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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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

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.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Abnormal Development Smoking

Desheng Sun, Qinghai Li, Dandan Ding, Xiaochen Li, Min Xie, Yongjian Xu, Xiansheng Liu Role of Krüppel-like factor 4 in cigarette smoke-induced pulmonary vascular remodeling. Am J Transl Res: 2018, 10(2);581-591 PubMed 29511453

Bláithín Ní Bhuachalla, Christine A McGarrigle, Neil O'Leary, Kwadwo Owusu Akuffo, Tunde Peto, Stephen Beatty, Rose Anne Kenny Orthostatic hypertension as a risk factor for age-related macular degeneration: Evidence from the Irish longitudinal study on ageing. Exp. Gerontol.: 2018; PubMed 29501627

Line Elmerdahl Frederiksen, Andreas Ernst, Nis Brix, Lea Lykke Braskhøj Lauridsen, Laura Roos, Cecilia Høst Ramlau-Hansen, Charlotte Kvist Ekelund Risk of Adverse Pregnancy Outcomes at Advanced Maternal Age. Obstet Gynecol: 2018; PubMed 29420406

Melek Rousian, Maria P H Koster, Annemarie G M G J Mulders, Anton H J Koning, Régine P M Steegers-Theunissen, Eric A P Steegers Virtual reality imaging techniques in the study of embryonic and early placental health. Placenta: 2018; PubMed 29409677

James H Cole, Matthan W A Caan, Jonathan Underwood, Davide De Francesco, Rosan A van Zoest, Ferdinand W N M Wit, Henk J M M Mutsaerts, Rob Leech, Gert J Geurtsen, Peter Portegies, Charles B L M Majoie, Maarten F Schim van der Loeff, Caroline A Sabin, Peter Reiss, Alan Winston, David J Sharp, COBRA collaboration No evidence for accelerated ageing-related brain pathology in treated HIV: longitudinal neuroimaging results from the Comorbidity in Relation to AIDS (COBRA) project. Clin. Infect. Dis.: 2018; PubMed 29309532

Search term: Pregnancy Smoking

Tina Djernis Gundersen, Lone Krebs, Ellen Christine Leth Loekkegaard, Steen Christian Rasmussen, Julie Glavind, Tine Dalsgaard Clausen Postpartum urinary tract infection by mode of delivery: a Danish nationwide cohort study. BMJ Open: 2018, 8(3);e018479 PubMed 29540408

George W Taylor, Wenche S Borgnakke Self-Reported Periodontal Disease: Validation in an Epidemiological Survey. J. Periodontol.: 2007, 78 Suppl 7S;1407-1420 PubMed 29539090

Yoshihiro Miyake, Keiko Tanaka, Hitomi Okubo, Satoshi Sasaki, Masashi Arakawa Maternal caffeine intake in pregnancy is inversely related to childhood peer problems in Japan: The Kyushu Okinawa Maternal and Child Health Study. Nutr Neurosci: 2018;1-8 PubMed 29534651

Giuseppe Chiossi, Stefano Palomba, Maged M Costantine, Angela I Falbo, Hassan M Harirah, George R Saade, Giovanni B La Sala Reference intervals for hemoglobin and hematocrit in a low risk pregnancy cohort: implications of racial differences. J. Matern. Fetal. Neonatal. Med.: 2018;1-131 PubMed 29534635

Simone Accordini, Lucia Calciano, Ane Johannessen, Laura Portas, Bryndis Benediktsdóttir, Randi Jacobsen Bertelsen, Lennart Bråbäck, Anne-Elie Carsin, Shyamali C Dharmage, Julia Dratva, Bertil Forsberg, Francisco Gomez Real, Joachim Heinrich, John W Holloway, Mathias Holm, Christer Janson, Rain Jögi, Bénédicte Leynaert, Andrei Malinovschi, Alessandro Marcon, Jesús Martínez-Moratalla Rovira, Chantal Raherison, José Luis Sánchez-Ramos, Vivi Schlünssen, Roberto Bono, Angelo G Corsico, Pascal Demoly, Sandra Dorado Arenas, Dennis Nowak, Isabelle Pin, Joost Weyler, Deborah Jarvis, Cecilie Svanes, Ageing Lungs in European Cohorts (ALEC) Study A three-generation study on the association of tobacco smoking with asthma. Int J Epidemiol: 2018; PubMed 29534228


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. (2018, March 19) Embryology Abnormal Development - Smoking. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Smoking

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