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Exposure to perfluorinated alkyl substances and health effects in pregnant women and their children

Ebel, Matilda LU orcid (2024) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Per- and polyfluorinated alkyl substances (PFAS) are chemicals that have gained attention during the last years. There are about 10,000 different PFAS compounds, and due to their unique chemical characteristics, PFAS has been used in a variety of industrial applications and household products since the 1950s. Today, concerns about their toxicity and persistence have led to the regulation and banning of individual PFAS, but new substances have been introduced in their place. New directives will enter into force in 2026 regarding PFAS levels in drinking water in Sweden, and a proposal to ban all PFAS has been authored by several countries. About 2,100 sites with a point source of high PFAS contamination, so-called hotspots, have been... (More)
Per- and polyfluorinated alkyl substances (PFAS) are chemicals that have gained attention during the last years. There are about 10,000 different PFAS compounds, and due to their unique chemical characteristics, PFAS has been used in a variety of industrial applications and household products since the 1950s. Today, concerns about their toxicity and persistence have led to the regulation and banning of individual PFAS, but new substances have been introduced in their place. New directives will enter into force in 2026 regarding PFAS levels in drinking water in Sweden, and a proposal to ban all PFAS has been authored by several countries. About 2,100 sites with a point source of high PFAS contamination, so-called hotspots, have been discovered around Europe and it is expected that more sites will emerge in the future.

Almost everyone in the world is exposed to PFAS, and the most common sources are food, drinking water, and the indoor environment. PFAS accumulate in the human body and have elimination half-lives of several years as they bind to albumin in the blood and are effectively reabsorbed in the major excretion routes. PFAS are also transferred from mother to child during pregnancy through the placenta. The mechanisms of PFAS toxicity are not clear, but several adverse health conditions are associated with exposure, for example, impaired immune function, testicular and kidney cancer, increased cholesterol levels, and thyroid disease.

The overall aim of this thesis was to use epidemiological methods to investigate the effects of PFAS exposure on complications during pregnancy, and the health and development of children after prenatal PFAS exposure. Studies I, III, and IV were based on the Ronneby population which was exposed for decades to high levels of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonic acid (PFHxS) in drinking water after firefighting foam had leaked into the groundwater from a military airport. One out of two water treatment plants in Ronneby distributed the contaminated water, providing drinking water to a third of the population.

Study I is a register-based cohort study investigating the association between high exposure to PFAS and gestational hypertension, preeclampsia, and gestational diabetes mellitus. The exposure was assessed using a proxy variable based on residential history and the outcomes were retrieved from the National Medical Birth Register. We considered body mass index (BMI), birth country, educational status, maternal smoking, parity, and maternal age as confounders. We did not find evidence of an association between high or intermediate exposure to PFAS and gestational hypertension, preeclampsia, or gestational diabetes mellitus.

Study II is a case-control study investigating the association between prenatal background-level exposure to PFAS and the risk of overweight at 4 years of age. Serum samples from the Southern Sweden Maternity Cohort biobank were analyzed for PFAS concentrations, and the outcome was retrieved from medical journals from 11child health care centers in Malmö. Information on confounders was retrieved from a self-administered questionnaire. We found no association between prenatal PFAS exposure and overweight at 4 years of age.

Study III is a register-based cohort study, investigating the association between high prenatal exposure to PFAS and developmental language disorders in children aged 0-7 years. The exposure was assessed using a proxy based on maternal residential history, which was validated against measured serum concentrations in the same population. The outcome was retrieved from the administrative regional healthcare register. We considered educational status, maternal smoking, parity, and maternal age as confounders. Girls who had high prenatal PFAS exposure were found to have a 62% higher (HR 1.62, 95% CI 1.12-2.35) risk of being diagnosed with developmental language disorders and a 36% (HR 1.36, 95% CI 1.02-1.80) higher risk of being referred to a speech and language pathologist compared to girls who had prenatal exposure at background levels. We found no associations for children with intermediate prenatal PFAS exposure.

Study IV is a register-based cohort study, investigating the association between high prenatal exposure to PFAS and common infectious diseases in children aged 0-7 years. The exposure was assessed by using a proxy based on maternal residential history and the outcome was retrieved from the regional healthcare register. We considered educational status, maternal smoking, parity, and maternal age as confounders. We found an increased risk of 28% (HR 1.28, 95% CI 1.05-1.55) for urinary tract infections and a 9% (HR 1.09, 95% CI 1.00-1.19) increased risk of ear infections in children who had high prenatal PFAS exposure compared to children with prenatal exposure at background levels. We also found an increased risk of 6% (HR 1.06, 95% CI 1.02-1.11) for upper respiratory tract infections among children with intermediate prenatal PFAS exposure, compared to children with prenatal background exposure.

