July 9, 2024

expert reaction to exposure to air pollution in pregnancy and cerebral palsy in babies

A study published in JAMA Network Open looks at the association between air pollution exposure during pregnancy and the risk of babies with cerebral palsy. 

Prof Cathy Thornton, Lead, Clean Air Programme RESPIRE consortium (studying the effects of air pollution on pregnant women); and Professor of Human Immunology, Swansea University, said:

“This population-based study of around 1.6 million live births in Canada is large enough to provide strong evidence of an association between elevated residential exposure during pregnancy to fine particulate matter derived (mostly) from fossil fuels and the birth of a term baby with cerebral palsy.  While this measure of air pollution could be an indicator for other factors such as the socioeconomic status of participants, the investigators have done all they can to control for this in their analysis.  It is now one of many studies suggesting associations of air pollution with harmful outcomes on pregnancy that also includes increased risk of preterm birth and miscarriage.  Most of these studies identify an association rather than a direct link of heightened levels of air pollution particulates with these various pregnancy outcomes but there is plenty of evidence to suggest that air pollution particulates are causing these problems.

“We know from previous research that fossil fuel particulates can be found in the human placenta and in the fetal brain as well as other fetal tissues such as the lungs and liver.  Many laboratory-based studies show that particulates have a negative impact on the proper functioning of cells and organs that could manifest as altered fetal neurodevelopment as occurs with cerebral palsy.  This study also highlights that even in a country with relatively low air pollution levels, there are associations with harmful outcomes on the most vulnerable of populations who will carry these effects for their entire lives which should motivate even greater effort to reduce fossil fuel particulates.”

Prof Kevin McConway, Emeritus Professor of Applied Statistics, Open University, said:

“In statistical terms, this is a good study that uses appropriate statistical methods.  But, inevitably, it leaves questions unanswered.  The researchers acknowledge this by proposing that further research is needed to explore the association that they found.

“Overall, my feeling is that the study can’t establish whether higher air pollution levels during pregnancy actually cause an increase in cerebral palsy risk, though that possibility certainly isn’t ruled out.  And in any case there are plenty of other reasons to aim to reduce air pollution.

“Probably the main difficulty with interpretation is that this is an observational study.  The researchers did not choose where the participants lived – people lived where they lived and the researchers recorded the air pollution levels, whether the children were diagnosed with cerebral palsy, and various other factors.  The researchers found an association, that is, a correlation, between the level of fine particulates (very small particles, measured as PM_2.5) in the air near where pregnant mothers lived, and the risk of a diagnosis of cerebral palsy in their babies.  Generally, the higher the particulate pollution, the higher the risk of cerebral palsy.  But this does not establish that it was the air pollution that caused the higher risk.  Mothers who lived in areas with different amounts of particulate pollution also differed in terms of many other factors, and some of these other factors could have been the actual cause of the risk increase, in whole or in part.

“The researchers were, naturally, aware of this issue and made several statistical adjustments to take into account other factors, including the mother’s age, season and year of their child’s birth, and various social, economic and other characteristics of the area where the mother lived, and the association was still there after these adjustments.  But one can never be sure that everything appropriate was adjusted for – the researchers point this out themselves in their section on limitations of the study.  Therefore a single study of this sort just can’t establish whether particulate air pollution is the cause of the increased cerebral palsy risk.  It might be, or it might not be.

“Pretty well any single observational study of an association between a possible risk factor and a health risk is subject to this limitation on knowing about cause and effect.  If many studies of the same association are all showing the same thing, and if there is other evidence that points strongly enough in the direction of cause and effect, researchers can eventually conclude something solid about cause.  But that isn’t the case here – according to the researchers, this is the first study of association between air pollution and cerebral palsy risk.  Also, it cannot provide any evidence on how particulate pollution might work in the pregnant woman’s body to increase the risk of cerebral palsy in her child.  The research paper gives some suggestions about this, but they are based on previous research, for instance on whether particles can cross the placenta into the bloodstream of the fetus, not on this new study’s findings.  So doubts must remain on cause and effect here, and that’s why the researchers recommend further research.

“I should mention that, even if eventually it turns out that air pollution doesn’t increase the risk of cerebral palsy, there are so many other health issues where there is evidence of harms from air pollution that the uncertainty in this study shouldn’t hold up the aim to reduce air pollution.

“The new research found no evidence of an association between the other air pollutants they looked at, nitrogen dioxide and ozone, and cerebral palsy risk.

