- Email: [email protected]
Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant and Non-Pregnant Smokers
Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant and Non-pregnant Smokers Ivan Berlin M.D., Ph.D., Edward G. Singleton Ph.D., Stephen J. Heishman Ph.D. PII: DOI: Reference:
S0740-5472(15)00318-9 doi: 10.1016/j.jsat.2015.12.008 SAT 7389
To appear in:
Journal of Substance Abuse Treatment
Received date: Revised date: Accepted date:
19 June 2015 2 December 2015 3 December 2015
Please cite this article as: Berlin, I., Singleton, E.G. & Heishman, S.J., Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant and Non-pregnant Smokers, Journal of Substance Abuse Treatment (2015), doi: 10.1016/j.jsat.2015.12.008
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Running head: TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
1
RI P
and Non-pregnant Smokers
T
Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant
SC
Ivan Berlin1 Faculté de médicine, Université P. and M. Curie
NU
Edward G. Singleton2 Interactive Professional Services
ED
MA
Stephen J. Heishman3 National Institute on Drug Abuse
1
AC
Word count Abstract: 214 Text: 4362 2 tables, 1 figure
CE
PT
Ivan Berlin, M.D., Ph.D., Hôpital Pitié-Salpêtrière AP-HP -Faculté de médicine, Université P. and M. Curie - INSERM U1178, Paris, France 2 Edward G. Singleton, Ph.D., Interactive Professional Services, Catonsville, MD, USA 3 Stephen J. Heishman, Ph.D., Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA
Correspondence: Dr Ivan Berlin, Hôpital Pitié-Salpêtrière, Département de Pharmacologie, 47, bd de l’Hôpital, 75013 Paris, France. Email: [email protected] Phone: +33 1 42 16 16 78, Fax: +33 1 42 16 16 88
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
Abstract
T
Although pregnant smokers are aware of the negative peri- and postnatal health consequences of
RI P
smoking, the cessation rate in pregnancy is low, raising the question of why pregnant smokers have difficulty quitting. Reasons might be that pregnant smokers experience more intense
SC
craving and withdrawal symptoms than non-pregnant smokers. We compared craving and withdrawal in 306 pregnant smokers versus 93 non-pregnant women using data from two
NU
smoking cessation trials. Complete data were analyzed using pre-quit and post-quit (two weeks
MA
after quit date) craving and withdrawal measured by the 12-item French Tobacco Craving Questionnaire (FTCQ-12) and French Minnesota Nicotine Withdrawal Scale (FMNWS).
ED
Pregnant smokers started smoking and smoked regularly earlier and succeeded far less at quitting smoking by week 2 than the general population of smokers (11% versus 43%). Post-quit date
PT
FTCQ-12 general score was higher in pregnant smokers compared to comparison groups, and
CE
was driven by elevated emotionality and expectancy. FMNWS decreased significantly less among pregnant smokers than among non-pregnant smokers. Insufficient reduction of craving
AC
and withdrawal symptoms in response to a quit attempt may partially explain why pregnant smokers may have more difficulty quitting than non-pregnant smokers. Because this was a historical comparison, findings are preliminary; however, they might foster further investigation of differences in craving and withdrawal symptoms in pregnant versus non-pregnant smokers.
Keywords: pregnant smokers, non-pregnant female smokers, craving to smoke, withdrawal symptoms, smoking cessation
2
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY 1. Introduction Maternal smoking during pregnancy is associated with (a) increased risk of perinatal negative
T
health outcomes such as miscarriage, preterm birth, low birth weight, infant mortality, and birth
RI P
defects (Centers for Disease Control and Prevention, 2010; Schneider, Huy, Schütz, & Diehl, 2010; Räisänen, Gissler, Saari, Kramer, & Heinonen et al., 2013); (b) post-natal health disorders
SC
such as attention-deficit/hyperactivity disorder (ADHD) in children (Surgeon General, 2014; Zhu
NU
et al., 2014); (c) the development of allergic disease (Burke et al., 2012; Thacher et al., 2014), rheumatoid arthritis, and other inflammatory and autoimmune conditions (Jaakkola & Gissler,
MA
2005); (d) psychiatric morbidity and increased mortality in childhood, adolescence, and young adulthood (Ekblad, Gissler, Lehtonen, & Korkeila, 2010); and (e) nicotine dependence (Buka,
ED
Shenassa, & Niaura, 2003). Despite the gravity of these consequences, on average only 1 in 5
PT
pregnant smokers quit smoking and remain abstinent at 6 month follow-up (Heil et al., 2006). Several socio-demographic and smoking-related characteristics associated with smoking
CE
during pregnancy have been identified: being white, less education, unemployment, lower
AC
socioeconomic status, few financial resources, and emotional problems (DiClemente, DolanMullen, & Windsor, 2000; Schneider et al., 2010; Flemming, Graham, Heirs, Fox, & Sowden 2013; Hartmann-Boyce, Stead, Cahill, & Lancaster 2014). These studies also reported that high rates of tobacco consumption, high expired air carbon monoxide (CO) concentration, and years of smoking are predictors of continued smoking. Pregnant women are well aware of the health risks of smoking during pregnancy, yet such knowledge seems insufficient in motivating all of them to quit (Schneider & Schütz, 2008; Ingall & Cropley, 2010). In fact, according to representative data of US pregnant smokers, among women who smoked at conception only 23% self-reported having quit smoking (Kim, England, Kendrick, Dietz, & Callaghan, 2009) and
3
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY among those who smoked 3 months before pregnancy (N=3559), 42 % (N=1490) quit and 58 % (N=2069) smoked by the 3rd trimester in 2009-2010 (Kapaya, Tong and Ding, 2015).
T
According to 2010 data from France, and despite strong tobacco control campaigns targeting
RI P
pregnant smokers, 17.1% of pregnant women self-reported having smoking at the 3rd trimester (Blondel & Kermarrec, 2011). Among them 72% smoked 1 to 9 cigarettes per day and 18%
SC
smoked ≥10 cigarettes per day.
NU
The major correlates of smoking relapse are craving, withdrawal symptoms, slips and lapses (Shiffman, West, Gilbert, & SRNT Work Group on the Assessment of Craving and
MA
Withdrawal in Clinical Trials, 2004; Allen, Bade, Hatsukami, & Center, 2008; Piper et al., 2008; Zhou et al., 2009). Craving is most prominent during the first two weeks of quitting (Shiffman &
ED
Ferguson, 2008). Surprisingly, studies of craving, withdrawal and the process of smoking
PT
cessation during pregnancy are rare. However, some authors have noted that there might be something inherent about pregnancy that worsens withdrawal. Heil, Higgins, Mongeon, Badger,
CE
& Bernstein (2006) characterized craving and withdrawal in pregnant smokers using the
AC
Minnesota Nicotine Withdrawal Scale (MNWS; Hughes & Hatsukami, 1986). Pregnant smokers who abstained or smoked at very low levels (below baseline) during the first five days of a cessation attempt had greater difficulty concentrating and were more frustrated, angry, irritable, restless, and impatient compared to pregnant smokers who continued to smoke at or above smoking levels reported at baseline. Craving (viz., desire to smoke), anxiety and nervousness, anger, irritability, frustration, impatience, and restlessness also declined significantly over the five-day assessment period, independent of smoking status. Other research (Oncken et al., 2009) also found that pregnant smokers have elevated levels of withdrawal prior to smoking cessation, but the authors noted that some withdrawal symptoms (e.g., insomnia, weight gain, and
4
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY irritability) also occurred during pregnancy. In the absence of a comparison group of nonpregnant smokers, findings may have been largely affected by the condition of pregnancy, rather
T
than the process of smoking cessation itself.
RI P
Ussher, Etter, Giatras, and Coleman (2012) examined abstinent pregnant and nonpregnant smokers, including a “smoking as usual” group to demonstrate that abstinence
SC
increased withdrawal symptoms (MNWS-Revised and additional withdrawal items) and the
NU
intensity of urge to smoke. After adjusting for baseline cigarette consumption and withdrawal scores, pregnant women had lower scores than non-pregnant women for MNWS-Revised scores
MA
and for the three individual MNWS withdrawal symptoms, angry, anxious, and impatient after 24-hour abstinence. Despite differences in the patterns of individual items, findings indicated
ED
that pregnant abstinent smokers endorsed withdrawal symptoms in a manner similar to non-
PT
pregnant abstinent smokers, although their symptoms were less severe. Although the Ussher et al. data (2012) contradict the assumption that pregnancy worsens
CE
withdrawal, the analysis was conducted exclusively among those in the abstinent group. While
AC
abstinence ordinarily increases tobacco craving, yet craving is also influenced by ongoing smoking and is itself a strong predictor of smoking satisfaction and smoking (Baker, Breslau, Covey, & Shiffman, 2012). Without a comparison group of non-abstinent smokers, it is impossible to determine whether pregnant smokers are substantively different than their nonpregnant counterparts. A clinical trial of smoking cessation in the general population of male and female smokers using French versions of the brief Tobacco Craving Questionnaire FTCQ-12) and Minnesota Nicotine Withdrawal Scale (FMNWS) (Berlin, Singleton, & Heishman, 2010) found that abstinent smokers had significantly lower craving scores than non-abstinent smokers and the
5
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY total withdrawal score decreased in abstainers, but did not change in non-abstainers (Berlin et al., 2011). A recent meta-analysis demonstrated that withdrawal symptoms improve among abstinent
T
versus continuing smokers in the general population of smokers and in smokers with psychiatric
RI P
disorders (Taylor et al., 2014). The fact that pregnant smokers continue to smoke during pregnancy despite knowledge of its major negative health effects suggest that patterns of craving
SC
and withdrawal symptoms may be different compared with non-pregnant smokers and males. We
NU
therefore compared craving and withdrawal symptoms in pregnant versus non-pregnant smokers using data of two previously published clinical trials (Berlin et al., 2011; Berlin, Grangé, Jacob,
MA
& Tanguy, 2014). We addressed the research question: Are there differences between pregnant smokers and non-pregnant smokers for FTCQ-12 craving and FMNWS withdrawal at baseline
ED
and after quit date at the end of the critical two-week period? Findings could facilitate planning
well as the unborn child.
AC
2.1. Participants
CE
2. Material and methods
PT
for future research aimed at improving health and substance use treatment in pregnant women as
We analyzed data from smokers who participated in the Study of Nicotine Patch in Pregnancy (SNIPP; Identifier: ClinicalTrials.gov NCT00507975) and the Adjustment of DOses of NIcotine in Smoking (ADONIS; ClinicalTrials.gov Identifier: NCT00235313) clinical trials of smoking cessation. The SNIPP trial was a randomized, double blind, placebo controlled, parallel group, multicenter study assessing the efficacy of 16-hr nicotine patches with doses individually adjusted according to saliva cotinine concentration and could range from 10 to 30 mg/day. Pregnant smokers older than 18 years, between 12 to 20 weeks of gestation who smoked at least five cigarettes per day and scored ≥ 5 on a scale of motivation to quit (ranging 0 to10) were
6
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY enrolled. The ADONIS trial enrolled a general population of smokers attending smoking cessation clinics in France. This study compared nicotine replacement therapy (NRT) efficacy
T
when the NRT daily dose was determined by progressive dose adaptation, based on saliva
RI P
cotinine concentration, to obtain 100% substitution versus the standard monthly decreasing dose of NRT without saliva cotinine determination. We included only data from female smokers.
SC
Women were included if they were 18 years old or older, smoked ≥ 10 cigarettes per day,
NU
intended to stop smoking in the coming weeks, and scored ≥ 5 on a scale of motivation to quit (ranging 0 to 10), used an effective contraceptive method (hormonal contraception or intrauterine
MA
device), or were menopausal. Breastfeeding and pregnant women were excluded. In both studies, socio-demographic and smoking-related variables were collected at
ED
baseline. Craving and withdrawal were assessed simultaneously at baseline and two weeks after
PT
the quit date. Self-reported smoking status (abstinent = 0, smoking = 1) was verified by expired air CO (abstinent if CO ≤ 8 ppm; Smokelyzer; Bedfont Scientific Ltd, Rochester, Kent, UK). For
CE
the pregnant vs. non-pregnant comparisons, the combined sample consisted of complete data on
AC
399 smokers (ADONIS: n = 93 non-pregnant women vs. SNIPP: n = 306 pregnant women). All participants provided written informed consent prior to the study. Research protocols for both studies were approved by the Ethics Committee of the Pitié-Salpêtrière Hospital, Paris, France. Full details of the ADONIS and SNIPP studies have been published (Berlin et al., 2011; Berlin et al., 2014). 2.2. Measures French Tobacco Craving Questionnaire. Multidimensional craving was assessed by the brief version of the French Tobacco Craving Questionnaire (FTCQ-12; Berlin et al., 2010). The FTCQ-12 is a valid and reliable 12-item self-report instrument that assesses the same four
7
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY dimensions [factors 1-4; respectively: Emotionnalité (Emotionality), Attente (Expectancy), Compulsion (Compulsivity), and Anticipation (Purposefulness)] as the standard version of the
T
FTCQ (Berlin et al., 2005) and the brief and standard English versions of the Tobacco Craving
RI P
Questionnaire (Heishman, Singleton, & Moolchan, 2003; Heishman, Singleton, & Pickworth,
SC
2008). Items were rated on an interval scale (1 to 7, strongly disagree to strongly agree). Four items were reverse-keyed to reduce acquiescence. During data analysis, raw scores on the
NU
reverse-keyed items were inverted. Factor scores were calculated by summing item scores for each factor, then dividing by the number of items for each respective factor. The FTCQ-12
MA
general craving score was derived by summing the four factor scores then dividing by the total number of items. In the initial validation study (Berlin et al., 2010), Cronbach’s alpha
ED
coefficients and average interitem correlations (in parentheses) were 0.78 (0.47), 0.62 (0.35),
PT
0.60 (0.34), 0.44 (0.21), and 0.79 (0.25) for factors 1 to 4 and the general craving score, respectively.
