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. 2023 Dec;131(12):127018.
doi: 10.1289/EHP12863. Epub 2023 Dec 26.

Prenatal Exposure to Poly- and Perfluoroalkyl Substances (2009-2014) and Vaccine Antibody Titers of Measles, Mumps, Rubella, and Varicella in Children Four to Eight Years Old from the Healthy Start Cohort

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Prenatal Exposure to Poly- and Perfluoroalkyl Substances (2009-2014) and Vaccine Antibody Titers of Measles, Mumps, Rubella, and Varicella in Children Four to Eight Years Old from the Healthy Start Cohort

Lauren M Zell-Baran et al. Environ Health Perspect. 2023 Dec.

Abstract

Background: Prenatal exposures to certain poly- and perfluoroalkyl substances (PFAS) are associated with reduced humoral responses to some childhood immunizations.

Objective: We estimated associations between prenatal PFAS exposure and child antibody titers for measles, mumps, rubella (MMR), and varicella after immunization.

Methods: We measured serum antibody titers of 145 children (4-8 y old) enrolled in the Healthy Start cohort in Colorado, whose mothers had PFAS quantified mid-pregnancy (2009-2014). We used linear and logistic regression models to assess the relationship between five PFAS detected in >65% of mothers and continuous or non-high-censored ("low") antibody titers and quantile g-computation to evaluate the overall effect of the PFAS mixture.

Results: Median concentrations of individual PFAS were at or below the median reported among females in the United States. After receiving two vaccine doses, seropositive levels of antibodies were detected among most (93%-100%) children. Each log-unit increase in perfluorononanoate was associated with 2.09 [95% confidence interval (CI): 1.13, 3.87] times higher odds of a low measles titer, and each log-unit increase in perfluorooctanoate was associated with 2.46 (95% CI: 1.28, 4.75) times higher odds of a low mumps titer. Odds ratios for all other PFAS were elevated, but CIs included the null. Each quartile increase in the PFAS mixture was associated with 1.35 (95% CI: 0.80, 2.26) times higher odds of a low measles titer and 1.44 (95% CI: 0.78, 2.64) times higher odds of a low mumps titer. No significant associations were observed between PFAS and varicella or rubella antibodies. In stratified analyses, associations were negative among female children, except for perfluorohexane sulfonate and varicella, whereas they were positive among males.

Discussion: Some prenatal PFAS were associated with lower antibody titers among fully immunized children. The potential for immunotoxic effects of PFAS requires further investigation in a larger study, because exposure is ubiquitous globally. https://doi.org/10.1289/EHP12863.

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Figures

Figure 1 is a flowchart with five steps. Step 1: Under Healthy Start, there were 1410 pregnant women enrolled between 2009 and 2014, out of which 21 pregnancies ended in fetal demise or child death. Step 2: There are 652 women selected via convenience sample to have poly- and perfluoroalkyl substances (PFAS) measured mid-pregnancy. Step 3: There are 290 offspring with serum available from the early childhood visit for vaccine antibody titer analyses, out of which 52 are incomplete vaccine records. Step 4: 238 offspring had completed vaccine record abstractions, out of which 4 vaccines had less than two weeks of titer. Step 5: 145 offspring were fully immunized at the time of titer analysis.
Figure 1.
Flow diagram for selection of mother–child pairs for analysis from the Healthy Start Cohort (2009–2014).
Figures 2A to 2B are horizontal bar graphs titled Measles, plotting positive and negative weights, ranging as natural logarithm (perfluorodecanoate), natural logarithm (perfluorononanoate), natural logarithm (perfluorooctanoate), natural logarithm (perfluorooctane sulfonate), natural logarithm (perfluorohexane sulfonate) (y-axis) across unadjusted and adjusted (x-axis) for one quartile increase in mixture odds ratio 1.44 (0.86, 2.39) and one quartile increase in mixture odds ratio 1.35 (0.80, 2.26). Figures 2C and 2D are horizontal bar graphs titled Mumps, plotting positive and negative weights, ranging as natural logarithm (perfluorodecanoate), natural logarithm (perfluorononanoate), natural logarithm (perfluorooctanoate), natural logarithm (perfluorooctane sulfonate), natural logarithm (perfluorohexane sulfonate) (y-axis) across unadjusted and adjusted (x-axis) for one quartile increase in mixture odds ratio 1.54 (0.85, 2.80) and one quartile increase in mixture odds ratio 1.44 (0.78, 2.64).
Figure 2.
Quantile-based g-computation mixture ORs (95% CIs) and positive or negative weights for each PFAS for non–high-censored antibody titer concentrations among children (n=143) with completed vaccinations at early childhood visit. (A) Unadjusted measles model; (B) measles model adjusted for child’s sex and time since immunization; (C) unadjusted mumps model; (D) mumps model adjusted for child’s sex and time since immunization. Note: CI, confidence interval; PFAS, poly- and perfluoroalkyl substances; OR, odds ratio; PFDA, perfluorodecanoate; PFHxS, perfluorohexane sulfonate; PFNA, perfluorononanoate; PFOA, perfluorooctanoate; PFOS, perfluorooctane sulfonate.
Figures 3A to 3B are horizontal bar graphs titled Rubella, plotting positive and negative weights, ranging as natural logarithm (perfluorodecanoate), natural logarithm (perfluorononanoate), natural logarithm (perfluorooctanoate), natural logarithm (perfluorooctane sulfonate), natural logarithm (perfluorohexane sulfonate) (y-axis) across unadjusted and adjusted (x-axis) for one quartile increase in mixture: beta 8.58 (negative 9.71, 26.87) and one quartile increase in mixture: beta 11.87 (negative 6.30, 30.03). Figures 3C and 3D are horizontal bar graphs titled natural logarithm varicella, plotting positive and negative weights, ranging as natural logarithm (perfluorodecanoate), natural logarithm (perfluorononanoate), natural logarithm (perfluorooctanoate), natural logarithm (perfluorooctane sulfonate), natural logarithm (perfluorohexane sulfonate) (y-axis) across unadjusted and adjusted (x-axis) for one quartile increase in mixture: beta negative 0.03 (negative 0.30, 0.24) and one quartile increase in mixture: beta 0.04 (negative 0.21, 0.29).
Figure 3.
Quantile-based g-computation mixture linear regression beta estimates for the difference in antibody titer per quartile increase in PFAS (95% CIs) and positive or negative weights for each PFAS for continuous antibody titer concentrations among children with completed vaccinations at early childhood visit. (A) Unadjusted rubella model (n=143); (B) rubella model adjusted for time since immunization (n=143); (C) unadjusted ln(varicella) model (n=130); (D) ln(varicella) model adjusted for time since immunization (n=130). Note: CI, confidence interval; PFAS, poly- and perfluoroalkyl substances; PFDA, perfluorodecanoate; PFHxS, perfluorohexane sulfonate; PFNA, perfluorononanoate; PFOA, perfluorooctanoate; PFOS, perfluorooctane sulfonate.

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