Maternal smoking during pregnancy predicts nicotine disorder (dependence or withdrawal) in young...

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1 Maternal smoking during pregnancy predicts nicotine disorder (dependence or withdrawal) in young adults - a birth cohort study Frances V. O’Callaghan a , Abdullah Al Mamun b , Michael O’Callaghan c , Rosa Alati b , Jake M. Najman bd , Gail M. Williams b and William Bor c a School of Psychology, Griffith University, Gold Coast, QLD 4222, Australia, b School of Population Health, The University of Queensland, Brisbane, QLD 4072, Australia, c Mater Misericordiae Hospital, Brisbane, QLD 4101, Australia, d School of Social Science, The University of Queensland, Brisbane, QLD 4072 Address for correspondence: Dr Frances O’Callaghan School of Psychology, Griffith University, Gold Coast QLD, Australia, 4222 Ph: 61 7 555 28606 Fax: 61 7 555 28291 E-mail: [email protected] Funding: The core study was funded by the National Health and Medical Research Council (NHMRC) of Australia. This work was funded by the NHMRC grant number: 252834 and took place in Brisbane, Queensland, Australia.

Transcript of Maternal smoking during pregnancy predicts nicotine disorder (dependence or withdrawal) in young...

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Maternal smoking during pregnancy predicts nicotine disorder (dependence or

withdrawal) in young adults - a birth cohort study

Frances V. O’Callaghana, Abdullah Al Mamunb, Michael O’Callaghanc, Rosa Alatib, Jake

M. Najmanbd, Gail M. Williamsb and William Borc

aSchool of Psychology, Griffith University, Gold Coast, QLD 4222, Australia, bSchool of

Population Health, The University of Queensland, Brisbane, QLD 4072, Australia, cMater

Misericordiae Hospital, Brisbane, QLD 4101, Australia, dSchool of Social Science, The

University of Queensland, Brisbane, QLD 4072

Address for correspondence:

Dr Frances O’Callaghan

School of Psychology,

Griffith University, Gold Coast

QLD, Australia, 4222

Ph: 61 7 555 28606

Fax: 61 7 555 28291

E-mail: [email protected]

Funding: The core study was funded by the National Health and Medical Research Council

(NHMRC) of Australia. This work was funded by the NHMRC grant number: 252834 and

took place in Brisbane, Queensland, Australia.

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Abstract

Objective: To investigate whether maternal smoking during pregnancy predicts offspring

nicotine disorder (dependence or withdrawal) at 21 years.

Method: Participants comprised a prospective birth cohort involving 7223 singleton

children whose mothers were enrolled between 1981 and 1983 at the first antenatal visit to

the Mater Mothers’ Hospital, Brisbane, Queensland. The present sub-cohort consisted of

2571 youth who completed the Composite International Diagnostic Interview-computerized

version (CIDI-Auto) which assesses nicotine dependence and withdrawal according to

DSM-IV diagnostic criteria, at the 21-year follow-up.

Results: 12.8% of offspring met criteria for nicotine dependence and 8.5% met criteria for

withdrawal. 16.6% met criteria for either dependence or withdrawal. Smoking during

pregnancy resulted in offspring being more likely to have dependence or withdrawal at 21

years than offspring of mothers who never smoked (age adjusted odds ratio 1.53 (95%

confidence interval: 1.19, 1.96). The odds of nicotine disorder among offspring whose

mothers stopped smoking during pregnancy, but who then smoked at other times were

similar to those whose mothers had never smoked. This relationship was independent of

potential confounding and mediating factors including adolescent behaviour.

Conclusions. Findings emphasise the long-term adverse effects of maternal smoking

during pregnancy, including nicotine dependence in young adult offspring.

Implications. Public health approaches should strengthen arguments for mothers to cease

smoking during pregnancy in view of the long-term health implications for offspring, and

reinforce measures to help smokers among pregnant women and women of childbearing

age to stop.

