Secondhand smoke linked to childhood meningitis

«Meningitis link to smoking in pregnancy: Cigarettes can treble child’s chance of developing the disease,» the Daily Mail reports.

The headlines follow the publication of a review that has looked at whether children exposed to secondhand smoke (passive smoking) could be at increased risk of meningococcal meningitis. Meningococcal meningitis (caused by the bacteria Neisseria meningitidis) is the most common type of bacterial meningitis in the UK. If it progresses to a blood infection (septicaemia), the condition can be fatal.

The 18 studies included in the review found that children and adolescents exposed to any secondhand smoke in the home were at more than double the risk of meningococcal meningitis or septicaemia.

However, it is difficult to conclude that secondhand smoke is the direct cause of the increased risk. This is because the studies did not all take into account other factors that could be influencing the association. The individual studies that were pooled in the review also differed quite considerably in their methods, the study populations included, the smoking exposures and the meningitis outcomes that they measured. Also, despite the media’s focus on smoking in pregnancy, only one study actually examined this and this study alone doesn’t provide reliable evidence of the risk.

Despite its limitations, this valuable review does suggest another possible harm from passive smoking, in addition to those already established.

Where did the story come from?

The study was carried out by researchers from the University of Nottingham and was funded by Cancer Research UK, the British Heart Foundation and the UK Clinical Research Collaboration.

It was published in the open-access medical journal BMC Public Health. The current publication is provisional, meaning that although the article has been accepted, there may be some revisions in the final publication.

The Mail’s focus on smoking during pregnancy is unjustified. This review included 18 studies and only one looked at the effect of smoking in pregnancy. Much more study is needed to examine this link before more reliable conclusions can be drawn.

What kind of research was this?

The researchers claim that growing evidence suggests children exposed to secondhand smoke – for example at home – can be at increased risk of meningococcal meningitis. The current study is a systematic review and meta-analysis. It explores the evidence by combining the results of observational studies that have looked at the association between a child’s secondhand smoke exposure and meningitis risk. The researchers have looked, in particular, at the size of the risk associated with smoking:

• by any household member
• by individual family members
• by maternal smoking before and after birth

Prospective cohort studies are the best way of looking at whether a particular exposure, such as secondhand smoking, is associated with an increased risk of a disease outcome, such as meningitis. Case-control studies can be used for rare diseases, such as meningitis, and they usually look back at past exposures. However, this can reduce the reliability of the assessments because people have to remember what happened in the past. The other main limitation to observational studiessuch as cohort and case-control studies, is that factors other than that being investigated may differ between the groups being compared (these are called confounding factors).

A systematic review is the best way of looking at all existing research on a question of interest. However, they have inherent limitations because the design, quality and methods of the individual studies often vary – for example, the methods used to assess smoking exposure and meningitis outcomes. The included studies may also have differed in whether they adjusted for confounders, such as socio-economic status, diet and activity.

What did the research involve?

The researchers searched medical literature databases to identify any cohort, case-control or cross-sectional studies published up to June 2012 that had looked at the association between secondhand smoke exposure and risk of meningococcal meningitis in under 18s.

The researchers searched for studies looking at any type of secondhand smoke exposure, including parental or household exposure, exposure from a carer or other family members. They included studies in which secondhand smoke was either self-reported or measured biologically (such as looking at nicotine by-products in saliva samples). The researchers categorised secondhand smoke exposure as occurring:

• before birth (while the baby was in the womb)
• after birth (postnatal)
• during infancy (no clear distinction is given in the paper of when they considered the ‘postnatal’ period to have ended and the ‘infancy’ period to have started)
• during childhood

The researchers did not include studies looking at active smoking by the child.

The outcomes they looked at were meningococcal meningitis (or septicaemia) diagnosed by a doctor or by laboratory confirmation (such as meningococcal bacteria in the blood).

Different researchers assessed the quality of the included studies and carried out statistical tests looking at how different the results of the individual studies were (heterogeneity).

What were the basic results?

The researchers identified 18 eligible studies. These included 15 case-control studies (looking at groups of children with and without meningococcal meningitis and whether they had been exposed to secondhand smoke) and two cohort studies (which followed children exposed and not exposed to secondhand smoke and looked at whether they went on to develop meningococcal meningitis).

