Elsevier

Paediatric Respiratory Reviews

Volume 21, January 2017, Pages 27-33
Paediatric Respiratory Reviews

Mini-Symposium: Maternal Diseases Effecting the Newborn
Pulmonary Effects of Maternal Smoking on the Fetus and Child: Effects on Lung Development, Respiratory Morbidities, and Life Long Lung Health

https://doi.org/10.1016/j.prrv.2016.08.005Get rights and content

Summary

Maternal smoking during pregnancy is the largest preventable cause of abnormal in-utero lung development. Despite well known risks, rates of smoking during pregnancy have only slightly decreased over the last ten years, with rates varying from 5-40% worldwide resulting in tens of millions of fetal exposures. Despite multiple approaches to smoking cessation about 50% of smokers will continue to smoke during pregnancy. Maternal genotype plays an important role in the likelihood of continued smoking during pregnancy and the degree to which maternal smoking will affect the fetus. The primary effects of maternal smoking on offspring lung function and health are decreases in forced expiratory flows, decreased passive respiratory compliance, increased hospitalization for respiratory infections, and an increased prevalence of childhood wheeze and asthma. Nicotine appears to be the responsible component of tobacco smoke that affects lung development, and some of the effects of maternal smoking on lung development can be prevented by supplemental vitamin C. Because nicotine is the key agent for affecting lung development, e-cigarette usage during pregnancy is likely to be as dangerous to fetal lung development as is maternal smoking.

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

  • Development of more effective smoking cessation strategies during pregnancy.

  • Evaluate the effect of the maternal use of electronic nicotine delivery systems on the developing lung and develop strategies to prevent such usage.

  • 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.

  • Better understanding of the role of epigenetics in mediating lifetime effects of in-utero tobacco exposure on offspring

Educational Aims

  • To review the changes in pulmonary function in offspring after in-utero smoke or nicotine exposure.

  • To consider the key mechanisms by which in-utero smoke/nicotine affects lung development.

  • 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.

References (66)

  • N.N. Dhalwani et al.

    A comparison of UK primary care data with other national data sources for monitoring the prevalence of smoking during pregnancy

    J Public Health (Oxf)

    (2015)
  • K.B. Filion et al.

    The effect of smoking cessation counselling in pregnant women: a meta-analysis of randomised controlled trials

    BJOG

    (2011)
  • V.T. Tong et al.

    Trends in smoking before, during, and after pregnancy--Pregnancy Risk Assessment Monitoring System, United States, 40 sites, 2000–2010

    MMWR Surveill Summ

    (2013)
  • N.L. Gilbert et al.

    Temporal trends in social disparities in maternal smoking and breastfeeding in Canada, 1992–2008

    Matern Child Health J

    (2014)
  • M.S. Hossain et al.

    Prevalence and correlates of smokeless tobacco consumption among married women in rural Bangladesh

    PLoS ONE

    (2014)
  • S.J. Anderson et al.

    Emotions for sale: cigarette advertising and women's psychosocial needs

    Tob Control

    (2005)
  • J.R. DiFranza et al.

    Tobacco promotion and the initiation of tobacco use: assessing the evidence for causality

    Pediatrics

    (2006)
  • R.S. Kahn et al.

    A reexamination of smoking before, during, and after pregnancy

    Am J Public Health

    (2002)
  • J.E. Sarginson et al.

    Markers in the 15q24 nicotinic receptor subunit gene cluster (CHRNA5-A3-B4) predict severity of nicotine addiction and response to smoking cessation therapy

    Am J Med Genet B Neuropsychiatr Genet

    (2011)
  • J.Z. Liu et al.

    Meta-analysis and imputation refines the association of 15q25 with smoking quantity

    Nat Genet

    (2010)
  • D. Shipton et al.

    Reliability of self reported smoking status by pregnant women for estimating smoking prevalence: a retrospective, cross sectional study

    BMJ

    (2009)
  • O. Alshaarawy et al.

    Month-wise estimates of tobacco smoking during pregnancy for the United States, 2002–2009

    Matern Child Health J

    (2015)
  • P. Rantakallio

    Relationship of maternal smoking to morbidity and mortality of the child up to the age of five

    Acta Paediatr Scand

    (1978)
  • D.M. Fergusson et al.

    Parental smoking and respiratory illness in infancy

    Arch Dis Child

    (1980)
  • B. Taylor et al.

    Maternal smoking during pregnancy and lower respiratory tract illness in early life

    Arch Dis Child

    (1987)
  • P.A. Margolis et al.

    Urinary cotinine and parent history (questionnaire) as indicators of passive smoking and predictors of lower respiratory illness in infants

    Pediatr Pulmonol

    (1997)
  • I.B. Tager et al.

    Lung function, pre- and post-natal smoke exposure, and wheezing in the first year of life

    Am Rev Respir Dis

    (1993)
  • R. Zlotkowska et al.

    Fetal and postnatal exposure to tobacco smoke and respiratory health in children

    Eur J Epidemiol

    (2005)
  • E. Lannero et al.

    Maternal smoking during pregnancy increases the risk of recurrent wheezing during the first years of life (BAMSE)

    Respir Res

    (2006)
  • A. Bjerg et al.

    A strong synergism of low birth weight and prenatal smoking on asthma in schoolchildren

    Pediatrics

    (2011)
  • S. Pattenden et al.

    Parental smoking and children's respiratory health: independent effects of prenatal and postnatal exposure

    Tob Control

    (2006)
  • F.D. Gilliland et al.

    Effects of maternal smoking during pregnancy and environmental tobacco smoke on asthma and wheezing in children

    Am J Respir Crit Care Med

    (2001)
  • M.N. Upton et al.

    Maternal and personal cigarette smoking synergize to increase airflow limitation in adults

    Am J Respir Crit Care Med

    (2004)
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