Key words: nicotine disorder, nicotine dependence, maternal smoking, birth cohort, young

adult

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Maternal smoking during pregnancy predicts nicotine disorder (dependence or

withdrawal) in young adults - a birth cohort study

Introduction

Nicotine dependence is a serious public health problem, with evidence suggesting that over

half of youth develop symptoms of nicotine dependence within weeks of the onset of

intermittent tobacco use.1 Since current nicotine dependence is a major indicator of

persistence of dependence and of chronic smoking,2 as well as a strong predictor of relapse

after cessation3, understanding its origins is an important issue. There has been growing

evidence suggesting that, apart from well-established predictors such as parental and peer

smoking,4 maternal smoking during pregnancy predicts the development of adolescent

smoking5 and smoking patterns of young adults.6 Yet little is known about the influence of

maternal smoking during pregnancy on the development of nicotine dependence.

To our knowledge, only two birth cohort studies have examined the association between

maternal smoking during pregnancy and the development of nicotine dependence in

offspring.7-8 The former study assessed offspring aged between 17 and 39 years and found

that the odds of progressing to nicotine dependence were almost twice as great for the

children of heavy smokers (one or more packs/day) compared to children of nonsmokers. 7

Although maternal smoking was assessed during pregnancy, subsequent maternal smoking,

maternal alcohol use and adverse parental and family factors were not controlled for. The

other study measured maternal smoking in pregnancy at offspring birth, and used a

questionnaire based on the Composite International Diagnostic Interview to assess 18-year

old offspring substance use during the previous two years.8 Adolescents whose mothers

smoked more than one pack/day during pregnancy had symptom rates that were between

1.4 and 2.5 times higher than offspring of mothers who did not smoke during pregnancy.

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However, the relationship attenuated towards the null after adjustments were made for a

range of confounding factors.

In a study of offspring first assessed at 14-17 years of age, higher rates of nicotine

dependence were reported in offspring of mothers who retrospectively reported smoking

regularly during pregnancy compared to children of both nonsmokers and those who

retrospectively reported they did not smoke during pregnancy.9 Alcohol consumption and

adverse parental and family factors were not controlled for.

Of three studies,7-9 two reported maternal smoking during pregnancy predicted

offspring nicotine dependence and one reported the association attenuated to the null after

adjusting for potential confounders. These conflicting findings warrant further study with a

larger sample size and more measures of potential confounders and mediators. Furthermore,

the pathways underlying the association between maternal and offspring smoking remain

unclear. For example, the effect of maternal smoking during the developmental/teenage

years may be more important than the exposure during pregnancy. Familial transmission of

substance abuse risk may be involved.10-11 Also, a history of mental health disorders that

are known to be strongly correlated with regular tobacco use12-13 may fully or partly explain

the relationship. Another pathway may involve childhood behaviour problems, in

particular, externalizing behaviours that are associated with prenatal nicotine exposure and

may be linked with later smoking.14 Therefore, the association could be due to in-utero

biological modifications, genetic predisposition to mental health disorders or other

environmental/modelling exposures.

The objectives of this study were (1) to investigate whether maternal smoking during

pregnancy predicts offspring nicotine dependence in young adulthood, when smokers have

typically passed through the risk period for the onset of nicotine dependence (assessed

using DSM-IV criteria) and (2) to explore the mechanisms underlying the association,

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especially whether it is mediated by adolescent behaviour. Our hypothesis was that

maternal smoking during pregnancy would predispose children to dependency as young

adults.

Methods

Participants were from the Mater-University of Queensland Study of Pregnancy

(MUSP).15 Initially, 8556 women attending their first antenatal clinic at the Mater

Misericordiae Mothers’ Hospital, Brisbane (1981-83), were invited to participate. At the

time of hospital discharge, 7223 singleton children were enrolled in an ongoing birth cohort

study.16 Mothers were interviewed at the first pregnancy visit (Mean = 19.8 + 6.0 weeks

gestation), several days after delivery, at 6 months, and at 5, 14 and 21 years. Offspring

were also assessed at 6 months and at 5, 14 and 21 years. The present cohort consisted of a

subgroup of 2546 youth (51.1 percent female) who completed the lifetime version of the

Composite International Diagnostic Interview-computerized version (CIDI-Auto)17 and

self-reported current smoking status at the 21-year follow-up. The study was approved by

the Mater Hospitals and University of Queensland Ethics Committees with written consent

being obtained from the mother at each stage of follow-up and from the youth at 21 years.

