Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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Smoking and pregnancy: More evidence is not enough against inertia and denial.
- Alain braillon (27 March 2009)
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Quitting Smoking Early in Pregnancy and Adverse Birth Outcomes: Questions Unanswered
- Muhammad T. Salam (28 March 2009)
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A Missing Element
- J Jonik (29 March 2009)
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Smoking cessation in pregnancy and reversibility of harm
- Michael J Davies (31 March 2009)
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How big were the effect of other confounders?
- Ralph Nanan, Peter Hsu, Michael J. Peek (1 April 2009)
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Re: Quitting Smoking Early in Pregnancy and Adverse Birth Outcomes: Questions Unanswered
- Lesley M McCowan, Robyn A North (2 April 2009)
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Re: Smoking cessation in pregnancy and reversibility of harm
- Lesley M McCowan, Robyn A North (2 April 2009)
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Re: Re: Quitting Smoking Early in Pregnancy and Adverse Birth Outcomes: Questions Unanswered
- Muhammad T Salam (3 April 2009)
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More details please
- Adrienne Einarson, Eunji Kim, Moumita Sarkar, Gideon Koren (8 April 2009)
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Re: Re: Re: Quitting Smoking Early in Pregnancy and Adverse Birth Outcomes: Questions Unanswered
- Les O. Simpson (9 April 2009)
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Re: Re: Re: Quitting Smoking Early in Pregnancy and Adverse Birth Outcomes: Questions Unanswered
- Lesley M McCowan, Robyn A North (11 April 2009)
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Re: How big were the effect of other confounders?
- Lesley M McCowan, Robyn A North (11 April 2009)
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Re: More details please
- Lesley ME McCowan, Robyn A North (23 April 2009)
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Failure of academics and healthcare professionals
- Munjed Farid Al Qutob (29 June 2009)
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What are the effects of cigarette smoking ?
- Leslie O Simpson (30 June 2009)
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Alain braillon, public health 80000 Amiens, France
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McCowan et al’s article is fine, nevertheless I doubt that is it can help against the long standing denial of the leading cause of prematurity and other perinatal complications.1 The publications from the EuroNatal Working Group in 20003 showing that smoking during pregnancy entailed the least frequent appropriate care delivery, as well as the highest impact on mortality and morbidity, and all others articles were granted too little attention. Indeed, in recent articles on prematurity in two major journals the word "tobacco" or "smoking" was not even mentioned once.2,3 The European Perinatal Health Report has just showed that France has the highest rate of smoking during pregnancy in Europe (22% vs 5% for the best country), and accordingly dramatic results on the perinatal indicators.6 Neverthess, the Department of Health has just cut funding to the non governmental organisation acting against smoking during pregnancy. In France, even many clinics offering amniocentesis and in vitro fertilization lack CO analysers, a cheap and easy-to-use equipment. CO analysers are needed to screen, adapt the medical treatment and motivate women. In the Picardy region (22,500 births per year) we observed that 35% of the maternity clinics did not even have one CO analyser. We implemented a program in 2008 with various sources of funding.7 Participation of practitioners was enthusiastic with 100 % of the 20 private and public maternity hospitals. Teaching sessions (two half days, one month apart) catered for obstetricians, paediatricians, midwives and nurses allowed to triple specifically trained professional resources. We distributed the new generation CO analysers measuring both maternal and foetal CO concentrations (BabyCO, Eolys) to all maternities. To secure this action, all maternity directors signed a charter including the treatment of maternal smoking as one of the strategic actions for their hospital. At present, Picardy is the region of France which offers the best (and yet minimal) care delivery for every pregnant woman who smokes. The second step which targets gynaecologists and midwives practising outside maternities began early 2009. Nevertheless the French mandatory health insurance system poorly reimburses long medical examinations and limits reimbursement of nicotine replacement therapy to €50 per year. Moreover, this reimbursement suffers from a specific, complex and inconvenient procedure. Accordingly, in Picardy, we observe that nicotine replacement therapy is being used by fewer than 5% of pregnant women who smoke (Braillon, un published observation). In contrast, Belguim has set up in 2005 a wisefull programme: the reimbursement scheme is directed not only to the mother but also to its smoking partner!8 In many European countries mothers are not helped to quit smoking and give birth to premature babies, they must initiate a class action. We cannot hope for an action from the direction of Health and Consumers (SANCO European commission). 