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Bayesian Methods for Exposure Misclassification Adjustment in a Mediation Analysis

Hemoglobin and Malnutrition in the Association Between Ascaris and IQ

Blouin, Brittanya,b; Casapia, Martinc; Kaufman, Jay S.b; Joseph, Lawrencea,b; Larson, Charlesb; Gyorkos, Theresa W.a,b

doi: 10.1097/EDE.0000000000001051

Background: Soil-transmitted helminth infections have been found to be associated with child development. The objective was to investigate hemoglobin levels and malnutrition as mediators of the association between Ascaris infection and intelligence quotient (IQ) scores in children.

Methods: We conducted a longitudinal cohort study in Iquitos, Peru, between September 2011 and July 2016. A total of 1760 children were recruited at 1 year of age and followed up annually to 5 years. We measured Ascaris infection and malnutrition at each study visit, and hemoglobin levels were measured as of age 3. The exposure was defined as the number of detected Ascaris infections between age 1 and 5. We measured IQ scores at age 5 and used Bayesian models to correct exposure misclassification.

Results: We included a sample of 781 children in the analysis. In results adjusted for Ascaris misclassification, mean hemoglobin levels mediated the association between Ascaris infection and IQ scores. The natural direct effects (not mediated by hemoglobin) (95% CrI) and natural indirect effects (mediated by hemoglobin) (95% CrI) were compared with no or one infection: −0.9 (−4.6, 2.8) and −4.3 (−6.9, −1.6) for the effect of two infections; −1.4 (−3.8, 1.0) and −1.2 (−2.0, −0.4) for three infections; and −0.4 (−3.2, 2.4) and −2.7 (−4.3, −1.0) for four or five infections.

Conclusion: Our results are consistent with the hypothesis that hemoglobin levels mediate the association between Ascaris infection and IQ scores. Additional research investigating the effect of including iron supplements in STH control programs is warranted.

From the aCentre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada

bDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada

cAsociación Civil Selva Amazónica, Urbanización Jardín No 27, Fanny 4ta cuadra, Iquitos, Perú.

Submitted June 22, 2018; accepted May 24, 2019.

Supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number P50AI098574. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was also supported by grants 02832-2 from the Thrasher Research Fund, MOP-110969 from the Canadian Institutes for Health Research, and CGV-140015 from the Canadian Institutes for Health Research.

The authors declare no conflicts of interest.

The data and computing code required to replicate the results can be obtained by contacting the corresponding author.

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Correspondence: Brittany Blouin, Centre for Outcomes Research and Evaluation, McGill University Health Centre, 5252 de Maisonneuve, Montreal, Quebec, Canada. E-mail:

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