Abnormal Development - Smoking

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No smoking sign

There is an association between physical defects among newborns and maternal smoking tobacco during pregnancy.

Spontaneous abortion, ectopic implantation, pre-term births, low-weight full-term babies, and fetal and infant deaths all occur more frequently among mothers who smoke during pregnancy than among those who do not. These developmental abnormalities are therefore environmental (maternal) in origin and not congenital (though there are probably genetics involved with a tendency to smoke).

The possible relationship to preterm birth generates one major clinical problem, as preterm birth results in 47% of all neonatal deaths (UK data).

Also of great concern is that smoking is a suggested causative factor for low infant birth weight (LBW) (2.500kg and below). LBW is in turn related to future (postnatal) health by the fetal origins hypothesis.

Environmental Links: Introduction | Low Folic Acid | Iodine Deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | Thalidomide | Herbal Drugs | Illegal Drugs | Smoking | Fetal Alcohol Syndrome | TORCH Infections | Viral Infection | Bacterial Infection | Zoonotic Infection | Toxoplasmosis | Malaria | Maternal Diabetes | Maternal Hypertension | Maternal Hyperthermia | Maternal Inflammation | Maternal Obesity | Hypoxia | Biological Toxins | Chemicals | Heavy Metals | Radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis

Some Recent Findings

  • The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice[1] "Electronic cigarette (E-cigarettes) emissions present a potentially new hazard to neonates through inhalation, dermal and oral contact. Exposure to nicotine containing E-cigarettes may cause significant systemic absorption in neonates due to the potential for multi-route exposure. Systemic absorption of nicotine and constituents of E-cigarette emissions may adversely impact weight and lung development in the neonate. ...These studies indicate that exposure to E-cigarette emissions during the neonatal period can adversely impact weight gain. In addition exposure to nicotine containing E-cigarettes can cause detectable levels of systemic cotinine, diminished alveolar cell proliferation and a modest impairment in postnatal lung growth." Respiratory System Development
  • Helping pregnant smokers to quit[2] "Although most smokers manage to quit during pregnancy, a proportion does not. In England, 26% of women smoke in the year before their pregnancy and 12% smoke through to delivery.1 The rate is similar in other high income countries, whereas in low and middle income countries, smoking rates are more variable and seem to be increasing among young women.2 In addition to the countless negative consequences for the smoker’s own mental and physical health, smoking in pregnancy is linked to a wide range of poor health outcomes for the child.3 Thus there is an urgent need to help pregnant smokers who find it difficult to quit."

Early Hum Dev. 2013 Jul;89(7):497-501. doi: 10.1016/j.earlhumdev.2013.03.007. Epub 2013 Apr 8.

  • Smoking overrules many other risk factors for small for gestational age birth in less educated mothers.[3] "In this study fully completed data were available for 3793 pregnant women of Dutch origin from a population-based cohort (ABCD study). Path-analysis was conducted to examine the role of explanatory factors in the relation of maternal education to SGA. ...Among a large array of potential factors, the elevated risk of SGA birth among low-educated women appeared largely attributable to maternal smoking and to a lesser extent to maternal height. To reduce educational inequalities more effort is required to include low-educated women especially in prenatal intervention programs such as smoking cessation programs instead of effort into reducing other SGA-risk factors, though these factors might still be relevant at the individual level."
  • Influence of Smoking and Alcohol during Pregnancy on Outcome of VLBW Infants[4] "Nicotine and alcohol consumption have been associated with premature delivery and adverse neonatal outcome. We wanted to analyze the influence of self-reported nicotine and alcohol consumption on outcome of VLBW infants.In an ongoing multicenter study 2 475 parents of former very low birth weight (VLBW) infants born between January 2009 and December 2011 answered questionnaires about maternal smoking habits and alcohol consumption during pregnancy. ...Smoking during pregnancy results in a high rate of growth restricted VLBW infants. Prenatal exposition to nicotine seems to increase postnatal complications such as BPD und ROP."
  • Maternal smoking during pregnancy and kidney volume in the offspring: the Generation R Study[5] "An adverse fetal environment leads to smaller kidneys, with fewer nephrons, which might predispose an individual to the development of kidney disease and hypertension in adult life. ... Among mothers who continued smoking, we observed dose-dependent associations between the number of cigarettes smoked during pregnancy and kidney volume in fetal life. Smoking less than five cigarettes per day was associated with larger fetal combined kidney volume, while smoking more than ten cigarettes per day tended to be associated with smaller fetal combined kidney volume (p for trend: 0.002). This pattern was not significant for kidney volume at the age of 2 years. Our results suggest that smoking during pregnancy might affect kidney development in fetal life with a dose-dependent relationship."
  • Quantitative effects of tobacco smoking exposure on the maternal-fetal circulation[6] "In pregnant women who smoke, higher arterial resistance indices and lower birth weights were observed, and these findings were associated with increasing levels of tobacco smoking exposure. The values were significantly different when compared to those found in non-smoking pregnant women. This study contributes to the findings that smoking damage during pregnancy is dose-dependent, as demonstrated by the objective methods for measuring tobacco smoking exposure."
More recent papers
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  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
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References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