1 McCowan LME, Dekker GA, Chan E et al. Spontaneous preterm birth and small for gestational age infants in women who stop smoking early in pregnancy: prospective cohort study. BMJ 2009;338:b1081 2 Richardus JH, Graafmans WC, Bergsjø P, et al.. Suboptimal care and perinatal mortality in ten European regions: methodology and evaluation of an international audit. J Matern Fetal Neonatal Med 2003 ;14: 267-76. 3 Richardus JH, Graafmans WC, Verloove-Vanhorick SP, Mackenbach JP, EuroNatal International Audit Panel, EuroNatal Working Group. Differences in perinatal mortality and suboptimal care between 10 European regions: results of an international audit. BJOG 2003 ; 110: 97-105. 4 Simhan HN, Caritis SN. Prevention of preterm delivery. N Engl J Med 2007; 357: 477-87. 5 Editorial. Preterm birth: what can be done. Lancet 2008; 371: 2 6 www.europeristat.com 7 Braillon A, Robillart H, Delcroix M, Gomez C, Delmas-Lanta S, Dubois G. Grossesse sans tabac. Une mobilisation régionale des professionnels des maternités de Picardie. J Gynecol Obstet Biol Reprod (Paris) 2009 (in press) 8 www.bips.uni-bremen.de/euro-scip/tabagisme_et_grossesse2006.pdf Competing interests: None declared |
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Muhammad T. Salam, Research Associate Preventive Medicine, Univ of Southern California, 1540 Alcazar St, CHP-236, Los Angeles, CA 90007
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McCowan et al's finding that stopping smoking early in pregnancy could prevent some adverse birth outcomes such as spontaneous preterm birth and small for gestational age is welcoming information for both expectant mothers and their obstetricians.1 However, there are some areas which the authors could further investigate. One such area would be to evaluate the complex interrelationships among cigarette smoking, social disadvantage (i.e., education, work status, etc.), obesity (BMI >24.9kg/m2), and psychological factors (any stress, anxiety or depression) and how these factors affect birth outcomes. It would also be important to understand whether any of these factors modified the associations between smoking status and birth outcomes. It is possible that there are synergistic effects of smoking and maternal physical and psychosocial factors on birth outcomes. In a previous paper, Wisborg and colleagues have reported that mothers who stopped smoking by first trimester had no increase in risk of still birth and infant mortality compared to non-smoking mothers.2 It would be important to evaluate this association in this cohort again. Beside the issues regarding the pathobiology of the associations, there are some concerns regarding the analytic strategies that were implemented. Given the distribution of the timeline for stopping smoking, it could be argued that the results are driven by mothers who stopped smoking by 12 weeks of gestation, as only 6% stopped smoking between 12-15 weeks. In addition, the authors did not evaluate the impact of number of cigarette smoked by these mothers on the birth outcomes. Because the "stopped smoker" group smoked about 10 cigarettes/day or less, one would be interested in knowing whether birth outcomes differed between children born to "current smoker" using less than 10 cigarettes/day and those who consumed more. In summary, the results would have been more appealing if the authors could provide data to show whether the effects of maternal smoking on adverse birth outcomes varied by maternal physical and psychosocial factors, and whether there is any dose-response or threshold effect of smoking. Additionally, a replication of earlier finding of a comparable rates of stillbirth and infant death between non-smoking mothers and those who quit smoking by first trimester would be reassuring. References: 1. McCowan LME, Dekker GA, Chan E, Stewart A, Chappell LC, Hunter M, et al. Spontaneous preterm birth and small for gestational age infants in women who stop smoking early in pregnancy: prospective cohort study. BMJ 2009;338:b1081. 2. Wisborg K, Kesmodel U, Henriksen TB, Olsen SF, Secher NJ. Exposure to tobacco smoke in utero and the risk of stillbirth and death in the first year of life. Am J Epidemiol 2001;154(4):322-7. Competing interests: None declared |
