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Paternal smoking during pregnancy and the risk of childhood brain tumors: results of a meta-analysis.

OBJECTIVE
Prior epidemiological studies suggest a possible association between paternal smoking during pregnancy and risk of childhood brain tumors (CBT). A meta-analysis was performed statistically pooling all available observational studies on this topic in order to evaluate this suspected association.


METHODS
Using previously described methods, a protocol was developed for a meta-analysis examining the association between paternal smoking during pregnancy and subsequent development of primary brain tumors in their offspring. Literature search techniques study inclusion criteria and statistical procedures were prospectively defined. Data from epidemiological studies were pooled using a general variance based meta-analytic method employing confidence intervals previously described by Greenland. The outcome of interest was a summary relative risk (RRs) reflecting the risk of childhood brain tumor development associated with father's smoking during the index pregnancy. Sensitivity analyses were performed when necessary to explain any observed statistical heterogeneity and/or to evaluate the impact of demographic or study characteristics on the summary estimate of effect.


RESULTS
Seven observational studies meeting protocol specified inclusion criteria were obtained via a comprehensive literature search. These studies enrolled a total of 3,600 patients. Analysis for homogeneity demonstrated that the data were homogeneous (P = 0.52) and could be statistically combined. Pooling all seven reports yielded a RRs of 1.29 (1.07-1.53), a statistically significant result suggesting a 29% increased risk of brain tumor development associated with paternal smoking during pregnancy. An analysis of father's smoking impact on CBT risk based on "ever" versus "never" smoking history gave a RRs of 1.14 (0.98-1.34), a marginally non-statistically significant result.


CONCLUSION
The available epidemiological data suggest an association between paternal smoking during pregnancy and pediatric brain tumor development. Although this association is biologically plausible, limitations in study designs limit definitive conclusions based on available data.