Participants who were lost to follow-up (i.e. did not attend the 21-year follow-up) were

more likely to be males, their mothers were more likely to be less educated, to be teenage

mothers, to be not married (single/defacto/other during pregnancy), from lower income

families at their birth, to use tobacco and alcohol during pregnancy and to be anxious and

depressed at their first antenatal visit (all p-values < 0.01; Table 1).

Nicotine dependence and withdrawal

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The young adults completed the lifetime version of the CIDI-Auto.17 It has excellent

reliability and acceptable validity.18 Its use in a range of epidemiological studies has further

confirmed its reliability and validity as a survey instrument in this type of research.19 The

CIDI-Auto assesses psychiatric disorders according to DSM-IV diagnostic criteria.20 It was

used to assess current diagnoses of nicotine dependence and withdrawal at 21 years.

Subjects meeting criteria for either nicotine dependence or withdrawal were classified in

this study as having a nicotine disorder.

Maternal smoking

At the first clinical visit (FCV) when the women were on average 18-weeks of

gestation, then 3-5 days post-delivery, at 6-months, 5-years and 14-years follow-up,

mothers were asked to record whether they smoked (yes or no). If they smoked, they were

asked to report the frequency and quantity of tobacco use in the previous week. In addition,

at the FCV women were asked about whether and how much they smoked before they

became pregnant. At 3 to 5 days after delivery, mothers were asked to recall their smoking

level over the last trimester.

We defined maternal smoking status in three mutually exclusive categories: never

smoked (responded ‘no’ at all stages of the study), smoked throughout pregnancy and at

other times, and smoked before and/or after pregnancy but not during pregnancy (women

who responded ‘no’ throughout pregnancy but ‘yes’ either to smoking before pregnancy

and/or at any stage of follow-up to the 14 year follow-up) (Table 2).

Confounding and mediating factors

Measures at time of pregnancy consisted of maternal age, education (did not complete

secondary school, completed secondary school, completed further/higher education),

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depression (using the Delusions Symptoms States Inventory),21 dyadic adjustment (using the

Dyadic Adjustment Scale),22 alcohol consumption (non drinker vs drinker),23 and

breastfeeding (never, less than 4 months, 4+ months). This categorisation of breastfeeding

has been used in previous research. 24 Breastfeeding information was collected at a 6-month

follow-up of the mothers, at which time some mothers were in fact between 4 and 6 months

postdelivery. The response options in the original question regarding breastfeeding duration

were: never, 2 weeks or less, 3-6 weeks, 7 weeks – 3 months, 4-6 months, and still

breastfeeding. Because women were at least 4 months post-delivery when they responded to

this question, the final two categories were combined into ‘breastfed for greater than 4

months’. As there were too few women in the categories from 2 weeks to 3 months to enable

meaningful analyses, the final categories used in the analyses were those noted above (i.e.

never, less than 4 months, 4+ months).

At 5 years, degree of parenting control25 and measures assessing number of children in

the household were considered as potential confounders. Family communication at 14

years, measured using the 20-item Parent-Adolescent Communication Scale26 (e.g. I have

trouble believing my child), was used as a confounder. Child externalizing and internalizing

behaviour problems were assessed with the Child Behaviour Checklist at 14-year follow-

up. 27 The externalizing behaviour subscale addresses aggression and delinquency while the

internalizing subscale addresses social withdrawal, anxiety/depression, and somatic

complaints. These were used as mediating factors. Potential confounders and mediators

were chosen because of their known or likely associations with smoking, and their

availability in the data set.2,4,28

Statistical analysis

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We first tabulated the different patterns of maternal smoking into six, and then three

mutually exclusive exposure groups (Table 2). The relationship between maternal cigarette

smoking and the outcome of current diagnosis (based on CIDI-Auto lifetime criteria) of

nicotine disorder in 21 year-old offspring was examined using chi-square tests. Unadjusted

odds ratios and 95 percent confidence intervals were estimated using logistic regression,

with the reference categories being mothers who never smoked (Table 2) and offspring who

reported no nicotine disorder at 21 years (Table 3).

Factors that were statistically significant in the univariate analysis were included in a

series of multiple logistic regression models (see footnotes to Table 4) to assess the

association between maternal smoking status in the same three mutually exclusive

categories and offspring nicotine dependence at age 21 years, taking into account potential

confounding and mediating factors. These results are for the 2101 young adults and their

mothers with complete data on all variables included in the model.