CE
French Minnesota Nicotine Withdrawal Scale. We used the French version of the eight-
AC
item Minnesota Nicotine Withdrawal Scale (MNWS; Hughes & Hatsukami, 1986) to assess craving and withdrawal symptoms. Items (sadness or depressed mood; insomnia; irritability, frustration, anger; anxiety; difficulty concentrating; nervousness; increased appetite or weight gain; and urge to smoke) were summed and divided by eight to yield a total average score (hereafter the FMNWS general withdrawal score). FMNWS items were rated on an interval scale (0 to 3, not present to severe). The FMNWS has established construct validity with French populations (Berlin et al., 2010; Berlin, Singleton, & Heishman, 2013). Socio-demographic and smoking-related characteristics. To describe the samples and control for possible confounds, socio-demographic information was assessed at baseline,
8
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY including age, gender, marital status, race, income, and professional status. Smoking-related characteristics included: age of smoking initiation, age at which regular smoking began, number
T
of cigarettes smoked per day (CPD), number of previous quit attempts, Fagerström Test for
RI P
Cigarette Dependence [FTCD, Fagerström, 2012; formerly the Fagerström Test for Nicotine Dependence (FTND), Heatherton, Kozlowski, Frecker, & Fagerström, 1991], and alcohol use
SC
(four-item CAGE questionnaire total score; Ewing, 1984). We used FTCD total score to
NU
distinguish highly dependent (≥ 6) from less dependent (≤ 5) smokers (Fagerström et al., 1996; Ferguson et al., 2003). A CAGE total score ≥ 1 indicated a clinically significant alcohol problem
MA
because any drinking during pregnancy was considered problematic. 2.3. Data analyses
ED
Data were analyzed using two-way multivariate analysis of covariance (MANCOVA)
PT
models with group (pregnant smokers vs. non-pregnant [female] smokers) and smoking status (abstinence vs. smoking) as factors. FTCQ-12 general factor and FMNWS withdrawal scores
CE
were covariates. All socio-demographic and smoking-related variables were control variables as
AC
well as treatment (intervention group), although NRT did not increase smoking cessation rates despite adjustment of nicotine dose to match levels attained when smoking or higher than usual doses in either the ADONIS or SNIPP trial (Berlin et al., 2011; Berlin et al., 2014). To determine the relative contribution of individual factors and items, analysis of covariance (ANCOVA) was performed using FTCQ-12 factors 1 to 4 and FMNWS withdrawal items 1 to 8 as follow-up for statistically significant findings for FTCQ-12 general factor and FMNWS withdrawal. We used Weighted Least Squares (WLS) to adjust for the contribution of individual cases to outcomes, weighting cases by the reciprocal of the size of the groups. The test of significance was based the F value (Pillia’s trace) using Type III sums of squares (SS), MANCOVA results were considered
9
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY significant at p < 0.05. Post hoc statistical tests were Bonferroni adjusted. All analyses were conducted with STATISTICA Version 5.5 (StatSoft, Inc., Tulsa, OK).
T
3. Results
RI P
3.1. Baseline differentials
Socio-demographic and smoking related characteristics. Table 1 shows that pregnant
SC
smokers were significantly younger than non-pregnant smokers (median: 30 vs. 49 years,
NU
respectively). Pregnant smokers were 1.6 times more likely to be living with a spouse or significant other, 1.3 times more likely to be working or going to school, and 1.3 times more
MA
likely to be middle (12000 – 30000 euros per year) or high-income (> 30000 euros per year) than non-pregnant smokers. CPD during the week prior to enrollment for pregnant smokers was less
ED
than half that of non-pregnant smokers (Table 2). Pregnant smokers were approximately two
PT
years younger when they first tried smoking and nearly three years younger when regular smoking began compared to non-pregnant smokers. FTCQ-12 general score and FTCQ-12
CE
factors 1 - 3 were lower, while FTCQ-12 factor 4 was greater in pregnant smokers compared to
AC
non-pregnant smokers at baseline. In pregnant smokers, the incidence of smoking two weeks after the quit date was also 1.6 times that of non-pregnant smokers (all previous p values < 0.05). 3.2. Process of smoking cessation MANCOVA yielded a significant main effect for group [F(13,370) = 18.21, p < 0.001] and smoking status [F(13,370) = 3.26, p < 0.01], but not for group x smoking status interaction (p > 0.05). Figure 1 presents results for all of the Bonferroni adjusted post hoc tests associated with change in craving among pregnant and non-pregnant smokers. Figure 1a shows first that FTCQ-12 general craving score decreased less in pregnant smokers than non-pregnant smokers between baseline and two weeks after quit date. Figure 1a also shows that FTCQ-12 factors 1
10
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY (Emotionality) and 2 (Expectancy) decreased less among pregnant than among non-pregnant smokers and is likely responsible for the difference.
T
FMNWS general withdrawal score also decreased less in pregnant smokers than non-
RI P
pregnant smokers (X ¯ DIF = -0.13, 95% CI = -0.25 to -0.01, p < 0.05). We examined changes between baseline and week 2 in individual symptoms and found that the mean change in
= -0.25, p < 0.05). Insomnia actually increased in both groups, but increased less in pregnant
NU
DIF
SC
FMNWS “insomnia” was significantly lower in pregnant smokers than non-pregnant smokers (X ¯
smokers compared to non-pregnant smokers (0.32 cf. 0.70). FMNWS items “anxiety” and “urge
MA
to smoke” were significantly higher in pregnant smokers than non-pregnant smokers (X ¯ DIF = 0.38 and 0.32, respectively, both p < 0.001). Anxiety increased in pregnant smokers (0.70), but
ED
decreased (-0.30) in non-pregnant smokers, while the urge to smoke decreased less in pregnant
PT
smokers than non-pregnant smokers during the two-week period (X ¯ DIF = -0.14 cf. -0.51). There were no significant group differences in FMNWS items “sadness/depressed mood”,
CE
“irritability/frustration/anger”, “difficulty concentrating”, “nervousness”, or “increased
AC
appetite” (all p > 0.05).
Irrespective of group differences, FTCQ-12 general craving decreased less in smokers compared to abstainers, with FTCQ-12 factors 2 - 4 largely responsible for the differences (Figure 1b). Mean overall FMNWS general withdrawal was significantly higher in abstainers
compared to smokers (X ¯ DIF = 0.15, 95% CI = 0.01 to 0.14, p < 0.05). Mean FMNWS general withdrawal actually increased in abstainers (0.05), but decreased (-0.10) in smokers. FMNWS items “insomnia” and “increased appetite” were significantly lower in smokers than abstainers (X ¯ DIF = -0.41 and -0.36, respectively; both p < 0.01). Insomnia and appetite increased over time, but increased more by week two in abstainers compared to smokers (0.49 vs. 0.08 and 0.61 vs.
11
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY 0.18, respectively). The “urge to smoke” item decreased more in abstainers than smokers (-0.42 vs. -0.25). The “sadness/depressed mood” item decreased in abstainers, but increased in smokers
T
(-0.14 vs. 0.11). There were no significant differences between smokers and abstainers for
RI P
FMNWS items “irritability/frustration/anger”, “anxiety”, “difficulty concentrating”, and “nervousness” (all p > 0.05).
SC
3.3. Barriers to abstinence
NU
Stepwise regression (backward elimination) indicated that absolute change from baseline (increase) in FTCQ-12 factor 2 (expectancy) (β = 0.053, 95% CI = 0.033 to 0.073, t = 5.23, p <
MA
0.001), baseline FTCQ-12 factor 4 (purposefulness) (β = 0.034, 95% CI = 0.011 to 0.057, t = 2.98, p < 0.01), and baseline FMNWS “nervousness” (β = 0.051, 95% CI = 0.015 to 0.087, t =
ED
2.79, p < 0.01) were significantly associated with smoking two weeks after the quit date in
PT
pregnant smokers. In non-pregnant female smokers, only baseline FMNWS item “increased appetite” was significantly associated with post-quit date smoking (β = 0.044, 95% CI = 0.003 to
AC
4. Discussion
CE
0.090, t = 2.11, p < 0.04).
We analyzed data from two independent clinical trials to characterize craving and withdrawal during a critical two-week period of smoking cessation and to identify distinctions between pregnant smokers and non-pregnant smokers. Participants were randomly assigned subsequent to enrollment and there were no treatment effects in any of the studies (Berlin et al., 2011; Berlin et al., 2014). Beyond the expected demographic and smoking characteristic differences, such as lower daily cigarette consumption and FTCD score, pregnant smokers started smoking and smoked regularly earlier and succeded much less at smoking cessation by week 2 after quit date than
12
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY non-pregnant smokers. Craving to smoke and sadness/depressed mood decreased more among abstinent than among continuing smokers.
T
FTCQ-12 and FMNWS responses to smoking cessation were also largely different
RI P
between pregnant smokers and non-pregnant smokers. Post-quit FTCQ-12 general score was higher in pregnant smokers compared with comparison groups and was driven by elevated
SC
Emotionality and Expectancy. FMNWS decreased less among pregnant smokers than among
NU
non-pregnant smokers, especially with respect to anxiety and urge to smoke. Smoking at 2 weeks post-quit date was predicted by baseline FTCQ-12 factor 2 (Expectancy), factor 4
MA
(Purposefulness) and FMNWS item “nervousness” among pregnant smokers and by FMNWS item “increased appetite” among non-pregnant smokers. These findings support the hypothesis
ED
that smoking cessation involves different aspects of craving and withdrawal symptoms in
PT
pregnant smokers compared with non-pregnant smokers. However, no group by smoking status interaction occurred, suggesting that pregnant smokers’ craving and withdrawal responses to
CE
cessation are qualitatively similar to non-pregnant smokers and that differences lie in the
AC
intensity of responses.
Several differences have been identified between pregnant smokers able to quit compared to those unable to quit (Massey & Compton, 2013), but comparisons with non-pregnant smokers are scarce (Ussher et al., 2012; Parrott et al., 2014), especially concerning the major predictors of successful quitting, craving and withdrawal symptoms. Our findings differ from research (Ussher et al., 2012) demonstrating that pregnant smokers endorsed withdrawal symptoms in a manner similar to non-pregnant smokers, although their symptoms were less severe. Most withdrawal symptoms do not peak until 48 hours after quitting smoking, and a reasonable explanation for the
13
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY differences is that pregnant women might report less severe withdrawal than non-pregnant smokers on the first day of abstinence compared to 2 weeks after the quit date.
T
The general craving score was higher in pregnant smokers compared to non-pregnant
RI P
smokers. It was largely driven by two specific factors, Emotionality and Expectancy. Emotionality decreased less in pregnant smokers than non-pregnant smokers and Expectancy
SC
remained relatively stable during smoking cessation among pregnant smokers while it decreased
NU
in the non-pregnant smokers. In parallel, the urge to smoke and anxiety were also greater in pregnant smokers compared to non-pregnant smokers. These findings suggest that cessation
MA
increases anxious feelings and a persistent craving in anticipation of relief from withdrawal (Emotionality) and craving in anticipation of the positive benefits of smoking (Expectancy).
