral chelant medications used in medical management of moderate-severe lead poisoning are not “kid friendly.” They have sulfur or amines in them causing them to taste bad and smell like rotten eggs. Getting a child with autism to swallow either d-penicillamine or dimercaptosuccinic acid can be a challenge. Disguising the medication by mixing it in a child’s favorite food, such as applesauce or peanut butter, is a strategy successfully employed by many parents. However, children with ASD often have restricted diets. By disguising dimercaptosuccinic acid in their food, there is the risk that they will recognize it and potentially reject one of the few foods contributing to their nutrition. Thus, adherence to the twice or 3-times daily dosing schedule can be particularly difficult.

The use of chelants to treat ASD itself in children who do not have documented lead poisoning is discouraged as a scientifically unfounded practice that may produce untoward consequences or even neurotoxic adverse effects.^43-45 Several iatrogenic deaths due to hypocalcaemia have been reported by the mistaken use by alternative practitioners of Na₂ EDTA instead of CaNa₂ EDTA in the treatment of children with lead poisoning, including children with ASD who had lead poisoning.^46-48

A child with ASD may be taking a regimen of daily medications, such as anticonvulsants, antipsychotics, or serotonin reuptake inhibitors.⁴⁹ The clinician must be cognizant of concomitant adverse effects if supplemental iron or chelation medications must be added to his or her regimen. There may be new side-effects or little studied drug-drug interactions to consider in the treatment of these patients

Some parents take their children to alternative health care providers for assessment of their ASD. Complementary and alternative therapies proposed in patients with ASD range in safety from generally safe to dangerous and range in efficacy from ineffective to effective to unknown efficacy.⁵⁰ When alternative practitioners find the hair or urine lead elevated, such practitioners may recommend chelation or unconventional, scientifically unsupported, costly, and potentially dangerous detoxification regimens.⁵⁰ These children may have very low BLLs and no evidence of exposure to environmental lead and therefore no need for such management strategies.

Some children with ASD may have nutritional deficiencies, such as iron, calcium, magnesium, or vitamin D. Iron-deficiency anemia is a known comorbidity of childhood lead poisoning.⁵¹ Such deficiencies may result in increased lead absorption through the intestinal wall active transport system for metals. Ensuring adequate dietary or supplemental sources of iron, magnesium, calcium, and vitamin D are likely to help protect the child from lead absorption in the gastrointestinal tract.

Some children with elevated blood lead levels may have previously undiagnosed ASD or other developmental delays. Indeed, there has been a recommendation that all children with an elevated BLL receive Early Intervention Program services.⁵² Some children with ASD, recognized or unrecognized, may not be getting ABA special educational services for which they are qualified and deserve.

The lead abatement of a residence often requires days or weeks to accomplish. During the work, for safety, children cannot stay in the house and the family must relocate to a second temporary residence, such as another hazard-free apartment or house, hotel, shelter, or the home of a family member or friend. Such a move interferes with the family’s usual routines and transitions the children to new surroundings, which may have noise-level restrictions and other constraints. Children with autism have difficulty tolerating changes in their routine. They often react negatively with transitions and changes in their caretakers, teachers, or living environments. The abatement of lead hazards in a home can be costly to the parents. This adds an economic burden on a family already laboring under multiple stressors. The necessity of close medical monitoring and/or hospitalization requires that the parent miss considerable days of work and may threaten the parent’s job security, adding to family stress.

Federal policies and lead regulations in many states protect children under the age of 6 years from lead hazards in their environment, requiring hazard abatement if the child is found to have an elevated lead level and lead-contaminated surfaces are discovered at the time of inspection of their residence. These laws were designed with younger children in mind, since they are most vulnerable to the deleterious effects of lead and explore their environment through pica and hand-to-mouth behaviors. However, both pica and oral exploratory habits may not extinguish in preschool years in children with ASD and instead persist throughout childhood and into adolescence. Laws regarding residential lead hazards are not adequately protective for children with ASD and persistent pica behaviors living in a contaminated environment. They may not be afforded the same rights to a lead-free environment as younger children who have been exposed to lead.