Smoking Reduction In Gravid Women With Substance Use Disorders (SIGS): A Randomized Controlled Trial
Phase: NA
Conditions: Tobacco Smoking in Mother Complicating Pregnancy, Tobacco Use Disorder, Tobacco Smoking
Sponsor: University of Alabama at Birmingham

 
1
Smoking Reduction in Gravid Women with Substance Use Disorders (SIGS): 
A Randomized Controlled Trial 
Protocol 
NCT04132232 
April 14, 2020 
 
 
 

 
2
Table of Contents 
Page 
1. Study abstract 
3 
   1.1 Primary hypothesis 
3 
   1.2 Secondary hypothesis 
3 
   1.3 Purpose of the study protocol 
4 
2. Background 
5 
   2.1 Smoking in Pregnancy 
5 
   2.2 Substance use disorders and smoking 
5 
   2.3 Smoking cessation in pregnancy  
5 
   2.4 Exhaled carbon monoxide monitoring 
5- 
   2.5 Exhaled carbon monoxide monitoring in pregnancy 
6 
   2.6 Rationale for a clinical trial  
6 
   2.7 Innovation 
6 
3. Study design 
7 
   3.1 Primary research question 
7 
   3.2 Secondary research aims 
7 
   3.3 Design summary 
7 
   3.4 Study population and eligibility criteria 
7-8 
   3.5 Study groups 
8 
   3.6 Informed consent 
8 
4. Study procedures 
9 
   4.1 Screening for eligibility and consent 
9 
   4.2 Randomization 
9 
   4.3 Management of patients who develop exclusion criteria 
9 
   4.4 Management of intervention group 
9 
   4.5 Management of control group   
9 
   4.6 Adherence 
9 
   4.7 Participant follow-up 
10 
   4.8 Adverse event reporting 
10 
   4.9 Study outcome measurement and ascertainment 
10 
      4.9.1 Primary outcome 
10 
      4.9.2 Secondary outcomes 
10-11 
      4.9.3 Follow-up and outcome ascertainment periods 
11 
5. Statistical considerations 
12 
   5.1 Sample size for primary outcome 
12 
   5.2 Power for other outcomes 
12 
   5.3 Analysis plan 
12 
6. Future studies 
13 
7. References 
14-15 
8. Appendix  
16- 
   8.1 Smoking in pregnancy counseling  
16-18 
   8.2 Informed consent form  
19-26 
   8.3 Study flyer  
27 
   8.4 Smokerlyzer chart interpretation 
28 
   8.5 Patient questionnaire 
29-30 
   8.6 Patient survey 
31 
 
 

 
3
1. Study Abstract 
In 2018, 12.0% of adult women in the US smoked,1 and approximately 7% of women continue 
smoking during pregnancy.2 Rates of smoking are even higher among women with substance 
use disorders. While only 16% of the US adult population reports smoking, 66% of those with a 
substance use disorder report smoking.3 
Smoking accounts for almost 3,000 stillbirths in high-income countries annually.4 Any smoking is 
associated with an 20-40% increase in the odds of stillbirth compared to not smoking, and 
heavy smoking (defined as ≥10 cigarettes/day) increases the odds of stillbirth by 50-80%.4,5 
Maternal smoking is also associated with an increase in the risk of neonatal death, preterm 
birth, and low birth weight.6 
Unfortunately, nicotine replacement therapy has not helped women quit smoking during 
pregnancy.7-10 Limited data on other smoking cessation agents such as varenicline and 
buproprion limit their widespread use in pregnancy11. 
Exhaled carbon monoxide monitors, such as the Smokerlyzer® device, can be used as a 
motivational tool to encourage women to quit smoking. Studies in non-pregnant populations 
using this device to encourage smoking cessation have been promising.12,13 The use of such 
monitors to measure smoking in pregnancy has also been validated and used in other studies of 
smoking cessation in pregnancy.14-17 Exhaled carbon monoxide can also be directly correlated 
to fetal carboxyhemoglobin levels, a direct byproduct of in utero exposure to cigarette smoke. 
Therefore, we propose a randomized controlled trial to evaluate the efficacy of monitoring 
exhaled carbon monoxide in smoking cessation during pregnancy in women with substance use 
disorders. We hypothesize that women who undergo exhaled carbon monoxide monitoring will 
have greater smoking cessation rates that those who do not undergo exhaled carbon monoxide 
monitoring.  
 
