Lead poisoning is a potentially devastating condition that threatens about 5 % of American pre-schoolers. When lead-based paint peels and chips off of older walls, it can be inhaled and cause permanent damage to a young child's nervous system. Recurrent exposure to even small amounts of lead may result in lead poisoning since lead can accumulate in the body. Neurobehavioral abnormalities of mild lead poisoning may manifest as lowered IQ scores, decreased attention span, impaired hearing, speech and other developmental delays; however, most children of pre-school age with mild lead poisoning are asymptomatic. The probability of developing encephalopathy, the most serious complication of lead poisoning, increases as the exposure to lead and blood level of lead rises. Encephalopathy may be preceded by abdominal pain, headaches, vomiting, and constipation. The Centers for Disease Control and Prevention defines lead poisoning as a blood lead level of 10 mg/dL. As sustained blood levels rise above 10 to 15 mg/dL, young children under age 6 years are at progressively increasing risk not only for future neurobehavioral and cognitive problems, but also for development of recurrent symptomatic episodes of physical manifestations of lead poisoning.

Screening for elevated lead levels in asymptomatic children at increased risk for lead exposure has been demonstrated to improve clinical outcomes. If capillary blood is used as a screening test, elevated lead levels should be confirmed by measurement of venous blood lead.

The optimal frequency of screening for lead exposure in children, or for repeated testing of children previously found to have elevated blood lead levels, is unknown and is left to clinical discretion.

Kosnett et al (2007) summarized a body of published literature that establishes the potential for hypertension, effects on renal function, cognitive dysfunction, and adverse female reproductive outcome in adults with whole-blood lead concentrations less than 40 microg/dL. Based on this literature, and these researchers' collective experience in evaluating lead-exposed adults, they recommended that individuals be removed from occupational lead exposure if a single blood lead concentration exceeds 30 microg/dL or if 2 successive blood lead concentrations measured over a 4-week interval are greatet than or equal to 20 microg/dL. Removal of individuals from lead exposure should be considered to avoid long-term risk to health if exposure control measures over an extended period do not decrease blood lead concentrations to less than 10 microg/dL or if selected medical conditions exist that would increase the risk of continued exposure. Recommended medical surveillance for all lead-exposed workers should include quarterly blood lead measurements for individuals with blood lead concentrations between 10 and 19 microg/dL, and sem-iannual blood lead measurements when sustained blood lead concentrations are les than 10 microg/dL. It is advisable for pregnant women to avoid occupational or avocational lead exposure that would result in blood lead concentrations greater than 5 microg/dL. Chelation may have an adjunctive role in the medical management of highly exposed adults with symptomatic lead intoxication but is not recommended for asymptomatic individuals with low blood lead concentrations.

The United States Occupational Safety and Health Administration (OSHA) mandates lead testing for individuals who have workplace lead exposures. According to OSHA (1995), the blood lead level of all employees who are exposed to inorganic lead above 30 ug/m(3) for more than 30 days per year is to be determined at least every 6 months. The frequency is increased to every 2 months for employees whose last blood lead level was between 40 ug/100 g whole blood. For employees who are removed from exposure to lead due to an elevated blood lead, a new blood lead level must be measured monthly.

There is insufficient evidence to recommend for or against routine screening for lead exposure in asymptomatic pregnant women.

An UpToDate review on "Adult lead poisoning" (Goldman and Hu, 2015) states that "Laboratory testing – The key clinical monitoring test for diagnosing lead toxicity is the blood lead level [BLL]. Measuring lead in urine, hair, or other media is not as accurate or reliable. The blood lead level is a good indicator of exposure that has occurred within the previous few weeks. In interpreting the results, it is important to use levels appropriate to adult toxicity, rather than children's (which sometimes are the ranges of concern reported by the testing laboratories)".

An UpToDate review on "Childhood lead poisoning: Clinical manifestations and diagnosis" (Hurwitz and Lee, 2015) states that "Bone and dentine lead levels, measured by K x-ray fluorescence spectroscopy or atomic absorption spectroscopy, respectively, are better indicators of the child's total lead burden than BLLs. However, these tests are not routinely available, and are not recommended by the Centers for Disease Control and Prevention (CDC). BLLs remain the gold standard for the diagnosis of lead poisoning in children".

