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Developmental Biology - Pollution

Polluted Air Decreases Prenatal Brain Size

Prenatal exposure to pollution linked to behavior problems...

Within limits set by the European Union, particulate matter found in the air we breath is associated with a decrease in the volume of an infant's brain corpus callosum — a structure linked to both attention deficit hyperactivity and autism spectrum disorders. Over the past few decades, various studies have investigated the impact of air pollution on cognitive capacities in children. But little research exists on air pollution and children's growing brains.
Now a new study led by the Barcelona Institute for Global Health (ISGlobal) and supported by "la Caixa", has found a link between air pollution and changes in the corpus callosum — a brain region associated with neurodevelopmental problems like attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

In the new study of 186 children from 40 schools in Barcelona, Spain, researchers examined prenatal exposure to particulate matter in urban air and compared its volume to the size of the corpus callosum. Each mother and child were exposed to a particulate matter of 2.5, calculated based on the residential history of each child and the European Study of Cohorts for Air Pollution Effects - ESCAPE. Information about a child's brain anatomy was obtained through magnetic resonance imaging and behavioural data collected by parent and teacher completed questionnaires. The research appears in Environmental Research.

"Knowing what brain damage occurs during prenatal stages could be very useful in predicting and treating behavioural problems often diagnosed later in childhood," explains Jesús Pujol PhD, research director at the Hospital del Mar Medical Research Institute (IMIM), who performed the magnetic resonance imaging.
The findings reveal prenatal exposure to particulate matter, especially during the last trimester of pregnancy, can induce structural changes in the corpus callosum later found between the ages of 8 and 12 years old. Specifically, an increase of 7 ug/m3 in PM2.5 level is associated with a nearly 5% decrease in the volume of the corpus callosum.

"Our findings are cause for concern for various reasons," explains Jordi Sunyer, head of the study and of the Childhood and Environment Programme at ISGlobal. "First, in cases studied ofchronic prenatal exposure, the PM2.5 levels were below the limit of 25 ug/m3 established by the European Union. Second, reduced volume of the corpus callosum is a common characteristic of ADHD and ASD, although it is not an alteration specific to these disorders. Finally, children with a 5% reduction in corpus callosum volume showed higher levels of hyperactivity."

BiSC Project Calls on Pregnant Women to Participate

The Barcelona Life Study Cohort, or BiSC Project, is continuing to pursue the lines of research opened by BREATHE. "We now want to go a step further and analyze the brain before and after birth, to assess individual exposure," commented Sunyer.

BiSC requires participation of approximately 1,200 pregnant volunteers. Women interested in participating in the BiSC study can request information and join the project by visiting the BiSC website.

Air pollution (AP) may affect neurodevelopment, but studies about the effects of AP on the growing human brain are still scarce. We aimed to investigate the effects of prenatal exposure to AP on lateral ventricles (LV) and corpus callosum (CC) volumes in children and to determine whether the induced brain changes are associated with behavioral problems.

Among the children recruited through a set of representative schools of the city of Barcelona, (Spain) in the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) study, 186 typically developing participants aged 8–12 years underwent brain MRI on the same 1.5T MR unit over a 1.5-year period (October 2012–April 2014). Brain volumes were derived from structural MRI scans using automated tissue segmentation. Behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) and the criteria of the Attention Deficit Hyperactivity Disorder DSM-IV list. Prenatal fine particle (PM2.5) levels were retrospectively estimated at the mothers’ residential addresses during pregnancy with land use regression (LUR) models. To determine whether brain structures might be affected by prenatal PM2.5 exposure, linear regression models were run and adjusted for age, sex, intracranial volume (ICV), maternal education, home socioeconomic vulnerability index, birthweight and mothers’ smoking status during pregnancy. To test for associations between brain changes and behavioral outcomes, negative binomial regressions were performed and adjusted for age, sex, ICV.

Prenatal PM2.5 levels ranged from 11.8 to 39.5 ug/m3 during the third trimester of pregnancy. An interquartile range increase in PM2.5 level (7ug/m3) was significantly linked to a decrease in the body CC volume (mm3) (B = -53.7, 95%CI, 95%CI [-92.0, -15.5] corresponding to a 5% decrease of the mean body CC volume) independently of ICV, age, sex, maternal education, socioeconomic vulnerability index at home, birthweight and mothers’ smoking status during the third trimester of pregnancy. A 50 mm3 decrease in the body CC was associated with a significant higher hyperactivity subscore (Rate Ratio (RR)=1.09, 95%CI [1.01, 1.17) independently of age, sex and ICV. The statistical significance of these results did not survive to False Discovery Rate correction for multiple comparisons.

Prenatal exposure to PM2.5 may be associated with CC volume decrease in children. The consequences might be an increase in behavioral problems.

Marion Mortamais, Jesus Pujol, Gerard Martínez-Vilavella, Raquel Fenolle Christell Reynes, Robert Sabatier, Ioar Rivas, Joan Forns, Natàlia Vilor-Tejedor, Silvia Alemany, Marta Cirach, Mar Alvarez-Pedrerol, Mark Nieuwenhuijsen and Jordi Sunyer.

The authors thank M. Thomson for the NANOG–eGFP ES cells, T. Kunath for Erk2-KO cells, N. Festuccia for Esrrb-KO cells, H.H. Ng for the KLF2 and TFCP2L1 antibodies, the Brickman laboratory members for critical discussions, Y. Spector for sequencing assistance, H. Neil, M. Michaut and the DanStem Genomics Platform for technical expertise, support, and the use of instruments, S. Pozzi, N. Festuccia and P. Navarro Gil for advice on ChIP protocols, K. Stewart-Morgan for help with ATAC-seq, A. Azad and J. A. R. Herrera for bioinformatics advice and P. van Dieken for technical support and proof reading. This work was funded by grants from the Novo Nordisk Foundation, Danish Council for Independent Research (8020-00100B), Danish National Research Foundation (DNRF116) and Human Frontiers in Science (RGP0008/2012). The Novo Nordisk Foundation Centers for Stem Cell Biology and Protein Research are supported by a Novo Nordisk Foundation grant numbers NNF17CC0027852 and NNF14CC0001. R.S.M. is supported by a fellowship from the Lundbeck Foundation (R303-2018-2939).

The study was carried out as a part of BREATHE, a project whose earlier findings suggest that air pollution has harmful effects on cognitive functions in schoolchildren and is also associated with functional changes in the brain.

The BiSC Project is one of the most extensive studies on how air pollution affects both infant health and brain development before and after birth. The project is in Barcelona and coordinated by ISGlobal, in collaboration with BCNatal (Hospital Sant Joan de Déu, Hospital Clínic and the University of Barcelona) and Hospital de la Santa Creu i Sant Pau.

The authors declare no competing interests.

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Nov 13 2019   Fetal Timeline   Maternal Timeline   News  

Infant  brain corpus callosum

The BiSC Project is one of the most extensive studies carried out to date on how
air pollution affects infant health and brain development both before and after birth.
Corpus Callosum (RED Outline) CREDIT Autism Science Foundation.

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