Mini-Symposium: Maternal Diseases effecting the newbornAir pollution during pregnancy and lung development in the child
Introduction
Exposure to air pollution in-utero has long-term implications for respiratory health. Exposure events during pregnancy can significantly influence foetal and postnatal development and maturation. Germ and foetal cells are particularly sensitive to external exposure events due to their faster rates of replication, faster differentiation and higher sensitivity to surrounding signals compared with mature cells [1]. Prenatal environmental exposures may lead to an impaired organ development resulting in long term complications and disease in later life [2]. There is also growing evidence that environmental factors may affect gene expression permanently with trans-generational effects of intrauterine exposures. Children whose grandmothers smoked during pregnancy have a higher risk of developing asthma, independent of the smoking activity of the mother [3]. These data suggest an interplay of environmental and epigenetic effects [4], [5], and thus exposure events might influence prenatal development heterogeneously in individuals.
The importance of air pollution on respiratory health is amplified through its broad exposure. Although the health impact of air pollution on the individual might be smaller than other dangerous exposures, such as tobacco smoke, its significance as an environmental toxicant is ubiquitous as it cannot be avoided and affects large numbers of individuals. Evidence on the effects of prenatal exposure to tobacco smoke [6] and adverse effects of air pollution on neonatal health in general are reviewed elsewhere in detail [7], [8], [9], [10]. Exposure to air pollution during pregnancy plays also an important role in lung development and has been shown to affect respiratory health in different ways. Lung disease is a leading cause of morbidity and mortality world-wide, therefore, the effect of air pollution on lung health is of great interest, especially from a public health point of view [11]. This review will summarize current epidemiological evidence on the effects of air pollution exposure during pregnancy on lung function in childhood and children's respiratory health. As premature birth, lower birth weight and impaired development of the immune system could be associated with later respiratory disease in life, we also briefly summarize the influence of air pollution on these risk factors in this review.
Section snippets
Lung and Airway Development
Lung morphogenesis and development of airways begin at 4-7 weeks of gestation and reaches the alveolar phase at around 36 weeks of gestational age. Alveolarisation continues until adolescence or even early adulthood [12], thus, compared to other organs, the maturational process of the lung takes place over a relatively long time period. During early pregnancy, cellular differentiation and branching morphogenesis can be disturbed, whereas in late pregnancy, an impairment of structural and
Air pollution during pregnancy and lung function in childhood
A number of studies, in both unselected and in asthmatic children, have reported associations between maternal exposure to different pollutants during pregnancy and impaired lung function during infancy and childhood. Those studies are summarized in Table 1.
In the BILD (Basel-Bern infant lung development cohort) study [17], a prospective birth cohort study of unselected infants, air pollution exposure was assessed during pregnancy and lung function measurements were performed at the postnatal
Air pollution during pregnancy and respiratory health in children
If prenatal exposure to air pollution leads to impaired lung growth and airway development, it is likely that air pollution also leads to increased respiratory morbidity in those children. Indeed, a number of studies have found associations between prenatal exposure to air pollution and respiratory symptoms (detailed results are presented in Table 2). Jedrychowski and co-authors show that prenatal PM2.5 and PAH exposure are associated with more frequent episodes of wheezing in the first 2 years
Air pollution during pregnancy and prematurity and low birth weight
It is well established, that premature birth and/or low birth weight (LBW) are risk factors for a worse respiratory outcome later in life, including more frequent respiratory symptoms and lower lung function measurements [33], [34], [35], [36], [37]. Thus, the association between air pollution and premature birth and/or LBW needs to be taken into account. Both premature birth and LBW are important markers of intrauterine growth and development and are important predictors of morbidity. Both of
Air pollution during pregnancy and the development of the immune system
Another aspect that has to be taken into account when investigating the impact of prenatal air pollution on respiratory health is the role of the immune system early in life, as it is known to strongly influence later asthma development [48], [49]. Immune maturation and immune responses can be influenced by environmental exposures in early life [50] and thus, exposure to air pollution may influence immune programming [51]. Several studies have shown that maternal smoke exposure during pregnancy
Air pollution during pregnancy and infant mortality
Good evidence exists for an association between air pollution exposure during pregnancy and infant mortality as reported in a 2005 World Health Organisation review [58]. As the leading cause of post-neonatal mortality is for respiratory reasons, the impact of air pollution exposure on infant mortality may be significant [59]. A large study with a population of 3,583,495 births including 6,639 post neonatal deaths in 96 counties throughout the United States showed elevated odds for respiratory
Methodological considerations and possible mechanisms
To completely understand the associations between air pollution during pregnancy and lung health, important methodological issues regarding exposure assessment need to be considered. The precision of assessing individual exposure is crucial in estimating effects of air pollution on health. Estimating exposure during pregnancy is especially difficult, as women change their life style dramatically during pregnancy (e.g. stopping working, not performing the same sporting activities as usual or
Conclusion
As organogenesis of the lung continues throughout pregnancy, harmful effects of prenatal exposure to air pollutants on lung development seems inevitable and may continue to impact lung development later in life. Evidence for impaired lung function outcomes and increased respiratory symptoms following prenatal air pollution exposure are clearly supported by epidemiological studies. In addition to affecting lung development directly, air pollution exposure during pregnancy increases the risks of
Author disclosures
Insa Korten: no conflicts of interest exist.
Kathryn Ramsey: no conflicts of interest exist.
Philipp Latzin: no conflicts of interest exist.
Funding
The review was supported by the Fondation Botnar.
Educational aims
The reader will come to appreciate that:
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Air pollution in pregnancy leads to adverse birth effects.
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Air pollution in pregnancy influences postnatal lung development and respiratory health.
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There is interplay of direct and indirect impacts of prenatal air pollution on lung health.
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Environmental and epigenetic factors and individual exposure may contribute to the heterogeneous effects in different subjects.
Directions for future research
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Summarized in Table 3
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