Per the American College of Obstetricians and Gynecologists (ACOG, 2012), routine blood lead testing of all pregnant women is not recommended; however, risk assessment of lead exposure should take place at the earliest contact with pregnant or lactating women. If a single risk factor is identified (see Table in Appendix), blood lead testing should be performed.

Screening for Elevated Blood Lead Levels in Children and Pregnant Women

Curry and colleagues (2019) updated the 2006 USPSTF recommendation on screening for elevated blood lead levels in children and pregnant women. The USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of elevated blood lead levels. In this update, an elevated blood lead level was defined according to the CDC reference level of 5 μg/dL. The USPSTF found adequate evidence that questionnaires and other clinical prediction tools to identify asymptomatic children with elevated blood lead levels were inaccurate. The USPSTF found adequate evidence that capillary blood testing accurately identified children with elevated blood lead levels. The USPSTF found inadequate evidence on the effectiveness of treatment of elevated blood lead levels in asymptomatic children 5 years and younger and in pregnant women. The USPSTF found inadequate evidence regarding the accuracy of questionnaires and other clinical prediction tools to identify asymptomatic pregnant women with elevated blood lead levels. The USPSTF found inadequate evidence on the harms of screening for or treatment of elevated blood lead levels in asymptomatic children and pregnant women. The USPSTF concluded that the current evidence is insufficient, and that the balance of benefits and harms of screening for elevated blood lead levels in asymptomatic children 5 years and younger and in pregnant women cannot be determined. The USPSTF concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for elevated blood lead levels in asymptomatic children (I statement). The USPSTF concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening for elevated blood lead levels in asymptomatic pregnant persons (I statement).

Analysis of Lead in the Hair of Children With Autism Spectrum Disorder

Wang and associates (2019) noted that inorganic arsenic (iAs) and Pb rank first and second on the U.S. Environmental Protection Agency (EPA)'s priority list of hazardous substances. Both are known neurotoxic metals that cause detrimental effects on brain development and lead to deficits in cognitive function and behavioral performance in children. Studies have indicated a potential link between iAs and Pb exposure and a higher risk for autism spectrum disorders (ASD). To provide further insight into whether developmental exposure to iAs or Pb is associated with ASD, these investigators carried out a systematic review and combined data into a meta-analysis to examine the available human evidence on the relationships. They reviewed relevant studies published through December 30, 2018 and identified 14 studies on iAs and 37 studies on Pb exposure and their respective associations with ASD. Among them, 8 (53.3 %) and 19 (51.3 %) studies reported a positive association for iAs and Pb, respectively, and none reported a sole inverse association. In the following meta-analysis, these researchers found statistically significant higher iAs concentrations, in hair and in blood, for children diagnosed with ASD compared with controls across studies. However, the findings on Pb exposure were inconsistent, with a significant association for hair Pb, no association for urinary Pb, and an inverse association for blood Pb. After considering strengths and limitations of the body of research, the authors concluded that there is consistent evidence supporting a positive association between early life iAs exposure and diagnosis of ASD and inconsistent evidence for Pb exposure and ASD risk. They believed it is in the best interest of policy makers and the public to reduce exposures to iAs and Pb among pregnant women and children. These investigators stated that their research supported the need for large, perspective human studies with accurate measurement and determination of the long-term body burden of iAs and Pb exposures to examine the impact of iAs and Pb exposures on ASD risk.