1.1. 
Primary Hypothesis 
Women who receive exhaled carbon monoxide (eCO) monitoring will be more likely to quit 
heavy smoking prior to delivery than women do not undergo eCO monitoring. 
1.2. 
Secondary Hypotheses 
 
Women who receive eCO monitoring are more likely to quit smoking prior to delivery 
than women who do not receive eCO monitoring. 
 
Women undergoing eCO monitoring will give birth to larger infants and fewer infants that 
are small for gestational age. 
 
eCO levels at delivery will correlate to infant birth weight. 
 
Women undergoing eCO monitoring will give birth to infants closer to term (37 weeks 
gestation) 
 
Women using eCO monitoring will have infants with higher APGAR scores at 5 minutes 
 
Women undergoing eCO monitoring will be more satisfied with their prenatal care and 
smoking cessation experience. 
 
 

 
4
1.3. 
Purpose of the Study Protocol 
The purpose of this study is to determine whether eCO monitoring will aid in smoking cessation 
during pregnancy. This protocol describes the rationale, design, and organization of the study. 
 
 

 
5
2. Background 
2.1. 
Smoking in Pregnancy 
Pregnancy is considered a time when women are highly motivated to commit to change.18-20 
Therefore, encouraging all pregnant women to quit smoking, even those with substance use 
disorders, can significantly improve birth outcomes. Although quitting prior to 15 weeks 
gestation is the most beneficial for the pregnancy, quitting prior to the third trimester improves 
infant birth weight.21 
2.2. 
Substance Use Disorders and Smoking 
Women with substance use disorders frequently also smoke. Smoking cessation is not a 
component of treatment for substance use disorders, and tobacco abuse is all too frequently 
forgotten in the face of encouraging abstinence from cocaine, heroin, and amphetamines. 
However, continued tobacco use is associated with relapse.22,23 Therefore, encouraging 
smoking cessation during treatment for substance use disorders is essential. 
2.3. 
Smoking Cessation in Pregnancy 
 
Smoking cessation in pregnancy is recommended not only by the U.S Preventative Service 
Task Force (USPSTF) but also by the American College of Obstetricians and Gynecologists 
(ACOG). More specifically, the USPSTF recommends that all pregnant women be asked about 
tobacco use in pregnancy as well as offer intervention to pregnant smokers at their first prenatal 
visit. Such interventions that are available are using the 5A’s (ask, advise, assess, assist, and 
arrange) as well as the 1-800-QUIT-NOW line10.   
 
The rate of reduction or cessation for smoking in pregnancy reduced from 18.4% to 13.2% in 
1990 to 2006, respectively. Overall, when pregnant, most women are motivated to stop 
smoking. Of those who desire smoking cessation, 46% of prepregnancy smokers quit 
successfully before or during pregnancy7.  
 
The benefits of smoking cessation can improve reduction in low birth weight caused by maternal 
smoking as well as decrease the risks associated with maternal smoking such as placental 
abruption, placenta previa, preterm birth, miscarriage and stillbirth11.  
 
2.4. 
Exhaled Carbon Monoxide Monitoring 
Carbon monoxide is a toxic, odorless, colorless and tasteless gas that is formed by the incomplete 
combustion of organic materials at high temperatures. This gas is created when smoking tobacco 
cigarettes and toxic as it displaces oxygen in the bloodstream to form carboxyhemoglobin (Ernst). This 
displacement restricts the body’s tissue of oxygen leading to fatigue and other health problems. Carbon 
monoxide can remain in the bloodstream for up to 24 hours, has a half-life of 5 hours, and crosses the 
placenta causing decreased oxygenation to an unborn fetus. 
 
The Smokerlyzer® device is one that has been used to aid in smoking cessation for non-pregnant and 
male patients, and now has the ability to measure not only maternal carbon monoxide levels but also 
record the fetal carboxyhemoglobin levels and correlate the percentage of vital oxygen that has been 
replaced in the bloodstream.  
 

 
6
The device works by measuring the carbon monoxide from a 15 second inhaled breath that is blow 
slowly into a mouth piece until all the air in the lungs are completely exhaled. The screen then displays 
the maternal carbon monoxide, percent carboxyhemoglobin and percent fetal carboxyhemoglobin levels 
and is recorded on to the device.  
 
