British Journal of Preventive and Social Medicine, 1977, 31, 6-12 Randomised controlled trial of anti-smoking advice in pregnancy J. W. DONOVAN* From the Department of Medical Statistics and Epidemiology, London School of Hygiene and Tropical Medicine SUMMARY In a randomised controlled trial intensive individual anti-smoking advice given in parallel with hospital antenatal care did not influence the outcome of pregnancy. The belief that retardation of fetal growth caused by maternal smoking occurs in late pregnancy is not well based, and the advice may not have been given in time to be effective. Other possible interpretations of the results, that maternal smoking is merely an index of some other factor that retards growth or that those counselled did not reduce their smoking sufficiently to influence outcome, cannot be excluded. The association between maternal smoking and retarded fetal growth was first described in 1957, and is now well known. Since then, the retardation of growth and development has been shown to persist at least until the age of 11 years, and associations of maternal smoking with increased risks of abortion, perinatal death, and certain malformations have also been described (Butler and Goldstein, 1973; US Public Health Service, 1973). Many of these reports did not consider that the associations might not be cause and effect, and concluded that pregnant patients should be advised against smoking. Others considered that the retarded growth and other effects were caused by smoking, but recognised that proof could be provided only by experiment. The remaining reports claimed that the observed associations were due to some unidentified factor or factors of which smoking was merely an index. This paper reports on a randomised controlled trial measuring the effects of intensive individual anti-smoking advice given in parallel with hospital antenatal care in a test and a control group. The results of the outcome in these groups are compared with those in three other groups of mothers who had stopped smoking, had never smoked, orwho were irregular smokers. Methods Consecutive series of patients who were in contact with three maternity units concerning their hospital confinement were sent by post a reply-paid *Present address: Department of Health, PO Box 100, Woden, A.C.T. 2606, Australia. questionnaire with the hospital administrative documents. The questionnaire sought information on smoking habits as well as obstetric and medical data. Questionnaires returned at or before the first antenatal examination were used to select patients for study. Incomplete questionnaires were accepted if patients could be allotted unambiguously to one of the groups described below. CONTROLLED TRIAL GROUPS Patients, either married or single, were admitted to the controlled trial if they were currently smoking five or more cigarettes a day and had been smoking one or more cigarettes a day at the beginning of pregnancy, were less than 30 weeks' maturity at first examination, had been born in 1937 or later (in effect aged up to 35 years, as the study was carried out in 1972 and 1973), gave no history of a perinatal death, and were not known to have been seeking termination of pregnancy. A table of random numbers was used to allocate each patient into one of two groups: The control group These patients received the antenatal care usually provided by the hospital, including any anti-smoking advice that might have been given routinely. The test group These patients were seen at each antenatal visit by a doctor who gave intensive individual anti- smoking advice; the methods used are described elsewhere (Donovan et al., 1975). The doctor also took a standard smoking history at the first visit. Their hospital records were labelled with a request 6 copyright. on July 3, 2020 by guest. Protected by http://jech.bmj.com/ Br J Prev Soc Med: first published as 10.1136/jech.31.1.6 on 1 March 1977. Downloaded from
Transcript
British Journal of Preventive and Social Medicine, 1977, 31, 6-12
Randomised controlled trial of anti-smoking advicein pregnancy
J. W. DONOVAN*
From the Department of Medical Statistics and Epidemiology, London School of Hygiene and TropicalMedicine
SUMMARY In a randomised controlled trial intensive individual anti-smoking advice given inparallel with hospital antenatal care did not influence the outcome of pregnancy. The belief thatretardation of fetal growth caused by maternal smoking occurs in late pregnancy is not well based,and the advice may not have been given in time to be effective. Other possible interpretations of theresults, that maternal smoking is merely an index of some other factor that retards growth or thatthose counselled did not reduce their smoking sufficiently to influence outcome, cannot be excluded.
The association between maternal smoking andretarded fetal growth was first described in 1957,and is now well known. Since then, the retardationof growth and development has been shown topersist at least until the age of 11 years, andassociations of maternal smoking with increasedrisks of abortion, perinatal death, and certainmalformations have also been described (Butler andGoldstein, 1973; US Public Health Service, 1973).Many of these reports did not consider that theassociations might not be cause and effect, andconcluded that pregnant patients should be advisedagainst smoking. Others considered that theretarded growth and other effects were caused bysmoking, but recognised that proof could beprovided only by experiment. The remainingreports claimed that the observed associations weredue to some unidentified factor or factors of whichsmoking was merely an index.
