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Harm of In Utero Tobacco Smoke ExposureHarm of In Utero Tobacco Smoke: A Heritable Trait? FREE TO VIEW

Harold J. Farber, MD, MSPH, FCCP
Author and Funding Information

From the Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine, Texas Children’s Hospital.

Correspondence to: Harold J. Farber, MD, MSPH, FCCP, Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine, Texas Children’s Hospital, 6701 Fannin, Ste 1040.00, Houston, TX 77030; e-mail: hjfarber@texaschildrens.org


Financial/nonfinancial disclosures: The author has reported to CHEST the following conflicts of interest: Dr Farber serves as Associate Medical Director for Texas Children’s Health Plan and on the executive committee of the (provisional) Section on Tobacco Control of the American Academy of Pediatrics. He is a member of the American Academy of Pediatrics Julius B. Richmond Center of Excellence Tobacco Consortium and Faculty Expert Panel.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(6):1182-1184. doi:10.1378/chest.13-2868
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Published online

The substantial harms of tobacco smoke exposure are becoming increasingly well documented. In utero tobacco smoke exposure is associated with an increased risk for prematurity, low birth weight,1 stillbirth, congenital malformations,2 sudden infant death,3 childhood obesity,4 behavior problems, and neurocognitive deficits.5 Prenatal exposure is associated with an increased risk of wheezing and poorly controlled asthma in early life and when assessed again during later childhood.6,7

Could in utero tobacco smoke exposure affect not only children but also grandchildren? The article by Miller et al8 in this issue of CHEST (see page 1213) suggests that it very well might.

The Avon Longitudinal Study of Parents and Children (ALSPAC) prospectively followed women and their children from pregnancy to the child’s 8th year of life. In utero tobacco smoke exposure of the parent was assessed retrospectively on interview during the pregnancy. The presence of asthma in the child (mother’s report of physician-diagnosed asthma) was assessed on prospective follow-up of the outcomes of the pregnancy. In a priori subgroup analyses from this dataset, Miller et al8 found that if the mother did not smoke during pregnancy and if the father was exposed to tobacco smoke in utero (ie, the prenatal exposure was that of the father during his gestation), the child’s risk of asthma is increased, especially if the child is a girl.

These results are exciting and provocative; however, there are a number of weaknesses in the study largely due to methodologic challenges in studying the impact of events that occurred 20 to 40 years previously in large observational samples. Secondhand tobacco smoke exposure was not assessed in the children’s grandmothers when the parent was in utero and, thus, could bias results toward the null. Tobacco-dependent grandparents serving as caregivers for their grandchild could bias results away from the null. Although secondhand exposure of the child was assessed, the assessment of whether the child had been present in a room with someone smoking can substantially underestimate his or her tobacco smoke exposure.9

That tobacco smoke exposure of one generation may affect the next generation is provocative and plausible. Tobacco smoke is a complex mixture of toxicants, mutagens, and carcinogens, and there is ample evidence that it can have an impact on genes and gene expression. Rodent studies have shown that nicotine exposure of the parents from gestation through early life can alter DNA methylation patterns in their gonadal tissue, with different effects on testes vs ovaries, and goes on to have an adverse impact on the lung function of second-generation offspring, even when the offspring had no nicotine exposure themselves.10 Studies of genetic material from newborns showed that in utero exposure is associated with altered DNA methylation patterns, with the degree of alteration proportional to the cord blood cotinine levels.11 DNA methylation patterns influence gene expression. Epigenetics refers heritable changes in gene activity that are not caused by changes in the DNA sequence. It is a mechanism where the environment can influence gene expression in a manner that can be passed down through generations. Epigenetic mechanisms have been postulated to account for the impact of in utero tobacco smoke exposure on the development of asthma and allergies.12 Whether epigenetic changes are reversible is not known; however, because adverse impacts of in utero tobacco smoke exposure on disease can be detected many years later, it is likely that many of these changes persist.

There is still much to be learned about how mutagenic and toxic exposures of one generation can affect the next. The study by Miller et al8 adds to an evolving literature by providing population-based evidence to suggest that tobacco exposure not only harms the smoker and his or her children but also can extend to the grandchildren. Because rodent studies implicate nicotine as a causative factor, the current rise in promotion of electronic nicotine delivery systems (eg, e-cigarettes, hookah sticks) to youth of reproductive age is particularly disconcerting.13 Although not a definitive study, when combined with existing knowledge on the substantial harms of in utero tobacco smoke exposure, the results should further escalate our concerns not just for our generation but for future generations as well.

References

Jaakkola JJ, Jaakkola N, Zahlsen K. Fetal growth and length of gestation in relation to prenatal exposure to environmental tobacco smoke assessed by hair nicotine concentration. Environ Health Perspect. 2001;109(6):557-561. [CrossRef]
 
Leonardi-Bee J, Britton J, Venn A. Secondhand smoke and adverse fetal outcomes in nonsmoking pregnant women: a meta-analysis. Pediatrics. 2011;127(4):734-741. [CrossRef]
 
Mitchell EA, Ford RP, Stewart AW, et al. Smoking and the sudden infant death syndrome. Pediatrics. 1993;91(5):893-896.
 