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J Jonik, freelancer USA 19125
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It seems, from this overview of the study, that the researchers forgot that typical cigarettes are contaminated with chlorine pesticide residues and chlorine bleached paper...thus putting high levels of chlorine by-product, dioxin, into the smoke...and into unwitting, unprotected mothers. Since dioxin is already known to cause exactly the risks and symptoms described....and more, which is why the UK and over 100 other countries signed the Stockholm Convention to phase dioxin, and eleven other worst of the worst industrial pollutant off the earth...it is absurd to make the insinuation that smoke from tobacco is at fault for those harms to children, and it is cold cruelty to blame the victimized mothers. This study, as reported, reeks of unsound science. It, troublingly, serves to protect the cigarette makers from charges of deadly product adulteration, it protects the chlorine/pesticide/paper interests, and it protects complicit officials who allowed such a threat to consumers...and their babies. It does nothing to fully inform, protect, or achieve compensation for, those mothers. It appears that researchers failed to so much as test the mothers for body burdens of fetal damaging and pregnancy disrupting industrial substances that may have come from typical cigarettes or other pollutants at their jobs or homes. It's as if they investigated a shooting, but failed to look for a gun...or even consider a gun as the weapon. If the researchers found that the pesticides and dioxins in typical (very non-organic) cigarettes were somehow destroyed or neutralized by the nicotine, that would be Nobel Prize-level news...and would be an integral part of the report. As it is, either the researchers did not know what the test subjects were smoking, or we are not being told. Sure, mothers are well-advised to not smoke, or drink, or play rugby, during pregnancy, but to do so is no crime...yet. Secret poisoning of consumer products and experimenting on unwitting subjects without Informed Consent is. Competing interests: None declared |
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Michael J Davies, A/Professor Research Centre for the Early Origins of Health and Disease, Adelaide, 5005
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The recent paper by McCowan et al (1) provides additional valuable information on the consequences of smoking in pregnancy & clearly sets a research agenda for further research in the area. I wish to offer two points of clarification on the matter of ‘reversibility’, which is an extremely important concept when attempting to tease apart risk and public health interventions. Does risk change because the harm is ‘undone’ by quitting, or because the observed harm is yet to happen? The first comment concerns the timing of enrolment into the study.
Now, the matter is perhaps somewhat moot as smoking cessation is clearly beneficial in later pregnancy, but the question remains. Does the fetus get ‘better’ as a consequence of maternal quitting, or simply not continue to accumulate harm? To consider this we need to be rather particular about the concepts of prevention and reversal. 1 McCowan LME, Dekker GA, Chan E et al. Spontaneous preterm birth and small for gestational age infants in women who stop smoking early in pregnancy: prospective cohort study. BMJ 2009;338:b1081. 2 Winter E, Wang J, Davies MJ, Norman RJ. Early pregnancy loss following assisted reproductive technology treatment. Human Reproduction 2002;17:3220-3223. Competing interests: None declared |
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Ralph Nanan, Professor of Paediatrics The University of Sydney, Nepean Clinical School, Peter Hsu, Michael J. Peek
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McCowan et al. concluded in their prospective cohort study, that stopping smoking before 15 weeks of gestation results in rates of spontaneous preterm birth and small for gestational age (SGA) infants similar to those in non-smokers. There are however important differences in demographics of known risk factors for both IUGR and preterm birth between the groups of non-smokers, stopped smokers and current smokers. In particular, a significant higher percentage of current smokers had BMI < 20, younger maternal age, poorer socio-economic and educational status and higher alcohol consumption. Also the current smokers smoked significantly more (twice the amount) cigarettes per day pre pregnancy compared to stopped smokers. We acknowledge that the authors adjusted for these potential confounders using logistic regression analysis. However, it would be valuable to describe the impact of these confounders on the outcome measures compared to smoking cessation. In addition, was there a change of these confounders after smoking cessation, e.g. an increase in BMI after smoking cessation? Competing interests: None declared |