This paper reports on a randomised controlledtrial measuring the effects of intensive individualanti-smoking advice given in parallel with hospitalantenatal care in a test and a control group. Theresults of the outcome in these groups are comparedwith those in three other groups of mothers whohad stopped smoking, had never smoked, orwho wereirregular smokers.
Methods
Consecutive series of patients who were in contactwith three maternity units concerning their hospitalconfinement were sent by post a reply-paid*Present address: Department of Health, PO Box 100, Woden, A.C.T.2606, Australia.
questionnaire with the hospital administrativedocuments. The questionnaire sought informationon smoking habits as well as obstetric and medicaldata. Questionnaires returned at or before the firstantenatal examination were used to select patientsfor study. Incomplete questionnaires were acceptedif patients could be allotted unambiguously to oneof the groups described below.
CONTROLLED TRIAL GROUPSPatients, either married or single, were admittedto the controlled trial if they were currentlysmoking five or more cigarettes a day and had beensmoking one or more cigarettes a day at thebeginning of pregnancy, were less than 30 weeks'maturity at first examination, had been born in1937 or later (in effect aged up to 35 years, as thestudy was carried out in 1972 and 1973), gave nohistory of a perinatal death, and were not known tohave been seeking termination of pregnancy. Atable of random numbers was used to allocate eachpatient into one of two groups:
The control groupThese patients received the antenatal care usuallyprovided by the hospital, including any anti-smokingadvice that might have been given routinely.
The test groupThese patients were seen at each antenatal visitby a doctor who gave intensive individual anti-smoking advice; the methods used are describedelsewhere (Donovan et al., 1975). The doctor alsotook a standard smoking history at the first visit.Their hospital records were labelled with a request
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Randomised controlled trial of anti-smoking advice in pregnancy
for hospital staff to reinforce the advice; generalpractitioners and local authority clinic doctorssharing care were asked to collaborate.
OTHER SMOKERSAll current smokers ineligible for the controlledtrial were admitted to the study.
STOPPED SMOKERSWomen who had been smokers at any time duringthe preceding year but who were not smoking at thetime they completed the questionnaire were admitted.All but two of these patients had smoked at thestart of the pregnancy.
NON-SMOKERSFrom the women who had not smoked regularly inthe previous year but who met the other conditionsfor the controlled trial a sample was chosen tomatch the control group for year of birth (withinthree years), parity (0, 1, 2, 3+), and country ofbirth (also broadly grouped). Not all control grouppatients could be matched in this way, andsubstitutes with incomplete matching were notsought. As a result this group was smaller thanthose in the controlled trial, particularly formothers aged 18 and under.
For all groups weights of infants and othermeasurements made in labour wards were taken fromhospital records. As soon as possible after delivery(usually within 48 hours) an interview including ahistory of smoking was administered in the postnatalward. The head circumference, crown-rump, andcrown-heel lengths of fit babies were measured.Examinations of the baby were repeated about sixweeks after confinement.
Patients admitted to the study were excluded ifsubsequently they were discovered not to bepregnant, refused to participate (consent was soughtat the first antenatal visit before smoking wasmentioned), had their pregnancies terminated, orceased attending the hospital before confinement.Nearly all those in the last category are known tohave transferred to the care of another hospital, butit is possible that a few miscarried without notifyingthe hospital and should thus have been retainedin the study; as bookings were controlled by thehospital alone and allocation to test or controlgroups was random this should not have introducedany bias. The numbers in each group, after theexclusions, are shown in Table I; the term'miscarried' includes pregnancies ending before 28weeks measured from the last menstrual periodas stated on the questionnaire. In fact, three ofthese 'premature deliveries' (two test, one non-
smoker) survived, although the birthweights oftwo of them suggested that gross errors had beenmade in the dates given by the mothers. Thesepregnancies are not referred to further in thispaper; exclusion of the three survivors does notaffect the conclusions. The twin pregnancies alsoare excluded from the analysis. Any discrepanciesbetween the numbers in Table 1 and those in latertables are due to missing items of data.
Social class was derived from statements ofoccupation using the Classification of Occupations,(Registrar General, 1970). Where occupation wasobtained for both parents that of the father wasused.
Cigarette consumptions were estimated as follows:in the initial questionnaire patients were asked'How many cigarettes do you usually smoke perday at present?' and '...... at about the time youbecame pregnant?' The postnatal interview includedthe question 'How many cigarettes did you usuallysmoke each day towards the end ofyour pregnancy?/and in the middle months of your pregnancy?/andin early pregnancy?/and before you became preg-nant?' Patients who answered with a range (suchas 8 to 10) were treated as if smoking at the upperend of the range (in this case 10 cigarettes a day).