To determine whether non-response affected the validity of our findings we undertook a

weighted analysis using inverse probability (of having missing outcome data) weights.29

Probability weights were computed by using a logistic regression model with the outcome

being complete data or not. The influence of all other covariates used in our primary

analyses on having complete data or not was assessed in combination in a logistic

regression model. The regression coefficients from this model were then used to determine

probability weights for the covariates in the main analyses (e.g. if the probability of non-

response was 0.7 for a mother who did not complete secondary school, the inverse

probability of weight would be 1.44). All analyses were undertaken using Stata version

10.0 (Stata Inc., Texas).

Results

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Of the 2546 offspring who completed the CIDI-Auto, 12.8 percent met the criteria for

nicotine dependence and 8.4 percent met the criteria for nicotine withdrawal. 16.5 percent

met the criteria for either dependence or withdrawal and are the subjects described in

further analyses as having nicotine disorder. At 21 years, 25.7% of offspring reported

regular smoking, and of these, 65.3% showed either nicotine dependence or withdrawal. Of

the 25% who reported that they occasionally smoked or used to smoke, 34.2% showed

nicotine dependence or withdrawal.

Table 2 shows the prevalence of current diagnosis of nicotine disorder in offspring at 21

years by maternal smoking status categorised into three mutually exclusive groups from

pre-pregnancy to 14 years. In this unadjusted analysis, smoking during pregnancy added an

additional risk for later nicotine problems. Possible confounding factors and their

relationship to youth nicotine disorder are shown in Table 3. Maternal age at birth,

education, duration of breastfeeding, parental communication at 14 years and internalizing

and externalizing behaviour problems in adolescence were all associated with young adult

nicotine disorder.

Table 4 shows the odds ratios for nicotine disorder at age 21years, comparing each

maternal smoking category to the reference group of never smoking. Potential confounders

and mediators were adjusted for in a series of multiple logistic regression models to

examine the effect of specific confounders. These results are for the 2101 young adults and

their mothers with complete data on all variables included in the model. The age adjusted

odds ratio for smoking in pregnancy was 1.53 (95 percent confidence interval (CI): 1.19,

1.96). This association remained consistent in the final model including all potential

confounders and mediators (Adj OR 1.45, 95% CI: 1.12,1.87). Smoking at other times but

not in pregnancy was 1.03 (95 percent CI: 0.69, 1.56).

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We repeated the analysis considering maternal smoking before and/or after pregnancy

as the reference category to examine whether the relationship between smoking during

pregnancy and nicotine disorder was independent of maternal smoking either before or after

pregnancy. The point estimate did not attenuate substantially (unadjusted odds ratio 1.43

(95 percent CI: 0.96, 2.15) and the confidence interval became wider, as expected.

When we repeated the analyses removing the 69 women who reported smoking before

the birth of their child but at no other time the results did not differ from those presented

here. Similarly, when we repeated the analyses removing the 30 women who reported

smoking during their child’s pregnancy but then quit after the pregnancy, the results did not

alter. When we repeated the analyses using weights for factors that predicted non-response

the results did not differ from those presented here.

Discussion

Compared to mothers who did not smoke at all, offspring of mothers who smoked

during pregnancy and at other times had an age adjusted OR of 1.53 (95% CI: 1.19, 1.96)

for nicotine disorder (dependence or withdrawal) while offspring of mothers who smoked

at other times, but not during pregnancy, had an age adjusted OR of 1.03 (95% CI: 0.69,

1.56).