ED
Major contributors to the incidence of smoking two weeks after the quit date in pregnant
PT
women were a cessation-related increase in expectancy and elevated nervousness and purposefulness before quit date. Anxiety is frequently associated with pregnancy, which for
CE
some women is a stressful life event (Kowalyk, Hadjistavropoulos, & Jones, 2009). Smoking
AC
even a single cigarette has been associated with high levels of pregnancy-specific, prenatal anxiety (Huizink et al., 2014). Pregnant quitters have also reported that they return to smoking because they experience irresistible cravings when stressed, and having a cigarette is extremely pleasurable right at that moment (Herbec et al., 2014). We also found previously that slips and lapses to smoking are triggered by craving in anticipation of the positive benefits of smoking coupled with intent and planning to smoke (Berlin et al., 2013). Several withdrawal symptoms established in populations of non-pregnant smokers might be confounded by pregnancy itself. Pregnancy is physiologically associated with weight gain, increased appetite, better sleep and, in some women, with anxiety. An example is that insomnia
14
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY increased less among pregnant compared to non-pregnant smokers in the current study. Because these symptoms are not specific to tobacco withdrawal, their value in pregnant smokers is
T
doubtful. Further research should establish the symptoms occuring during smoking cessation that
RI P
can be attributed to quitting, which are not confounded by symptoms associated with pregnancy. The difference between pregnant and non-pregnant smokers is supported by the findings that
SC
week 2 smoking status was positively predicted by FTCQ-12 Expectancy, Purposefulness, and
NU
pre-quit nervousness among pregnant smokers and by pre-quit increased appetite among nonpregnant smokers—the latter being a demostrated predictor of smoking lapse in the general
Japuntich, Baker, & Cook, 2014) .
MA
population of smokers (Leyro, Zvolensky, Vujanovic, & Bernstein, 2008; Leventhal, Piper,
ED
Nicotine’s clearance is increased by 60% (and that of cotinine by 140%) during
PT
pregnancy compared to postpartum (Dempsey, Jacob, & Benowitz, 2002) probably by sex hormonal induction of liver cytochrome 2A6 and flavin-containing monooxygenase 3 (FMO3)
CE
(Hukkanen, Dempsey, Jacob, & Benowitz, 2005). Increased nicotine clearance may contribute to
AC
increased craving and withdrawal symptoms among pregnant smokers compared to the general population of smokers. However, saliva cotinine-adapted nicotine replacement therapy leading to close to 100% nicotine substitution did not improve the abstinence rate and did not affect FTCQ12 craving scores among pregnant smokers (Berlin et al., 2014). Endocrine mechanisms may also be associated with relapse to smoking or increased craving and withdrawal symptoms. Relapse to smoking may be associated with increased plasma cortisol concentration in women (Al’Absi et al., 2015) but not in men. A recent meta-analysis demonstrated that among non-pregnant women withdrawal symptoms are greater in the luteal than in the follicular phase and craving to smoke shows a similar tendency (Weinberger et al.,
15
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY 2015). Progesterone surge is a physiological effect in pregnancy. Plasma progesterone levels are usually 10 to 20 times higher in pregnancy than progesterone levels in the luteal phase in non-
T
pregnant women. Higher levels of craving and withdrawal symptoms among pregnant smokers
RI P
than among non-pregnant smokers are likely associated with the physiological, pregnancyrelated surge in plasma progesterone concentration.
SC
Strengths and Limitations
NU
The major limitation of this study was the historical comparison of pregnant smokers to non-pregnant smokers. All participants were also treatment-seeking smokers motivated to quit
MA
and enrolled in a smoking cessation clinical trial reducing generalizability of the findings. Women who continue to smoke during pregnancy, however, are likely unique because many
ED
women quit smoking shortly after learning they are pregnant and require no assistance quitting
PT
smoking (Kapaya et al., 2015). Thus, usual measures of tobacco dependence, such as the FTCD based on cigarette per day consumption, may underestimate pregnant smokers’ dependence who
CE
usually smoke less (Haug, Fugelli, Aarø, & Foss, 1994; Ussher et al., 2012). Therefore, measures
AC
of craving to smoke or withdrawal symptoms might be better predictors of ability to quit among pregnant smokers than tobacco dependence measures (Fidler, Shahab, & West, 2011). These limitations reduce the generality of the findings. On the other hand, both clinical trials included only smokers with a motivation score to quit ≥ 5 on a scale of 0 to 10 making motivation homogeneous. Other strengths include use of the same measures for craving, withdrawal symptoms, and tobacco dependence and the same post-quit date time point of assessments, which add validity to the findings. The sample distributions reflect populations of French smokers mostly of European ancestry, thus, results need to be confirmed using independent samples from other countries, nationalities, and ethnicities.
16
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY A further limitation is the small sample of non-pregnant smokers and the unequal pregnant/non-pregnant sample although the WLS adjustment statististically compensated for
T
unqual sample size. Our analyses also required baseline adjustments, while a better
RI P
understanding of why pregnant smokers have difficulty quitting would require comparing their smoking cessation process with that of a matched sample of non-pregnant female smokers. This
SC
was a retrospective study, thus subjects were not randomly included. Future research should
NU
randomly assign representative and larger samples of pregnant, non-pregnant, and the general population of smokers to ensure comparability of socio-demographic characteristics and
MA
smoking-related behaviors. Nevertheless, our subjects were randomly assigned subsequent to enrollment and there were no treatment effects in any of the studies (Berlin et al., 2011; Berlin et
ED
al., 2014). In lieu of randomization, models were estimated using all possible confounding
PT
covariates. Low p values and consistency of results suggest the populations were distinct, and the
5. Conclusions
CE
results were more likely attributable to the condition of pregnancy itself as opposed to chance.
AC
Adjusting for baseline differences, craving decreased less in pregnant smokers than nonpregnant female smokers. These findings partially explain why pregnant smokers may have more difficulty quitting than other smokers. Withdrawal decreased less in pregnant smokers than nonpregnant smokers, suggesting that smoking cessation may be substantially different for pregnant smokers than other females. Some withdrawal symptoms may be confounded by symptoms physiologically associated with pregnancy or by symptoms frequently present among pregnant women. Understanding why pregnant smokers have difficulty quitting requires comparing their smoking cessation processes with those of a matched sample of non-pregnant smokers. Surprisingly, to the best of our knowledge, this has not been studied. Our findings are
17
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY preliminary; however, they might foster further investigation of differences in craving and withdrawal symptoms between pregnant and non-pregnant smokers. Better knowledge about
T
patterns and specificity of craving and withdrawal among pregnant smokers would improve
AC
CE
PT
ED
MA
NU
SC
RI P
smoking cessation interventions in this population, thereby reducing prenatal smoking.
18
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
Funding sources and Disclosures
T
The ADONIS study was supported by the French Ministry of Health Programme
RI P
Hospitalier de Recherche Clinique Loco-regional 2004 (AOR04001//P040406, registration number: 050558) by the Agence française de sécurité sanitaire des produits de santé, Convention
SC
Pharmacologie Clinique et Thérapeutique 2003, RAF02020. The SNIPP study was funded by the Ministry of Health, France, Grant Number MA05 001050. E. G. Singleton was partly funded by
NU
the same research grant. S. J. Heishman was supported by the National Institute on Drug Abuse,
MA
Intramural Research Program. The funding sources had no other role than financial support. I. Berlin acquired the data. I. Berlin and E. G. Singleton had full access to the data and
ED
take responsibility for the accuracy of the data analysis. All authors were involved in the study concept and design, analysis and interpretation of data, and preparation of the manuscript.
AC
CE
PT
None of the authors report conflict of interest.
19
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY References Al'Absi, M., Nakajima, M., Allen, S., Lemieux, A., & Hatsukami, D. (2015). Sex differences in
T
hormonal responses to stress and smoking relapse: a prospective examination.
RI P
Nicotine and Tobacco Research, 17, 382-389. http://dx.doi.org/10.1093/ntr/ntu340. Allen, S. S., Bade, T., Hatsukami, D., & Center, B. (2008). Craving, withdrawal, and smoking
SC
urges on days immediately prior to smoking relapse. Nicotine and Tobacco Research, 10,
NU
35-45. http://dx.doi.org/10.1080/14622200701705076
Baker, T. B., Breslau, N., Covey, L., & Shiffman, S. (2012). DSM criteria for tobacco use
MA
disorder and tobacco withdrawal: a critique and proposed revisions for DSM-5. Addiction, 107, 263-275. http://dx.doi.org/10.1111/j.1360-0443.2011.03657.x.
ED
Berlin, I., Vorspan, F., Singleton, E. G., Warot, D., Notides, C., & Heishman, S. J. (2005).
PT
Reliability and validity of the French version of the Tobacco Craving Questionnaire. European Addiction Research, 11, 62-68.
CE
Berlin, I., Singleton, E. G., & Heishman, S. J. (2010). Validity of the 12-item French version of
AC
the Tobacco Craving Questionnaire in treatment-seeking smokers. Nicotine and Tobacco Research, 12, 500-507. http://dx.doi.org/10.1093/ntr/ntq039 Berlin, I., Jacob, N., Coudert, M., Perriot, J., Schultz, L., & Rodon, N. (2011). Adjustment of nicotine replacement therapies according to saliva cotinine concentration: the ADONIS* trial-a randomized study in smokers with medical comorbidities. Addiction, 106, 833843. http://dx.doi.org/10.1111/j.1360-0443.2010.03306.x Berlin, I., Singleton, E. G., & Heishman, S. J. (2013). Predicting smoking relapse with a multidimensional versus a single-item tobacco craving measure. Drug and Alcohol Dependence, 132, 513-520. http://dx.doi.org/10.1016/j.drugalcdep.2013.03.017
20
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Berlin, I., Grangé, G., Jacob, N., & Tanguy, M. L. (2014). Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy. British Medical Journal,
T
348, g1622. http://dx.doi.org/10.1136/bmj.g1622
RI P
Blondel, B., & Kemarrec, M. (2011). Enquête nationale périnatal 2010. Retrieved from http://www.sante.gouv.fr/IMG/pdf/Les_naissances_en_2010_et_leur_evolution_depuis_2
SC
003.pdf
NU
Buka, S. L., Shenassa, E. D., & Niaura, R. (2003). Elevated risk of tobacco dependence among offspring of mothers who smoked during pregnancy: a 30-year prospective study.
MA
American Journal of Psychiatry, 160, 1978-1984.
Burke, H., Leonardi-Bee, J., Hashim, A., Pine-Abata, H., Chen, Y., Cook, D. G.,... McKeever, T.
ED
M. (2012). Prenatal and passive smoke exposure and incidence of asthma and wheeze:
PT
systematic review and meta-analysis. Pediatrics, 129, 735-44. http://dx.doi.org/ 10.1542/peds.2011-2196
CE
Centers for Disease Control and Prevention. (2010). A report of the surgeon general: how
AC
tobacco smoke causes disease: what it means to you. Atlanta, GA Dempsey, D., Jacob, P., 3rd, Benowitz, N. L. (2002). Accelerated metabolism of nicotine and cotinine in pregnant smokers. Journal of Pharmacology and Experimental Therapeutics, 301, 594-598. DiClemente, C. C., Dolan-Mullen, P., & Windsor, R. A. (2000). The process of pregnancy smoking cessation: implications for interventions. Tobacco Control, 9(Suppl 3), 6-21. Ekblad, M., Gissler, M., Lehtonen, L., & Korkeila, J. (2010). Prenatal smoking exposure and the risk of psychiatric morbidity into young adulthood. Archives of General Psychiatry, 67, 841-849. http://dx.doi.org/10.1001/archgenpsychiatry.2010.92
21
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Ewing, J.A. (1984). Detecting alcoholism: the CAGE Questionnaire. JAMA, 252, 1905-1907. Fagerström, K. O., Kunze, M., Schoberberger, R., Breslau, N., Hughes, J. R., Hurt, R.
T
D.,…Zatoński, W. (1996). Nicotine dependence versus smoking prevalence: comparisons
RI P
among countries and categories of smokers. Tobacco Control, 5, 52-56. Fagerström K. (2012). Determinants of tobacco use and renaming the FTND to the Fagerstrom
SC
Test for Cigarette Dependence. Nicotine and Tobacco Research, 14, 75-78.
NU
http://dx.doi.org/10.1093/ntr/ntr137
Ferguson, J. A., Patten, C. A., Schroeder, D. R., Offord, K. P., Eberman, K. M., & Hurt, R. D.
MA
(2003). Predictors of 6-month tobacco abstinence among 1224 cigarette smokers treated for nicotine dependence. Addictive Behaviors, 28, 1203-1218.
ED
Fidler, J.A., Shahab, L., West, R. (2011). Strength of urges to smoke as a measure of severity of
PT
cigarette dependence: comparison with the Fagerström Test for Nicotine Dependence and its components. Addiction. 106, 631-638.
CE
Flemming, K., Graham, H., Heirs, M., Fox, D., & Sowden, A. (2013). Smoking in pregnancy: a
AC
systematic review of qualitative research of women who commence pregnancy as smokers. Journal of Advanced Nursing, 69, 1023-1036. http://dx.doi.org/ 10.1111/jan.12066 Hartmann-Boyce, J., Stead, L. F., Cahill, K., & Lancaster, T. (2014). Efficacy of interventions to combat tobacco addiction: cochrane update of 2013 reviews. Addiction, 109, 1414-1425. http://dx.doi.org/10.1111/add.12633 Haug, K., Fugelli, P., Aarø, L.E., Foss, O.P.(1994) Is smoking intervention in general practice more successful among pregnant than non-pregnant women? Fam Pract. 1994 Jun;11(2):111-6.
