Preliminary Data from the PROGRESS Cohort on Early Life Blood Lead Concentrations and Child MMR Vaccine Response

Abstract

Background: Despite convincing animal data, few human studies have examined potential immune dysregulation in relation to early life lead exposure. Furthermore, these studies often assess non-specific endpoints that limit causal and mechanistic inference. The present analysis addresses this, providing preliminary data on the association between early life blood lead levels (BLLs) and potential immunosuppression, using antigen-specific post-vaccination antibody levels to the measles, mumps, and rubella (MMR) vaccine. Methods: A subset of 43 mother-child pairs enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stress (PROGRESS) study in Mexico City, from 2007-2011, who had complete information on BLLs, antibody responses to the MMR vaccine, and covariates of interest were included. BLLs were determined in mothers (second and third trimesters, and at delivery) and in offspring (age 48 months). Vaccine-specific immunoglobulin (IgG) levels were determined at 48 months, and dates of MMR vaccination were abstracted from health records. Regression models were fit to estimate the effects of BLLs on MMR-specific antibody levels, adjusting for child sex and socioeconomic status. Results: The median maternal BLL at delivery was 3.5 μg/dL (IQR: 0.8-5.5 μg/dL), and the three maternal BLLs were strongly correlated with each other (r>0.8). Median 48-month BLLs were 1.4 μg/dL (IQR: 1.0-2.3 μg/dL) and moderately correlated with maternal BLLs (0.5<r<0.6). Each doubling of maternal delivery BLL was associated with a 15% lower anti-mumps IgG level (95% CI: -25.6, -3.3). Effect estimates were similar for second and third trimester lead measures. Anti-measles and anti-rubella antibodies were not associated with maternal BLLs. Child’s 48-month BLL was not associated with any of the anti-MMR antibody levels. Conclusions: Higher prenatal BLLs were associated with lower anti-mumps antibody levels at 48 months of age. Future work will integrate other time points and antibody responses to additional vaccines to better understand exposure-, outcome-, and age-specific effects.