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Search term: Abnormal Development Smoking

Kevin Marquez, Kalyan Chakravarthy Potu, Chad Laurich, Randall Lamfers Pulmonary Embolism Caused by Popliteal Vein Aneurysm: A Case Report. S D Med: 2017, 70(3);123-125 PubMed 28813774

Jesper Fleischer, Esben Laugesen, Simon Lebech Cichosz, Pernille Hoeyem, Thomas Fremming Dejgaard, Per Loegstrup Poulsen, Lise Tarnow, Troels Krarup Hansen Continuous glucose monitoring adds information beyond HbA1c in well-controlled diabetes patients with early cardiovascular autonomic neuropathy. J. Diabetes Complicat.: 2017; PubMed 28728915

Angela Zhang, Robert Marshall, Gary Kelsberg Clinical Inquiry: What effects--if any--does marijuana use during pregnancy have on the fetus or child? J Fam Pract: 2017, 66(7);462-466 PubMed 28700762

Nicole G Barra, Maria Lisyansky, Taylor A Vanduzer, Sandeep Raha, Alison C Holloway, Daniel B Hardy Maternal nicotine exposure leads to decreased cardiac protein disulfide isomerase and impaired mitochondrial function in male rat offspring. J Appl Toxicol: 2017; PubMed 28681937

Yu Lili, Ma Jian, Gao Junpeng, Zhai Kun, Zhu Jinfang, Huang Yongqing [Association between non-syndromic cleft lip with or without cleft palate and environmental factors in Ningxia]. Hua Xi Kou Qiang Yi Xue Za Zhi: 2017, 35(3);291-295 PubMed 28675015

Search term: Pregnancy Smoking

Sanne D van Otterdijk, Alexandra M Binder, Karin B Michels Locus-specific DNA methylation in the placenta is associated with levels of pro-inflammatory proteins in cord blood and they are both independently affected by maternal smoking during pregnancy. Epigenetics: 2017; PubMed 28820654

Emmanuel Angulo-Castro, Luis F Acosta-Alfaro, Alma M Guadron-Llanos, Adrian Canizalez-Román, Fernando Gonzalez-Ibarra, Ignacio Osuna-Ramírez, Joel Murillo-Llanes Maternal Risk Factors Associated with the Development of Cleft Lip and Cleft Palate in Mexico: A Case-Control Study. Iran J Otorhinolaryngol: 2017, 29(93);189-195 PubMed 28819616

Sulistyo E Dwi Putra, Christoph Reichetzeder, Martin Meixner, Karsten Liere, Torsten Slowinski, Berthold Hocher DNA methylation of the glucocorticoid receptor gene promoter in the placenta is associated with blood pressure regulation in human pregnancy. J. Hypertens.: 2017; PubMed 28817493

Jacob K Kresovich, Yinan Zheng, Andres Cardenas, Brian T Joyce, Sheryl L Rifas-Shiman, Emily Oken, Matthew W Gillman, Marie-France Hivert, Andrea A Baccarelli, Lifang Hou Cord blood DNA methylation and adiposity measures in early and mid-childhood. Clin Epigenetics: 2017, 9;86 PubMed 28814982