Both indirect and direct mechanisms may explain this relationship.30 Indirect

mechanisms from smoking during pregnancy include poor maternal nutrition, carbon

monoxide exposure, catecholamine constrictive effects, and the association between low

birth weight and behavioural problems that may be linked with a greater likelihood of

smoking among offspring. The addictive and neurotoxic effects of nicotine are well

documented.31 Direct effects include the action of nicotine on nicotine acetylcholine

receptors that are present from approximately eight weeks and prominent from mid-

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gestation.32-33 Stimulation of these receptors in animal models can lead to disturbances in

neural development and in associated catecholamine systems of the fetal brain including

dopamine pathways.34 Drugs of abuse, including nicotine, may cause dependence by acting

on the mesolimbic dopamine system which is the natural reward system of the brain.31,36

The results are consistent with two previous studies7,9 but differ from another.8 Our

study differs to the latter in that it included various factors measured at birth (i.e. maternal

smoking, alcohol and other drug use during pregnancy), whereas similar factors taken into

account in the current study were measured during pregnancy. Further, our analyses were

based on DSM-IV diagnoses of dependence and withdrawal while previous research8

involved scale measures of the number of DSM-IV symptoms reported. Ferguson et al.8

however, adjusted also for measures of parental characteristics and childrearing practices,

all of which were not included in our database.

Measures that may mediate or confound the association between maternal smoking

during pregnancy and adult nicotine disorder, such as behavioural problems, parenting style

and family communication were also examined in this study. Addictions and other

psychiatric disorders have common neurobiological pathways that mediate factors such as

reward responses, behavioural control and the anxiety or stress response.36 When we

controlled for these characteristics, the relationship between maternal smoking during

pregnancy and adult nicotine disorder remained consistent and significant. The association

was also independent of parenting style characterised by physical punishment, maternal

depression and poor family communication, which may represent another potential pathway

from maternal smoking to adult nicotine disorder. Finally the relationship remained robust

even when we accounted for the modifying effect of externalizing behaviour. Although

young age at first pregnancy is associated with a range of potential adverse outcomes, in

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this study, adjusting for age did not substantially alter the effect measure. This may reflect

the relatively small number of mothers in this group.

In previous research involving the present cohort, we found that the proportion of

young adults who smoked regularly at age 21, either with early (before age 14) or later

onset was greater among those whose mothers had smoked during pregnancy than those

whose mothers had never smoked or who smoked at other times but not during pregnancy.5

The association between maternal smoking during pregnancy and negative developmental

outcomes among offspring have also indicated a dose-response relationship8 and this issue

is being addressed in a subsequent investigation involving the current cohort. Although

higher levels of smoking are generally associated with a higher prevalence of nicotine

dependence37-38 there is only a modest association between cigarette consumption and

dependence,37 and no defined amount of smoking automatically leads to dependence.39

Recent studies showed that a substantial proportion of those engaging in daily and/or heavy

smoking were not nicotine dependent according to DSM-IV criteria,38,41 while some

smoking at relatively low levels were nicotine dependent.37 In the current study, we found

similar rates of regular smoking to those reported in national prevalence surveys (i.e. 23.7%

daily smokers among 20-29 year olds).42 According to DSM-IV criteria, dependence

involves a combination of physiological (e.g. tolerance, withdrawal symptoms), cognitive

(e.g. desire to quit) and behavioural symptoms (e.g. considerable time spent in smoking-

related activities) related to an individual’s continued use of a substance despite significant

substance related problems. As highlighted by the current and previous research, however,

failure to meet DSM-IV criteria does not imply that daily smoking poses a less serious

health risk or makes it easier for such individuals to quit smoking.

Overall, the current study has several important strengths. It is the first to examine

prospectively measured maternal smoking prior to and during pregnancy, and the

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development of nicotine dependence and withdrawal in young adult offspring; diagnostic

interviews based on DSM-IV criteria were used to assess offspring dependence; offspring

were assessed in young adulthood, by which time the risk period for the onset of nicotine

dependence has generally passed; and a range of confounding factors including childhood

and family influences were controlled for. The findings support the importance of prenatal

exposure in predicting both regular smoking and actual smoking dependence among young

adult offspring.

Notwithstanding the strengths of the current study, caution is needed when interpreting

the findings since the relationship may be accounted for by common genetic factors

associated with both maternal smoking during pregnancy and nicotine disorder in

adulthood. If this were so, however, the association may also have been evident in those

who smoked at other times, though not in pregnancy. Also, we could not measure peer

influences, which have been found to be important in the development of youth

smoking,40,43 nor did we have information on the father’s smoking during pregnancy.

