Discussion
The results of this study show that in utero exposure to maternal smoking is associated with a reduction in small airway flow rates, after accounting for any lifetime household ETS exposure. Although ETS exposure was also associated with lower small airway flows, the deficits were substantially reduced when adjusted for in utero exposure. Using mutually exclusive exposure categories, we found further evidence that in utero exposure is independently associated with small airway flows. There was little evidence that lung volume was adversely affected by either in utero or ETS exposures.
A growing body of evidence supports the plausibility that in utero exposure can produce persistent deficits in childhood lung function.5 7 9 10 13 17-21 Recent studies of lung function in neonates and infants of mothers who smoked during pregnancy have shown that in utero exposure is associated with reduced lung function in the perinatal period.7 9 12 18 20 Studies of neonates in East Boston and Perth, which excluded effects of ETS by measuring lung function near birth, reported an independent effect of in utero exposure on respiratory mechanics.7 12 The deficits observed at birth appear to persist into childhood and adolescence, especially in measures associated with small airway flow rates.5 19 21 The relative contribution of in utero exposure to maternal smoking and postnatal ETS exposure to persistent deficits in lung function is less clear.5 21 In an analysis of white children from 24 cites Cunninghamet al reported that the effect of maternal smoking during pregnancy on lung function was larger than that for current smoking and was not reduced by adjustment for current smoking.6 The effects of current smoking were small and were not significant after adjustment for smoking during pregnancy. These investigators also noted a larger effect on measures of small airway flows than on lung volumes. Another study of inner city children by the same group of investigators also suggested an independent effect of in utero exposure to maternal smoking.21 In contrast, studies conducted in the Netherlands and New Zealand found that in utero exposure had no effect or that the effects of ETS were independent of in utero exposure.22 23 A recent summary meta-analysis concluded that in utero exposure is likely to be associated with persistent deficits in flow indices.13 Our findings support the hypothesis that in utero exposure is independently associated with persistent deficits in lung function. Our data are also consistent with an additional contribution from ETS exposure to lung function deficits in those with in utero exposure. More studies are needed, especially results from longitudinal studies, to determine whether current exposure produces an additional decrement in lung function.
The biological mechanisms for deficits in lung function from in utero exposure to maternal smoking have not been clarified. Because the airways are fully developed at birth, it may be that the small airway deficits from in utero exposure reflect premature maturation or damage during critical periods of development that permanently alter the structure or function of the lung, such as its elastic recoil properties or immune function.13 The effects may also be mediated through the increased occurrence of perinatal respiratory problems or early infection associated with in utero exposure.24
There are some limitations that influence the interpretation of our cross sectional results. Exposure to tobacco smoke was assessed retrospectively using questionnaire responses and was not validated by objective measurements. However, exposure estimates based on questionnaire responses have been validated.3 25-28 It is possible that more misclassification of the ETS metrics than for in utero exposure could create a larger bias toward the null in the effect estimates for ETS exposure than for in utero exposure. However, because the routes and levels of exposure as well as the constituents vary qualitatively and quantitatively, the relative effects of misclassification are difficult to assess. We were unable to investigate any dose-response relationships for in utero exposure because we lacked information on the intensity or duration of exposure. We also lacked information on a number of potential confounders such as maternal nutritional status and intake of alcohol or other potentially toxic substances during pregnancy. Our modelling strategy for pulmonary function tests may also have introduced errors into our effect estimates.29 30 We used log-linear models to adjust for differences in pulmonary function tests arising from differences in anthropometric and demographic variables. Although pulmonary function tests are non-linearly related to height, we found that there was a linear relationship between the log transformed variables within age groups, indicating that the modelling assumptions are unlikely to be grossly violated. Furthermore, results from analyses stratified by grade, sex, or race were consistent with those from the models that included all participants. We also examined the validity of our assumptions using flexible models and found that the data were consistent with linear relationships. Our modelling approaches are unlikely to lead erroneously to the results presented in this study.
Our findings may have clinical and public health significance. The long term effects of in utero exposure on the growing lungs of children are of particular concern. In utero exposure is associated with lower lung function in childhood. The reductions in small airway flows may reflect more extensive underlying pathological and functional alterations in the distal airways than their magnitude suggest. If these deficits persist into adulthood, they may indicate increased risk for chronic obstructive pulmonary disease, lung cancer, and cardiovascular diseases.23 31-34 Reducing the burden of chronic respiratory diseases associated with tobacco smoke may require the reduction of smoking among women during their childbearing years.