Alice Panchaud, Sonia Hernandez-Diaz, Marlene P Freeman, Adele C Viguera, Sarah C MacDonald, Alexandra Z Sosinsky, Lee S Cohen Use of atypical antipsychotics in pregnancy and maternal gestational diabetes. J Psychiatr Res: 2017, 95;84-90 PubMed 28810177


Nicotine is a natural ingredient in tobacco leaves, where as an alkaloid it provides some protection for the plant being eaten by insects by acting as a botanical insecticide.

Tobacco also contains other minor alkaloids nornicotine, anatabine and anabasine.

There is a chemical datasheet for nicotine, the pure chemical, note that commercial tobacco products include many additional chemicals.

Neonates have a decreased ability to metabolise nicotine, with a 3-4 times longer half-life in newborns exposed to tobacco smoke compared with adults.

Cytochrome P450, Subfamily IIA, Polypeptide 6 (CYP2A6) is the main enzyme in the liver responsible for metabolism (oxidation) of nicotine. (More? OMIM Entry CYP2A6) and there are known mutations that occur in this gene which would also impact on nicotine metabolism.

See also the recent review paper Metabolism and disposition kinetics of nicotine. Hukkanen J, Jacob P 3rd, Benowitz NL. Pharmacol Rev. 2005 Mar;57(1):79-115. | Dempsey D, Jacob P 3rd, Benowitz NL. Nicotine metabolism and elimination kinetics in newborns. Clin Pharmacol Ther. 2000 May;67(5):458-65. | OMIM Entry CYP2A6

Carbon Monoxide

Mouse carbon monoxide exposure

Smoking tobacco is also a source of carbon monoxide (CO), a colourless and odorless gas formed mainly as a by-product of incomplete combustion of hydrocarbons and can cause cytotoxicity by tissue hypoxia.

A recent study has identified in a newborn mouse model, effects on neurodevelopment of even sub-clinical levels of carbon monoxide.[7]

Carbon monoxide:

  • enters circulation though the respiratory system
  • binding to haemoglobin to form carboxy-haemoglobin (COHb)
    • haemoglobin affinity is 240 times greater than for oxygen
    • fetal haemoglobin binds with even greater affinity
  • tissue hypoxia occurs when COHb levels are greater than 70%

Australian National Drug Strategy Household Survey 1995

Below are excerpted statistics from the 1995 household survey.

Smoking is higher among young women than young men, although males tend to smoke more heavily. Among 14-19 year olds: 13% are current regular smokers, 5% are occasional smokers, while 49% have never smoked.

For more information please email CEIDA Information Centre

Passive Smoking

Exposure of non-smokers to environmental tobacco smoke, "passive smoking", has been associated with a substantial increased disease risk (coronary heart disease, cancer) a recent study now adds diabetes to the possible deletirious effects. Houston TK, Kiefe CI, Person SD, Pletcher MJ, Liu K, Iribarren C. Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study. BMJ. 2006 May 6;332(7549):1064-9. "These findings support a role of both active and passive smoking in the development of glucose intolerance in young adulthood."

Smoking and Pregnancy

Smoking doubles the risk of having a low-birthweight baby and significantly increases the rate of perinatal mortality and several other adverse pregnancy outcomes. The mean reduction in birthweight for babies of smoking mothers is 200 g. High quality interventions to help pregnant women quit smoking produce an absolute difference of 8.1% in validated late-pregnancy quit rates. If abstinence is not achievable, it is likely that a 50% reduction in smoking would be the minimum necessary to benefit the health of mother and baby. Healthcare providers perform poorly in antenatal interventions to stop women smoking. Midwives deliver interventions at a higher rate than doctors. The efficacy of nicotine replacement therapy has not been established in pregnancy. Currently, its use should only be considered in women smoking more than 10 cigarettes per day who have made a recent, unsuccessful attempt to quit and who are motivated to quit. Relapse prevention programs have shown little success in the postpartum period. Data from: Quitting smoking in pregnancy Raoul A Walsh, John B Lowe, Peter J Hopkins (MJA 2001; 175: 320-323)