Further, mothers who give up smoking while pregnant may possess certain personality

factors that, in turn, may be related to styles of parenting or other family variables that were

not measured and that may have contributed to explanations of this association. The

accuracy of self-reported smoking has been discussed in a previous publication involving

this cohort. 44 Under-reporting and/or denial of smoking during pregnancy has been found

in previous research involving pregnant women45 and may have led to an underestimation

of the effects of smoking during pregnancy. It is therefore possible that outcomes relating to

nicotine disorder are greater than those reported here. It is also possible that over-estimation

of smoking may have contributed to some degree of error in the extent of outcomes

reported here, although efforts were made to maximize the accuracy of the information

provided by participants (e.g. assurances of confidentiality, the clinical setting, detailed

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questions, and trained interviewers). Finally, the attrition was substantial and greater than

the approximate 40 percent and 20 percent in two previous studies.8-9 This potentially may

lead to biased estimates, though the direction of the bias is likely to lead to our findings

being a modest underestimate of the strength of the association. As loss to follow-up and

nicotine disorder are both related to more adverse social circumstances and maternal

smoking in pregnancy, it is unlikely that the association would be less evident in those not

included, particularly given that we have found that those lost to follow-up are more likely

to be anxious/depressed, and to be smokers and drinkers.15

In conclusion, the current study suggests that smoking during pregnancy may

predispose offspring to nicotine disorder (dependence and withdrawal) in early adulthood.

Adjustment for confounding factors such as maternal age, education, breastfeeding and

family communication, and mediating factors such as externalizing behaviour and

internalizing problems of adolescents, did not alter the relationship materially, suggesting a

direct association between maternal smoking and offspring nicotine disorder in adulthood.

The results extend the public health significance of findings in this area and highlight the

importance of intensifying efforts to reduce maternal smoking during pregnancy.

Acknowledgments

We thank all participants in the study, the MUSP data collection team, and data manager,

University of Queensland who has helped to manage the data for the MUSP.

Funding: The core study was funded by the National Health and Medical Research Council

(NHMRC) of Australia. AAM and RA are funded by NHMRC Career Development Awards

in Population Health ( ID 519756 and ID 519721 respectively). The views expressed in the

paper are those of the authors and not necessarily those of any funding body and no funding

body influenced how the data were analysed and presented.

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21

Table 1: Comparison of study and non-study groups.

Non-Study

(n = 4426)

Study

(n = 2571)

p Value

n % n %

Maternal Education

Incomplete high 838 18.93 410 16.06

Complete high 2861 64.64 1634 64.00

Post high 727 16.43 509 19.94 <0.001

Maternal Age (years)

13-19 669 15.12 293 11.40

20-34 3562 80.48 2135 83.04

> 34 195 4.41 143 5.56 <0.001

Marital Status

Married 3191 72.10 2081 81.48

Single 494 11.16 208 7.14

Defacto 604 13.65 223 8.73

Other 137 3.10 42 1.64 <0.001

Gross Family Income

Low 1502 33.94 731 28.43

Medium 2230 50.38 1408 54.76

High 410 9.26 309 12.02

Missing 284 6.42 123 4.78 <0.001

Maternal Cigs Early

Preg

Nil 2662 60.14 1652 64.81

22

Non-Study

(n = 4426)

Study

(n = 2571)

p Value

n % n %

Light smokers (1-19

cigarettes per day)

1359 30.70 709 27.81

Heavy smokers (20 or

more cigarettes per day)

405 9.15 188 7.38 < 0.001

Maternal alcohol during

pregnancy

Abstainer 2278 51.47 1222 47.87

Light or 1 drink per day 2148 48.53 1331 52.13 0.004

Child Gender

Male 2374 53.64 1258 48.93

Female 2052 46.36 1313 51.07 <0.001

Maternal depression

Not depressed 4120 93.09 2441 96.25

Depressed 306 6.91 95 3.75 <0.001

Child birth weight

(gram)

<2500 203 4.59 111 4.32

2501-3000 737 16.65 413 16.07

3001-3500 1656 38.09 995 38.72

3501 and more 1800 40.67 1051 40.89 0.855

23

Table 2: Classification of maternal smoking behaviour and association with offspring

nicotine disorder.