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Lesley M McCowan, Associate Professor Department of Obstetrics and Gynaecology,University of Auckland,Auckland,New Zealand, Robyn A North
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Muhammad T. Salam makes an important point about the relationship between smoking social disadvantage and stress. Our logistic regression models adjusted for potential confounders including age, self assigned ethnicity, marital status, employment, and body mass index and also measures of stress anxiety and depression (see methods in our paper). We agree that our results could be driven by mothers who stopped smoking by 12 weeks of gestation and have consequently recommended that women stop smoking as early in pregnancy as possible. Future large studies should investigate these temporal relationships further. A dose dependent effect of number of cigarettes smoked /day on birth outcomes has previously been well established by other authors and was not investigated in the current analysis. Our primary interest was in the comparison between stopped smokers and non- smokers. It was not possible to examine the relationship between rare events such as stillbirth, which occurs in <1% of women in our centres, and smoking status in the current study. Competing interests: None declared |
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Lesley M McCowan, Associate Professor Department of Obstetrics and Gynaecology,University of Auckland,Auckland,New Zealand, Robyn A North
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We would like to thank Professor Davies for his lucid discussion of the concepts of reversal or prevention of adverse events due to smoking in pregnancy. As our study design did not include a 15 week scan we are unable to determine whether the beneficial effects we observed on fetal growth were due to reversible effects. It may have been more appropriate to have used the term prevention rather than reversible in our paper. We agree with Professor Davies comment regarding the increased risk of miscarriage associated with smoking in the first trimester. While our study demonstrates cessation of smoking by 15 weeks has a major impact on late pregnancy complications, it is important that women and maternity caregivers understand that ceasing to smoke prior to pregnancy is necessary to prevent early pregnancy complications, such as miscarriage and ectopic pregnancy. Competing interests: None declared |
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Muhammad T Salam, Research Associate Preventive Medicine, Univ of Southern California, 1540 Alcazar St, CHP-236, Los Angeles, CA 90033
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I appreciate the authors' response to my letter. However, they did not provide adequate information on the following major concerns: 1. Were the risk of adverse birth outcomes in children born to mothers who continued smoking less than 10 cigarettes/day statistically significantly different from children born to mothers (a) who continued to smoke more than 10 cigarettes/day and (b) those who stopped smoking by 15 weeks? The adverse birth outcomes from smoking could be a time-dependent effect, as the authors concluded but it could also be a function of duration and dosage of the offending factor, smoking in this case, such that risk associated with smoking less than 10 cigarettes/day over the entire pregnancy is not different than stopping smoking by 12 weeks, or not smoking at all. Because most non-smoking mothers do not start smoking during pregnancy, whether timing of exposure is associated with adverse birth outcomes cannot be fully examined. However, the authors have the data to examine the dose and duration of exposure effects and compare the risk estimates with mothers who did not smoke and those who stopped smoking early in pregnancy. 2. Having the three smoking groups so different in physical (BMI) and psychosocial factors, mere adjustment of these factors without assessing and reporting their impacts on the outcomes of interest (as confounders and effect modifiers) is likely to influence the results and could potentially lead the readers to biased conclusions. I will very much appreciate if the authors revisit their data to answer these key research questions in a following letter. Having the data that could answer critical scientific questions and not addressing those to the fullest extent is definitely unjustifiable. Competing interests: None declared |
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Adrienne Einarson, Assistant Director, The Motherisk Program The Hospital for Sick Children, Toronto, Canada, M5G 1X8, Eunji Kim, Moumita Sarkar, Gideon Koren
