Final Research Plan
Elevated Blood Lead Levels in Children and Pregnant Women: Screening
October 13, 2016
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.
The draft Research Plan was available for comment from June 16 until July 13, 2016 at 8:00 p.m., ET.
Screening for Elevated Blood Lead Levels in Childhood
The figure depicts the six Key Questions (KQs) to be addressed in the systematic review. The figure illustrates how screening asymptomatic children age 5 years and younger for elevated blood lead levels may improve health outcomes (KQ 1) and that screening may have associated harms (KQ 3). The figure also depicts the accuracy of using questionnaires or clinical prediction tools to identify children who have elevated blood lead levels (KQ 2a) and the accuracy of capillary blood lead testing (KQ 2b). KQ 4 depicts whether interventions reduce blood lead levels in asymptomatic children with elevated blood lead levels, and KQ 5 depicts whether interventions improve health outcomes. The figure also depicts whether there are harms associated with the interventions (KQ 6).
Screening for Elevated Blood Lead Levels in Pregnancy
The figure depicts the six Key Questions (KQs) to be addressed in the systematic review. The figure illustrates how screening asymptomatic pregnant women for elevated blood lead levels may improve health outcomes (KQ 1a) and that the effectiveness of screening may vary by gestational age (KQ 1b). Screening may also have associated harms (KQ 3). The figure also depicts the accuracy of using questionnaires or clinical prediction tools to identify pregnant women who have elevated blood lead levels (KQ 2). The figure illustrates whether interventions reduce blood lead levels or gestational hypertension (KQ 4) in asymptomatic pregnant women with elevated blood lead levels, and KQ 5 depicts whether interventions improve health outcomes. The figure also depicts whether there are harms associated with the interventions (KQ 6).
Screening for Elevated Blood Lead Levels in Childhood
- Is there direct evidence that screening for elevated blood lead levels in asymptomatic children age 5 years and younger improves health outcomes (i.e., reduced cognitive or behavioral problems or learning disorders)?
- a. What is the accuracy of questionnaires or clinical prediction tools that identify children who have elevated blood lead levels?
b. What is the accuracy of capillary blood lead testing in children? - What are the harms of screening for elevated blood lead levels (with or without screening questionnaires) in children?
- Do counseling and nutritional interventions, residential lead hazard control techniques, or chelation therapy reduce blood lead levels in asymptomatic children with elevated blood lead levels?
- Do counseling and nutritional interventions, residential lead hazard control techniques, or chelation therapy improve health outcomes in asymptomatic children with elevated blood lead levels?
- What are the harms of interventions in asymptomatic children with elevated blood lead levels?
Screening for Elevated Blood Lead Levels in Pregnancy
- a. Is there direct evidence that screening for elevated blood lead levels in asymptomatic pregnant women improves health outcomes (i.e., reduced cognitive problems in offspring, adverse perinatal outcomes, and adverse maternal outcomes)?
b. Does the effectiveness of screening in asymptomatic pregnant women vary by gestational age? - What is the accuracy of questionnaires or clinical prediction tools that identify pregnant women who have elevated blood lead levels?
- What are the harms of screening for elevated blood lead levels (with or without screening questionnaires) in asymptomatic pregnant women?
- Do counseling and nutritional interventions, residential lead hazard control techniques, or chelation therapy reduce blood lead levels and rates of gestational hypertension in asymptomatic pregnant women with elevated blood lead levels?
- Do counseling and nutritional interventions, residential lead hazard control techniques, or chelation therapy improve health outcomes in asymptomatic pregnant women with elevated blood lead levels?
- What are the harms of interventions in asymptomatic pregnant women with elevated blood lead levels?
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
Screening for Elevated Blood Lead Levels in Childhood
- What is the reliability of capillary and venous blood lead testing at various lead levels in children?
- What is the association between reduced blood lead levels and improved health outcomes in asymptomatic children with elevated blood lead levels?*
- Are there valid risk prediction tools available that identify communities at highest risk for lead exposure that could be used in primary care practices to target screening efforts in children?
Screening for Elevated Blood Lead Levels in Pregnancy
- What is the reliability of venous blood lead testing at various lead levels in pregnant women?
- What is the association between reduced blood lead levels and improved health outcomes in asymptomatic pregnant women with elevated blood lead levels?*
- Are there valid risk prediction tools available that identify communities at highest risk for lead exposure that could be used in primary care practices to target screening efforts in pregnant women?
