Researchers have published a paper in Jama Pediatrics suggesting a link between exposure to bisphenol-A and asthma symptoms in children. A before the headlines analysis accompanied this roundup.
Prof Jean Golding, Emeritus Professor of Paediatric & Perinatal Epidemiology at the University of Bristol, said:
‘It is important to determine whether bisphenol A has an adverse effect on child development. This study, alas, is based on a relatively small number of children, and the results are inconsistent. It is important that larger studies are undertaken before any conclusions can be reached.’
Prof Richard Sharpe, Group Leader of Male Reproductive Health Research Team, University of Edinburgh, said:
“This study has examined the relationship between the urinary levels of bisphenol A in pregnant women and the incidence of respiratory disorders, such as wheezing, in the resulting children. The authors report that higher maternal BPA exposure is associated with increased likelihood of respiratory disorders in the children.
“The vast majority (>95%) of BPA consumed by humans comes from what we eat and drink and consumption of a ‘Western’ style (unhealthy) diet is particularly associated with higher BPA intake. Therefore, all studies of BPA and health – such as this one – must consider the diet itself, as we know that unhealthy diets can lead to obesity and other disorders; and that maternal diet and obesity can considerably impact the health of resulting children.
“There are already numerous studies showing that maternal obesity is associated with increased risk of wheezing in the resulting children. We can’t assume that mothers with higher BPA exposure are obese, but many studies have found positive associations between BPA exposure and obesity, including in women – probably because of a poor diet. It is a huge omission from this study that key maternal characteristics such as obesity and diet have been left out.
“The available evidence already suggests that BPA is inactivated so quickly in the gut that humans do not get effectively exposed to biologically active BPA. I am not convinced by the associations reported in this study, especially given the lack of information on the diet and BMI of the mothers.”
Prof Seif Shaheen, Clinical Professor of Respiratory Epidemiology at Queen Mary University of London, said:
“Epidemiological research into a possible link between exposure to bisphenol A before and after birth and risk of childhood wheezing and asthma has produced inconsistent results. These latest findings from a small birth cohort study add to the muddied waters and should be treated with caution for a number of reasons.
“First, statistical evidence for an association with wheezing overall is weak, and the result for persistent wheeze which is highlighted may be a chance finding.
“Second, the reported association with lung function at four years of age is surprising as it is usually difficult to obtain reliable lung function measurements of this kind under six years of age; data on lung function were available from less than half the children with wheezing information, and it is puzzling why an association with lung function at five years of age was not also seen.
“Third, although the authors list potential confounding factors which they collected information on, it is not clear from the paper whether all these variables were controlled for in the analyses.
“Finally, a plausible mechanism by which bisphenol A might influence human fetal lung development has not been proposed.
“Given these limitations, and previously conflicting data, evidence for a causal link is extremely unconvincing. A larger study is needed in the first instance, with follow-up beyond five years of age, to determine whether high bisphenol A exposure before birth is associated with an increased risk of doctor-diagnosed asthma and impaired lung function in children of school age.
Prof Paul Pharoah, Professor of Cancer Epidemiology at the University of Cambridge, said:
“This appears to be a carefully conducted cohort study of the effect of exposure to chemicals used in plastics in pregnant women on lung function in children 4 and 5 years later. These women were exposed to ordinary levels of chemicals from standard consumer products. The researchers have used an objective measure of the exposure of pregnant women to a chemical called BPA – urine BPA concentration at 16 and 26 weeks gestation. The babies were then followed up regularly for 5 years to assess their lung function.
“The researchers then looked for a correlation between maternal BPA exposure and lung function in the children.
“There are many different correlations reported in the paper, but the researchers highlight only the positive findings.
“It should be noted that if many statistical tests are carried out, some will be “significant” simply because of the play of chance.
“There is little consistency between findings, which suggests that the positive correlations may simply be the result of chance. For example, they report that a 10-fold increase in maternal BPA exposure with a 14 per cent reduction in lung function at 4 years of age, but no effect at 5 years of age. They also report an association of chemical exposure at week 16 of pregnancy with persistent wheeze (odds ratio 4.27) but no association for exposure at 26 weeks and persistent wheeze and no association with exposure at 16 weeks and late-onset wheeze.
