Prenatal Tobacco Smoke Exposure Increases Hospitalizations for Bronchiolitis in Infants

Marcello Lanari; Silvia Vandini; Fulvio Adorni; Federica Prinelli; Simona Di Santo; Michela Silvestri; Massimo Musicco

Disclosures

Respiratory Research. 2015;16(152) 

In This Article

Discussion

The results of this study demonstrate that passive TSE and heavy active smoke exposure during pregnancy increases the risk of hospitalization for bronchiolitis during the first year of life, and in particular, during the first 3 months of life, while postnatal TSE does not significantly increase the risk in our cohort. These results could be explained by the fact that passive exposure is less preventable than active smoking, which is often interrupted during pregnancy. Our results suggest that the detrimental effect on lung development and subsequent higher risk for hospitalization may depend mostly on prenatal exposure rather than to postnatal TSE. This could be due to the fact that most mothers quit smoking during the first trimester, however by this time, the pulmonary system reaches its full development and therefore deleterious influences could play a major role.

The detrimental effects of TSE during pregnancy on fetal growth and lung development have been widely studied. Fetal TSE increases the risk for intrauterine growth retardation, prematurity and impaired lung development through placental vascular damage induced by cotinine, which causes placental insufficiency and nutritional deprivation that may interfere with growth and lung maturation[22] and through epigenetic mechanisms.[23–25] These mechanisms are determined by several metabolites derived from tobacco smoke that have low molecular weight and are able to cross the placenta and induce oxidative damage, mitochondrial dysfunction and chronic hypoxia leading to genetic modifications that affect fetal growth and development.[26,27] Appropriate development of fetal lung requires adequate nutritional intake and placental blood flow as well as the precisely timed gene expression that is, in part, dependent from the extensive combination of DNA methylation and histone modifications. Thus the interference with the normal epigenetic modifications during fetal life can alter gene transcription and may alter lung growth and function.[24,27]

Recently, some authors have observed that fetal growth is also influenced by maternal grandmother smoking habits during pregnancy[28,29] of non-smoking mothers, likewise, the attitude toward smoking of the grandmother is associated to an elevated risk of asthma in children.[30,31] The mechanism hypothesized for these effects include a cascade of metabolic knock-on effects involving initial somatic metabolic in utero "programming" of the mother and a direct effect of grandmaternal smoking on oogenesis of her own daughter when she was a fetus.[32,33] It is possible that by modifying DNA methylation patterns in the fetal oocytes, tobacco-derived metabolites may interfere with both immune function and xenobiotic detoxification mechanisms in the offspring, resulting in an increased susceptibility to respiratory diseases affecting the subsequent generation.

In our study, we found that active smoking during pregnancy has an effect on the risk for bronchiolitis hospitalization that is dose-dependent. We defined heavy smoking mothers who smoked more than 15 cigarettes/day, as previously done in another study,[34] with the aim to emphasize the effect of a discrete number of cigarettes. The dose-dependency of active smoking during pregnancy was observed also for growth restriction in previous studies.[27,35] This result suggests that a reduction in the number of smoked cigarettes, particularly in heavy smokers, may reduce the risk for hospitalization in infants. Moreover, active smoking during pregnancy was associated to lower GA, confirming the effect of tobacco smoke on the risk of preterm birth; the effect of active smoke however was confirmed by the multivariate analysis, establishing that it is independent from GA.

To date, only a few studies have distinguished between prenatal and postnatal TSE and their consequences on respiratory health in early life.[36,37]

The study by Jaakkola et al.[38] demonstrates the strongest adverse effects of tobacco smoke on the lower respiratory tract when smoking takes place during pregnancy. In prenatally exposed children, postnatal exposure from either parent did not significantly increase the occurrence of the respiratory health outcomes analysed by Fuentes-Leonarte et al..[39]

TSE in infants may cause bronchial hyper-reactivity and direct toxic and irritant effects on the lungs and the airways.[23] TSE may increase the susceptibility to pathogens due to impaired protective mechanisms of the airways and bronchial tree, such as mucociliary clearance.[4] Infants of women smokers are more likely to have diminished lung function soon after birth, which could contribute to the development of acute respiratory outcomes such as infections as its concomitant symptoms.[40] We found that postnatal TSE during the first year of life was associated to a slightly higher hospitalization rate without reaching the statistical significance. This limited time span may underestimate the total effect of exposure since assessing respiratory tract infections at older ages might show stronger effects. However, our results are consistent with those obtained by Duijts et al.[41] which analysed a prenatally enrolled birth-cohort and showed weak evidence for an association of maternal smoking in the early postnatal period with bronchiolitis in infants in the first 6 months of life.[41]

The strength of the present study is the prospective analysis of a large birth cohort and the inclusion of a large number of other variables that may interact with TSE in the increase of bronchiolitis severity and hospitalization.

One of the limits of the present study is that TSE was assessed on subjective parent report, however other studies reported good agreement between self-reported exposure and biochemical markers dosed in the household environment and in urine samples.[42–44] Another limitation is related to the fact that we considered only hospitalizations for bronchiolitis and therefore factors related to both the propensity to recur to hospitalization and to TSE, such as socio-cultural conditions of the parents, which may act as confounders of our results. Nevertheless, we hold the conviction that the universal coverage of the Italian National Health Service, which is free for every Italian citizen, guarantees virtually equal access to hospital medical care to everyone in cases concerning severe bronchiolitis. In our cohort study, heavy active smoking during pregnancy was associated to lack of breastfeeding and to crowded living conditions, and it was more frequent if parents had only primary level education. This data could be explained by the lower attention paid by a subgroup of women during pregnancy to campaigns promoting prenatal and neonatal health. This is an interesting note as it could be useful to identify pregnant women that may require an implementation of counselling to promote breastfeeding and to improve the overall living conditions of their newborns.

Our study supports the evidence of the strongest effects of TSE during pregnancy and supports that smoking cessation campaigns should target all family and household members as well as colleagues in workplaces of non-smoking expecting mothers. Moreover, the knowledge of the detrimental effects of TSE on infants could increase awareness regarding the importance of reducing second-hand smoke exposure, not only in public places but in private households as well as.

Health professionals play a pivotal role in promoting the cessation of active smoking and passive smoke exposure in pregnant women and more should be done: a recent Australian study[45] reported that less than half pregnant women were discourage to stop smoking by healthcare professionals.

Data obtained in the present study could be used by practitioners, obstetricians, neonatologists, pediatricians, midwives and other healthcare professionals in order to improve the information provided during counselling to pregnant women and new parents about the risks of TSE on their offspring. Extended follow up of this cohort of children will allow us to establish whether these exposures are important predictors of asthma in later childhood and a possible cause of permanent impairment of pulmonary function. Moreover, further investigations could be useful to clarify the effect of TSE in pediatric patients with other well known risk factors for hospitalization for bronchiolitis (i.e., prematurity, congenital heart disease, chronic lung disease, immunodeficiency, neuromuscular disease.

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