Maternal smoking status in the three mutually exclusive categories used in main

analyses

Smoker classification n Prevalence p value Unadjusted

OR* 95% CI*

Never smoked 1118 13.60 <0.001 1.00

Smoked before and /or after

pregnancy but NOT during

pregnancy

231 15.15 1.13 0.76, 1.69

Smoked during pregnancy 779 20.03 1.59 1.25, 2.03

* OR, odds ratio; CI, confidence interval.

24

Table 3: Prevalence of young adult nicotine disorder by maternal and child factors.

Maternal and child factors n

Prevalence

of nicotine

disorder at

21 yrs

(%)

p

Value

Unadjusted

OR* 95% CI*

Sex

Males 1258 16.61 1.00

Females 1313 16.60 0.994 1.00 0.81, 1.23

Maternal age at pregnancy

13-19 293 23.21 1.00

20-34 2135 15.88 0.62 0.46, 0.84

>34 143 13.99 0.005 0.54 0.31, 0.93

Maternal education

Did not complete secondary 410 21.95 1.00

Secondary completed 1634 15.97 0.68 0.52, 0.88

Post High 509 14.15 0.004 0.59 0.42, 0.82

Maternal depression at pregnancy

Not depressed 2320 16.29 1.00

Depressed 216 19.44 0.233 1.24 0.87, 1.77

Dyadic adjustment at pregnancy

Good adjustment 2156 16.05 1.00

Not good adjustment 323 18.83 1.19 0.88,1.62

No partner 70 20.00 0.172 1.31 0.72,2.38

Maternal alcohol consumption at

25

Maternal and child factors n

Prevalence

of nicotine

disorder at

21 yrs

(%)

p

Value

Unadjusted

OR* 95% CI*

pregnancy

Abstainer 1222 16.78 1.00

Light or 1+ per day 1303 16.45 0.827 0.98 0.79, 1.20

Parenting style (degree of control)

Low 326 18.71 1.00

Moderate 1738 15.88 0.82 0.60, 1.11

High 226 14.16 0.311 0.72 0.45, 1.14

Number of children in family at 5

yr follow-up

<4 1926 16.30 1.00

> 4 380 15.26 0.614 0.92 0.68, 1.25

Breastfeeding

Never 459 18.74 1.00

Less than 4 months 927 17.48 0.92 0.69, 1.23

4 or more months 1090 14.31 0.048 0.72 0.54, 0.97

Openness family communication

Good 1986 15.16 1.00

Fair 230 18.70 1.29 0.90, 1.83

Poor 232 23.71 0.002 1.74 1.25, 2.41

Problems-family communication

26

Maternal and child factors n

Prevalence

of nicotine

disorder at

21 yrs

(%)

p

Value

Unadjusted

OR* 95% CI*

Few 1916 14.67 1.00

Some 313 19.81 1.44 1.06, 1.95

Many 219 25.57 <0.00

1

2.00 1.44, 2.78

Child externalizing behaviour

No 2231 15.33 1.00

Yes 215 26.51 <0.00

1

1.99 1.44, 2.76

Child internalizing behaviour

No 2215 15.53 1.00

Yes 231 23.81 0.001 1.70 1.23, 2.35

* OR, odds ratio; CI, confidence interval.

27

Table 4: Adjusted odds-ratios of offspring being smoking dependent at age 21, comparing

mothers in three categories (n=2101).

Model Never

smoked

Smoked before and /or

after pregnancy but

NOT during pregnancy

OR* 95% CI*

Smoked during

pregnancy

OR 95% CI

Model 1 1.00 1.11 0.74, 1.66 1.59 1.24, 2.03

Model 2 1.00 1.03 0.69, 1.56 1.53 1.19, 1.96

Model 3 1.00 1.04 0.69, 1.56 1.47 1.14, 1.90

Model 4 1.00 1.05 0.69, 1.58 1.50 1.16, 1.92

Model 5 1.00 1.01 0.67, 1.53 1.49 1.15, 1.91

Model 6 1.00 1.04 0.69, 1.57 1.45 1.12, 1.87

* OR, odds ratio; CI, confidence interval.

Model 1: unadjusted

Model 2: adjusted by age

Model 3: adjusted by age, maternal education and breastfeeding

Model 4: adjusted by age and parent-child communication reported at 14 years follow-up

Model 5: adjusted by age and behavioural and internalizing problems reported at 14 years

follow-up

Model 6: adjusted by all covariates mentioned above