Placental Function

A review[8] of three placental markers showed "maternal smoking impairs human placental development by changing the balance between cytotrophoblast (CTB) proliferation and differentiation"


Australian Indigenous birthweight graph 42.jpg

Data in this graph from AIHW 2014 Report, Birthweight of babies born to Indigenous mothers.[9]

Links: Birth Weight


  1. Sharon A McGrath-Morrow, Madoka Hayashi, Angela Aherrera, Armando Lopez, Alla Malinina, Joseph M Collaco, Enid Neptune, Jonathan D Klein, Jonathan P Winickoff, Patrick Breysse, Philip Lazarus, Gang Chen The Effects of Electronic Cigarette Emissions on Systemic Cotinine Levels, Weight and Postnatal Lung Growth in Neonatal Mice. PLoS ONE: 2015, 10(2);e0118344 PubMed 25706869 | PLoS One.
  2. Leonie S Brose Helping pregnant smokers to quit. BMJ: 2014, 348;g1808 PubMed 24620362
  3. Gerrit van den Berg, Manon van Eijsden, Francisca Galindo-Garre, Tanja G M Vrijkotte, Reinoud J B J Gemke Smoking overrules many other risk factors for small for gestational age birth in less educated mothers. Early Hum. Dev.: 2013, 89(7);497-501 PubMed 23578734
  4. J Spiegler, R Jensen, H Segerer, S Ehlers, T Kühn, A Jenke, C Gebauer, J Möller, T Orlikowsky, F Heitmann, K Boeckenholt, E Herting, W Göpel Influence of smoking and alcohol during pregnancy on outcome of VLBW infants. Z Geburtshilfe Neonatol: 2013, 217(6);215-9 PubMed 24363249
  5. H Rob Taal, J J Miranda Geelhoed, Eric A P Steegers, Albert Hofman, Henriette A Moll, Maarten Lequin, Albert J van der Heijden, Vincent W V Jaddoe Maternal smoking during pregnancy and kidney volume in the offspring: the Generation R Study. Pediatr. Nephrol.: 2011, 26(8);1275-83 PubMed 21617916
  6. Julia de B Machado, V M Plínio Filho, Guilherme O Petersen, José M Chatkin Quantitative effects of tobacco smoking exposure on the maternal-fetal circulation. BMC Pregnancy Childbirth: 2011, 11;24 PubMed 21453488
  7. Cheng Y, Thomas A, Mardini F, Bianchi SL, Tang JX, et al. (2012) Neurodevelopmental Consequences of Sub-Clinical Carbon Monoxide Exposure in Newborn Mice. PLoS ONE 7(2): e32029. PLoS One
  8. T Zdravkovic, O Genbacev, M T McMaster, S J Fisher The adverse effects of maternal smoking on the human placenta: a review. Placenta: 2005, 26 Suppl A;S81-6 PubMed 15837073
  9. AIHW 2014. Birthweight of babies born to Indigenous mothers. Cat. no. IHW 138. Canberra: AIHW. Viewed 5 August 2014 http://www.aihw.gov.au/publication-detail/?id=60129548202


Eric Jauniaux, Graham J Burton Morphological and biological effects of maternal exposure to tobacco smoke on the feto-placental unit. Early Hum. Dev.: 2007, 83(11);699-706 PubMed 17900829


Carolina C Venditti, Richard Casselman, Graeme N Smith Effects of chronic carbon monoxide exposure on fetal growth and development in mice. BMC Pregnancy Childbirth: 2011, 11;101 PubMed 22168775

Olga Genbacev, Michael T McMaster, Tamara Zdravkovic, Susan J Fisher Disruption of oxygen-regulated responses underlies pathological changes in the placentas of women who smoke or who are passively exposed to smoke during pregnancy. Reprod. Toxicol.: 2003, 17(5);509-18 PubMed 14555188

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Cite this page: Hill, M.A. 2017 Embryology Abnormal Development - Smoking. Retrieved August 20, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Smoking

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