Inhaling habits were determined from theinterview question: 'When you smoke do youinhale a lot?/inhale a fair amount?/inhale just alittle?/ or do you not inhale at all?'
Results
The results of the descriptive parts of the studywere similar to those of earlier studies. For example,mean birthweight in the control group (those whodid not receive intensive anti-smoking advice) was159 g below that in the non-smoker group, andmean maturity in these two groups was verysimilar. Characteristics of the groups at entry to thestudy are given in Table 2 and details of outcomein Table 3.
EFFECT OF COUNSELLING ON PATIENTSThe methods of counselling used are described fullyelsewhere (Donovan et al., 1975), but some aspectsneed to be mentioned here.
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Mean values, standard errors in parentheses; weights of infants and placenta rounded to nearest gram.
In the controlled trial, pregnant patients were tobe advised to stop smoking for the sake of thechild. As it was not known how they would reactto this, efforts were made to anticipate or keepout of the trial patients who might react adversely.For example, for those with a history of perinataldeath, anti-smoking advice might have resulted infeelings of guilt. The extent to which patientsinterpreted counselling as applying to their existingchildren born of pregnancies in which they smoked,as well as to the current pregnancy, showed that thisexclusion was necessary.Minor objections with which patients attempted
to justify continuing smoking were common, butthere were four patients in whom counselling hadto be abandoned. Two were under psychiatric care,not admitted on the questionnaire, and a third
was epileptic, with an aggressive personality.The fourth, so far as could be told, just objectedstrongly to being advised to do something shedid not wish to do; after having a 2350 g infant sheceased co-operating with the study staff.
General practitioners and local authority doctorssharing in the care of test group patients wererequested to reinforce the advice given. The pro-portions of test and control group patientsrecalling such advice at postnatal interview were31% and 25% respectively; the difference is notstatistically significant.
EFFECT OF COUNSELLING ON OUTCOMEAt entry to the trial the test and control groupswere similar with respect to amounts smoked and toother maternal factors likely to relate to the
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outcome of pregnancy such as age, height, parity,and social and educational status (first twocolumns of Table 2). At the end of the trialweights, lengths, and head circumferences of theinfants at birth and at six weeks were all similar inthe two groups. Maturity, placental weight, andincidence of fetal distress and perinatal mortalitywere also unaffected (first two columns of Table 3).There was thus no evidence that the anti-smoking
advice influenced the outcome of the pregnancies.The rest of this section of the report presents otherresults of the study that bear on interpretationof this main finding.
RECALL OF AMOUNTS SMOKEDThe postnatal recall of the amounts the subjectsbelieved that they had smoked in early pregnancycan be compared with their contemporaneousstatements. At entry to the trial both test andcontrol groups had stated that their meanconsumption was 15 2 cigarettes a day (Table 2)but at the postnatal interview their estimatedconsumption, in early pregnancy averaged 17-1(test) and 14-7 (control) cigarettes a day (Table 4).Responses of each patient at entry and at postnatalinterview were therefore compared. In the controlgroup discrepancies in recall were usual, but therewas no systematic bias. In the test group postnatalexaggeration of early pregnancy consumption wasstrongly associated with heavy inhaling (Table 5).The poor recall of smoking habits is best
illustrated by the group of 'stopped smokers', 174of whom were interviewed postnatally. At this
Table 4 Mean stated amounts smoked at each stageofpregnancy, as obtained at postnatal interview
Table 5 Relationship between inhaling habits andpostnatal recall after counselling ofamounts smokedin early pregnancy
InhaleTotal
Lot Fair Littlelamount not
Patients overestimatingconsumption in earlypregnancy by more thanfive cigarettes a day 17 19 8 44Remainder of test group 41 98 79 218Total 58 117 87 262
Early pregnancy consumption as recalled postnatally minus currentconsumption at entry to study versus inhaling. X2 = 10-12, P < 0-01.
interview, 54 admitted smoking in late pregnancybut 11 of them denied ever having stopped. Amongthe 120 who did not resume, 28 claimed to havegiven up before they became pregnant (contrastedwith two such claims at entry), and three deniedever having been smokers.