2.5. 
Exhaled Carbon Monoxide Monitoring in Pregnancy 
 
Expired carbon monoxide levels to aid in smoking cessation have been used in non-pregnant patients. A 
previous study conducted using a device that measured expired carbon monoxide was completed and 
reflected accurate smoking levels in the pregnant population. However, no study has been completed 
using a carbon monoxide test to promote smoking cessation in the pregnant population.   
 
2.6. 
Rationale for a Clinical Trial 
 
Currently, the management for smoking in pregnancy is to provide patients with resources for 
cessation and inform them of the risk for the fetus. Despite counseling patients, there is no way 
to show patients how their smoking is directly affecting their baby. Historically, it has been 
known that pregnant smokers overall have smaller babies. Although eCO levels can aid non-
pregnant patients in smoking cessation, a randomized controlled trial is needed to determine 
whether measuring the maternal eCO and associated fetal carboxyhemoglobin levels in 
pregnancy will reduce adverse outcomes associated with smoking in pregnancy.  
 
2.7. 
Innovation 
This novel handheld device can be used in the clinic setting to provide immediate feedback for 
the patient and provider on smoking; this real time information can be used for biofeedback and 
counseling on smoking cessation. 
 
 

 
7
3. Study Design 
3.1. 
Primary Research Question 
Does eCO monitoring decrease the rate of smoking ≥10 cigarettes day at the time of delivery in 
women with substance use disorders? 
3.2. 
Secondary Research Questions 
 
Does eCO monitoring decrease the number of cigarettes smoked per day? 
 
Does eCO monitoring increase infant birth weight? 
 
Does maternal eCO at delivery correlate with infant birth weight? 
 
Does maternal eCO prior to 24 weeks correlate with infant birth weight? 
 
Does percent fetal carboxyhemoglobin at final measurement correlate with birth weight? 
 
Does eCO monitoring at delivery correlate with APGAR scores? 
 
Does eCO monitoring increase gestational age at delivery? 
 
Does eCO monitoring improve patient satisfaction with prenatal care and smoking 
cessation? 
 
3.3. 
Design Summary 
This is a randomized control trial.  Women with a known substance use disorder who meet 
inclusion criteria will be offered participation in the study. Both groups will undergo eCO 
monitoring at enrollment, each prenatal visit and delivery. Women in the intervention group will 
be informed of their exhaled carbon monoxide measurement at each visit as well as the 
correlation to fetal carboxyhemoglobin. At each visit, women in the intervention group will 
receive counseling on fetal impact of smoking based on fetal carboxyhemoglobin level and 
institutional and state information on smoking cessation will be provided. The control group will 
not receive any information about their exhaled carbon monoxide or fetal carboxyhemoglobin 
level. At each visit, women in the control group will be provided institutional and state 
information on smoking cessation if they report continued smoking. Additional medications to 
quit smoking (nicotine replacement or other medical therapies) will not be provided to either 
group (although patients in either group may receive NSRIs as medically indicated for 
indications other than smoking cessation). The primary outcome is the number of women each 
group smoking ≥10 cigarettes/day at their final prenatal visit, as determined by exhaled carbon 
monoxide measurements. Analysis will be on an intent to treat basis. 
3.4 Study Population and Eligibility Criteria 
The study population of women with substance use disorders was selected for several reasons. 
First, women with substance use disorders have a significantly higher rate of smoking than 
women without substance use disorders.3 Secondly, women with substance use disorders who 
continue to smoke have a higher rate of relapse than those who quit smoking, 22,23 suggesting 
that this population will uniquely benefit from smoking cessation during pregnancy. 
a. Inclusion criteria: 
i. Age 16-45 
ii. Singleton gestation 
iii. Gestational age at enrollment <24 weeks 
iv. Substance use disorder defined as modified NIDA ASSIST ≥4 

 
8
v. Cigarette smoker using ≥10 cigarettes/day interested in quitting 
 
b. Exclusion criteria: 
i. Known or suspected fetal growth restriction at enrollment 
ii. Known fetal anomaly, aneuploidy, or demise 
iii. Not interested in smoking cessation or reduction during pregnancy 
iv. E-cigarette use 
3.5 Study groups 
There will be two intervention groups: 
a. Group 1 (Standard Care treatment) 
Patient exhale into Smokerlyzer® device but are blinded to maternal carbon 
monoxide and subsequent fetal carboxyhemoglobin levels. 
 
b. Group 2 (Intervention/eCO Monitoring) 
Patients exhale into Smokerlyzer® device and are informed of the maternal carbon 
monoxide and subsequent fetal carboxyhemoglobin results. The patient will then 
view a chart with the levels and correspond them to the current smoking amount as 
well as counseled on its effects on maternal and fetal health. 
 