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The Editor BMJ April 8th 2009 We are writing a letter regarding a recent publication: “McCowan LM, Dekker GA, Chan E, Stewart A, Chappell LC, Hunter M, Moss- Morris R, North RA; SCOPE consortium. Spontaneous preterm birth and small for gestational age infants in women who stop smoking early in pregnancy: prospective cohort study. BMJ. 2009 Mar 26;338: b1081 “ We believe that this is an excellent attempt to study in more detail whether the effects of smoking on spontaneous abortion and preterm birth, by examining if the time of quitting smoking in pregnancy makes a difference. Smoking in pregnancy certainly does have important public health implications and this information would give women an added incentive to quit. However, there is information about the women, not available, that we would be interested in knowing about. The authors stated that almost 50% of the women were only smoking 1-5 cigarettes/day and they themselves stated that a dose response has been previously reported. We were surprised that a sub-analysis was not conducted on the 50% who smoked more than 10/day. We were also surprised other exposures such as alcohol, drugs of abuse and other medications were not documented, as these are known to affect pregnancy outcomes.1,2, Alcohol use was noted in the table, but we were not told how much was used; was it just a yes or no answer to the question, or in more detail? Finally, we would really have liked to have known how many of the women were taking antidepressants, because several studies have been published recently that have reported an increase risk for preterm birth, low birth weight and SGA.3,4,5 We applaud the authors for asking the women to complete an EPDS at 15 weeks, however this only records symptoms in the previous week, so we do not know if any of the women were depressed late in pregnancy, when the outcomes of interest occurred. This type of research is very complex and we feel that the authors did an excellent job, we would just like to have those questions answered before we make any definitive conclusions about this study. It is important for women not to smoke during pregnancy, however in our eagerness to find solutions, we must make conclusions based being cognizant of all the facts. References 1. O'Leary CM, Nassar N, Kurinczuk JJ, Bower C. The effect of maternal alcohol consumption on fetal growth and preterm birth. BJOG. 2009 Feb;116(3):390- 400. 2. Schempf AH. Illicit drug use and neonatal outcomes: a critical review. Obstet Gynecol Surv. 2007 Nov;62(11):749-57. Review 3. Einarson A The safety of psychotropic drug use during pregnancy: a Review.MedGenMed. 2005 Oct 5;7(4):3. Review. 4. Wisner KL, Sit DK, Hanusa BH, Moses-Kolko EL, Bogen DL, Hunker DF, Perel JM, Jones-Ivy S, Bodnar LM, Singer LT.Major Depression and Antidepressant Treatment: Impact on Pregnancy and Neonatal Outcomes. Am J Psychiatry. 2009 Mar 16. 5. Suri R, Altshuler L, Hellemann G, Burt VK, Aquino A, Mintz J Effects of antenatal depression and antidepressant treatment on gestational age at birth and risk of preterm birth. Am J Psychiatry. 2007 Aug;164(8):1206-13. Adrienne Einarson RN, Assistant Director, The Motherisk Program Eunji Kim BSc, Counselor, The Motherisk Alcohol and Substance Use Helpline Line Moumita Sarkar MSc, PHD candidate, counselor, The Motherisk Alcohol and Substance Use Helpline Line Gideon Koren MD, Director, The Motherisk Program The Hospital for Sick Children, Toronto, Canada Competing interests: None declared |
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Les O. Simpson, retired experimental pathologist Dunedin, New Zealand 9077
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Dr.Salam raised the question of the consequences of continuing to smoke less that 10 cigarettes daily in comparison with smoking more than 10 cigarettes a day, in contrast to the effects of stopping smoking by 15 weeks. As smoking increases blood viscosity and reduces red cell deformability in a dose dependent fashion, it is unlikely that there would be differences in those smoking 9 cigarettes a day from those smoking 11 cigarettes a day. But differences in blood viscosity could be expected in those smoking 5 cigarettes a day from those smoking 20 cigarettes a day. However, as Ernst and Matrai (1) have reported that after 8 weeks of not smoking there was a gradual normalization of blood rheology factors, benefits could be expected if smoking was stopped at 15 weeks of pregnancy. Reference. 1. Ernst E, Matrai A. Abstention from smoking normalises blood rheology. Athersclerosis 1987;64:75-7. Competing interests: None declared |
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Lesley M McCowan, Associate Professor Department of Obstetrics and Gynaecology, University of Auckland,Private Bag 92019 Auckland, Robyn A North