“The researchers mention other limitations of their study, in their research paper, as well as the issues about causation (where they mention ‘unmeasured and residual confounding’).  I’d add that the air pollution measures are made on a fairly coarse grid, and air pollution level can in some places vary quite a lot over small distances, so that the air pollution measure may not match the position at the mother’s residence very accurately.

“Also, these figures are only for children whose pregnancies went to full term (at least 37 weeks).  Since other research has found associations between air pollution levels and the risk of a preterm (premature) birth, and since the risk of cerebral palsy is higher in premature births, this may affect the overall picture of the association between air pollution and cerebral palsy, possibly in a complicated way.

“Finally, I’ll mention that the absolute risks here are rather small.  In 10,000 full-term pregnancies of mothers similar to those in this study, one would expect about 20 diagnoses of cerebral palsy on the basis of the data from this study.  Suppose all the women were subject to considerably higher levels of fine particulate pollution during pregnancy – in fact suppose the level were higher by about a third of the average amount actually observed in this study, which would be a considerable increase.  (That’s the level of increase on which the researchers report, for good statistical reasons.  I’m talking about an increase of 2.7 mg/m³ of PM_2.5, compared to the median level in this study of 8.6 mg/m³.)  Then, if the increase in cerebral palsy risk were actually caused by this pollution (and we don’t know that it is), the number of cerebral palsy diagnoses in the 10,000 pregnancies would increase to somewhere between 21 and 24, with a best estimate of about 22.  So, even if the association is one of cause and effect, an increase of between 1 and 4 diagnoses in 10,000 pregnancies is not very large.  However, this isn’t to say that such an increase would be unimportant – and there are many other reasons apart from an association with cerebral palsy risk to aim to reduce particulate air pollution.”

Prof Anna Hansell, Professor of Environmental Epidemiology; and Director of the Centre for Environmental Health and Sustainability, University of Leicester, said:

“This is a well-conducted study, using a very large Canadian database of clinical birth records in the Province of Ontario for 1.6 million children.  These were related to a careful estimation of air pollution concentrations at mothers’ homes during pregnancy.

“Cerebral palsy is a rare condition causing neurodevelopment problems in children.  It usually caused by damage to the brain before or during birth and severity varies.  In this database, CP was diagnosed in 2 in 1000 births.

“This study found that fine particles (PM_2.5), which are a small enough size to pass deep into the lung and can cross into the bloodstream, were associated with a small (~10%) increase in risk of cerebral palsy, comparing mothers experiencing higher vs lower concentrations during pregnancy.  The study did not find associations of cerebral palsy with other air pollutants (nitrogen dioxide or ozone).  This type of study is not able to tell us about the mechanisms involved, which would need further research.

“Canada experiences lower concentrations of PM_2.5 than many areas of the UK – mean levels of PM_2.5 in this study at mother’s homes were 8.3 µg/m³.  For comparison, the mean concentrations of PM_2.5 in England in 2023 at comparable locations was 12.3 µg/m³ (measured at urban background sites, representative of locations of majority of homes, as reported in https://assets.publishing.service.gov.uk/media/6629080d3b0122a378a7e5f0/fig05_pm10_annual.csv/preview).  The targets set by government in the 2021 Environment act, were for an average PM_2.5 level in England Annual Mean Concentration Target (‘concentration target’) of 10 µg/m³ to be met across England by 2040 (https://uk-air.defra.gov.uk/networks/monitoring-methods?view=PM-Environment-Act-MonitoringMethods).

“This new study and many other studies have suggested effects of fine particulate pollution on many parts of the body, affecting development as a baby (this study), growth as a child and disease development in adulthood, supported by toxicological evidence giving information on mechanisms.  These impacts are increasingly being detected even at low levels of air pollution.  Continuing efforts to reduce air pollution concentrations to as low as possible are likely to have important benefits for public health.”

‘Prenatal Exposure to Ambient Air Pollution and Cerebral Palsy’ by Yu Zhang et al. was published in JAMA Network Open at 16:00 UK time on Tuesday 9 July 2024.

DOI: :10.1001/jamanetworkopen.2024.20717

Declared interests

Prof Cathy Thornton: “I have no declarations of interest.”

Prof Kevin McConway: “I am a Trustee of the SMC and a member of its Advisory Committee. My quote above is in my capacity as an independent professional statistician.”

Prof Anna Hansell: “I do not have conflicts of interest to report.

I am Chair of the Committee on the Medical Effects of Air Pollution (COMEAP), but comments here are in a personal capacity as Professor in Environmental Epidemiology at the University of Leicester.”