3.6 Informed Consent 
Institutional Review Board (IRB) approved informed consent forms will be presented to the 
patient, and informed consent must be obtained prior to enrolling the patient in this randomized 
controlled trial. The full list of potential risks to the patient and her neonate will be listed in the 
informed consent. The nature and purpose of the study will also be detailed in the informed 
consent. The patient will be provided a copy of the signed informed consent. The informed 
consent will only be in English, and thus, only English-speaking individuals may participate in 
the study. 
 
 

 
9
4. Study Procedures 
4.1 Screening for Eligibility and Consent 
All patients will be identified utilizing the IRB-approved UAB Obstetric Automated Recording 
(OBAR) system (IRB X030604010). This system will be used to identify patients entering 
prenatal care <24 weeks of pregnancy. Women will be approached at a prenatal care visit, 
where a member of the research team will confirm eligibility and present the study which will 
include the risks, benefits, procedures, and alternatives. The informed consent will be signed 
after all questions have been answered.   
4.2 Randomization 
Randomization will occur after eligibility/exclusion criteria are confirmed and informed consent is 
obtained. Randomization will occur by a predetermined computer-generated block 
randomization scheme prepared by a study statistician. A variable block design will be utilized.  
4.3 Management of patients who develop exclusion criteria (stillbirth, new fetal anomaly 
or aneuploidy diagnosis) 
Patients that develop the exclusion criteria of stillbirth, new fetal or aneuploidy diagnosis will 
continue to be followed for outcomes but will be excluded from any secondary analyses that 
include infant outcomes.  
4.4 Management of intervention group 
At each prenatal visit, in addition to receiving standard prenatal care, women randomized to the 
intervention group will: 
1) Be asked to report how many cigarettes they have smoked per day in the last week 
2) Measure eCO 
3) Be counseled on their exhaled carbon monoxide level and corresponding fetal 
carboxyhemoglobin level 
4) Receive smoking cessation materials if reports continued smoking or eCO indicates 
continued smoking 
4.5. Management of control group 
At each prenatal visit, in addition to receiving standard prenatal care, women randomized to the 
intervention group will: 
1) Be asked to report how many cigarettes they have smoked per day in the last week 
2) Measure eCO 
3) Receive smoking cessation materials if reports continued smoking 
4.6 Adherence 
Study personnel will monitor each participant at each clinic visit to conduct the exhaled carbon 
monoxide measurement. Study personnel will record any deviations from the protocol and 
adherence to the protocol will be reported in the primary manuscript. 
 

 
10 
4.7 Participant follow-up 
Participants will be followed through discharge after delivery. At hospital admission for delivery, 
a final exhaled carbon monoxide measurement will be obtained. Patients will be asked to 
complete a survey prior to hospital discharge. Maternal and infant outcomes will be ascertained 
until discharge. 
4.8 Adverse Event Reporting 
As this is a low-risk study, an independent data safety monitoring board will not be formed. 
We defined an adverse event as an undesirable experience or outcome occurring in a research 
participant, regardless of whether participation in the research study caused the event to occur.  
For example, placental abruption and/or stillbirth are known risks of pregnancy, and while not 
associated with the Smokerlyzer® device, would be considered an adverse event if it occurred 
during the study. All serious adverse events will be reported to the IRB. A serious adverse event 
will include the following events. 
a. Death 
a. Maternal  
b. Fetal (stillbirth) 
b. Life-threatening 
c. Prolonged hospitalization  
d. Disability or permanent damage 
e. Other serious or important medical events: 
a. Placental abruption 
b. Any other serious event necessitating an unanticipated higher level of care, 
such as a transfer to an intensive-care unit (not including anticipated transfers 
to neonatal ICU for prematurity, neonatal withdrawal syndrome) 
f. 
Any other event not listed that the investigators believe may have been caused by 
the intervention. 
4.9 Study Outcome Measurements and Ascertainment 
4.9.1. Primary outcome 
Prevalence of smoking ≥10 cigarettes/day in each group at final measurement (last 
prenatal visit prior to delivery or at delivery), as measured by exhaled carbon monoxide 
 
