Mini-Symposium: Maternal Diseases Effecting the NewbornPulmonary Effects of Maternal Smoking on the Fetus and Child: Effects on Lung Development, Respiratory Morbidities, and Life Long Lung Health
Introduction
Maternal smoking during pregnancy continues to be a large public health problem and can have lifelong effects on childhood respiratory health [1], [2]. In-utero smoke exposure has significant effects on the developing lungs with long lasting/permanent structural changes, altered pulmonary function, increased respiratory illness, and an increased risk of asthma. It is also the largest preventable cause of preterm delivery and low birth weight, which are also important determinants of childhood pulmonary function. This review will outline the current epidemiology of smoking during pregnancy with its complex underpinnings and evidence of lifelong pulmonary effects. We will then synthesize the current evidence of the important mechanisms by which in-utero smoke affects lung development including genetic/epigenetic influences of susceptibility. Finally, we will discuss emerging alternative modes of nicotine exposure and important areas of future research to protect lung development.
Section snippets
Prevalence of smoking during pregnancy
Internationally, the prevalence of maternal smoking during pregnancy varies widely by country, and widely by state in the United States (US). Among European countries, smoking during pregnancy rates range from lows of 5% in countries such as Sweden, Austria, and Switzerland to mid-levels of 15-20% in the Netherlands, Serbia, and Croatia, and to highs of 40% in Greece [3], [4], [5]. Rates are generally lower in Asia, Africa and the Middle East, though the rate approaches 15% in Turkey [6]. While
Childhood respiratory health after maternal smoking in pregnancy
Multiple studies have shown increased lower respiratory illness in infants born of mothers who smoke [20], [21], [22], [23]. Taylor and Wadsworth [22] studied 12,743 children and found significantly increased bronchitis and hospital admissions for lower respiratory illness in children from smoking mothers. Tager et al. [24] also found increased lower respiratory illness with prenatal but not with postnatal exposure. Similarly, multiple studies have shown increased wheezing and asthma in
Childhood pulmonary function testing
Infants born after in-utero smoke exposure are reported to have altered pulmonary function tests soon after delivery and prior to any significant postnatal smoke exposure, supporting the impact of in-utero smoke exposure on fetal lung development. These changes include altered tidal breathing patterns, decreased passive respiratory compliance, and decreased forced expiratory flows [33], [34], [35]. Such changes in pulmonary function test (PFT) measurements were also seen in preterm infants
Genetic and epigenetic factors
Not all children born after in-utero smoke exposure have decreased PFTs and increased respiratory morbidity. This variability in manifestation may, in part, be due to differences in maternal and fetal genetic susceptibility and/or epigenetic factors. The role of genotype relative to the development of asthma, sensitivity to maternal smoking, and difficulty in quitting smoking have been demonstrated in recent studies [37], [38], [39].
CYP1A1 and GSTT1 are enzymes involved in the metabolism and
Lessons from animal models: the role of in-utero nicotine in affecting lung development
As outlined above, there is robust data that in-utero smoke exposure leads to reduced pulmonary function in the offspring. There are many potential mechanisms through which in-utero smoke exposure may impact lung development including the thousands of chemicals found in tobacco smoke, hypoxemia due to carbon monoxide, alterations in placental structure, and toxins among many other factors. Tobacco smoke contains thousands of compounds such that identifying whether one or more plays a key role
Potential approaches for primary prevention
A recent Cochrane review [50] concluded that smoking cessation programs reduce the proportion of women who smoke and reduce the rate of preterm birth. This review concluded that the effect was larger when counseling was combined with other strategies such as providing feedback with biochemical measures. It also found incentive based interventions to be effective, but these randomized controlled trials were underpowered to assess the effect on preterm births. A recent meta-analysis [51]
Risks of e-cigarette use during pregnancy
Given that nicotine appears to be the primary ingredient in tobacco smoke that affects lung development, use of electronic nicotine delivery devices (referred to as e-cigarettes from here on) during pregnancy is an area of major concern [57]. In the last few years, use of e-cigarettes has increased almost exponentially especially among younger people [58]. This increase in use is coupled with a perception of safety of e-cigarettes that has yet to be proven. While e-cigarettes are potentially
Conclusions
The developing fetal lung is very sensitive to the effects of in-utero tobacco products with altered lung function demonstrated at birth that is long lasting and likely affects subsequent lung trajectory and lung health. These deficits are consistently demonstrated as decreases in forced expiratory flows, among others, and are likely mediated by nicotine crossing the placenta to interact with nicotinic acetylcholine receptors that are expressed in fetal lung. Since in-utero smoke/nicotine
Directions for Future Research
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Development of more effective smoking cessation strategies during pregnancy.
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Evaluate the effect of the maternal use of electronic nicotine delivery systems on the developing lung and develop strategies to prevent such usage.
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Development of strategies such as vitamin C supplementation to reduce the risk of adverse childhood lung outcomes in the face of in-utero smoke exposure.
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Better understanding of the role of epigenetics in mediating lifetime effects of in-utero tobacco exposure on offspring
Educational Aims
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To review the changes in pulmonary function in offspring after in-utero smoke or nicotine exposure.
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To consider the key mechanisms by which in-utero smoke/nicotine affects lung development.
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To outline potential interventions (both smoking cessation and therapeutic) which might protect lung development and improve lung trajectories.
Acknowledgement
NIH grants HL080231 with co-funding from ODS, HL087710, HL105447, UL1 RR024140 and P51 OD011092, CA 151601.
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