UNSW Embryology

Maternal Effects - Smoking

© Dr Mark Hill (2008)

Acknowledgements

Introduction

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

Spontaneous abortion, 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 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.

These smoking effects are 100% preventable.

Page Links: Introduction | Some Recent Findings | Nicotine | Australian National Drug Strategy Household Survey 1995 | Smoking and Pregnancy | Placental Function | Passive Smoking | Behavioural Tips to Quit Smoking | References | Search PubMed | British Medical Journal |NHMRCrecommendations | Web Links |

Some Recent Findings

Jaddoe VW, Verburg BO, de Ridder M, Hofman A, Mackenbach JP, Moll HA, Steegers EA, Witteman JC. Maternal Smoking and Fetal Growth Characteristics in Different Periods of Pregnancy: The Generation R Study. Am J Epidemiol. 2007 Feb 28

"The authors concluded that maternal smoking during pregnancy is associated with reduced growth in fetal head circumference, abdominal circumference, and femur length. The larger effect on femur length suggests that smoking during pregnancy affects primarily peripheral tissues. "

Feng Z, Hu W, Hu Y, Tang MS. Acrolein is a major cigarette-related lung cancer agent: Preferential binding at p53 mutational hotspots and inhibition of DNA repair. Proc Natl Acad Sci U S A. 2006 Oct 9.

""The tumor suppressor gene p53 is frequently mutated in cigarette smoke (CS)-related lung cancer. ...Acrolein (Acr) is abundant in CS, and it can directly adduct DNA. Together these results suggest that Acr is a major etiological agent for CS-related lung cancer and that it contributes to lung carcinogenesis through two detrimental effects: DNA damage and inhibition of DNA repair. "

Nicotine

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

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 recent study of three placental markers showed "maternal smoking impairs human placental development by changing the balance between cytotrophoblast (CTB) proliferation and differentiation"

Zdravkovic T, Genbacev O, McMaster MT, Fisher SJ. The adverse effects of maternal smoking on the human placenta: a review. Placenta. 2005 Apr;26 Suppl A:S81-6. Review.

Shiverick KT, Salafia C. Cigarette smoking and pregnancy I: ovarian, uterine and placental effects. Placenta. 1999 May;20(4):265-72. Review.

Behavioural Tips to Quit Smoking

The five Ds

Recall and practise the five Ds when they feel the urge to smoke:

Delay, even for a short while

Drink water

Deep breathing

Do something different and

Discuss the craving with another person

Other tips

• Write out a list of reasons to quit and display it prominently (eg, on the fridge)
• Get rid of all tobacco products, ashtrays, lighters, matches, etc.
• Clean all clothes to remove cigarette smell.
• Enlist the support of non-smoking friends, relatives and workmates.
• Change habits associated with smoking (eg, instead of smoking after meals, chew on a toothpick or change rooms).
• Change environmental cues. For example, the telephone often causes a "reflex action" to smoke &emdash; so move the telephone to another place to change the cue.
• Change the daily routine to minimise the association of tobacco with certain activities or times of the day.
• Keep hands busy (eg, knitting, gardening, drawing, origami).
• Sit in non-smoking areas.
• Escape situations that invite a relapse.
• Talk positively, think positively about quitting and your future.
• Try to avoid stress immediately after quitting.
• Substitute another activity for smoking (eg, go for a walk when the urge to smoke strikes).
• Try daily exercise to keep occupied, to relieve stress, to maintain a positive frame of mind and to become fit.
• Set aside the money previously spent on cigarettes to buy something as a reward.
• Do not drink alcoholic beverages, as these are associated with relapse and are best avoided in pregnancy.
• Avoid, even temporarily, social situations normally associated with smoking.
• Practise saying, "No thank you, I don´t smoke".
• Ask other smokers not to give cigarettes, offer to buy cigarettes or smoke in your presence.
• View quitting as a day-at-a-time process rather than an immediate lifelong commitment.

(from Quitting smoking in pregnancy Raoul A Walsh, John B Lowe, Peter J Hopkins (MJA 2001; 175: 320-323)

See also Woolcock Institute of Medical Research - smoking cessation

References

In 2005 a PubMed search results "smoking and pregnancy" will retrieve 8247 citations and 920 reviews.

Shiverick KT, Salafia C. Cigarette smoking and pregnancy I: ovarian, uterine and placental effects. Placenta. 1999 May;20(4):265-72. Review.