REDUCTION IN AMOUNT SMOKED, AND ITSTIMINGIt is a possible interpretation of the results of thiscontrolled trial that the counselling was not actedupon sufficiently, or in time for fetal growth to beaffected. As recalled postnatally, the mean statedamount smoked in late pregnancy in the test groupwas 56% (9-2/16-4) of that in the control group,and in the middle months it was 82% of that in thecontrols (Table 4), and the percentages weresimilar in each inhaling category. Contemporaneousrecords of consumption in the test group indicatethat the reductions in smoking that were achievedoccurred soon after counselling started, with littlefurther reduction after 28 weeks of gestation.However, any interpretation of these findings ismade uncertain by the biased recall in the testgroup.The number of mothers who change their smoking
habits during pregnancy is small if there is nopressure upon them to do so and even with suchintervention the proportion who change is not large.As a result statistical analyses which would be ableto differentiate between the effects which might bedue to smoking at particular stages of pregnancyrequire large studies. Most earlier studies have onlybeen able to compare mothers who had stoppedsmoking early in pregnancy with those who did notsmoke at all or who continued to smoke. This presentstudy confirms the previous findings that thosewho stopped smoking had the same outcome as thenon-smokers (Table 3) but it also demonstrates thatthose mothers who reported that they had stoppedsmoking in early pregnancy had smoked less at thebeginning of pregnancy than those who were tocontinue (Table 2). Many 'stopped smokers' reportedthat they resumed smoking in late pregnancy whichallows a further comparison to be made. Of the 174'stopped smokers' at the first antenatal attendance,54 resumed smoking before delivery and theirmean consumption at this time was reported as 7 0cigarettes a day. The birthweight of the infants ofthese 'resumed smokers' was 3404 g (standard error62 g) whereas the mean birthweight of the infantsdelivered by the 120 'persistent stopped smokers'was 3324 g (standard error 52 g). The two groupswere similar in other respects including theirsmoking habits in early pregnancy. The differenceof 80 g between the birthweights is not statistically
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significant but it is in the opposite direction tothat which would be expected if smoking in latepregnancy reduced the birth weight of an infant.
OBSERVED GROWTH RETARDATION MAY NOTBE DUE TO SMOKINGThe failure of anti-smoking advice to alter outcomeis compatible with the hypothesis that smoking inpregnancy does not itself cause low birthweightbut that it is an index of some other harmful factoror factors.One of the arguments used to support this hypo-
thesis concerns the findings of Yerushalmy (1972a)on smokers who were asked the ages at which theyhad started to smoke. These ages were comparedwith ages at previous confinements, where birth-weights were also known. It was inferred that thepatients were or were not smoking during theseearlier pregnancies, where the proportions of low(below 2501 g) birthweight infants were 8 * 9%and 9 5% respectively. Thus, it was argued, lowbirthweight was an attribute of the mother and notof whether she smoked in the particular pregnancy.Those in the test group were asked the age at which
smoking was started both at the first antenatal visitand postnatally. There was no systematic error butmost patients gave different answers on the twooccasions (Table 6). The two sets of answers were
Table 6 Discrepancy between patients' answers to'How old were you when you began to smoke at leastone cigarette per day?' asked at first antenatal visitand again postnatally*Discrepancy (years) No. %
therefore checked against dates of previous confine-ments. If those obtained at the first antenatal visitwere correct five patients had their first child beforethey started smoking. If those obtained at the post-natal interview were correct three patients had theirfirst child before they started smoking. Only one childwas in both groups; the other six mothers withpregnancies 'before they started smoking' wereunreliable witnesses of the ages at which they hadstarted to smoke. Yerushalmy's interpretation maybe based on misclassification due to errors of recall.One other result which might support the
other-factor hypothesis is the lack, within the
groups of smokers, of any statistically significantrelationship between birthweight and amountssmoked; the major difference was between smokersand non-smokers (details available on request).
Discussion
The trial did not show any influence of intensiveanti-smoking advice on the retardation of fetalgrowth that descriptive studies have shown to beassociated with maternal smoking. It did showthat advising patients not to smoke without firstdetermining all relevant circumstances carried risks,and that practising health professionals generallydid not reinforce the advice given, even whenrequested to do so.From the unanimity of findings of descriptive
studies it might have been expected that the anti-smoking advice would have led to an increase in themean birthweight of the test group infants.Possible reasons for the apparent conflict are thatthe counselling may not have been acted uponsufficiently, that any action taken was too late forfetal growth to benefit, or that maternal smokingmight be merely an index of some other factorthat influences growth. Combinations of these threereasons are also possible.As no biochemical measurements were made the
claimed reductions in smoking cannot be substan-tiated; the limited evidence that is available maybe used to argue both for and against their havingoccurred. It should, however, be noted that if thefindings of Butler et al. (1972) on birthweightsassociated with changes in smoking habits madearound the fourth month of pregnancy are used tocalculate expected birthweight in the test andcontrol group infants, the observed outcome iswithin the limits of chance.