The case-control studies included between 47 and 505 children with meningococcal meningitis and between 51 and 9,240 controls. The cohort studies included 288 and 283,291 people, with the former including 144 children with meningococcal meningitis and the latter 55 children with meningococcal meningitis.

All of the included studies assessed exposure to secondhand smoke using questionnaires. Ten of the studies looked at both laboratory diagnoses of meningococcal meningitis (or septicaemia) and clinically suspected but unconfirmed cases of infection. Eight studies included only those with laboratory diagnosis. Studies were performed internationally and included study populations from countries in Europe, Australasia, America and Africa.

A pooled analysis of 17 studies demonstrated that children with any secondhand smoke exposure in the home had at least double the odds of meningococcal meningitis or septicaemia (odds ratio 2.18, 95% confidence interval 1.63 to 2.92). There was significant heterogeneity between the studies, demonstrating that the results of individual studies were quite different. When splitting the studies according to quality, they found that poorer quality studies found stronger risk associations (higher risks of infection associated with secondhand smoke) than the better quality studies.

When looking at the effect of secondhand smoke according to the age of the child they found that the effect tended to be greater in younger children. Exposure to secondhand smoke was associated with about 2.5 times the odds of meningitis or septicaemia in the five studies where the children were specifically described to be under 5 years (odds ratio 2.48, 95% confidence interval 1.51 to 4.09). This compared with a doubling of the odds in the 12 studies where the children were aged less than 18 years (odds ratio 2.02, 95% confidence interval 1.44 to 2.85).

Only one study looked at the specific effect of maternal smoking during pregnancy. This single study found an almost tripled risk of childhood meningococcal disease in children whose mother smoked during pregnancy (odds ratio 2.93, 95% confidence interval 1.52 to 5.66). Seven studies (with significant heterogeneity) had specifically looked at the effect of smoking by the mother after birth (postnatal exposure) and found that the risk was more than doubled (odds ratio 2.26, 95% confidence interval 1.54 to 3.31).

The distribution of the results of the published studies suggested that there may have been other studies that did not find a link between secondhand smoke and meningococcal disease that have not been published. The researchers used a method to estimate what the results of these studies might be and pooled them with the published studies. This gave a smaller increase in risk associated with secondhand smoke, but it was still statistically significant (odds ratio 1.59, 95% confidence interval 1.17 to 2.15).

Using their overall results the researchers estimated that an extra 630 cases of childhood meningococcal disease a year arise due to secondhand smoke exposure in UK homes. If they used the results that took into account potentially missing studies this reduced the number to an extra 350 cases of childhood meningococcal disease a year arising due to secondhand smoke exposure in UK homes.

How did the researchers interpret the results?

The researchers report that secondhand smoke exposure significantly increases the risk of childhood meningococcal disease. In their conclusions they take a more cautious approach, saying that “there seems to be some evidence to support secondhand smoke as a causative factor of meningococcal disease”.

Conclusion

This valuable review provides further evidence of the potential harmful effects of smoking. This time research suggests that children exposed to secondhand smoke may be at increased risk of developing meningococcal meningitis. The review has strengths in that it has systematically looked at and included all available observational studies that have examined the link, and that it focused specifically on one type of meningitis.

However, there are important limitations that make it difficult to conclude that passive smoking is the direct cause of the association:

• The individual studies did not all take into account potential confounding factors that could be involved in the association between smoke exposure and meningitis risk. Relevant confounders may include factors such as socio-economic status, diet and activity levels of the parents and their children.
• The individual studies have also differed in their study populations, the smoking exposures that they measured and the outcomes they included. The pooled results had a high degree of statistical heterogeneity, demonstrating that the individual studies had results that were quite different from each other. This makes it difficult to know for sure what the true size of the association is.
• While the media has focused on risk from smoking during pregnancy, only one of the 18 studies examined this association. More prospective studies that followed up over time the children of mothers who smoked during pregnancy would be needed to see if there were a clear link.

Despite the limitations this valuable review provides evidence of another possible harm from passive smoking, in addition to those already well established.