4.9.2. Secondary outcomes 
1. Average number of cigarettes smoked/day in each group, as measured by exhaled 
carbon monoxide at final measurement 
2. Prevalence of smoking ≥10 cigarettes/day in each group at delivery, per patient report 
3. Average number of cigarettes smoked/day in each group, per patient report 
4. Average exhaled carbon monoxide at final measurement 
5. Average percent fetal carboxyhemoglobin at final measurement 
6. Infant birthweight  
7. APGAR at 5 minutes  
8. Small for gestational age at birth (<10th percentile)  
9. Gestational age at delivery  

 
11 
10. Patient satisfaction at final prenatal visit, measured by PANAS scales (positive and 
negative affect scales) and select questions on Stop Smoking Service Client Satisfaction 
Survey 
 
4.9.3. Follow-up and Outcome Ascertainment Periods 
The primary outcome will be obtained by exhaled carbon monoxide level at the final prenatal 
visit, within 4 weeks of delivery. If the patient has been lost to follow up prior to delivery, every 
attempt will be made to obtain an exhaled carbon monoxide level at admission for delivery. 
Patient satisfaction will also be assessed at the final measurement. Each patient will be asked 
about number of cigarettes smoked per day for the last week at each prenatal visit. Delivery 
outcomes will be assessed prior to discharge. 
 
 

 
12 
5. Statistical Considerations 
5.1 Sample Size for Primary Outcome 
In order to calculate our sample size, we targeted an alpha of 0.05 and a power of 90%. Based 
on our clinic population, we estimated the prevalence of smoking ≥10 cigarettes/day among 
women with substance use disorders who smoke at delivery is 90%.  We target a reduction to 
50% of women smoking ≥10 cigarettes/day at delivery in the intervention group. With a 20% 
loss to follow up, the required sample size is 74 women (37 women per group). 
Baseline 
Estimate of 
Smoking ≥10 
cigarettes/day 
at delivery 
Targeted 
Prevalence of 
Smoking ≥10 
cigarettes/day 
at delivery  
Relative Risk 
Number per 
group 
Total Sample 
Size with 
20% Loss to 
Follow UP 
90% 
60% 
0.67 
49 
118 
 
50% 
0.55 
31 
74 
 
40% 
0.44 
21 
50 
80% 
60% 
0.75 
119 
286 
 
50% 
0.63 
58 
140 
 
40% 
0.5 
35 
84 
 
5.2. Power for Other Outcomes 
We will have ample power to detect differences in the secondary outcomes of number of 
cigarettes smoked at final visit, average exhaled carbon monoxide, and average percent fetal 
carboxyhemoglobin between groups. Infant outcomes are likely to be underpowered and are 
considered exploratory. Similarly, patient satisfaction with the Smokerlyzer® device is an 
exploratory analysis. 
5.3. Analysis Plan 
Standard baseline characteristics between the two groups will be collected at baseline, including 
baseline exhaled carbon monoxide. It is assumed that randomization will evenly distribute 
baseline characteristic differences between the two groups, and thus, we do not anticipate 
adjusting for these in the primary analysis. Secondary analyses will, though, be analyzed using 
regression adjustments to account for any possible confounding covariates between the two 
groups. The primary analysis will be done in an intent-to-treat basis.  
The primary analysis will compare the total admission to delivery time in minutes between the 
two groups. This will be analyzed using a two-sided student’s t-test.  
 
 

 
13 
6. Future studies 
If this small trial demonstrates efficacy in smoking reduction in women with substance use 
disorders, we will pursue two future avenues of study. 1) Use of the expired maternal carbon 
monoxide and associated fetal carboxyhemoglobin to encourage smoking cessation in the 
general pregnancy population. 2) A larger study of women with substance use disorders to 
detect smaller improvements in smoking cessation and long-lasting smoking cessation post-
partum. 
 
 