“Even if the results are taken at face value they would appear to be of little relevance to most women. The researchers indicate a very wide range for exposure of pregnant women to BPA, but a very small proportion of women have high exposure levels. If you were to take the 2 per cent of women with the lowest exposure and compare them with the two per cent of women with the highest exposure the difference in exposure would be just 30 per cent (or 1.3-fold). This would result in less than 2 per cent reduction in lung function at 4 years with no difference at 5 years.
“In summary, the findings are of some scientific interest, but they raise more questions than they answer. These data do not provide convincing evidence that there is any association between chemical exposure during pregnancy in normal environments and lung function in children.”
Prof David Coggon, Professor of Occupational and Environmental Medicine at the University of Southampton, said:
“The study appears to have been well-conducted, but interpretation is difficult because BPA in mother’s urine was measured at only two time points during pregnancy (16 and 26 weeks), and the levels were poorly correlated.
“The implication is that mothers’ exposures varied from day to day, and that more time points would need to be studied to characterise their exposures reliably. This, along with the inconsistency of associations with measures of children’s respiratory health (reduced lung function at four but not five years), means that no strong conclusions can be drawn. The results do not suggest that exposure to BPA during pregnancy has a major impact on asthma during childhood, but as the authors conclude, more research would be needed to resolve continuing uncertainties.”
Prof David Spiegelhalter, Winton Professor of the Public Understanding of Risk at the University of Cambridge, said:
“This is a careful study but the results are selected from a large number of comparisons: there is an association with lung function at 4 years old but not at 5 years old, with BPA exposure at 16 and not 26 weeks gestation, and so on. And the quoted effects are for a 10-fold increase in BPA which is a very large change in exposure.”
Before The Headlines
|Title, Date of Publication & Journal|
|Bisphenol A Exposure and the Development of Wheeze and Lung Function in Children Through Age 5 Years6 October 2014
|Claim supported by evidence?|
|The paper does not support the claim that BPA exposure causes asthma symptoms, neither in the form of diminished lung function nor persistent wheeze in children|
|The authors acknowledge that the study’s results are inconsistent but suggest that this is a basis for further research to confirm whether or not BPA exposure is a risk factor for development of asthma.The strongest effect that they observe is on FEV1 measured in 4-year-olds. However, this effect disappears entirely by the time the same children reach 5 years of age, and isn’t particularly strong to begin with.|
|There are many limitations, some of which the authors acknowledge in the paper. However, there are some further limitations:A lot of data on confounding factors was collected but it is unclear whether these were included in the final models
Nearly 400 mothers were recruited into the study but follow-up data was only collected for a little over 200 infants – we don’t know how different the missing half of the patients are to those that were followed up
Many potential confounding factors were omitted, including diet, and maternal smoking history (although current smoking level was measured)
All the stats are reported using a “10-fold increase in BPA” as the benchmark. However it is unclear whether many 10-fold increases are covered in the data – there may be a few outliers with very high BPA exposure and this may be heavily influencing the results.
The results show many inconsistencies, suggesting that BPA may not be the underlying cause:
|FEV1 – forced expiratory volume in one second. It can be measured in litres, but is most commonly expressed as a percentage of a benchmark normal figure based on the patient’s age, sex and height|
|Any specific expertise relevant to studied paper (beyond statistical)?|
|Experience of statistical consultancy work on data from respiratory trials.|
Before The Headlines is a service provided to the SMC by volunteer statisticians: members of the Royal Statistical Society (RSS), Statisticians in the Pharmaceutical Industry(PSI) and experienced statisticians in academia and research. A list of contributors, including affiliations, is available at http://www.sciencemediacentre.org/working-with-us/for-journalists/headlines-for-journalists/
‘Bisphenol A Exposure and the Development of Wheeze and Lung Function in Children Through Age 5 Years’ by Adam J. Spanier et al. published in Jama Pediatrics on Monday 6th October.
All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/?s=bisphenol&cat=