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Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age
Philippe Grandjean1,2, Carsten Heilmann3, Pal Weihe4
1a Department of Environmental Health , Harvard T.H. Chan School of Public Health , Boston , MA , USA.
Insights
Early life exposure to Per- and Polyfluoroalkyl Substances (PFAS) significantly reduces vaccine antibody responses in children. Breastfeeding amplifies these PFAS exposures, particularly in the first six months, impacting infant immune system development.
Area of Science:
- Environmental Health
- Immunotoxicology
- Pediatric Health
Background:
- Per- and Polyfluoroalkyl Substances (PFAS) are persistent environmental contaminants with potential immunotoxic effects.
- Infant exposure to PFAS, including through breastfeeding, may attenuate antibody responses to childhood vaccines.
- The developing immune system's vulnerability to environmental toxins during early life is a growing concern.
Purpose of the Study:
- To investigate the association between prenatal and early infancy exposure to PFAS and antibody concentrations against tetanus and diphtheria vaccines at age 5.
- To determine critical windows of vulnerability for PFAS-induced immunotoxicity during infancy.
- To assess the impact of breastfeeding on PFAS exposure profiles and subsequent vaccine responses.
Main Methods:
- A prospective birth cohort study in the Faroe Islands with clinical examinations and blood sample collection at 18 months and 5 years.
- Measurement of PFAS concentrations at birth and during follow-up; estimation of infant serum PFAS profiles using breastfeeding data.
- Analysis of serum antibody concentrations against tetanus and diphtheria vaccines at age 5, with pooled analysis including a previous cohort.
Main Results:
- Prenatal PFAS exposure was inversely associated with antibody concentrations at age 5 (up to 20% decrease per doubling).
- Estimated PFAS concentrations at 3 and 6 months of infancy showed the strongest inverse associations with antibody levels at age 5, especially for tetanus.
- Joint analyses revealed significant decreases (19-29%) in tetanus antibody concentrations at age 5 per doubling of early infancy PFAS exposure.
Conclusions:
- The developing adaptive immune system is particularly susceptible to PFAS immunotoxicity during infancy.
- The first six months of life represent a critical window of vulnerability, influenced by breastfeeding-related PFAS exposures.
- These findings highlight the need to minimize early life exposure to PFAS to protect vaccine efficacy and long-term immune health.
Abstract:
Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth cohort, 275 and 349 participated in clinical examinations and provided blood samples at ages 18 months and 5 years. PFAS concentrations were measured at birth and at the clinical examinations. Using information on duration of breastfeeding, serum-PFAS concentration profiles during infancy were estimated. As outcomes, serum concentrations of antibodies against tetanus and diphtheria vaccines were determined at age 5. Data from a previous cohort born eight years earlier were available for pooled analyses. Pre-natal exposure showed inverse associations with the antibody concentrations five years later, with decreases by up to about 20% for each two-fold higher exposure, while associations for serum concentrations at ages 18 months and 5 years were weaker. Modeling of serum-PFAS concentration showed levels for age 18 months that were similar to those measured. Concentrations estimated for ages 3 and 6 months showed the strongest inverse associations with antibody concentrations at age 5 years, particularly for tetanus. Joint analyses showed statistically significant decreases in tetanus antibody concentrations by 19-29% at age 5 for each doubling of the PFAS exposure in early infancy. These findings support the notion that the developing adaptive immune system is particularly vulnerable to immunotoxicity during infancy. This vulnerability appears to be the greatest during the first 6 months after birth, where PFAS exposures are affected by breast-feeding.
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