Fiłon and colleagues (2020) stated that explanation of the pathogenesis and treatment of ASD is one of the most significant challenges for scientists today. It is believed that a major pathogenetic factor of this condition is epigenetic changes caused by environmental factors, including toxic metals (e.g., aluminum [Al], arsenic [As]cadmium [Cd], lead [Pb], and mercury [Hg]). The nervous system may also be affected by deficiencies of both micro- and macro-elements (e.g., calcium [Ca], and zinc [Zn]). These researchers analyzed the concentrations of As, Ca, and Pb in the hair of children with ASD and a control group. The materials for the study comprised hair samples collected from 30 children diagnosed with ASD (case group) and 30 children randomly selected from the general population of Bialystok and surrounding region (control group). Concentrations of As, Ca, and Pb were tested with electron microscopy scanning method. Next, the content of the analyzed elements in the hair was assessed as well as their impact on autism development in the children and the mutual interactions between them. The obtained results were statistically analyzed with Statistica PL 12.5., using the Mann-Whitney U test, and Spearman correlation coefficient. Mean Ca level in the hair of the case group was lower than the mean level of this element in the control group. Mean As and Pb concentration in the hair of children with ASD was statistically significantly higher than the mean concentration of this element in the hair of children without neurological disorders. Statistically insignificant weak positive correlations between Ca and As content and negative between Ca and Pb in the hair of children from the case group were noted. Furthermore, statistically significant mean positive correlations between Pb and As were observed. The authors concluded that in this small study, according to the observations, children diagnosed with ASD suffered from Ca deficiency and toxic metal over-load (As and Pb). These abnormalities may play the main role, as an environmental factor, in the pathogenesis of the analyzed disorder. Moreover, these researchers stated that further research is needed to ascertain the relationships between ASD and heavy metals exposure.

The authors stated that this study had several drawbacks. The main drawback of this trial was the small number of cases and the strong regional focus of this study. Samples were taken only from 1 mid-size city in Poland in a region with rather low pollution levels. The narrow group of only 30 cases of diagnosed children was also too population-specific and probably was not representative of neurodevelopmental disorders in the whole country. The limited number of cases also did not provide adequate statistical confidence. However, this study was the first (of its kind) in Poland and hopefully could be the basis for future studies that will have greater (country) range and contribute to the global picture of ASD. Second, there was a very limited number of studies in Europe on the subject of metal concentration in the hair of children with ASD. In the case of research into relationships between metals content in the hair and neurodevelopment disorders, tests should be performed within larger social groups (preferably international) to avoid falsifying the results through any local influence. Third, the study did not plan to collect other data on the study subjects. The influence of socio-demographic and environmental factors (e.g., diet, environmental contamination, medical history, and metabolic abnormalities) on the content of these metals in the hair was also not taken into account. The research results lacked information regarding the exposure of mothers before pregnancy and during pregnancy as well as infants / children at a very early age. Fourth, cosmetic procedures had a significant impact on the content of elements determined in the hair. In this research, these investigators did not include the types of cosmetics (e.g., shampoos) used by the children. These researchers only assumed that the examined group consisted of rather small children so they probably used only basic hygiene products, which was not necessarily true. Thus, future studies should consider the relationship between children’s cosmetics and contamination in hair. Finally, there were no generally applicable standards for the content of trace elements in the hair of any people (healthy or with any diseases).

Appendix

Table: Risk Factors for Lead Exposure in Pregnant and Lactating Women Risk Factors for Lead Exposure in Pregnant and Lactating Women Recent emigration from or residency in areas where ambient lead contamination is high—women from countries where leaded gasoline is still being used (or was recently phased out) or where industrial emissions are not well controlled. Living near a point source of lead—examples include lead mines, smelters, or battery recycling plants (even if the establishment is closed). Working with lead or living with someone who does—women who work in or who have family members who work in an industry that uses lead (e.g., lead production, battery manufacturing, paint manufacturing, ship building, ammunition production, or plastic manufacturing). Using lead-glazed ceramic pottery—women who cook, store, or serve food in lead-glazed ceramic pottery made in a traditional process and usually imported by individuals outside the normal commercial channels. Eating nonfood substances (pica)—women who eat or mouth nonfood items that may be contaminated with lead, such as soil or lead-glazed ceramic pottery. Using alternative or complementary substances, herbs, or therapies—women who use imported home remedies or certain therapeutic herbs traditionally used by East Indian, Indian, Middle Eastern, West Asian, and Hispanic cultures that may be contaminated with lead. Using imported cosmetics or certain food products—women who use imported cosmetics, such as kohl or surma or certain imported foods or spices that may be contaminated with lead. Engaging in certain high-risk hobbies or recreational activities—women who engage in high-risk activities (e.g., stained glass production or pottery making with certain leaded glazes and paints) or have family members who do. Renovating or remodeling older homes without lead hazard controls in place—women who have been disturbing lead paint, creating lead dust, or both or have been spending time in such a home environment. Consumption of lead-contaminated drinking water—women whose homes have leaded pipes or source lines with lead. Having a history of previous lead exposure or evidence of elevated body burden of lead—women who may have high body burdens of lead from past exposure, particularly those who have deficiencies in certain key nutrients (calcium or iron). Living with someone identified with an elevated lead level—women who may have exposure in common with a child, close friend, or other relative living in the same environment.

