To investigate the role of maternal asthma in offspring asthma, we performed a meta-analysis of multiple studies to determine if a parent of origin effect exists. In our meta-analysis of 33 studies, maternal asthma predisposes offspring to disease more so than paternal asthma. This effect is modest (OR 3.04 versus 2.44), but statistically significant. This demonstrates that non-genetic in utero
and/or post-natal factors may play a significant role in the transmission of asthma susceptibility. How these factors could induce asthma susceptibility has not been elucidated. However, animal models have demonstrated the potential for transplacental passage of ‘pro-asthmatic’ mediators (e.g. Th2 cytokines, immunologic cells, etc.), which could theoretically be capable of modifying the developing fetal immune system [reviewed 
]. Alternatively, or in addition to, it is possible that post-natal exposures such as maternal breast milk could shape the developing immune system. Murine models have demonstrated that breast milk from asthmatic mothers can induce asthma susceptibility in offspring 
. Human studies have also demonstrated that breast feeding can affect offspring asthma/lung function 
. The mechanisms for the phenomenon demonstrated in this meta-analysis require further study using animal models.
When analyzing the studies in which asthma was diagnosed by a physician, in studies which were population based or in studies with a patient population >/
5 years of age, the maternal effect remained more prominent than the paternal effect, though the magnitude of the difference was attenuated for some analyses. The subgroup analyses had fewer individuals and thus reduced power in comparison to the overall analysis. When analysing smaller subgroups subsequent to the principal analysis the chance of spurious findings may increase. Had more studies fit the quality criteria, then the differences may not have been attenuated. There were also potential confounding factors for this analysis that were not considered. These are discussed below.
This meta-analysis has several drawbacks that warrant discussion. There are multiple known risk factors for asthma, which this meta-analysis did not control for. For example, both in utero
and ex utero
exposure to tobacco smoke can increase the risk of wheezing/asthma 
. Lower socioeconomic status is also associated with increased asthma susceptibility 
. In addition, breasting feeding can affect asthma risk and lung function depending on timing and maternal disease status 
. This meta-analysis did not exclude studies that did not control for such exposures, nor was it used as quality criteria. This was because few studies controlled for such exposures. Exposure to such factors is likely to happen independent of maternal or paternal disease status. Therefore, inclusion of these studies would make it less likely to discover a significant difference between maternal and paternal asthma. Despite this, the overall summary OR of this study demonstrated that maternal asthma, more so than paternal asthma, is a significant risk factor for offspring asthma. The inclusion of studies that did not control for exposures to asthma risk factors may explain in part why the trend was preserved in subgroup analysis, but lost statistical significance.
It should also be noted that 4 retrieved studies were not used in this analysis because their data was not compatible with our meta-analysis. Of the four papers, two showed a greater role for paternal asthma versus maternal asthma in offspring asthma risk 
. As these papers used regression, it is difficult to extrapolate how they would have affected the analysis were their data able to be included.
A common problem in meta-analysis is publication bias. Based on Eggers test and a symmetrical funnel plot, this study is free from publication bias. Also, for most of the studies used in this paper, the finding that maternal asthma conferred greater risk to offspring was not the primary endpoint. This further decreased the likelihood of publication bias.
Based on this meta-analysis, maternal asthma increases offspring disease risk to a greater extent than paternal disease. This can be interpreted to mean that the increased asthma risk conferred by maternal disease is not due solely to genetic inheritance. These findings are consistent with experimental studies demonstrating that maternal asthma/exposures in animal models can induce asthma susceptibility in offspring 
, and support the need for further work in elucidating the mechanisms for the ‘maternal effect.’