22
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., & Fagerström, K. O. (1991). The Fagerstrom Test for Nicotine Dependence: A revision of the Fagerstrom Tolerance Questionnaire.
T
British Journal of Addictions, 86, 1119-1127.
RI P
Heil, S. H., Higgins, S. T., Mongeon, J. A., Badger, G. J., & Bernstein, I. M. (2006).
Clinical Psychopharmacology, 14, 165-170.
SC
Characterizing nicotine withdrawal in pregnant cigarette smokers. Experimental and
NU
Heishman, S. J., Singleton, E. G., & Moolchan, E. T. (2003). Tobacco Craving Questionnaire: reliability and validity of a new self-report instrument. Nicotine and Tobacco Research,
MA
53, 75-81.
Heishman, S. J., Singleton, E. G., & Pickworth, W. B. (2008). Reliability and validity of a short
ED
form of the Tobacco Craving Questionnaire. Nicotine and Tobacco Research, 10, 643-
PT
651.
Herbec, A., Beard, E., Brown, J., Gardner, B., Tombor, I., & West, R. (2014). The needs and
CE
preferences of pregnant smokers regarding tailored internet-based smoking cessation
AC
interventions: a qualitative interview study. BioMed Central Public Health, 14, 1070. http://dx.doi.org/10.1186/1471-2458-14-1070 Hughes, J. R., & Hatsukami, D. (1986). Signs and symptoms of tobacco withdrawal. Archives of General Psychiatry, 43, 289-294. Huizink, A. C., Menting, B., Oosterman, M., Verhage, M. L., Kunseler, F. C., & Schuengel, C. (2014). The interrelationship between pregnancy-specific anxiety and general anxiety across pregnancy: a longitudinal study. Journal of Psychosomatic Obstetrics and Gynecology, 35, 92-100. http://dx.doi.org/10.3109/0167482X.2014.944498
23
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Hukkanen, J., Dempsey, D., Jacob, P., 3rd, & Benowitz, N. L. (2005). Effect of pregnancy on a measure of FMO3 activity. British Journal of Clinical Pharmacology, 60, 224-226.
T
Ingall, G., & Cropley, M. (2010). Exploring the barriers of quitting smoking during pregnancy: a
RI P
systematic review of qualitative studies. Women and Birth, 23, 45-52. http://dx.doi.org/ 10.1016/j.wombi.2009.09.004
SC
Jaakkola, J. J., & Gissler, M. (2005). Maternal smoking in pregnancy as a determinant of
NU
rheumatoid arthritis and other inflammatory polyarthropathies during the first 7 years of life. International Journal of Epidemiology, 34, 664-671.
MA
Kapaya, M., Tong, V., & Ding H. (2015). Nicotine replacement therapy and other interventions for pregnant smokers: Pregnancy Risk Assessment Monitoring System, 2009-2010.
ED
Preventive Medicine, 78, 92-100. doi: 10.1016/j.ypmed.2015.07.008. Epub 2015 Jul 16.
PT
Kim, S. Y., England, L. J., Kendrick, J. S., Dietz, P. M., Callaghan, W. M. (2009). The contribution of clinic-based interventions to reduce prenatal smoking prevalence among
CE
US women. Am J Public Health. 99, 893-898. http://dx.doi: 10.2105/AJPH.2008.144485.
AC
Kowalyk, K. M., Hadjistavropoulos, H. D., & Jones, S. L. (2009). What impact does pregnancy have on anxiety about health? Journal of Psychosomatic Obstetrics and Gynaecology, 30, 223-230. http://dx.doi.org/10.3109/01674820903276453 Leventhal, A. M., Piper, M. E., Japuntich, S. J., Baker, T. B., & Cook, J. W. (2014). Anhedonia, depressed mood, and smoking cessation outcome. Journal of Consulting and Clinical Psychology, 82, 122-129. http://dx.doi.org/10.1037/a0035046 Leyro, T. M., Zvolensky, M. J., Vujanovic, A. A., & Bernstein, A. (2008). Anxiety sensitivity and smoking motives and outcome expectancies among adult daily smokers: replication
24
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY and extension. Nicotine and Tobacco Research, 10, 985-994. http://dx.doi.org/ 10.1080/14622200802097555
T
Massey, S. H., & Compton, M. T. (2013). Psychological differences between smokers who
RI P
spontaneously quit during pregnancy and those who do not: a review of observational studies and directions for future research. Nicotine and Tobacco Research, 15, 307-319.
SC
http://dx.doi.org/10.1093/ntr/nts142
NU
Oncken, C., Campbell, W., Chan, G., Hatsukami, D., Kranzler, H. R., Oncken, C., Campbell, W.,…Kranzler, H. R. (2009). Effects of nicotine patch or nasal spray on nicotine and
MA
cotinine concentrations in pregnant smokers. Journal of Maternal-Fetal and Neonatal Medicine, 22, 751-758. http://dx.doi.org/10.3109/14767050902994515
ED
Parrott, C. E., Rathnayaka, N., Blalock, J. A., Minnix, J. A., Cinciripini, P. M., Vincent,
PT
J.P.,…Green, C. (2014). Examination of the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) factor structure in a sample of pregnant smokers.
CE
Nicotine Tobacco Research, Dec 4. pii: ntu238. [Epub ahead of print]
AC
Piper, M. E., Federmen, E. B., McCarthy, D. E., Bolt, D. M., Smith, S. S., Fiore, M. C., & Baker, T. B. (2008). Using mediational models to explore the nature of tobacco motivation and tobacco treatment effects. Journal of Abnormal Psychology, 117, 94-105. http://dx.doi.org/ 10.1037/0021-843X.117.1.94 Räisänen, S., Gissler, M., Saari, J., Kramer, M., & Heinonen, S. (2013). Contribution of risk factors to extremely, very and moderately preterm births – register-based analysis of 1,390,742 singleton births. PLOS ONE, 8, e60660. http://dx.doi.org/ 10.1371/journal.pone.0060660
25
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Schneider, S., & Schütz, J. (2008). Who smokes during pregnancy? A systematic literature review of population-based surveys conducted in developed countries between 1997 and
RI P
http://dx.doi.org/10.1080/13625180802027993
T
2006. European Journal of Contraception and Reproductive Health Care, 13, 138–147.
Schneider, S., Huy, C., Schütz, J., & Diehl, K. (2010). Smoking cessation during pregnancy: a
SC
systematic literature review. Drug and Alcohol Review, 29, 81-90. http://dx.doi.org/
NU
10.1111/j.1465-3362.2009.00098.x
Shiffman, S., & Ferguson, S.G. (2008). The effect of a nicotine patch on cigarette craving over
MA
the course of the day: results from two randomized clinical trials. Current Medical Research and Opinion, 24, 2795-2804. http://dx.doi.org/10.1185/03007990802380341
ED
Shiffman, S., West, R., Gilbert, D., & SRNT Work Group on the Assessment of Craving and
PT
Withdrawal in Clinical Trials. (2004). Recommendation for the assessment of tobacco
599-614.
CE
craving and withdrawal in smoking cessation trials. Nicotine and Tobacco Research, 6,
AC
Surgeon General. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General (2014). Retrieved from http://www.surgeongeneral.gov/library/reports/50-years-of-progress/sgr50-chap-9.pdf Taylor, G., McNeill, A., Girling, A., Farley, A., Lindson-Hawley, N., & Aveyard, P. (2014). Change in mental health after smoking cessation: systematic review and meta-analysis. British Medical Journal, 348, g1151. http://dx.doi.org/10.1136/bmj.g1151 Thacher, J. D., Gruzieva, O., Pershagen, G., Neuman, A., Wickman, M., Kull, I.,…Bergström A. (2014). Pre- and postnatal exposure to parental smoking and allergic disease through adolescence. Pediatrics, 134, 428-434. http://dx.doi.org/10.1542/peds.2014-0427
26
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Ussher, M., Etter, J. F., Giatras, N., & Coleman, T. (2012). Tobacco withdrawal symptoms and urges to smoke in pregnant versus non-pregnant smokers. Addictive Behaviors, 37, 1353-
T
1357. http://dx.doi.org/10.1016/j.addbeh.2012.07.008
RI P
Weinberger, A. H., Smith, P. H., Allen, S. S., Cosgrove, K. P., Saladin, M. E., Gray, K. M.,…McKee, S. A. (2015). Systematic and meta-analytic review of research examining
SC
the impact of menstrual cycle phase and ovarian hormones on smoking and cessation.
NU
Nicotine and Tobacco Research, 17, 407-21. http://dx.doi.org/10.1093/ntr/ntu249. Zhu, J. L., Olsen, J., Liew, Z., Li, J., Niclasen, J., Obel, C. (2014). Parental smoking during
MA
pregnancy and ADHD in children: the danish national birth cohort. Pediatrics, 134, e382-
AC
CE
PT
ED
8. http://dx.doi.org/10.1542/peds.2014-0213
27
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
28
Table 1. Socio-demographic characteristics of the samples.
47.3 18.3 34.4
87.3 12.7
50 43
53.8 46.2
86 159 61
28.1 52.0 19.9
41 37 15
44.1 39.8 16.1
291 15
95.1 4.9
89 4
95.7 4.3
MA ED PT
T
44 17 32
267 39
CE AC
61.4 18.6 19.9
SC
188 57 61
Non-pregnant smokers (n = 93) Count Percent 5 5.4 29 31.2 59 63.4
NU
Age: 18 to 30 31 to 45 >45 Professional status: Employed/Student Homemaker Unemployed Marital status: Married/Cohabiting Single/Separated/Divorced Annual income (€): <12 000 12 000 to 30 000 >30 000 Ethnicity: European Other
RI P
Pregnant smokers (n = 306) Count Percent 173 56.5 133 43.5 0 0.0
Characteristic
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
29
Table 2. Smoking-related history of the samplesa. Non-pregnant smokers
Pregnant smokers
Mean
SD
Mean
SD
Number of cigarettes per day (CPD) Number of previous quit attempts Age of smoking initiation Age at onset of regular smoking Total FTCD score Proportion highly nicotine dependent Total CAGE score Proportion clinical alcohol problem Incidence of smoking (2-wk post-quit) FTCQ-12 general craving score Factor 1 (emotionality) score Factor 2 (expectancy) score Factor 3 (compulsivity) score Factor 4 (purposefulness) score FMNWS general withdrawal score
23.4 1.8 16.8 19.3 6.8 72% 0.6 24% 56% 3.6 2.5 4.9 3.1 4.5 1.0
11.9 3.1 9.0 10.0 3.9 9% 2.3 9% 15% 2.4 3.4 3.1 3.5 3.4 1.3
11.9 1.3 14.7 16.5 4.5 33% 0.3 14% 89% 3.3 1.8 4.6 2.7 5.0 1.1
8.0 2.0 3.5 3.6 2.8 6% 1.0 5% 12% 1.3 1.5 2.0 1.8 2.0 0.9
CE
RI P
SC NU MA
ED
PT
Values are weighted adjustments.
AC
a
T
Characteristic
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
RI P
T
Figure caption Figure 1. Group and smoking status effects on FTCQ-12 craving: Non-pregnant female smokers (NPS) versus pregnant smokers (PS). All values represent Weighted Least Squares (WLS) adjustment of absolute change from baseline (pre-quit) to 2 weeks post-quit date. Error bars are 95% Confidence Intervals. Note: Statistically significant mean differences: * p < 0.05, ** p < 0.01, and *** p < 0.001.
General
Factor 1
Factor 2
MA
-0.5 *
ED
***
PT
-1.5
-2.5
CE
-2
***
Non-Pregnant Smokers (NPS)
AC
Change from baseline
0
-1
Factor 3
NU
0.5
SC
1a) Main Effect of Group
Pregnant Smokers (PS)
Factor 4
30
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
1b) Main Effect of Smoking Status General
Factor 1
Factor 2
Factor 3
Factor 4
T
0.5
RI P SC
-0.5
NU
-1 ***
MA
-1.5
-2
ED
***
-2.5
CE
PT
Abstinence
AC
Change from baseline
0
Smoking
**
*
31
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant and Non-pregnant Smokers
Smoking cessation rate in pregnancy is relatively low, raising the question of why
RI P
T
Highlights
SC
pregnant smokers have difficulty quitting.
We compared craving for tobacco and withdrawal symptoms in 306 pregnant smokers to
NU
93 non-pregnant female smokers.
Post-quit craving and withdrawal symptoms diminished less in pregnant compared to
Insufficient reduction of craving and withdrawal symptoms may partially explain why
CE
PT
ED
pregnant smokers have difficulty quitting.
AC
MA
non-pregnant smokers.
