Periodic Reporting for period 1 - PFAS-ITOX (Developmental immunotoxicity of perfluoroalkyl substances (PFASs) in a population of highly-exposed children)
Período documentado: 2022-06-01 hasta 2025-02-28
Exposures to perfluoroalkyl substances (PFASs), a class of persistent chemicals, have been linked to an array of adverse health outcomes including reduced antibody response to vaccination. However, there is a lack of epidemiological studies on clinical immune outcomes (e.g. infections or asthma) in children, whose developing immune system is highly sensitive to chemical exposures. This project addresses this research gap by leveraging a unique cohort of children with a wide range of PFAS exposures (background to highly exposed) and detailed medical records to investigate the potential immunotoxic effects of prenatal and childhood PFAS exposures on clinically relevant immune outcomes.
It was discovered in 2013 that one of two municipal water supplies in Ronneby, Sweden was delivering water that was highly contaminated by PFASs from firefighting foam runoff at a nearby military airport. Earlier studies in Ronneby found that serum PFAS concentrations corresponded closely with residential address history, allowing residential history to be used as an accurate proxy for exposure. PFAS-ITOX uses this natural experiment to create a longitudinal cohort of children and evaluate whether high PFAS exposures are associated with clinical outcomes related to immunosuppression (e.g. counts of common childhood infections) and hypersensitivity (e.g. incidence of asthma). While existing studies of PFAS immunotoxicity rely on self-reported data or hospital admission records, I used the Skåne Healthcare Register, unique to southern Sweden, to identify outcomes at all levels of care, including primary care where many immune outcomes are diagnosed. Results from my project will inform future PFAS research, provide necessary evidence for risk assessments, and provide critical information to health practitioners caring for highly-exposed individuals.
It was discovered in 2013 that one of two municipal water supplies in Ronneby, Sweden was delivering water that was highly contaminated by PFASs from firefighting foam runoff at a nearby military airport. Earlier studies in Ronneby found that serum PFAS concentrations corresponded closely with residential address history, allowing residential history to be used as an accurate proxy for exposure. PFAS-ITOX uses this natural experiment to create a longitudinal cohort of children and evaluate whether high PFAS exposures are associated with clinical outcomes related to immunosuppression (e.g. counts of common childhood infections) and hypersensitivity (e.g. incidence of asthma). While existing studies of PFAS immunotoxicity rely on self-reported data or hospital admission records, I used the Skåne Healthcare Register, unique to southern Sweden, to identify outcomes at all levels of care, including primary care where many immune outcomes are diagnosed. Results from my project will inform future PFAS research, provide necessary evidence for risk assessments, and provide critical information to health practitioners caring for highly-exposed individuals.
PFAS-ITOX encompassed a wide range of research activities and achievements.
The first area of research was a historical exposure assessment for PFAS exposure in Ronneby, Sweden. Although high PFAS levels in the drinking water were discovered in 2013, public officials did not know when the drinking water contamination started or how it may have changed over time. We measured PFAS concentrations in dried blood spots that were collected from infants born between 1985-2013 and biobanked in the Swedish Phenylketonuria (PKU) Biobank. We were able to compare PFAS concentrations in infants born to mothers who lived in addresses that were eventually provided with contaminated water to infants born in other areas of Blekinge county. This research demonstrated that PFAS exposure likely started before 1985 (previously thought to be the start of exposure) and reached its maximum in 2007. To our knowledge, this is the first study to use biobanked dried blood spots to conduct a historical PFAS exposure assessment. Results will be used to build a model for prenatal PFAS exposure in Ronneby, which will improve future epidemiological studies in the population. Our results were published in the peer-reviewed article, “Estimating historical PFAS exposures in Ronneby, Sweden using biobanked dried blood spots from newborns” (DOI: 10.1016/j.envres.2025.121397).
A second area of research conducted under PFAS-ITOX was a series of studies describing prenatal and early-life exposures to PFAS via transplacental transfer and breastfeeding. While early-life exposures have been characterized in children exposed to low levels of PFAS, this was the first comprehensive investigation in a population that included high-exposed children. This research led to three peer-reviewed articles.
A third area of research was investigating the possible immunotoxic effects of PFAS exposure, and specifically estimating the association between prenatal PFAS exposure and the incidence of infections in childhood in Blekinge county, Sweden. We estimated infection incidence using electronic primary care records from Region Blekinge, making this the first study to our knowledge to use primary care records rather than self-report or hospitalization records. We identified an association between very high prenatal PFAS exposure and an increased hazard of ears, eyes and urinary tract infections. This research was published in the peer-reviewed article, “Common infections in children aged 6 months to 7 years after high prenatal exposure to perfluoroalkyl substances from contaminated drinking water in Ronneby, Sweden” (DOI: 10.1016/j.envres.2025.120787)
Finally, I also investigated a possible association between prenatal PFAS exposure and childhood incidence of asthma. We identified incident cases of wheeze and asthma from administrative health records, and validated cases against primary care records. Using a Rubin Causal Model, we demonstrated a significant increase in the cumulative incidence of asthma in very-high exposed children due to their prenatal PFAS exposure. This is the first study to detect a potential association between high PFAS exposures and asthma incidence, and suggests an important public health impact of AFFF-associated PFAS contamination. This study is under preparation for publication.