In summary, my thesis contributes to new knowledge about high PFAS exposure and its effect on pregnant women and their prenatally exposed children. This information is important not only for the populations that are affected today but also for emerging hotspot populations. My studies provide a missing piece of information to the big puzzle of how different PFAS exposure profiles and exposure levels affect human health, by providing estimates of health effects from a population highly exposed to primarily PFOS and PFHxS from drinking water contamination by firefighting foam run-off. The results from this thesis are valuable for decision-making regarding new restrictions and phase-outs of PFAS compounds and for public health management in PFAS hotspots. (Less)
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author
supervisor
opponent
  • Professor Bornehag, Carl-Gustaf, Department of Health Sciences, Karlstad University, Karlstad
organization
publishing date
type
Thesis
publication status
published
subject
keywords
perfluorinated alkyl substances, epidemiology, prenatal exposure, maternal health, child health, register studies
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2024:2
pages
70 pages
publisher
Lund University, Faculty of Medicine
defense location
Room 104, The Pufendorf Institute, Biskopsgatan 3, Lund
defense date
2024-01-12 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-495-7
language
English
LU publication?
yes
id
6b3dd273-5521-4ba9-8dbf-7337711f2305
date added to LUP
2023-12-13 10:06:47
date last changed
2024-01-03 09:38:31
@phdthesis{6b3dd273-5521-4ba9-8dbf-7337711f2305,
  abstract     = {{Per- and polyfluorinated alkyl substances (PFAS) are chemicals that have gained attention during the last years. There are about 10,000 different PFAS compounds, and due to their unique chemical characteristics, PFAS has been used in a variety of industrial applications and household products since the 1950s. Today, concerns about their toxicity and persistence have led to the regulation and banning of individual PFAS, but new substances have been introduced in their place. New directives will enter into force in 2026 regarding PFAS levels in drinking water in Sweden, and a proposal to ban all PFAS has been authored by several countries. About 2,100 sites with a point source of high PFAS contamination, so-called hotspots, have been discovered around Europe and it is expected that more sites will emerge in the future. <br/><br/>Almost everyone in the world is exposed to PFAS, and the most common sources are food, drinking water, and the indoor environment. PFAS accumulate in the human body and have elimination half-lives of several years as they bind to albumin in the blood and are effectively reabsorbed in the major excretion routes. PFAS are also transferred from mother to child during pregnancy through the placenta. The mechanisms of PFAS toxicity are not clear, but several adverse health conditions are associated with exposure, for example, impaired immune function, testicular and kidney cancer, increased cholesterol levels, and thyroid disease.<br/><br/>The overall aim of this thesis was to use epidemiological methods to investigate the effects of PFAS exposure on complications during pregnancy, and the health and development of children after prenatal PFAS exposure. Studies I, III, and IV were based on the Ronneby population which was exposed for decades to high levels of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonic acid (PFHxS) in drinking water after firefighting foam had leaked into the groundwater from a military airport. One out of two water treatment plants in Ronneby distributed the contaminated water, providing drinking water to a third of the population.<br/><br/>Study I is a register-based cohort study investigating the association between high exposure to PFAS and gestational hypertension, preeclampsia, and gestational diabetes mellitus. The exposure was assessed using a proxy variable based on residential history and the outcomes were retrieved from the National Medical Birth Register. We considered body mass index (BMI), birth country, educational status, maternal smoking, parity, and maternal age as confounders. We did not find evidence of an association between high or intermediate exposure to PFAS and gestational hypertension, preeclampsia, or gestational diabetes mellitus. <br/><br/>Study II is a case-control study investigating the association between prenatal background-level exposure to PFAS and the risk of overweight at 4 years of age. Serum samples from the Southern Sweden Maternity Cohort biobank were analyzed for PFAS concentrations, and the outcome was retrieved from medical journals from 11child health care centers in Malmö. Information on confounders was retrieved from a self-administered questionnaire. We found no association between prenatal PFAS exposure and overweight at 4 years of age.<br/><br/>Study III is a register-based cohort study, investigating the association between high prenatal exposure to PFAS and developmental language disorders in children aged 0-7 years. The exposure was assessed using a proxy based on maternal residential history, which was validated against measured serum concentrations in the same population. The outcome was retrieved from the administrative regional healthcare register. We considered educational status, maternal smoking, parity, and maternal age as confounders. Girls who had high prenatal PFAS exposure were found to have a 62% higher (HR 1.62, 95% CI 1.12-2.35) risk of being diagnosed with developmental language disorders and a 36% (HR 1.36, 95% CI 1.02-1.80) higher risk of being referred to a speech and language pathologist compared to girls who had prenatal exposure at background levels. We found no associations for children with intermediate prenatal PFAS exposure.<br/><br/>Study IV is a register-based cohort study, investigating the association between high prenatal exposure to PFAS and common infectious diseases in children aged 0-7 years. The exposure was assessed by using a proxy based on maternal residential history and the outcome was retrieved from the regional healthcare register. We considered educational status, maternal smoking, parity, and maternal age as confounders. We found an increased risk of 28% (HR 1.28, 95% CI 1.05-1.55) for urinary tract infections and a 9% (HR 1.09, 95% CI 1.00-1.19) increased risk of ear infections in children who had high prenatal PFAS exposure compared to children with prenatal exposure at background levels. We also found an increased risk of 6% (HR 1.06, 95% CI 1.02-1.11) for upper respiratory tract infections among children with intermediate prenatal PFAS exposure, compared to children with prenatal background exposure. <br/><br/>In summary, my thesis contributes to new knowledge about high PFAS exposure and its effect on pregnant women and their prenatally exposed children. This information is important not only for the populations that are affected today but also for emerging hotspot populations. My studies provide a missing piece of information to the big puzzle of how different PFAS exposure profiles and exposure levels affect human health, by providing estimates of health effects from a population highly exposed to primarily PFOS and PFHxS from drinking water contamination by firefighting foam run-off. The results from this thesis are valuable for decision-making regarding new restrictions and phase-outs of PFAS compounds and for public health management in PFAS hotspots.}},
  author       = {{Ebel, Matilda}},
  isbn         = {{978-91-8021-495-7}},
  issn         = {{1652-8220}},
  keywords     = {{perfluorinated alkyl substances; epidemiology; prenatal exposure; maternal health; child health; register studies}},
  language     = {{eng}},
  number       = {{2024:2}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Exposure to perfluorinated alkyl substances and health effects in pregnant women and their children}},
  url          = {{https://lup.lub.lu.se/search/files/166707509/Matilda_Ebel_kappa_e-spik.pdf}},
  year         = {{2024}},
}