Weng SF, Redsell SA, Nathan D, Swift JA, Yang M, Glazebrook C. Estimating overweight risk in childhood from predictors during infancy. Pediatrics. 2013;132(2):e414-e421. [CrossRef]
 
Kabir Z, Connolly GN, Alpert HR. Secondhand smoke exposure and neurobehavioral disorders among children in the United States. Pediatrics. 2011;128(2):263-270. [CrossRef]
 
Duijts L, Jaddoe VWV, van der Valk RJP, et al. Fetal exposure to maternal and paternal smoking and the risks of wheezing in preschool children: the Generation R Study. Chest. 2012;141(4):876-885. [CrossRef]
 
Oh SS, Tcheurekdjian H, Roth LA, et al. Effect of secondhand smoke on asthma control among black and Latino children. J Allergy Clin Immunol. 2012;129(6):1478-1483. [CrossRef]
 
Miller LL, Henderson J, Northstone K, Pembrey M, Golding J. Do grandmaternal smoking patterns influence the etiology of childhood asthma? Chest. 2014;145(6):1213-1218.
 
Farber HJ, Knowles SB, Brown NL, et al. Secondhand tobacco smoke in children with asthma: sources of and parental perceptions about exposure in children and parental readiness to change. Chest. 2008;133(6):1367-1374. [CrossRef]
 
Rehan VK, Liu J, Naeem E, et al. Perinatal nicotine exposure induces asthma in second generation offspring. BMC Med. 2012;10:129. [CrossRef]
 
Guerrero-Preston R, Goldman LR, Brebi-Mieville P, et al. Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds. Epigenetics. 2010;5(6):539-546. [CrossRef]
 
Tezza G, Mazzei F, Boner A. Epigenetics of allergy. Early Hum Dev. 2013;89(suppl 1):S20-S21. [CrossRef]
 
Centers for Disease Control and Prevention (CDC). Notes from the field: electronic cigarette use among middle and high school students - United States, 2011-2012. MMWR Morb Mortal Wkly Rep. 2013;62(35):729-730.
 

Figures

Tables

References

Jaakkola JJ, Jaakkola N, Zahlsen K. Fetal growth and length of gestation in relation to prenatal exposure to environmental tobacco smoke assessed by hair nicotine concentration. Environ Health Perspect. 2001;109(6):557-561. [CrossRef]
 
Leonardi-Bee J, Britton J, Venn A. Secondhand smoke and adverse fetal outcomes in nonsmoking pregnant women: a meta-analysis. Pediatrics. 2011;127(4):734-741. [CrossRef]
 
Mitchell EA, Ford RP, Stewart AW, et al. Smoking and the sudden infant death syndrome. Pediatrics. 1993;91(5):893-896.
 
Weng SF, Redsell SA, Nathan D, Swift JA, Yang M, Glazebrook C. Estimating overweight risk in childhood from predictors during infancy. Pediatrics. 2013;132(2):e414-e421. [CrossRef]
 
Kabir Z, Connolly GN, Alpert HR. Secondhand smoke exposure and neurobehavioral disorders among children in the United States. Pediatrics. 2011;128(2):263-270. [CrossRef]
 
Duijts L, Jaddoe VWV, van der Valk RJP, et al. Fetal exposure to maternal and paternal smoking and the risks of wheezing in preschool children: the Generation R Study. Chest. 2012;141(4):876-885. [CrossRef]
 
Oh SS, Tcheurekdjian H, Roth LA, et al. Effect of secondhand smoke on asthma control among black and Latino children. J Allergy Clin Immunol. 2012;129(6):1478-1483. [CrossRef]
 
Miller LL, Henderson J, Northstone K, Pembrey M, Golding J. Do grandmaternal smoking patterns influence the etiology of childhood asthma? Chest. 2014;145(6):1213-1218.
 
Farber HJ, Knowles SB, Brown NL, et al. Secondhand tobacco smoke in children with asthma: sources of and parental perceptions about exposure in children and parental readiness to change. Chest. 2008;133(6):1367-1374. [CrossRef]
 
Rehan VK, Liu J, Naeem E, et al. Perinatal nicotine exposure induces asthma in second generation offspring. BMC Med. 2012;10:129. [CrossRef]
 
Guerrero-Preston R, Goldman LR, Brebi-Mieville P, et al. Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds. Epigenetics. 2010;5(6):539-546. [CrossRef]
 
Tezza G, Mazzei F, Boner A. Epigenetics of allergy. Early Hum Dev. 2013;89(suppl 1):S20-S21. [CrossRef]
 
Centers for Disease Control and Prevention (CDC). Notes from the field: electronic cigarette use among middle and high school students - United States, 2011-2012. MMWR Morb Mortal Wkly Rep. 2013;62(35):729-730.
 
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