New research indicates that a pregnant mother’s exposure to a class of persistent synthetic chemicals is associated with specific structural and functional characteristics of her child’s brain. The findings are significant because these compounds, known as PFAS, are widespread in the environment and are found in the blood of nearly all people. The study was published in The Lancet Planetary Health.
Perfluoroalkyl and polyfluoroalkyl substances, or PFAS, are a large group of human-made chemicals. They have been used since the mid-20th century in numerous consumer and industrial products, including non-stick cookware, water-resistant clothing, and firefighting foams, because of their ability to resist heat, water, and oil. Their exceptionally strong chemical bonds mean they do not break down easily, earning them the nickname “forever chemicals.” As a result, they accumulate in the environment and in living organisms, including humans. People are exposed primarily through contaminated food and drinking water.
A team of researchers led by Aaron Barron of the University of Turku in Finland sought to understand if these chemicals could affect the developing human brain. Previous research has linked PFAS exposure to a variety of health problems, and some studies have suggested a connection to neurodevelopmental conditions like autism spectrum disorder, though the evidence has been inconsistent.
Because PFAS are known to cross the placenta from mother to fetus and can also pass through the protective blood-brain barrier, there is a clear pathway for them to potentially influence brain development directly. The researchers hypothesized that exposure during this sensitive prenatal period would be associated with observable differences in a child’s brain years later.
“Humans consume PFAS from drinking water, food, or in some cases exposure through occupation. They are ubiquitous in our blood, and our bodies do not break them down,” said Senior Researcher Aaron Barron, the lead author of the study.
The investigation was part of the ongoing FinnBrain Birth Cohort Study, which follows mothers and their children from pregnancy onward. For this specific analysis, the researchers used data from 51 mother-child pairs. They collected blood samples from the mothers during their 24th week of pregnancy and used a highly sensitive laboratory technique to measure the concentrations of 31 different PFAS. Seven of these chemicals were detected in the majority of samples.
When the children reached five years of age, they underwent magnetic resonance imaging scans. This non-invasive procedure provided the researchers with detailed pictures of the children’s brains. The team collected several types of images to assess different aspects of the brain, including the volume of grey matter (which contains most of the brain’s nerve cells), the structure of white matter (which connects different brain regions), and the brain’s surface area and thickness. They also collected functional magnetic resonance imaging data, which measures brain activity by detecting changes in blood flow.
To analyze this complex set of imaging data, the researchers used a sophisticated statistical method. They combined all the different structural brain measurements to create ten composite “components.” Each component represented a unique pattern of variation across the brain’s grey matter, white matter, and cortex. This allowed them to get a holistic picture of brain structure rather than just looking at one measure at a time. They then examined whether the levels of the seven PFAS found in the mothers’ blood could predict these brain components in their children, while accounting for other factors like the child’s age and sex.
The analysis revealed several distinct associations. One brain component, which primarily reflected the microscopic structure of the corpus callosum, was strongly linked to maternal PFAS levels. The corpus callosum is the largest bundle of white matter in the brain, and it is responsible for communication between the left and right cerebral hemispheres. Higher maternal blood concentrations of two specific PFAS, known as perfluorononanoic acid (PFNA) and linear perfluorooctanoic acid (PFOA), were associated with changes in this brain region’s structure.
Another brain component was also strongly predicted by maternal PFAS levels. This component represented greater grey matter volume and cortical surface area in the posterior parts of the brain, particularly the occipital lobe, which is the brain’s primary visual processing center. The relationships here were more complex. Higher levels of branched perfluorooctanoic acid (PFOA) were associated with a higher score on this brain component, while higher levels of branched perfluorohexanesulphonic acid (PFHxS) were associated with a lower score. This finding suggests that different types of PFAS can have different, and sometimes opposite, relationships with brain development.
“We were able to measure seven different PFAS in this study, and found that individual compounds had specific associations with offspring brain structure, and in some cases two different PFAS had opposite relationships with the same brain region,” explained Professor Tuulia Hyötyläinen from Örebro University.
The team also specifically investigated the hypothalamus, a small brain region that plays a major role in regulating hormones and metabolism. PFAS are known to accumulate in this area. They found that higher levels of branched perfluorooctanesulphonic acid (PFOS) in mothers were associated with changes in the microstructure of their children’s hypothalamus.
The researchers then looked at brain function. They discovered that the same PFAS associated with structural brain changes were also linked to differences in brain activity. For example, higher levels of PFNA and PFOA were connected to more synchronized local brain activity in a part of the brain involved in motor control, while higher levels of branched PFHxS were associated with less synchronized activity in the visual cortex. These functional findings were located in the same brain areas highlighted by the structural analysis, creating a consistent picture.
“At the moment, it is unclear whether PFAS are directly affecting brain development, although it’s known that they pass the placenta and the blood-brain barrier to accumulate in the brain, and can disturb developing brain cells. It’s also unclear whether these associations are harmful, beneficial, or neutral, and future studies will be needed to determine the functional implications of our findings,” said Professor Hasse Karlsson from the University of Turku.
The authors note some limitations to their work. The study size of 51 mother-child pairs is small, which can limit the certainty of the findings and means the results should be interpreted with caution. The participants were also relatively homogenous, consisting of White individuals with a higher socioeconomic status than the general population, which may limit how broadly the findings can be applied. Because the study is observational, it shows a correlation but cannot prove that PFAS exposure caused the observed brain differences. Other unmeasured factors, like diet or maternal occupation, could play a role.
Future research should aim to replicate these findings in larger and more diverse groups of people. It would also be important to study populations with higher levels of PFAS exposure, such as those living near contaminated sites. Researchers also need to investigate the potential health consequences of the newly developed PFAS that are replacing the older, “legacy” chemicals that were the focus of this study. Despite the limitations, this study adds to a growing body of evidence suggesting that even at the low levels found in the general population, these “forever chemicals” may influence the way the human brain develops.
The study, “Prenatal exposure to perfluoroalkyl substances predicts multimodal brain structural and functional outcomes in children aged 5 years: a birth cohort study,” was authored by Aaron Barron, Alex M Dickens, Jetro J Tuulari, Tuulia Hyötyläinen, Susanna Kortesluoma, Harri Merisaari, Elmo P Pulli, Eero Silver, Venla Kumpulainen, Anni Copeland, Ekaterina Saukko, John D Lewis, Linnea Karlsson, Matej Orešič, and Hasse Karlsson.