32
S0740-5472(15)00318-9 doi: 10.1016/j.jsat.2015.12.008 SAT 7389
To appear in:
Journal of Substance Abuse Treatment
Received date: Revised date: Accepted date:
19 June 2015 2 December 2015 3 December 2015
Please cite this article as: Berlin, I., Singleton, E.G. & Heishman, S.J., Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant and Non-pregnant Smokers, Journal of Substance Abuse Treatment (2015), doi: 10.1016/j.jsat.2015.12.008
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Running head: TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
1
RI P
and Non-pregnant Smokers
T
Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant
SC
Ivan Berlin1 Faculté de médicine, Université P. and M. Curie
NU
Edward G. Singleton2 Interactive Professional Services
ED
MA
Stephen J. Heishman3 National Institute on Drug Abuse
1
AC
Word count Abstract: 214 Text: 4362 2 tables, 1 figure
CE
PT
Ivan Berlin, M.D., Ph.D., Hôpital Pitié-Salpêtrière AP-HP -Faculté de médicine, Université P. and M. Curie - INSERM U1178, Paris, France 2 Edward G. Singleton, Ph.D., Interactive Professional Services, Catonsville, MD, USA 3 Stephen J. Heishman, Ph.D., Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA
Correspondence: Dr Ivan Berlin, Hôpital Pitié-Salpêtrière, Département de Pharmacologie, 47, bd de l’Hôpital, 75013 Paris, France. Email: [email protected] Phone: +33 1 42 16 16 78, Fax: +33 1 42 16 16 88
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
Abstract
T
Although pregnant smokers are aware of the negative peri- and postnatal health consequences of
RI P
smoking, the cessation rate in pregnancy is low, raising the question of why pregnant smokers have difficulty quitting. Reasons might be that pregnant smokers experience more intense
SC
craving and withdrawal symptoms than non-pregnant smokers. We compared craving and withdrawal in 306 pregnant smokers versus 93 non-pregnant women using data from two
NU
smoking cessation trials. Complete data were analyzed using pre-quit and post-quit (two weeks
MA
after quit date) craving and withdrawal measured by the 12-item French Tobacco Craving Questionnaire (FTCQ-12) and French Minnesota Nicotine Withdrawal Scale (FMNWS).
ED
Pregnant smokers started smoking and smoked regularly earlier and succeeded far less at quitting smoking by week 2 than the general population of smokers (11% versus 43%). Post-quit date
PT
FTCQ-12 general score was higher in pregnant smokers compared to comparison groups, and
CE
was driven by elevated emotionality and expectancy. FMNWS decreased significantly less among pregnant smokers than among non-pregnant smokers. Insufficient reduction of craving
AC
and withdrawal symptoms in response to a quit attempt may partially explain why pregnant smokers may have more difficulty quitting than non-pregnant smokers. Because this was a historical comparison, findings are preliminary; however, they might foster further investigation of differences in craving and withdrawal symptoms in pregnant versus non-pregnant smokers.
Keywords: pregnant smokers, non-pregnant female smokers, craving to smoke, withdrawal symptoms, smoking cessation
2
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY 1. Introduction Maternal smoking during pregnancy is associated with (a) increased risk of perinatal negative
T
health outcomes such as miscarriage, preterm birth, low birth weight, infant mortality, and birth
RI P
defects (Centers for Disease Control and Prevention, 2010; Schneider, Huy, Schütz, & Diehl, 2010; Räisänen, Gissler, Saari, Kramer, & Heinonen et al., 2013); (b) post-natal health disorders
SC
such as attention-deficit/hyperactivity disorder (ADHD) in children (Surgeon General, 2014; Zhu
NU
et al., 2014); (c) the development of allergic disease (Burke et al., 2012; Thacher et al., 2014), rheumatoid arthritis, and other inflammatory and autoimmune conditions (Jaakkola & Gissler,
MA
2005); (d) psychiatric morbidity and increased mortality in childhood, adolescence, and young adulthood (Ekblad, Gissler, Lehtonen, & Korkeila, 2010); and (e) nicotine dependence (Buka,
ED
Shenassa, & Niaura, 2003). Despite the gravity of these consequences, on average only 1 in 5
PT
pregnant smokers quit smoking and remain abstinent at 6 month follow-up (Heil et al., 2006). Several socio-demographic and smoking-related characteristics associated with smoking
CE
during pregnancy have been identified: being white, less education, unemployment, lower
AC
socioeconomic status, few financial resources, and emotional problems (DiClemente, DolanMullen, & Windsor, 2000; Schneider et al., 2010; Flemming, Graham, Heirs, Fox, & Sowden 2013; Hartmann-Boyce, Stead, Cahill, & Lancaster 2014). These studies also reported that high rates of tobacco consumption, high expired air carbon monoxide (CO) concentration, and years of smoking are predictors of continued smoking. Pregnant women are well aware of the health risks of smoking during pregnancy, yet such knowledge seems insufficient in motivating all of them to quit (Schneider & Schütz, 2008; Ingall & Cropley, 2010). In fact, according to representative data of US pregnant smokers, among women who smoked at conception only 23% self-reported having quit smoking (Kim, England, Kendrick, Dietz, & Callaghan, 2009) and
3
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY among those who smoked 3 months before pregnancy (N=3559), 42 % (N=1490) quit and 58 % (N=2069) smoked by the 3rd trimester in 2009-2010 (Kapaya, Tong and Ding, 2015).
T
According to 2010 data from France, and despite strong tobacco control campaigns targeting
RI P
pregnant smokers, 17.1% of pregnant women self-reported having smoking at the 3rd trimester (Blondel & Kermarrec, 2011). Among them 72% smoked 1 to 9 cigarettes per day and 18%
SC
smoked ≥10 cigarettes per day.
NU
The major correlates of smoking relapse are craving, withdrawal symptoms, slips and lapses (Shiffman, West, Gilbert, & SRNT Work Group on the Assessment of Craving and
MA
Withdrawal in Clinical Trials, 2004; Allen, Bade, Hatsukami, & Center, 2008; Piper et al., 2008; Zhou et al., 2009). Craving is most prominent during the first two weeks of quitting (Shiffman &
ED
Ferguson, 2008). Surprisingly, studies of craving, withdrawal and the process of smoking
PT
cessation during pregnancy are rare. However, some authors have noted that there might be something inherent about pregnancy that worsens withdrawal. Heil, Higgins, Mongeon, Badger,
CE
& Bernstein (2006) characterized craving and withdrawal in pregnant smokers using the
AC
Minnesota Nicotine Withdrawal Scale (MNWS; Hughes & Hatsukami, 1986). Pregnant smokers who abstained or smoked at very low levels (below baseline) during the first five days of a cessation attempt had greater difficulty concentrating and were more frustrated, angry, irritable, restless, and impatient compared to pregnant smokers who continued to smoke at or above smoking levels reported at baseline. Craving (viz., desire to smoke), anxiety and nervousness, anger, irritability, frustration, impatience, and restlessness also declined significantly over the five-day assessment period, independent of smoking status. Other research (Oncken et al., 2009) also found that pregnant smokers have elevated levels of withdrawal prior to smoking cessation, but the authors noted that some withdrawal symptoms (e.g., insomnia, weight gain, and
4
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY irritability) also occurred during pregnancy. In the absence of a comparison group of nonpregnant smokers, findings may have been largely affected by the condition of pregnancy, rather
T
than the process of smoking cessation itself.
RI P
Ussher, Etter, Giatras, and Coleman (2012) examined abstinent pregnant and nonpregnant smokers, including a “smoking as usual” group to demonstrate that abstinence
SC
increased withdrawal symptoms (MNWS-Revised and additional withdrawal items) and the
NU
intensity of urge to smoke. After adjusting for baseline cigarette consumption and withdrawal scores, pregnant women had lower scores than non-pregnant women for MNWS-Revised scores
MA
and for the three individual MNWS withdrawal symptoms, angry, anxious, and impatient after 24-hour abstinence. Despite differences in the patterns of individual items, findings indicated
ED
that pregnant abstinent smokers endorsed withdrawal symptoms in a manner similar to non-
PT
pregnant abstinent smokers, although their symptoms were less severe. Although the Ussher et al. data (2012) contradict the assumption that pregnancy worsens
CE
withdrawal, the analysis was conducted exclusively among those in the abstinent group. While
AC
abstinence ordinarily increases tobacco craving, yet craving is also influenced by ongoing smoking and is itself a strong predictor of smoking satisfaction and smoking (Baker, Breslau, Covey, & Shiffman, 2012). Without a comparison group of non-abstinent smokers, it is impossible to determine whether pregnant smokers are substantively different than their nonpregnant counterparts. A clinical trial of smoking cessation in the general population of male and female smokers using French versions of the brief Tobacco Craving Questionnaire FTCQ-12) and Minnesota Nicotine Withdrawal Scale (FMNWS) (Berlin, Singleton, & Heishman, 2010) found that abstinent smokers had significantly lower craving scores than non-abstinent smokers and the
5
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY total withdrawal score decreased in abstainers, but did not change in non-abstainers (Berlin et al., 2011). A recent meta-analysis demonstrated that withdrawal symptoms improve among abstinent
T
versus continuing smokers in the general population of smokers and in smokers with psychiatric
RI P
disorders (Taylor et al., 2014). The fact that pregnant smokers continue to smoke during pregnancy despite knowledge of its major negative health effects suggest that patterns of craving
SC
and withdrawal symptoms may be different compared with non-pregnant smokers and males. We
NU
therefore compared craving and withdrawal symptoms in pregnant versus non-pregnant smokers using data of two previously published clinical trials (Berlin et al., 2011; Berlin, Grangé, Jacob,
MA
& Tanguy, 2014). We addressed the research question: Are there differences between pregnant smokers and non-pregnant smokers for FTCQ-12 craving and FMNWS withdrawal at baseline
ED
and after quit date at the end of the critical two-week period? Findings could facilitate planning
well as the unborn child.
AC
2.1. Participants
CE
2. Material and methods
PT
for future research aimed at improving health and substance use treatment in pregnant women as
We analyzed data from smokers who participated in the Study of Nicotine Patch in Pregnancy (SNIPP; Identifier: ClinicalTrials.gov NCT00507975) and the Adjustment of DOses of NIcotine in Smoking (ADONIS; ClinicalTrials.gov Identifier: NCT00235313) clinical trials of smoking cessation. The SNIPP trial was a randomized, double blind, placebo controlled, parallel group, multicenter study assessing the efficacy of 16-hr nicotine patches with doses individually adjusted according to saliva cotinine concentration and could range from 10 to 30 mg/day. Pregnant smokers older than 18 years, between 12 to 20 weeks of gestation who smoked at least five cigarettes per day and scored ≥ 5 on a scale of motivation to quit (ranging 0 to10) were
6
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY enrolled. The ADONIS trial enrolled a general population of smokers attending smoking cessation clinics in France. This study compared nicotine replacement therapy (NRT) efficacy
T
when the NRT daily dose was determined by progressive dose adaptation, based on saliva
RI P
cotinine concentration, to obtain 100% substitution versus the standard monthly decreasing dose of NRT without saliva cotinine determination. We included only data from female smokers.
SC
Women were included if they were 18 years old or older, smoked ≥ 10 cigarettes per day,
NU
intended to stop smoking in the coming weeks, and scored ≥ 5 on a scale of motivation to quit (ranging 0 to 10), used an effective contraceptive method (hormonal contraception or intrauterine
MA
device), or were menopausal. Breastfeeding and pregnant women were excluded. In both studies, socio-demographic and smoking-related variables were collected at
ED
baseline. Craving and withdrawal were assessed simultaneously at baseline and two weeks after
PT
the quit date. Self-reported smoking status (abstinent = 0, smoking = 1) was verified by expired air CO (abstinent if CO ≤ 8 ppm; Smokelyzer; Bedfont Scientific Ltd, Rochester, Kent, UK). For
CE
the pregnant vs. non-pregnant comparisons, the combined sample consisted of complete data on
AC
399 smokers (ADONIS: n = 93 non-pregnant women vs. SNIPP: n = 306 pregnant women). All participants provided written informed consent prior to the study. Research protocols for both studies were approved by the Ethics Committee of the Pitié-Salpêtrière Hospital, Paris, France. Full details of the ADONIS and SNIPP studies have been published (Berlin et al., 2011; Berlin et al., 2014). 2.2. Measures French Tobacco Craving Questionnaire. Multidimensional craving was assessed by the brief version of the French Tobacco Craving Questionnaire (FTCQ-12; Berlin et al., 2010). The FTCQ-12 is a valid and reliable 12-item self-report instrument that assesses the same four
7
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY dimensions [factors 1-4; respectively: Emotionnalité (Emotionality), Attente (Expectancy), Compulsion (Compulsivity), and Anticipation (Purposefulness)] as the standard version of the
T
FTCQ (Berlin et al., 2005) and the brief and standard English versions of the Tobacco Craving
RI P
Questionnaire (Heishman, Singleton, & Moolchan, 2003; Heishman, Singleton, & Pickworth,
SC
2008). Items were rated on an interval scale (1 to 7, strongly disagree to strongly agree). Four items were reverse-keyed to reduce acquiescence. During data analysis, raw scores on the
NU
reverse-keyed items were inverted. Factor scores were calculated by summing item scores for each factor, then dividing by the number of items for each respective factor. The FTCQ-12
MA
general craving score was derived by summing the four factor scores then dividing by the total number of items. In the initial validation study (Berlin et al., 2010), Cronbach’s alpha
ED
coefficients and average interitem correlations (in parentheses) were 0.78 (0.47), 0.62 (0.35),
PT
0.60 (0.34), 0.44 (0.21), and 0.79 (0.25) for factors 1 to 4 and the general craving score, respectively.