* We will address these questions only if we find evidence from at least one randomized, controlled trial that eligible interventions are effective in reducing blood lead levels (Key Question 4) but no or limited evidence about whether screening or interventions improve eligible health outcomes (Key Questions 1 and 5, respectively).
The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).
Screening for Elevated Blood Lead Levels in Childhood
| Included | Excluded | |
|---|---|---|
| Populations | Asymptomatic children age ≤5 years | All other populationsa |
| Screening tests | KQs 1, 3: Measurement of blood lead level (using capillary or venous blood sampling), with or without screening questionnaires or risk prediction tools KQ 2a: Questionnaires or risk prediction tools that identify children who are more or less likely to have elevated blood lead levels (defined by a minimum threshold of 5 µg/dL) KQ 2b: Measurement of blood lead levels using capillary blood sampling |
All other screening tests, including point-of-care blood lead level assays that are not approved by the U.S. Food and Drug Administration and are not available in the United States |
| Interventions | KQs 4–6: Studies assessing interventions aimed at reducing blood lead levels, including one or more of the following: counseling families to reduce lead exposure, nutritional interventions, residential hazard control techniques, and chelation therapy | Policies, laws, or community-based interventions focused on the primary prevention of lead exposure
|
| Comparisons | KQs 1, 3: Screened vs. nonscreened groups KQ 2a: Measurement of blood lead levels using venous blood sampling KQ 2b: Studies on accuracy of capillary sampling to detect elevated blood lead levels must include a comparison with venous sampling KQs 4–6: Treatment vs. placebo, inactive control, or no treatment |
All other comparisons, including head-to-head comparisons of two different interventions |
| Outcomes | KQs 1, 5: Validated measures of cognitive and neurobehavioral outcomes in children, including assessment of IQ or developmentb KQ 2: Sensitivity, specificity, discrimination, and calibration KQ 3: Anxiety, distress, pain, or discomfort related to venous or capillary blood sampling; false-positive results or blood lead levels <5 µg/dL, leading to repeat testing, unnecessary treatment, or both KQ 4: Blood lead levelsb KQ 6: Anxiety or distress; inconvenience associated with intervention (e.g., school absenteeism associated with followup testing); morbidity attributed to chelation therapy (e.g., renal toxicity, sensitivity reactions) |
All other outcomes, including measures of household lead dust |
| Study designs | KQs 1, 4: RCTs KQ 2a: Observational studies assessing the accuracy of screening questionnaires for predicting elevated blood lead levels KQ 2b: Observational studies assessing the accuracy of capillary sampling to measure blood lead levels KQ 3: RCTs, CCTs, and cohort studies KQ 5: RCTs and CCTs KQ 6: RCTs, CCTs, prospective cohort studies with a concurrent control group, and case-control studies |
Systematic reviewsc, case series, case reports, or comparison with historical controls |
| Quality | Studies rated good or fair quality | Studies rated poor quality |
| Clinical Setting | All KQs: Settings applicable to U.S. primary care settings, including pediatric outpatient clinics, community health clinics, and school-based clinics KQs 4–6: The above plus settings referable from primary care settings |
All other settings, including community health case-finding (e.g., blood lead level monitoring after known environmental exposure) |
| Country Setting | KQs 1–3: Research conducted in the United States or in populations similar to U.S. populations with services and interventions applicable to U.S. practice (i.e., countries with a United Nations Human Development Index of "Very High") KQs 4–6: Any country |
KQs 1–3: Research not relevant to the United States or conducted in countries with a Human Development Index other than "Very High" |
| Language | English language | Languages other than English |
Abbreviations: CCT = controlled clinical trial; RCT = randomized, controlled trial.
a Studies enrolling older children will be eligible if at least 50% of the sample is age ≤5 years or if studies report outcomes separately for children age ≤5 years.
b We will include outcomes measured in family members (e.g., siblings, pregnant women in the same household) who are subsequently identified as having elevated blood lead levels after the index family member was found to have an elevated blood lead level during screening.
c Systematic reviews are excluded from the evidence review. However, we will conduct a separate search to identify relevant systematic reviews published since the last review to ensure that our database searches have captured all relevant studies. We will describe any relevant systematic reviews in the Discussion section of the report.