Salafia C, Shiverick K. Cigarette smoking and pregnancy II: vascular effects. Placenta. 1999 May;20(4):273-9. Review.

Stocks J, Dezateux C. The effect of parental smoking on lung function and development during infancy. Respirology. 2003 Sep;8(3):266-85. Review.

JP Hanrahan, etal. The effect of maternal smoking during pregnancy on early infant lung function Am Rev Respir Dis. 1992 May;145(5):1129-35.

Bibby E, Stewart A. The epidemiology of preterm birth. Neuro Endocrinol Lett. 2004 Dec;25 Suppl 1:43-7. Review.

Hukkanen J, Jacob P 3rd, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005 Mar;57(1):79-115. Review.

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 for the enzyme CYP2A6

Search PubMed

Enter a term in the window below to search the NCBI PubMed database or Bookshelf.

  Search PubMed Books for

British Medical Journal

The problem of tobacco smoking. BMJ  2004;328:217-219 (24 January)

Smoking and the sudden infant death syndrome: results from 1993-5 case-control study for confidential inquiry into stillbirths and deaths in infancy.BMJ 1996;313:195-198 (27 July)

Preterm delivery: effects of socioeconomic factors, psychological stress, smoking, alcohol, and caffeine. BMJ 1995;311:531-535 (26 August)

Smoking during pregnancy and congenital limb deficiency. BMJ 1994;308:1473-1476 (4 June)

The Australian NHMRC

1988 recommendations for neonates be assessed for follow-up care under the following conditions. (see the NHMRC WWW Page)

• Birthweight less than 1500g or gestational age less than 32 weeks
• Small-for-gestational-age neonates
• Perinatal asphyxia
• Apgar score less than 3 at 5 minutes
• clinical evidence of neurological dysfunction
• delay in onset of spontaneous respiration for more than 5 minutes and requiring mechanical ventilation
• Clinical evidence of central nervous system abnormalities ie., seizures, hypotonia
• Hyperbilirubinaemia of greater than 350umol/l in full term neonates
• Genetic, dysmorphic or metabolic disorders or a family history of serious genetic disorder
• Perinatal or serious neonatal infection including children of mothers who are HIV positive
• Psychosocial problems eg., infants of drug-addicted or alcoholic mothers.

Web Links

The National Tobacco Campaign (Australia)

Centres for Disease Control and Prevention (USA) - Tobacco

Tobacco-Free Kids

Action on Smoking and Health Australia (ASH)

Woolcock Institute of Medical Research - smoking cessation

Quitting smoking in pregnancy article 2001 Medical Journal of Australia

ABC Health review of above article

ABC Health Articles

Half of Australian babies are passive smokers - News in Science 14/12/1999

Vessel blockage linked to infant death - News in Science 18/2/1999

The effect of maternal smoking on babies - Health Report 23/4/2001

Finally

Each section of the notes covering early development and specific systems contain references to specific abnormalities (on Page 2 of each notes section). The best source for Australian statistical data is the Australian Institute of Health and Welfare National Perinatal Statistics Unit, UNSW which publishes "Congenital Malformations Australia" every 2 years. Be aware that some congenital abnormalities, by their nature, affect multiple systems. In the USA, the Center for Disease Control (CDC) keeps and publishes relevant statistical information. A very difficult issue in abnormal development are the many different Ethical implications.

This current page is a link to Normal and Abnormal Development and Population Data.

Where to Next?

Look at types of Abnormal Development that can occur during development.

Quick Links

Development Notes ----------------- Menstrual Cycle Week 1 Week 2 Week 3 Week 4 Placenta Serial Images Genes/DNA Molecular Dev Abnormal Dev Postnatal Dev Notes Index

System Notes ----------------- Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Eye Ear Nose Endocrine Urogenital Musculoskeletal Integumentary

Finally

For those wanting to see dynamic processes of development (and have a reasonably quick connection) then the Movies pages are good for watching changes occur.

Movies ----------------- Embryo Growth Carnegie Stages Ultrasound Images Stage 13/14 Embryo Stage 22 Embryo Heart Septation Neural Neural Crest Other Embryos Larsen Movies

Other Embryos

The study of human development has relied extensively on studying the process in other model animals. For those wanting to see the process of development in other species then the other embryos pages are a good start.

Other Embryos ----------------- Chicken Fly Frog Mouse Rabbit Rat Worm Zebrafish Guinea Pig

UNSW Embryology ISBN: 978 0 7334 2609 4

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