CE
French Minnesota Nicotine Withdrawal Scale. We used the French version of the eight-
AC
item Minnesota Nicotine Withdrawal Scale (MNWS; Hughes & Hatsukami, 1986) to assess craving and withdrawal symptoms. Items (sadness or depressed mood; insomnia; irritability, frustration, anger; anxiety; difficulty concentrating; nervousness; increased appetite or weight gain; and urge to smoke) were summed and divided by eight to yield a total average score (hereafter the FMNWS general withdrawal score). FMNWS items were rated on an interval scale (0 to 3, not present to severe). The FMNWS has established construct validity with French populations (Berlin et al., 2010; Berlin, Singleton, & Heishman, 2013). Socio-demographic and smoking-related characteristics. To describe the samples and control for possible confounds, socio-demographic information was assessed at baseline,
8
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY including age, gender, marital status, race, income, and professional status. Smoking-related characteristics included: age of smoking initiation, age at which regular smoking began, number
T
of cigarettes smoked per day (CPD), number of previous quit attempts, Fagerström Test for
RI P
Cigarette Dependence [FTCD, Fagerström, 2012; formerly the Fagerström Test for Nicotine Dependence (FTND), Heatherton, Kozlowski, Frecker, & Fagerström, 1991], and alcohol use
SC
(four-item CAGE questionnaire total score; Ewing, 1984). We used FTCD total score to
NU
distinguish highly dependent (≥ 6) from less dependent (≤ 5) smokers (Fagerström et al., 1996; Ferguson et al., 2003). A CAGE total score ≥ 1 indicated a clinically significant alcohol problem
MA
because any drinking during pregnancy was considered problematic. 2.3. Data analyses
ED
Data were analyzed using two-way multivariate analysis of covariance (MANCOVA)
PT
models with group (pregnant smokers vs. non-pregnant [female] smokers) and smoking status (abstinence vs. smoking) as factors. FTCQ-12 general factor and FMNWS withdrawal scores
CE
were covariates. All socio-demographic and smoking-related variables were control variables as
AC
well as treatment (intervention group), although NRT did not increase smoking cessation rates despite adjustment of nicotine dose to match levels attained when smoking or higher than usual doses in either the ADONIS or SNIPP trial (Berlin et al., 2011; Berlin et al., 2014). To determine the relative contribution of individual factors and items, analysis of covariance (ANCOVA) was performed using FTCQ-12 factors 1 to 4 and FMNWS withdrawal items 1 to 8 as follow-up for statistically significant findings for FTCQ-12 general factor and FMNWS withdrawal. We used Weighted Least Squares (WLS) to adjust for the contribution of individual cases to outcomes, weighting cases by the reciprocal of the size of the groups. The test of significance was based the F value (Pillia’s trace) using Type III sums of squares (SS), MANCOVA results were considered
9
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY significant at p < 0.05. Post hoc statistical tests were Bonferroni adjusted. All analyses were conducted with STATISTICA Version 5.5 (StatSoft, Inc., Tulsa, OK).
T
3. Results
RI P
3.1. Baseline differentials
Socio-demographic and smoking related characteristics. Table 1 shows that pregnant
SC
smokers were significantly younger than non-pregnant smokers (median: 30 vs. 49 years,
NU
respectively). Pregnant smokers were 1.6 times more likely to be living with a spouse or significant other, 1.3 times more likely to be working or going to school, and 1.3 times more
MA
likely to be middle (12000 – 30000 euros per year) or high-income (> 30000 euros per year) than non-pregnant smokers. CPD during the week prior to enrollment for pregnant smokers was less
ED
than half that of non-pregnant smokers (Table 2). Pregnant smokers were approximately two
PT
years younger when they first tried smoking and nearly three years younger when regular smoking began compared to non-pregnant smokers. FTCQ-12 general score and FTCQ-12
CE
factors 1 - 3 were lower, while FTCQ-12 factor 4 was greater in pregnant smokers compared to
AC
non-pregnant smokers at baseline. In pregnant smokers, the incidence of smoking two weeks after the quit date was also 1.6 times that of non-pregnant smokers (all previous p values < 0.05). 3.2. Process of smoking cessation MANCOVA yielded a significant main effect for group [F(13,370) = 18.21, p < 0.001] and smoking status [F(13,370) = 3.26, p < 0.01], but not for group x smoking status interaction (p > 0.05). Figure 1 presents results for all of the Bonferroni adjusted post hoc tests associated with change in craving among pregnant and non-pregnant smokers. Figure 1a shows first that FTCQ-12 general craving score decreased less in pregnant smokers than non-pregnant smokers between baseline and two weeks after quit date. Figure 1a also shows that FTCQ-12 factors 1
10
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY (Emotionality) and 2 (Expectancy) decreased less among pregnant than among non-pregnant smokers and is likely responsible for the difference.
T
FMNWS general withdrawal score also decreased less in pregnant smokers than non-
RI P
pregnant smokers (X ¯ DIF = -0.13, 95% CI = -0.25 to -0.01, p < 0.05). We examined changes between baseline and week 2 in individual symptoms and found that the mean change in
= -0.25, p < 0.05). Insomnia actually increased in both groups, but increased less in pregnant
NU
DIF
SC
FMNWS “insomnia” was significantly lower in pregnant smokers than non-pregnant smokers (X ¯
smokers compared to non-pregnant smokers (0.32 cf. 0.70). FMNWS items “anxiety” and “urge
MA
to smoke” were significantly higher in pregnant smokers than non-pregnant smokers (X ¯ DIF = 0.38 and 0.32, respectively, both p < 0.001). Anxiety increased in pregnant smokers (0.70), but
ED
decreased (-0.30) in non-pregnant smokers, while the urge to smoke decreased less in pregnant
PT
smokers than non-pregnant smokers during the two-week period (X ¯ DIF = -0.14 cf. -0.51). There were no significant group differences in FMNWS items “sadness/depressed mood”,
CE
“irritability/frustration/anger”, “difficulty concentrating”, “nervousness”, or “increased
AC
appetite” (all p > 0.05).
Irrespective of group differences, FTCQ-12 general craving decreased less in smokers compared to abstainers, with FTCQ-12 factors 2 - 4 largely responsible for the differences (Figure 1b). Mean overall FMNWS general withdrawal was significantly higher in abstainers
compared to smokers (X ¯ DIF = 0.15, 95% CI = 0.01 to 0.14, p < 0.05). Mean FMNWS general withdrawal actually increased in abstainers (0.05), but decreased (-0.10) in smokers. FMNWS items “insomnia” and “increased appetite” were significantly lower in smokers than abstainers (X ¯ DIF = -0.41 and -0.36, respectively; both p < 0.01). Insomnia and appetite increased over time, but increased more by week two in abstainers compared to smokers (0.49 vs. 0.08 and 0.61 vs.
11
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY 0.18, respectively). The “urge to smoke” item decreased more in abstainers than smokers (-0.42 vs. -0.25). The “sadness/depressed mood” item decreased in abstainers, but increased in smokers
T
(-0.14 vs. 0.11). There were no significant differences between smokers and abstainers for
RI P
FMNWS items “irritability/frustration/anger”, “anxiety”, “difficulty concentrating”, and “nervousness” (all p > 0.05).
SC
3.3. Barriers to abstinence
NU
Stepwise regression (backward elimination) indicated that absolute change from baseline (increase) in FTCQ-12 factor 2 (expectancy) (β = 0.053, 95% CI = 0.033 to 0.073, t = 5.23, p <
MA
0.001), baseline FTCQ-12 factor 4 (purposefulness) (β = 0.034, 95% CI = 0.011 to 0.057, t = 2.98, p < 0.01), and baseline FMNWS “nervousness” (β = 0.051, 95% CI = 0.015 to 0.087, t =
ED
2.79, p < 0.01) were significantly associated with smoking two weeks after the quit date in
PT
pregnant smokers. In non-pregnant female smokers, only baseline FMNWS item “increased appetite” was significantly associated with post-quit date smoking (β = 0.044, 95% CI = 0.003 to
AC
4. Discussion
CE
0.090, t = 2.11, p < 0.04).
We analyzed data from two independent clinical trials to characterize craving and withdrawal during a critical two-week period of smoking cessation and to identify distinctions between pregnant smokers and non-pregnant smokers. Participants were randomly assigned subsequent to enrollment and there were no treatment effects in any of the studies (Berlin et al., 2011; Berlin et al., 2014). Beyond the expected demographic and smoking characteristic differences, such as lower daily cigarette consumption and FTCD score, pregnant smokers started smoking and smoked regularly earlier and succeded much less at smoking cessation by week 2 after quit date than
12
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY non-pregnant smokers. Craving to smoke and sadness/depressed mood decreased more among abstinent than among continuing smokers.
T
FTCQ-12 and FMNWS responses to smoking cessation were also largely different
RI P
between pregnant smokers and non-pregnant smokers. Post-quit FTCQ-12 general score was higher in pregnant smokers compared with comparison groups and was driven by elevated
SC
Emotionality and Expectancy. FMNWS decreased less among pregnant smokers than among
NU
non-pregnant smokers, especially with respect to anxiety and urge to smoke. Smoking at 2 weeks post-quit date was predicted by baseline FTCQ-12 factor 2 (Expectancy), factor 4
MA
(Purposefulness) and FMNWS item “nervousness” among pregnant smokers and by FMNWS item “increased appetite” among non-pregnant smokers. These findings support the hypothesis
ED
that smoking cessation involves different aspects of craving and withdrawal symptoms in
PT
pregnant smokers compared with non-pregnant smokers. However, no group by smoking status interaction occurred, suggesting that pregnant smokers’ craving and withdrawal responses to
CE
cessation are qualitatively similar to non-pregnant smokers and that differences lie in the
AC
intensity of responses.
Several differences have been identified between pregnant smokers able to quit compared to those unable to quit (Massey & Compton, 2013), but comparisons with non-pregnant smokers are scarce (Ussher et al., 2012; Parrott et al., 2014), especially concerning the major predictors of successful quitting, craving and withdrawal symptoms. Our findings differ from research (Ussher et al., 2012) demonstrating that pregnant smokers endorsed withdrawal symptoms in a manner similar to non-pregnant smokers, although their symptoms were less severe. Most withdrawal symptoms do not peak until 48 hours after quitting smoking, and a reasonable explanation for the
13
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY differences is that pregnant women might report less severe withdrawal than non-pregnant smokers on the first day of abstinence compared to 2 weeks after the quit date.
T
The general craving score was higher in pregnant smokers compared to non-pregnant
RI P
smokers. It was largely driven by two specific factors, Emotionality and Expectancy. Emotionality decreased less in pregnant smokers than non-pregnant smokers and Expectancy
SC
remained relatively stable during smoking cessation among pregnant smokers while it decreased
NU
in the non-pregnant smokers. In parallel, the urge to smoke and anxiety were also greater in pregnant smokers compared to non-pregnant smokers. These findings suggest that cessation
MA
increases anxious feelings and a persistent craving in anticipation of relief from withdrawal (Emotionality) and craving in anticipation of the positive benefits of smoking (Expectancy).
ED
Major contributors to the incidence of smoking two weeks after the quit date in pregnant
PT
women were a cessation-related increase in expectancy and elevated nervousness and purposefulness before quit date. Anxiety is frequently associated with pregnancy, which for
CE
some women is a stressful life event (Kowalyk, Hadjistavropoulos, & Jones, 2009). Smoking
AC
even a single cigarette has been associated with high levels of pregnancy-specific, prenatal anxiety (Huizink et al., 2014). Pregnant quitters have also reported that they return to smoking because they experience irresistible cravings when stressed, and having a cigarette is extremely pleasurable right at that moment (Herbec et al., 2014). We also found previously that slips and lapses to smoking are triggered by craving in anticipation of the positive benefits of smoking coupled with intent and planning to smoke (Berlin et al., 2013). Several withdrawal symptoms established in populations of non-pregnant smokers might be confounded by pregnancy itself. Pregnancy is physiologically associated with weight gain, increased appetite, better sleep and, in some women, with anxiety. An example is that insomnia
14
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY increased less among pregnant compared to non-pregnant smokers in the current study. Because these symptoms are not specific to tobacco withdrawal, their value in pregnant smokers is
T
doubtful. Further research should establish the symptoms occuring during smoking cessation that
RI P
can be attributed to quitting, which are not confounded by symptoms associated with pregnancy. The difference between pregnant and non-pregnant smokers is supported by the findings that
SC
week 2 smoking status was positively predicted by FTCQ-12 Expectancy, Purposefulness, and
NU
pre-quit nervousness among pregnant smokers and by pre-quit increased appetite among nonpregnant smokers—the latter being a demostrated predictor of smoking lapse in the general
Japuntich, Baker, & Cook, 2014) .
