The relationship between childhood blood lead levels below 5 µg/dL and childhood intelligence quotient (IQ): Protocol for a systematic review and meta-analysis

Abstract

Background: The causal association between childhood lead (Pb) exposure and decrements in intelligence quotient (IQ) is well-established, and no safe blood lead level (BLL) in children has been identified. An international pooled analysis of seven prospective studies published by Lanphear et al. in 2005 quantified the relationship between childhood BLL and IQ. Further studies of Pb and IQ have been published more recently with mean BLLs generally lower than in the studies analyzed by Lanphear et al. In this article, we present the protocol for a systematic review to estimate an updated Pb-IQ relationship focusing on BLLs below 5 µg per deciliter (µg/dL).

Study question: What is the quantitative relationship between childhood BLLs and IQ at ages 3-17 years at BLLs below 5 μg/dL?

Data sources: A comprehensive search of the scientific literature will utilize citation mapping and key word searching. In the citation mapping approach, we will identify seed references that are relevant to our study question, and will then identify more recent references that have cited at least one of the seed references. The key word search will be conducted in the PubMed, Biosis Previews, Scopus, and Web of Science databases. We will also search electronic grey literature databases for conference proceedings, dissertations, and preprints.

Study eligibility criteria, study screening and data extraction: We will include studies that measured BLL in children at any age, assessed full-scale IQ of the same children (concurrent with or subsequent to BLL sample collection) at ages 3-17, and estimated a continuous quantitative relationship between BLL and IQ. We will consider only studies with a central tendency BLL < 10 µg/dL. The title and abstract of each record will be reviewed independently by two authors to determine whether the study in question satisfies the inclusion criteria. The full text of each article remaining after title-abstract screening will be reviewed independently by two authors to determine whether the study in question satisfies the inclusion criteria. Two authors will independently extract study characteristics and data from each included study.

Risk of bias assessment: Studies meeting inclusion criteria will be evaluated for risk of bias (RoB) using the Navigation Guide method applied in a previous systematic review of neurodevelopmental effects (Lam et al., 2017), with adaptation to our study question. Each study will be independently evaluated by two review authors.

Data analysis and synthesis: We intend to conduct a random-effects meta-analysis to summarize the effects of children's exposure to Pb on IQ scores. Additionally, we plan to perform sensitivity analyses using sub-group analyses and/or meta-regression techniques to assess the impact of study design and study population characteristics to examine potential heterogeneity of results across studies. We will assign a confidence level rating (high, moderate, low, or very low) to the effect estimate from the meta-analyses/meta-regressions.

Keywords: Blood lead; Children’s health; Concentration–response function; Intelligence quotient; Protocol; Systematic review.