Screening for Elevated Blood Lead Levels in Pregnancy
| Included | Excluded | |
|---|---|---|
| Populations | All KQs: Asymptomatic pregnant women KQ 2: Asymptomatic pregnant women and asymptomatic nonpregnant adults |
All other populations |
| Screening tests | KQs 1, 3: Measurement of venous blood lead level, with or without screening questionnaires or risk prediction tools KQ 2: Questionnaires or risk prediction tools that identify adults who are more or less likely to have elevated blood lead levels (defined by a minimum threshold of 5 µg/dL) |
All other screening tests, including point-of-care blood lead level assays that are not approved by the U.S. Food and Drug Administration and are not available in the United States |
| Interventions | KQs 4–6: Studies assessing interventions aimed at reducing blood lead levels, including one or more of the following: counseling families to reduce lead exposure, nutritional interventions, residential hazard control techniques, and chelation therapy | Policies, laws, or community-based interventions focused on the primary prevention of lead exposure |
| Comparisons | KQs 1, 3: Screened vs. nonscreened groups KQ 1b: Women screened early vs. later in pregnancy KQ 2: Measurement of blood lead levels using venous sampling KQs 4–6: Treatment vs. placebo, inactive control, or no treatment |
All other comparisons, including head-to-head comparisons of two different interventions |
| Outcomes | KQs 1, 5: Validated measures of cognitive and neurobehavioral outcomes in offspring, including assessment of IQ or developmenta; rates of adverse perinatal outcomes (e.g., premature birth, low birth weight); rates of adverse maternal outcomes (e.g., chronic kidney disease, cognitive decline, mortality) KQ 2: Sensitivity, specificity, discrimination, and calibration KQ 3: Anxiety or distress; false-positive results or blood lead levels <5 µg/dL, leading to repeat testing, unnecessary treatment, or both KQ 4: Reduction in blood lead levela; reduction in gestational hypertension KQ 5: Reduction in adverse perinatal outcomes and cognitive problems in offspring KQ 6: Anxiety or distress; inconvenience associated with intervention (e.g., need for temporary housing due to home lead abatement, work absenteeism associated with followup testing and treatment); morbidity attributed to chelation therapy (e.g., renal toxicity, sensitivity reactions); adverse effects of nutritional supplements (e.g., nausea) |
All other outcomes, including measures of household lead dust |
| Study designs | KQs 1, 4: RCTs KQ 2: Observational studies assessing the accuracy of screening questionnaires for predicting elevated blood lead levels KQ 3: RCTs, CCTs, or prospective cohort studies KQ 5: RCTs and CCTs KQ 6: RCTs, CCTs, prospective cohort studies with a concurrent control group, and case-control studies |
Systematic reviewsb, case series, case reports, or comparison with historical controls |
| Quality | Studies rated good or fair quality | Studies rated poor quality |
| Clinical Setting | All KQs: Settings applicable to U.S. primary care settings where women receive prenatal care, including obstetrics/gynecology outpatient and family medicine clinics KQs 4–6: The above plus settings referable from primary care settings |
All other settings, including community health case-finding (e.g., blood lead level monitoring after known environmental exposure) |
| Country Setting | KQs 1–3: Research conducted in the United States or in populations similar to U.S. populations with services and interventions applicable to U.S. practice (i.e., countries with a United Nations Human Development Index of "Very High") KQs 4–6: Any country |
KQs 1–3: Research not relevant to the United States or conducted in countries with a Human Development Index other than "Very High" |
| Language | English language | Languages other than English |
Abbreviations: CCT = controlled clinical trial; RCT = randomized, controlled trial.
a We will include outcomes measured in family members (e.g. siblings, pregnant women in the same household) who are subsequently identified as having elevated blood lead levels after the index family member was found to have an elevated blood lead level during screening.
b Systematic reviews are excluded from the evidence review. However, we will conduct a separate search to identify relevant systematic reviews published since the last review to ensure that our database searches have captured all relevant studies. We will describe any relevant systematic reviews in the Discussion section of the report.
The draft Research Plan was posted on the USPSTF Web site for public comment from June 16 to July 13, 2016. In response to these comments, the USPSTF revised the analytic framework, KQs, and eligibility criteria for screening in pregnancy to distinguish between "adverse maternal outcomes" and "adverse perinatal outcomes." The USPSTF also added a subquestion to KQ 1 to address whether the benefit of screening in pregnant women differs by the gestational age at which screening occurs. One comment asked for clarification on point-of-care blood lead level assays that are not approved by the U.S. Food and Drug Administration and not available in the United States; the USPSTF clarified that these assays will be excluded from the evidence review. Finally, the USPSTF removed mention of the reliability of capillary blood testing in children from KQ 2b and incorporated it into one of the Contextual Questions for screening in childhood.