MA
population of smokers (Leyro, Zvolensky, Vujanovic, & Bernstein, 2008; Leventhal, Piper,
ED
Nicotine’s clearance is increased by 60% (and that of cotinine by 140%) during
PT
pregnancy compared to postpartum (Dempsey, Jacob, & Benowitz, 2002) probably by sex hormonal induction of liver cytochrome 2A6 and flavin-containing monooxygenase 3 (FMO3)
CE
(Hukkanen, Dempsey, Jacob, & Benowitz, 2005). Increased nicotine clearance may contribute to
AC
increased craving and withdrawal symptoms among pregnant smokers compared to the general population of smokers. However, saliva cotinine-adapted nicotine replacement therapy leading to close to 100% nicotine substitution did not improve the abstinence rate and did not affect FTCQ12 craving scores among pregnant smokers (Berlin et al., 2014). Endocrine mechanisms may also be associated with relapse to smoking or increased craving and withdrawal symptoms. Relapse to smoking may be associated with increased plasma cortisol concentration in women (Al’Absi et al., 2015) but not in men. A recent meta-analysis demonstrated that among non-pregnant women withdrawal symptoms are greater in the luteal than in the follicular phase and craving to smoke shows a similar tendency (Weinberger et al.,
15
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY 2015). Progesterone surge is a physiological effect in pregnancy. Plasma progesterone levels are usually 10 to 20 times higher in pregnancy than progesterone levels in the luteal phase in non-
T
pregnant women. Higher levels of craving and withdrawal symptoms among pregnant smokers
RI P
than among non-pregnant smokers are likely associated with the physiological, pregnancyrelated surge in plasma progesterone concentration.
SC
Strengths and Limitations
NU
The major limitation of this study was the historical comparison of pregnant smokers to non-pregnant smokers. All participants were also treatment-seeking smokers motivated to quit
MA
and enrolled in a smoking cessation clinical trial reducing generalizability of the findings. Women who continue to smoke during pregnancy, however, are likely unique because many
ED
women quit smoking shortly after learning they are pregnant and require no assistance quitting
PT
smoking (Kapaya et al., 2015). Thus, usual measures of tobacco dependence, such as the FTCD based on cigarette per day consumption, may underestimate pregnant smokers’ dependence who
CE
usually smoke less (Haug, Fugelli, Aarø, & Foss, 1994; Ussher et al., 2012). Therefore, measures
AC
of craving to smoke or withdrawal symptoms might be better predictors of ability to quit among pregnant smokers than tobacco dependence measures (Fidler, Shahab, & West, 2011). These limitations reduce the generality of the findings. On the other hand, both clinical trials included only smokers with a motivation score to quit ≥ 5 on a scale of 0 to 10 making motivation homogeneous. Other strengths include use of the same measures for craving, withdrawal symptoms, and tobacco dependence and the same post-quit date time point of assessments, which add validity to the findings. The sample distributions reflect populations of French smokers mostly of European ancestry, thus, results need to be confirmed using independent samples from other countries, nationalities, and ethnicities.
16
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY A further limitation is the small sample of non-pregnant smokers and the unequal pregnant/non-pregnant sample although the WLS adjustment statististically compensated for
T
unqual sample size. Our analyses also required baseline adjustments, while a better
RI P
understanding of why pregnant smokers have difficulty quitting would require comparing their smoking cessation process with that of a matched sample of non-pregnant female smokers. This
SC
was a retrospective study, thus subjects were not randomly included. Future research should
NU
randomly assign representative and larger samples of pregnant, non-pregnant, and the general population of smokers to ensure comparability of socio-demographic characteristics and
MA
smoking-related behaviors. Nevertheless, our subjects were randomly assigned subsequent to enrollment and there were no treatment effects in any of the studies (Berlin et al., 2011; Berlin et
ED
al., 2014). In lieu of randomization, models were estimated using all possible confounding
PT
covariates. Low p values and consistency of results suggest the populations were distinct, and the
5. Conclusions
CE
results were more likely attributable to the condition of pregnancy itself as opposed to chance.
AC
Adjusting for baseline differences, craving decreased less in pregnant smokers than nonpregnant female smokers. These findings partially explain why pregnant smokers may have more difficulty quitting than other smokers. Withdrawal decreased less in pregnant smokers than nonpregnant smokers, suggesting that smoking cessation may be substantially different for pregnant smokers than other females. Some withdrawal symptoms may be confounded by symptoms physiologically associated with pregnancy or by symptoms frequently present among pregnant women. Understanding why pregnant smokers have difficulty quitting requires comparing their smoking cessation processes with those of a matched sample of non-pregnant smokers. Surprisingly, to the best of our knowledge, this has not been studied. Our findings are
17
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY preliminary; however, they might foster further investigation of differences in craving and withdrawal symptoms between pregnant and non-pregnant smokers. Better knowledge about
T
patterns and specificity of craving and withdrawal among pregnant smokers would improve
AC
CE
PT
ED
MA
NU
SC
RI P
smoking cessation interventions in this population, thereby reducing prenatal smoking.
18
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
Funding sources and Disclosures
T
The ADONIS study was supported by the French Ministry of Health Programme
RI P
Hospitalier de Recherche Clinique Loco-regional 2004 (AOR04001//P040406, registration number: 050558) by the Agence française de sécurité sanitaire des produits de santé, Convention
SC
Pharmacologie Clinique et Thérapeutique 2003, RAF02020. The SNIPP study was funded by the Ministry of Health, France, Grant Number MA05 001050. E. G. Singleton was partly funded by
NU
the same research grant. S. J. Heishman was supported by the National Institute on Drug Abuse,
MA
Intramural Research Program. The funding sources had no other role than financial support. I. Berlin acquired the data. I. Berlin and E. G. Singleton had full access to the data and
ED
take responsibility for the accuracy of the data analysis. All authors were involved in the study concept and design, analysis and interpretation of data, and preparation of the manuscript.
AC
CE
PT
None of the authors report conflict of interest.
19
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY References Al'Absi, M., Nakajima, M., Allen, S., Lemieux, A., & Hatsukami, D. (2015). Sex differences in
T
hormonal responses to stress and smoking relapse: a prospective examination.
RI P
Nicotine and Tobacco Research, 17, 382-389. http://dx.doi.org/10.1093/ntr/ntu340. Allen, S. S., Bade, T., Hatsukami, D., & Center, B. (2008). Craving, withdrawal, and smoking
SC
urges on days immediately prior to smoking relapse. Nicotine and Tobacco Research, 10,
NU
35-45. http://dx.doi.org/10.1080/14622200701705076
Baker, T. B., Breslau, N., Covey, L., & Shiffman, S. (2012). DSM criteria for tobacco use
MA
disorder and tobacco withdrawal: a critique and proposed revisions for DSM-5. Addiction, 107, 263-275. http://dx.doi.org/10.1111/j.1360-0443.2011.03657.x.
ED
Berlin, I., Vorspan, F., Singleton, E. G., Warot, D., Notides, C., & Heishman, S. J. (2005).
PT
Reliability and validity of the French version of the Tobacco Craving Questionnaire. European Addiction Research, 11, 62-68.
CE
Berlin, I., Singleton, E. G., & Heishman, S. J. (2010). Validity of the 12-item French version of
AC
the Tobacco Craving Questionnaire in treatment-seeking smokers. Nicotine and Tobacco Research, 12, 500-507. http://dx.doi.org/10.1093/ntr/ntq039 Berlin, I., Jacob, N., Coudert, M., Perriot, J., Schultz, L., & Rodon, N. (2011). Adjustment of nicotine replacement therapies according to saliva cotinine concentration: the ADONIS* trial-a randomized study in smokers with medical comorbidities. Addiction, 106, 833843. http://dx.doi.org/10.1111/j.1360-0443.2010.03306.x Berlin, I., Singleton, E. G., & Heishman, S. J. (2013). Predicting smoking relapse with a multidimensional versus a single-item tobacco craving measure. Drug and Alcohol Dependence, 132, 513-520. http://dx.doi.org/10.1016/j.drugalcdep.2013.03.017
20
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Berlin, I., Grangé, G., Jacob, N., & Tanguy, M. L. (2014). Nicotine patches in pregnant smokers: randomised, placebo controlled, multicentre trial of efficacy. British Medical Journal,
T
348, g1622. http://dx.doi.org/10.1136/bmj.g1622
RI P
Blondel, B., & Kemarrec, M. (2011). Enquête nationale périnatal 2010. Retrieved from http://www.sante.gouv.fr/IMG/pdf/Les_naissances_en_2010_et_leur_evolution_depuis_2
SC
003.pdf
NU
Buka, S. L., Shenassa, E. D., & Niaura, R. (2003). Elevated risk of tobacco dependence among offspring of mothers who smoked during pregnancy: a 30-year prospective study.
MA
American Journal of Psychiatry, 160, 1978-1984.
Burke, H., Leonardi-Bee, J., Hashim, A., Pine-Abata, H., Chen, Y., Cook, D. G.,... McKeever, T.
ED
M. (2012). Prenatal and passive smoke exposure and incidence of asthma and wheeze:
PT
systematic review and meta-analysis. Pediatrics, 129, 735-44. http://dx.doi.org/ 10.1542/peds.2011-2196
CE
Centers for Disease Control and Prevention. (2010). A report of the surgeon general: how
AC
tobacco smoke causes disease: what it means to you. Atlanta, GA Dempsey, D., Jacob, P., 3rd, Benowitz, N. L. (2002). Accelerated metabolism of nicotine and cotinine in pregnant smokers. Journal of Pharmacology and Experimental Therapeutics, 301, 594-598. DiClemente, C. C., Dolan-Mullen, P., & Windsor, R. A. (2000). The process of pregnancy smoking cessation: implications for interventions. Tobacco Control, 9(Suppl 3), 6-21. Ekblad, M., Gissler, M., Lehtonen, L., & Korkeila, J. (2010). Prenatal smoking exposure and the risk of psychiatric morbidity into young adulthood. Archives of General Psychiatry, 67, 841-849. http://dx.doi.org/10.1001/archgenpsychiatry.2010.92
21
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Ewing, J.A. (1984). Detecting alcoholism: the CAGE Questionnaire. JAMA, 252, 1905-1907. Fagerström, K. O., Kunze, M., Schoberberger, R., Breslau, N., Hughes, J. R., Hurt, R.
T
D.,…Zatoński, W. (1996). Nicotine dependence versus smoking prevalence: comparisons
RI P
among countries and categories of smokers. Tobacco Control, 5, 52-56. Fagerström K. (2012). Determinants of tobacco use and renaming the FTND to the Fagerstrom
SC
Test for Cigarette Dependence. Nicotine and Tobacco Research, 14, 75-78.
NU
http://dx.doi.org/10.1093/ntr/ntr137
Ferguson, J. A., Patten, C. A., Schroeder, D. R., Offord, K. P., Eberman, K. M., & Hurt, R. D.
MA
(2003). Predictors of 6-month tobacco abstinence among 1224 cigarette smokers treated for nicotine dependence. Addictive Behaviors, 28, 1203-1218.
ED
Fidler, J.A., Shahab, L., West, R. (2011). Strength of urges to smoke as a measure of severity of
PT
cigarette dependence: comparison with the Fagerström Test for Nicotine Dependence and its components. Addiction. 106, 631-638.
CE
Flemming, K., Graham, H., Heirs, M., Fox, D., & Sowden, A. (2013). Smoking in pregnancy: a
AC
systematic review of qualitative research of women who commence pregnancy as smokers. Journal of Advanced Nursing, 69, 1023-1036. http://dx.doi.org/ 10.1111/jan.12066 Hartmann-Boyce, J., Stead, L. F., Cahill, K., & Lancaster, T. (2014). Efficacy of interventions to combat tobacco addiction: cochrane update of 2013 reviews. Addiction, 109, 1414-1425. http://dx.doi.org/10.1111/add.12633 Haug, K., Fugelli, P., Aarø, L.E., Foss, O.P.(1994) Is smoking intervention in general practice more successful among pregnant than non-pregnant women? Fam Pract. 1994 Jun;11(2):111-6.