Supporters of the hypothesis that the observeddifference in birthweight associated with maternalsmoking is due to other factors base most of theirarguments on the work of Yerushalmy (1962, 1964,1971, 1972a). The present study contributes to thedispute over his findings concerning mothers whomhe inferred had changed their smoking habitsbetween pregnancies, and strengthens the argumentthat his analyses were methodologically unsound(Goldstein, 1972; Yerushalmy, 1972b).One particular finding of the present study that
appears to support the other-factors hypothesisis the lack of a gradient of birthweight withamounts smoked. This gradient has been found inlarger studies wherever it has been sought. In thissmaller study with distortion of stated consumptionsin the test group its absence is of no significance.
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TIMING OF ANTI-SMOKING ADVICETable 3 shows that the infants of the 'stoppedsmokers' were similar to those of non-smokers inevery respect. From similar findings in many earlierstudies it has been inferred that smoking is harmfulonly in 'later' pregnancy. This inference mightbe valid if the stopped smokers had in 'early'pregnancy been smoking and inhaling as much as
those who continued, but in fact this was not so
(Tables 2, 3); only Butler et al. (1972) andSchwartz et al. (1972) seem to have considered thispoint previously. The experience of smokers whostop smoking early in pregnancy but later resume
provides another test of the inference. In the presentstudy, in the group of mothers who resumed smokingin late pregnancy, the mean birthweight was higherthan in the group who did not. The only relevantearlier data came from Lowe (1959) who, withsimilar numbers of subjects, found the reverse. Thedifference between his findings and those of thepresent study is compatible with sampling variation.Where there is a difference in obstetric performance
between smokers and non-smokers at a particularstage of pregnancy it can be inferred that smokingif it has an influence is having an influence beforethat stage. From the larger descriptive studiesYerushalmy (1964) reported higher mean birth-weights in non-smokers from before 32 weeks'gestation (Whites) and from 32 weeks (Negroes).Some smaller surveys have found weight differencesin pregnancies confined from 28 weeks but othershave not (Frazier et al., 1961; Zabriskie, 1963;Russell et al., 1966). Taken together, these surveysindicate that smoking influences outcome of preg-nancy at least by 32 weeks, and perhaps by 28 weeks.There is more direct evidence that smoking
is harmful in early pregnancy. There are reports ofincreased incidence of certain malformations ininfants of smokers, although it is generally agreedthat the total incidence of malformations is notsignificantly increased. Likewise several authorshave found increased abortion rates in smokers,although others have not (US Public Health Service,1973).
It is not claimed that this brief review refutesdefinitively the widely held belief that smokingis harmful to the fetus mainly in late pregnancy,but merely that it is not well based. The currentstudy shows the limited value of smoking historiescollected after confinement, and casts doubts on
estimates of amounts smoked by those counselled.Further evidence could be provided by large descrip-tive studies in which smoking habits were recordedthroughout pregnancy, with some biochemicaltesting, and perhaps supported by ultrasonicmeasurements of fetal growth. Supportive evidence
might be provided by animal experiments in whichthe effect of smoking at each stage of pregnancywas tested; those reported to date have involvedexposure throughout pregnancy. The results ofcontrolled trials examining other presumed causesof retarded intrauterine growth might also berelevant. The most direct evidence on the desirabletiming of anti-smoking advice would come fromcontrolled trials of advice given before conceptionand to patients presenting very early in pregnancy,but these would be difficult to execute.
Finally, the late effects on development of retardedintrauterine growth are so important that despitethe results of this study it must still be asked whatsmoking education measures should be used in preg-nancy. The answer to this question depends onwhich of the possible explanations for the differencebetween the findings of the controlled trial andthe inference from previous studies proves to becorrect. If the growth retardation can be shownto be caused by some factor other than smoking,anti-smoking advice will be irrelevant. If it isthat the advice was acted upon too late, methodsthat depend upon waiting for patients to get intocontact with the health services will also fail.If it is that intensive individual advice was notsufficiently acted upon, other forms of healtheducation may yet prove successful, but theireffectiveness should be proved before they areadopted for routine use.
This study was planned during the tenure of aC. J. Martin Travelling Fellowship from theNational Health and Medical Research Council ofAustralia. Its execution was supported by theTobacco Research Council. The obstetric units ofUniversity College Hospital, Hammersmith Hospital,and the Royal Free Hospital collaborated in thestudy. I wish to thank the study staff for theirassistance and Professor D. V. I. Fairweather,Professor J. C. McClure Browne and ProfessorC. P. Douglas, and the other consultants in theirdepartments, for allowing access to their patients.To Professor D. D. Reid and Mr. G. F. Todd I amgrateful for encouragement and advice.
Reprints from the Secretary, Department of MedicalStatistics and Epidemiology, London School ofHygiene and Tropical Medicine, Keppel Street,London WC1E 7HT.
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