Tobacco Documents Online

3 (iv) The authors assume that they are talking of an ETS effect and that mothers who smoke in pregnancy would do so afterwards. However, this need not be so - why should an in utero effect be ruled out? While the study adds somewhat to the evidence of an association between ETS and meningococcal disease, it still leaves many unanswered questions. P N Lee 12.10.99

2 (i) In commenting on these findings a few points are relevant: The literature on meningococcal disease, which merits fuller review, is not all that consistent. Some studies report an association with ETS and not active smoking, some with active smoking and either not with ETS or more strongly with active smoking than with ETS (see my review 710). (ii) The interpretation of any relationship with ETS or active smoking, even if it can be clearly demonstrated, is difficult. It is evident that neisseria meningitidis is the major cause of the disease, and it seems unlikely that tobacco smoke would normally contain such an agent. Association might arise for various reasons, including: (a) smoke particles might act as a vehicle for transmission of infection. (b) smoking or ETS might effect the ability of the body to resist infection (e.g. as suggested by Yusuf el al by effects on mucosal integrity or on the immune system), and (c) smokers or passive smokers might have lifestyles that make them more prone to infection. In this context it is noteworthy that adjustment for other maternal characteristics substantially reduced the relative risk associated with maternal smoking during pregnancy, from 4.48 to 2.93. If such adjustment can explain so much (45%) of the crude excess risk, why should not fuller control for potential confounding variables explain much more, and perhaps all, of the association? (iii) There are no details on how data on maternal smoking in pregnancy (and other maternal characteristics) happen to be available in the "birth certificate file", but in the discussion it is noted that other researchers have estimated that about I in 3 women who smoke during pregnancy fail to admit it in this scenario. The authors comment that "under- reporting of material smoking would bias the potential association between smoking and meningococcal disease towards the null" but this is not necessarily so, if denial is associated with other relevant variables.

1 REVIEW 1073 CONFIDENTIAL Subiect ref 8d "Maternal cigarette smoking and invasive meningococcal disease: a cohort study among young children in Metropolitan Atlanta, 1989-1996" H R Yusuf et al American Journal of Public Health (1999), 89 712-717 This paper describes results of a study involving over 280,000 young children born to mothers residing in Atlanta, Georgia, USA in 1989-1995. A surveillance system identified 55 cases of invasive meningococcal disease, of which 8 were excluded from the study because they were not born in the study area or information was missing on maternal smoking during pregnancy or maternal education level. For the remaining 47, 4 of which died, data were available from the birth certificate data file on sex, birthweight and gestation of the child, and on the age, race, education, marital status and smoking habits during pregnancy of the mother and her use of Medicaid. In simple univariate analysis, the authors found that 16 of the cases of invasive meningococcal disease occurred in the 29,267 children whose mothers smoked during pregnancy, a rate, 0.0547%, which was 4.48 times higher (p < 0.05) than that (31/254024 = 0.0122%) in children whose mothers did not smoke during pregnancy. In a Cox multivariate analysis, which took into account length of follow-up and adjusted for five other characteristics (see Table 3) the relative risk was estimated to be 2.93 (95% CI 1.52 - 5.66). The authors, who cite evidence ofthe association between exposure to tobacco smoke and meningococcal disease in seven other studies, conclude that "Maternal smoking, a likely surrogate for tobacco smoke exposure following delivery, appears to be a modifiable risk factor for sporadic meningococcal disease in young children".