 
14 
References 
1. 
Cigarette Smoking Among Adults in the United States. (Accessed 04/05/2020, 2020, at 
https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm.) 
2. 
Drake P DA, Mathews TJ. Cigarette Smoking During Pregnancy: United States, 2016. In: Health 
and Human Services, ed.: Natinal Center for Health Statistics; 2018. 
3. 
Smith PH, Mazure CM, McKee SA. Smoking and mental illness in the US population. Tobacco 
Control 2014;23:e147-e53. 
4. 
Flenady V, Koopmans L, Middleton P, et al. Major risk factors for stillbirth in high-income 
countries: a systematic review and meta-analysis. Lancet 2011;377:1331-40. 
5. 
Marufu TC, Ahankari A, Coleman T, Lewis S. Maternal smoking and the risk of still birth: 
systematic review and meta-analysis. BMC Public Health 2015;15:239. 
6. 
Pineles BL, Hsu S, Park E, Samet JM. Systematic Review and Meta-Analyses of Perinatal Death 
and Maternal Exposure to Tobacco Smoke During Pregnancy. Am J Epidemiol 2016;184:87-97. 
7. 
Coleman T, Cooper S, Thornton JG, et al. A randomized trial of nicotine-replacement therapy 
patches in pregnancy. N Engl J Med 2012;366:808-18. 
8. 
Oncken C, Dornelas E, Greene J, et al. Nicotine gum for pregnant smokers: a randomized 
controlled trial. Obstet Gynecol 2008;112:859-67. 
9. 
Pollak KI, Oncken CA, Lipkus IM, et al. Nicotine replacement and behavioral therapy for smoking 
cessation in pregnancy. American journal of preventive medicine 2007;33:297-305. 
10. 
Siu AL. Behavioral and Pharmacotherapy Interventions for Tobacco Smoking Cessation in Adults, 
Including Pregnant Women: U.S. Preventive Services Task Force Recommendation Statement. Annals of 
internal medicine 2015;163:622-34. 
11. 
Committee on Underserved W, Committee on Obstetric P. Committee Opinion No. 721: 
Smoking Cessation During Pregnancy. Obstet Gynecol 2017;130:e200-e4. 
12. 
Beard E, West R. Pilot Study of the Use of Personal Carbon Monoxide Monitoring to Achieve 
Radical Smoking Reduction. Journal of Smoking Cessation 2012;7:12-7. 
13. 
Sejourne C, Parot-Schinckel E, Rouquette A, Pare F, Delcroix M, Fanello S. [Impact of exhaled CO 
measurement. A randomised study among 578 smoking patients in general practice]. Rev Mal Respir 
2010;27:213-8. 
14. 
Nanovskaya TN, Oncken C, Fokina VM, et al. Bupropion sustained release for pregnant smokers: 
a randomized, placebo-controlled trial. Am J Obstet Gynecol 2017;216:420 e1- e9. 
15. 
Usmani ZC, Craig P, Shipton D, Tappin D. Comparison of CO breath testing and women's self-
reporting of smoking behaviour for identifying smoking during pregnancy. Substance Abuse Treatment, 
Prevention, and Policy 2008;3:4. 
16. 
Lopez AS, Waddington A, Hopman WM, Jamieson MA. The Collection and Analysis of Carbon 
Monoxide Levels as an Indirect Measure of Smoke Exposure in Pregnant Adolescents at a 
Multidisciplinary Teen Obstetrics Clinic. J Pediatr Adolesc Gynecol 2015;28:538-42. 
17. 
Seidman DS, Paz I, Merlet-Aharoni I, Vreman H, Stevenson DK, Gale R. Noninvasive validation of 
tobacco smoke exposure in late pregnancy using end-tidal carbon monoxide measurements. J Perinatol 
1999;19:358-61. 
18. 
Edvardsson K, Ivarsson A, Eurenius E, et al. Giving offspring a healthy start: parents' experiences 
of health promotion and lifestyle change during pregnancy and early parenthood. BMC Public Health 
2011;11:936. 
19. 
Lindqvist M, Lindkvist M, Eurenius E, Persson M, Mogren I. Change of lifestyle habits – 
Motivation and ability reported by pregnant women in northern Sweden. Sexual & Reproductive 
Healthcare 2017;13:83-90. 

 
15 
20. 
Olander EK, Darwin ZJ, Atkinson L, Smith DM, Gardner B. Beyond the 'teachable moment' - A 
conceptual analysis of women's perinatal behaviour change. Women Birth 2016;29:e67-71. 
21. 
England LJ, Kendrick JS, Wilson HG, Merritt RK, Gargiullo PM, Zahniser SC. Effects of smoking 
reduction during pregnancy on the birth weight of term infants. Am J Epidemiol 2001;154:694-701. 
22. 
de Dios MA, Vaughan EL, Stanton CA, Niaura R. Adolescent tobacco use and substance abuse 
treatment outcomes. Journal of substance abuse treatment 2009;37:17-24. 
23. 
Weinberger AH, Platt J, Esan H, Galea S, Erlich D, Goodwin RD. Cigarette Smoking Is Associated 
With Increased Risk of Substance Use Disorder Relapse: A Nationally Representative, Prospective 
Longitudinal Investigation. J Clin Psychiatry 2017;78:e152-e60. 
 