Source: The American College of Obstetricians and Gynecologists (ACOG, 2012).

Scope of Policy

This Clinical Policy Bulletin addresses lead testing.

Medical Necessity

Aetna considers the following interventions medically necessary:

Blood lead testing (measurement of blood lead level)

For diagnosis of persons with signs and symptoms of lead poisoning (e.g., lowered IQ scores, decreased attention span, impaired hearing, speech and other developmental delays, abdominal pain, headaches, vomiting, and constipation);

For pregnant or lactating women who have any of the risk factors for lead exposure listed in the Appendix table.

Note:

Routine blood lead testing for average-risk pregnant women without risk factors is not considered medically necessary.

Lead screening

For persons with occupational lead exposures. Footnote * Footnotes for persons with occupational lead exposures.* The United States Occupational Safety and Health Administration (OSHA) mandates lead testing for individuals who have workplace lead exposures. Footnote1 *Note:

Some plans exclude coverage of medical services required for work. Please check benefit plan descriptions for details.

As a preventive health care service for children according to guidelines from the Centers for Disease Control and Prevention (CDC), the U.S. Preventive Services Task Force (USPSTF), the American Academy of Pediatrics (AAP), and the American Academy of Neurology (AAN).

Note:

Some Aetna plans exclude coverage of preventive services. Please check benefit plan descriptions.

The CDC, the USPSTF, the AAP, and the AAN recommend lead screening of preschool-age children in the following high-risk groups:

Are developmentally delayed;

or

Are exposed to contaminated dust or soil;

or

Are victims of abuse or neglect;

or

Have abnormal oral behaviors (e.g., pica) which place them at risk;

or

Have close contact with a person who has or had an elevated lead level;

or

Have emigrated (or have been adopted) from countries where lead poisoning is prevalent;

or

Have iron deficiency;

or

Have unexplained illness (e.g., abdominal pain, lethargy, seizures and severe anemia);

or

Live in communities in which the prevalence of lead levels requiring individual intervention, including residential lead hazard control or chelation, is high or undefined;

or

Live in or frequently visit a home or child care facility built before 1950;

or

Live in or regularly visit a home or child care facility built before 1978 that is being or has recently been renovated or remodeled;

or

Live near lead industry or heavy traffic;

or

Live with someone whose job or hobby involves lead exposures;

or

Take traditional ethnic remedies that contain lead;

or

Use lead-based pottery.

Experimental and Investigational

Aetna considers measurement of lead in bone, hair, teeth, or urine experimental and investigational because the effectiveness of these approaches has not been established.

Policy Limitations and Exclusions

Note on Retesting Persons Previously Tested with Magellan Diagnostics LeadCare Analyzer:

The U.S. Food and Drug Administration (FDA) has recalled the Magellan Diagostics LeadCare Lead Test Analyzer. The Centers for Disease Control and Prevension (CDC) recommends that healthcare providers re-test persons who:

1. Are younger than 6 years (72 months) of age at the time of the alert (May 17, 2017);

and

2. Had a venous blood lead test result of less than 10 micrograms per deciliter (μg/dL) analyzed using a Magellan Diagnostics LeadCare analyzer at an onsite (e.g., healthcare facility) or at an offsite laboratory.

The CDC also recommends that healthcare providers re-test currently pregnant or lactating women whose previous test was with the Magellan Diagnostics LeadCare Analyzer.