The first area of research was a historical exposure assessment for PFAS exposure in Ronneby, Sweden. Although high PFAS levels in the drinking water were discovered in 2013, public officials did not know when the drinking water contamination started or how it may have changed over time. We measured PFAS concentrations in dried blood spots that were collected from infants born between 1985-2013 and biobanked in the Swedish Phenylketonuria (PKU) Biobank. We were able to compare PFAS concentrations in infants born to mothers who lived in addresses that were eventually provided with contaminated water to infants born in other areas of Blekinge county. This research demonstrated that PFAS exposure likely started before 1985 (previously thought to be the start of exposure) and reached its maximum in 2007. To our knowledge, this is the first study to use biobanked dried blood spots to conduct a historical PFAS exposure assessment. Results will be used to build a model for prenatal PFAS exposure in Ronneby, which will improve future epidemiological studies in the population. Our results were published in the peer-reviewed article, “Estimating historical PFAS exposures in Ronneby, Sweden using biobanked dried blood spots from newborns” (DOI: 10.1016/j.envres.2025.121397).
A second area of research conducted under PFAS-ITOX was a series of studies describing prenatal and early-life exposures to PFAS via transplacental transfer and breastfeeding. While early-life exposures have been characterized in children exposed to low levels of PFAS, this was the first comprehensive investigation in a population that included high-exposed children. This research led to three peer-reviewed articles.
A third area of research was investigating the possible immunotoxic effects of PFAS exposure, and specifically estimating the association between prenatal PFAS exposure and the incidence of infections in childhood in Blekinge county, Sweden. We estimated infection incidence using electronic primary care records from Region Blekinge, making this the first study to our knowledge to use primary care records rather than self-report or hospitalization records. We identified an association between very high prenatal PFAS exposure and an increased hazard of ears, eyes and urinary tract infections. This research was published in the peer-reviewed article, “Common infections in children aged 6 months to 7 years after high prenatal exposure to perfluoroalkyl substances from contaminated drinking water in Ronneby, Sweden” (DOI: 10.1016/j.envres.2025.120787)
Finally, I also investigated a possible association between prenatal PFAS exposure and childhood incidence of asthma. We identified incident cases of wheeze and asthma from administrative health records, and validated cases against primary care records. Using a Rubin Causal Model, we demonstrated a significant increase in the cumulative incidence of asthma in very-high exposed children due to their prenatal PFAS exposure. This is the first study to detect a potential association between high PFAS exposures and asthma incidence, and suggests an important public health impact of AFFF-associated PFAS contamination. This study is under preparation for publication.
Results of PFAS-ITOX include the following:
High PFAS exposures in Ronneby, caused by AFFF contamination of the public drinking water, began before 1985 and peaked around 2007.
a. First study to use biobanked dried blood spots in a historical exposure assessment
b. Previous studies have not accounted for these time trends: new epidemiological research incorporate time trends via modeled PFAS exposures
Transfers of PFAS via the placenta and via breastmilk vary by PFAS compound, but do not show high variation by maternal PFAS exposure level
a. Children born to high-exposed mothers are at risk of high prenatal and postnatal exposures via transfer
b. Models of exposure need to account for differences across PFAS
Children exposed to high levels of PFAS prenatally may be at higher risk for infections and asthma
a. Results must be replicated in other high-exposed populations
b. Future research should investigate whether exposure timing (prenatal vs. postnatal) matters, and whether effects persist after exposure has stopped.
High PFAS exposures in Ronneby, caused by AFFF contamination of the public drinking water, began before 1985 and peaked around 2007.
a. First study to use biobanked dried blood spots in a historical exposure assessment
b. Previous studies have not accounted for these time trends: new epidemiological research incorporate time trends via modeled PFAS exposures
Transfers of PFAS via the placenta and via breastmilk vary by PFAS compound, but do not show high variation by maternal PFAS exposure level
a. Children born to high-exposed mothers are at risk of high prenatal and postnatal exposures via transfer
b. Models of exposure need to account for differences across PFAS
Children exposed to high levels of PFAS prenatally may be at higher risk for infections and asthma
a. Results must be replicated in other high-exposed populations
b. Future research should investigate whether exposure timing (prenatal vs. postnatal) matters, and whether effects persist after exposure has stopped.