22
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., & Fagerström, K. O. (1991). The Fagerstrom Test for Nicotine Dependence: A revision of the Fagerstrom Tolerance Questionnaire.
T
British Journal of Addictions, 86, 1119-1127.
RI P
Heil, S. H., Higgins, S. T., Mongeon, J. A., Badger, G. J., & Bernstein, I. M. (2006).
Clinical Psychopharmacology, 14, 165-170.
SC
Characterizing nicotine withdrawal in pregnant cigarette smokers. Experimental and
NU
Heishman, S. J., Singleton, E. G., & Moolchan, E. T. (2003). Tobacco Craving Questionnaire: reliability and validity of a new self-report instrument. Nicotine and Tobacco Research,
MA
53, 75-81.
Heishman, S. J., Singleton, E. G., & Pickworth, W. B. (2008). Reliability and validity of a short
ED
form of the Tobacco Craving Questionnaire. Nicotine and Tobacco Research, 10, 643-
PT
651.
Herbec, A., Beard, E., Brown, J., Gardner, B., Tombor, I., & West, R. (2014). The needs and
CE
preferences of pregnant smokers regarding tailored internet-based smoking cessation
AC
interventions: a qualitative interview study. BioMed Central Public Health, 14, 1070. http://dx.doi.org/10.1186/1471-2458-14-1070 Hughes, J. R., & Hatsukami, D. (1986). Signs and symptoms of tobacco withdrawal. Archives of General Psychiatry, 43, 289-294. Huizink, A. C., Menting, B., Oosterman, M., Verhage, M. L., Kunseler, F. C., & Schuengel, C. (2014). The interrelationship between pregnancy-specific anxiety and general anxiety across pregnancy: a longitudinal study. Journal of Psychosomatic Obstetrics and Gynecology, 35, 92-100. http://dx.doi.org/10.3109/0167482X.2014.944498
23
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Hukkanen, J., Dempsey, D., Jacob, P., 3rd, & Benowitz, N. L. (2005). Effect of pregnancy on a measure of FMO3 activity. British Journal of Clinical Pharmacology, 60, 224-226.
T
Ingall, G., & Cropley, M. (2010). Exploring the barriers of quitting smoking during pregnancy: a
RI P
systematic review of qualitative studies. Women and Birth, 23, 45-52. http://dx.doi.org/ 10.1016/j.wombi.2009.09.004
SC
Jaakkola, J. J., & Gissler, M. (2005). Maternal smoking in pregnancy as a determinant of
NU
rheumatoid arthritis and other inflammatory polyarthropathies during the first 7 years of life. International Journal of Epidemiology, 34, 664-671.
MA
Kapaya, M., Tong, V., & Ding H. (2015). Nicotine replacement therapy and other interventions for pregnant smokers: Pregnancy Risk Assessment Monitoring System, 2009-2010.
ED
Preventive Medicine, 78, 92-100. doi: 10.1016/j.ypmed.2015.07.008. Epub 2015 Jul 16.
PT
Kim, S. Y., England, L. J., Kendrick, J. S., Dietz, P. M., Callaghan, W. M. (2009). The contribution of clinic-based interventions to reduce prenatal smoking prevalence among
CE
US women. Am J Public Health. 99, 893-898. http://dx.doi: 10.2105/AJPH.2008.144485.
AC
Kowalyk, K. M., Hadjistavropoulos, H. D., & Jones, S. L. (2009). What impact does pregnancy have on anxiety about health? Journal of Psychosomatic Obstetrics and Gynaecology, 30, 223-230. http://dx.doi.org/10.3109/01674820903276453 Leventhal, A. M., Piper, M. E., Japuntich, S. J., Baker, T. B., & Cook, J. W. (2014). Anhedonia, depressed mood, and smoking cessation outcome. Journal of Consulting and Clinical Psychology, 82, 122-129. http://dx.doi.org/10.1037/a0035046 Leyro, T. M., Zvolensky, M. J., Vujanovic, A. A., & Bernstein, A. (2008). Anxiety sensitivity and smoking motives and outcome expectancies among adult daily smokers: replication
24
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY and extension. Nicotine and Tobacco Research, 10, 985-994. http://dx.doi.org/ 10.1080/14622200802097555
T
Massey, S. H., & Compton, M. T. (2013). Psychological differences between smokers who
RI P
spontaneously quit during pregnancy and those who do not: a review of observational studies and directions for future research. Nicotine and Tobacco Research, 15, 307-319.
SC
http://dx.doi.org/10.1093/ntr/nts142
NU
Oncken, C., Campbell, W., Chan, G., Hatsukami, D., Kranzler, H. R., Oncken, C., Campbell, W.,…Kranzler, H. R. (2009). Effects of nicotine patch or nasal spray on nicotine and
MA
cotinine concentrations in pregnant smokers. Journal of Maternal-Fetal and Neonatal Medicine, 22, 751-758. http://dx.doi.org/10.3109/14767050902994515
ED
Parrott, C. E., Rathnayaka, N., Blalock, J. A., Minnix, J. A., Cinciripini, P. M., Vincent,
PT
J.P.,…Green, C. (2014). Examination of the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) factor structure in a sample of pregnant smokers.
CE
Nicotine Tobacco Research, Dec 4. pii: ntu238. [Epub ahead of print]
AC
Piper, M. E., Federmen, E. B., McCarthy, D. E., Bolt, D. M., Smith, S. S., Fiore, M. C., & Baker, T. B. (2008). Using mediational models to explore the nature of tobacco motivation and tobacco treatment effects. Journal of Abnormal Psychology, 117, 94-105. http://dx.doi.org/ 10.1037/0021-843X.117.1.94 Räisänen, S., Gissler, M., Saari, J., Kramer, M., & Heinonen, S. (2013). Contribution of risk factors to extremely, very and moderately preterm births – register-based analysis of 1,390,742 singleton births. PLOS ONE, 8, e60660. http://dx.doi.org/ 10.1371/journal.pone.0060660
25
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Schneider, S., & Schütz, J. (2008). Who smokes during pregnancy? A systematic literature review of population-based surveys conducted in developed countries between 1997 and
RI P
http://dx.doi.org/10.1080/13625180802027993
T
2006. European Journal of Contraception and Reproductive Health Care, 13, 138–147.
Schneider, S., Huy, C., Schütz, J., & Diehl, K. (2010). Smoking cessation during pregnancy: a
SC
systematic literature review. Drug and Alcohol Review, 29, 81-90. http://dx.doi.org/
NU
10.1111/j.1465-3362.2009.00098.x
Shiffman, S., & Ferguson, S.G. (2008). The effect of a nicotine patch on cigarette craving over
MA
the course of the day: results from two randomized clinical trials. Current Medical Research and Opinion, 24, 2795-2804. http://dx.doi.org/10.1185/03007990802380341
ED
Shiffman, S., West, R., Gilbert, D., & SRNT Work Group on the Assessment of Craving and
PT
Withdrawal in Clinical Trials. (2004). Recommendation for the assessment of tobacco
599-614.
CE
craving and withdrawal in smoking cessation trials. Nicotine and Tobacco Research, 6,
AC
Surgeon General. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General (2014). Retrieved from http://www.surgeongeneral.gov/library/reports/50-years-of-progress/sgr50-chap-9.pdf Taylor, G., McNeill, A., Girling, A., Farley, A., Lindson-Hawley, N., & Aveyard, P. (2014). Change in mental health after smoking cessation: systematic review and meta-analysis. British Medical Journal, 348, g1151. http://dx.doi.org/10.1136/bmj.g1151 Thacher, J. D., Gruzieva, O., Pershagen, G., Neuman, A., Wickman, M., Kull, I.,…Bergström A. (2014). Pre- and postnatal exposure to parental smoking and allergic disease through adolescence. Pediatrics, 134, 428-434. http://dx.doi.org/10.1542/peds.2014-0427
26
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Ussher, M., Etter, J. F., Giatras, N., & Coleman, T. (2012). Tobacco withdrawal symptoms and urges to smoke in pregnant versus non-pregnant smokers. Addictive Behaviors, 37, 1353-
T
1357. http://dx.doi.org/10.1016/j.addbeh.2012.07.008
RI P
Weinberger, A. H., Smith, P. H., Allen, S. S., Cosgrove, K. P., Saladin, M. E., Gray, K. M.,…McKee, S. A. (2015). Systematic and meta-analytic review of research examining
SC
the impact of menstrual cycle phase and ovarian hormones on smoking and cessation.
NU
Nicotine and Tobacco Research, 17, 407-21. http://dx.doi.org/10.1093/ntr/ntu249. Zhu, J. L., Olsen, J., Liew, Z., Li, J., Niclasen, J., Obel, C. (2014). Parental smoking during
MA
pregnancy and ADHD in children: the danish national birth cohort. Pediatrics, 134, e382-
AC
CE
PT
ED
8. http://dx.doi.org/10.1542/peds.2014-0213
27
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
28
Table 1. Socio-demographic characteristics of the samples.
47.3 18.3 34.4
87.3 12.7
50 43
53.8 46.2
86 159 61
28.1 52.0 19.9
41 37 15
44.1 39.8 16.1
291 15
95.1 4.9
89 4
95.7 4.3
MA ED PT
T
44 17 32
267 39
CE AC
61.4 18.6 19.9
SC
188 57 61
Non-pregnant smokers (n = 93) Count Percent 5 5.4 29 31.2 59 63.4
NU
Age: 18 to 30 31 to 45 >45 Professional status: Employed/Student Homemaker Unemployed Marital status: Married/Cohabiting Single/Separated/Divorced Annual income (€): <12 000 12 000 to 30 000 >30 000 Ethnicity: European Other
RI P
Pregnant smokers (n = 306) Count Percent 173 56.5 133 43.5 0 0.0
Characteristic
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
29
Table 2. Smoking-related history of the samplesa. Non-pregnant smokers
Pregnant smokers
Mean
SD
Mean
SD
Number of cigarettes per day (CPD) Number of previous quit attempts Age of smoking initiation Age at onset of regular smoking Total FTCD score Proportion highly nicotine dependent Total CAGE score Proportion clinical alcohol problem Incidence of smoking (2-wk post-quit) FTCQ-12 general craving score Factor 1 (emotionality) score Factor 2 (expectancy) score Factor 3 (compulsivity) score Factor 4 (purposefulness) score FMNWS general withdrawal score
23.4 1.8 16.8 19.3 6.8 72% 0.6 24% 56% 3.6 2.5 4.9 3.1 4.5 1.0
11.9 3.1 9.0 10.0 3.9 9% 2.3 9% 15% 2.4 3.4 3.1 3.5 3.4 1.3
11.9 1.3 14.7 16.5 4.5 33% 0.3 14% 89% 3.3 1.8 4.6 2.7 5.0 1.1
8.0 2.0 3.5 3.6 2.8 6% 1.0 5% 12% 1.3 1.5 2.0 1.8 2.0 0.9
CE
RI P
SC NU MA
ED
PT
Values are weighted adjustments.
AC
a
T
Characteristic
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
RI P
T
Figure caption Figure 1. Group and smoking status effects on FTCQ-12 craving: Non-pregnant female smokers (NPS) versus pregnant smokers (PS). All values represent Weighted Least Squares (WLS) adjustment of absolute change from baseline (pre-quit) to 2 weeks post-quit date. Error bars are 95% Confidence Intervals. Note: Statistically significant mean differences: * p < 0.05, ** p < 0.01, and *** p < 0.001.
General
Factor 1
Factor 2
MA
-0.5 *
ED
***
PT
-1.5
-2.5
CE
-2
***
Non-Pregnant Smokers (NPS)
AC
Change from baseline
0
-1
Factor 3
NU
0.5
SC
1a) Main Effect of Group
Pregnant Smokers (PS)
Factor 4
30
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY
1b) Main Effect of Smoking Status General
Factor 1
Factor 2
Factor 3
Factor 4
T
0.5
RI P SC
-0.5
NU
-1 ***
MA
-1.5
-2
ED
***
-2.5
CE
PT
Abstinence
AC
Change from baseline
0
Smoking
**
*
31
ACCEPTED MANUSCRIPT TOBACCO CRAVING AND WITHDRAWAL DURING PREGNANCY Craving and Withdrawal Symptoms During Smoking Cessation: Comparison of Pregnant and Non-pregnant Smokers
Smoking cessation rate in pregnancy is relatively low, raising the question of why
RI P
T
Highlights
SC
pregnant smokers have difficulty quitting.
We compared craving for tobacco and withdrawal symptoms in 306 pregnant smokers to
NU
93 non-pregnant female smokers.
Post-quit craving and withdrawal symptoms diminished less in pregnant compared to
Insufficient reduction of craving and withdrawal symptoms may partially explain why
CE
PT
ED
pregnant smokers have difficulty quitting.
AC
MA
non-pregnant smokers.
32