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In response to Dr Salam¡¯s further request for data about subgroups of smokers we have produced the following table. Non smokers
N=1992 Stopped smokers
N=261 Current smokers <10/day N=158 Current smokers ¡Ý10/day
N=93
Spontaneous
preterm birth 4% 4% 9% 12%
SGA 10% 10% 13% 23%
Spontaneous preterm birth was significantly increased in women who smoked <10 cigarettes per day compared with stopped smokers but did not differ between smokers of < 10 and > 10 cigarettes per day. Consistent with previous literature the dose response for SGA is also suggested by our data, however our study is underpowered to detect small differences between groups. 2. As with all observational studies there is the possibility of bias even after adjustment for known confounders. The main aim of the SCOPE study is to develop predictive tests. The relationship between clinical risk factors and SGA babies/spontaneous preterm birth will be described in detail in future publications. Briefly risk factors other than smoking identified in our model for spontaneous preterm birth were previous: termination of pregnancy, 2 miscarriages, large loop excision of the transformation zone treatment of the cervix and increasing score for depression. Increasing maternal age and not being employed at 15 weeks were additional risk factors for SGA babies. Competing interests: None declared |
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Lesley M McCowan, Associate Professor Department of Obstetrics and Gynaecology, University of Auckland,Private Bag 92019 Auckland, Robyn A North
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We would like to thank Professor Nanan and colleagues for their enquiry about the relationship between confounding factors associated with smoking and the main pregnancy outcomes and refer them to our recent response to Dr Salam “Quitting smoking in early pregnancy and adverse birth outcomes: questions unanswered”. We don’t have end of pregnancy weight or BMI, but weight gain between 15 and 20 weeks did not differ between smokers and stopped smokers 2.7 (1.6) kg vs 2.8 (2.9) kg respectively, p=0.64. Competing interests: None declared |
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Lesley ME McCowan, Associate Professor University of Auckland, Private Bag 92019, Auckland, Robyn A North
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As women were recruited at 15 weeks, miscarriage was not an endpoint in this study. The primary outcomes were SGA infants and spontaneous preterm birth. For the question re smoking sub-groups < 10 versus >=10 cigarettes daily we refer to our recent response to Dr Salam “Quitting smoking in early pregnancy and adverse birth outcomes: questions unanswered”. Our logistic regression models for both spontaneous preterm birth and SGA included alcohol use at 15 weeks gestation (yes/no) and this did not have a significant effect on either outcome in this study. We have collected more detailed data about alcohol and drug exposure and these factors will be included in our analyses to investigate the prediction of spontaneous preterm birth and SGA infants. We do not have data about the number of women taking antidepressant medications nor do we have late pregnancy measures of depression. Competing interests: None declared |
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Munjed Farid Al Qutob, Dental Public Health specialist private practice
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McCowan et al raised valid points on the invaluable roles that can be played by health care professionals in smoking cessation programmes. However, their statement that "there were no difference in adverse pregancy outcomes between women who stopped smoking by 15 weeks gestation and non-smokers." is another poignant reminder that such roles have been overshadowed by greed and self interest rather than keeping an eye on patients' interest. Smoking ruins lives and wrecks families. The sheer magnitude of this plague (smoking kills 5.4 million worldwide) demonstrates that health care professionals and those in the academic world have failed to muster the strength to be truthful with patients about the detrimental effects of smoking. Competing interests: None declared |
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Leslie O Simpson, retired medical research worker Dunedin, New Zealand 9077
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A strange feature of both the original article and the comments by the many respondents is the failure to address this question. From a pathophysiological viewpoint, the most significant feature is the effect on blood viscosity with an adverse effect on capillary blood flow. A significant literature confirms such effects, as well as showing that the adverse effects are reversed when smoking stops. Competing interests: None declared |
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