 
 

 
16 
8. Appendix  
8.1 Smoking Cessation Resources 
Smoking During Pregnancy 
Smoking during pregnancy is unhealthy for you and your baby. Smoke from cigarettes, pipes, 
and cigars contains many chemicals that can cause cancer (carcinogens). Cigarettes also contain 
a stimulant drug (nicotine). When you smoke, harmful substances that you breathe in enter your 
bloodstream and can be passed on to your baby. This can affect your baby's development. 
 
If you are planning to become pregnant or have recently become pregnant, talk with your health 
care provider about quitting smoking. 
How does smoking affect me? 
Smoking increases your risk for many long-term (chronic) diseases. These diseases include 
cancer, lung diseases, and heart disease. Smoking during pregnancy increases your risk of: 
• 
Losing the pregnancy (miscarriage or stillbirth). 
• 
Giving birth too early (premature birth). 
• 
Pregnancy outside of the uterus (tubal pregnancy). 
• 
Having problems with the organ that provides the baby nourishment and oxygen 
(placenta), including: 
◦ 
Attachment of the placenta over the opening of the uterus (placenta previa). 
◦ 
Detachment of the placenta before the baby's birth (placental abruption). 
 
• 
Having your water break before labor begins (premature rupture of membranes). 
 
How does smoking affect my baby? 
Before Birth 
Smoking during pregnancy: 
• 
Decreases blood flow and oxygen to your baby. 
• 
Increases your baby’s risk of birth defects, such as heart defects. 

 
17 
• 
Increases your baby's heart rate. 
• 
Slows your baby's growth in the uterus (intrauterine growth retardation). 
 
After Birth 
Babies born to women who smoked during pregnancy may: 
• 
Have symptoms of nicotine withdrawal. 
• 
Need to stay in the hospital for special care. 
• 
May be too small at birth. 
• 
Have a high risk of: 
◦ 
Serious health problems or lifelong disabilities. 
◦ 
Sudden infant death syndrome (SIDS). 
◦ 
Becoming obese. 
◦ 
Developing behavior or learning problems. 
 
 
What can happen if changes are not made? 
When babies are born with a birth defect or illness, they often need to stay in the hospital longer 
before going home. Hospital stays may also be longer if you had any complications during labor 
or delivery. Longer hospital stays and more treatments result in higher costs for health care. 
Many health issues among babies born to mothers who smoke can have a lifelong impact. This 
may include the long-term need for certain medicines, therapies, or other treatments. 
What are the benefits of not smoking during pregnancy? 
You have a much better chance of having a healthy pregnancy and a healthy baby if you do not 
smoke while you are pregnant. Not smoking also means that you will have a better chance of 
living a long and healthy life, and your baby will have a better chance of growing into a healthy 
child and adult. 
What actions can be taken? 
Quitting smoking can be difficult. Ask your health care provider for help to stop smoking. You 
may also consider: 
• 
Counseling to help you quit smoking (smoking cessation counseling). 
• 
Psychotherapy. 
• 
Acupuncture. 
• 
Hypnosis. 
• 
Telephone QUIT hotlines. 
 

 
18 
If these methods do not help you, talk with your health care provider about other options. Do not 
take smoking cessation medicines or nicotine supplements unless your health care provider tells 
you to. 
Where to find more information: 
Learn more about smoking during pregnancy and quitting smoking from: 
• 
March of Dimes: www.marchofdimes.org/pregnancy/smoking-during-pregnancy.aspx 
• 
U.S. Department of Health and Human Services: women.smokefree.gov 
• 
American Cancer Society: www.cancer.org 
• 
American Heart Association: www.heart.org 
• 
National Cancer Institute: www.cancer.gov 
 
For help to quit smoking: 
• 
National smoking cessation telephone hotline: 1-800-QUIT NOW (784-8669) 
 
Contact a health care provider if: 
• 
You are struggling to quit smoking. 
• 
You are a smoker and you become pregnant or plan to become pregnant. 
• 
You start smoking again after giving birth. 
Summary 
• 
Tobacco smoke contains harmful substances that can affect a baby’s health and 
development. 
• 
Smoking increases the risk for serious problems, such as miscarriage, birth defects, or 
premature birth. 
• 
If you need help to quit smoking, ask your health care provider. 
This information is not intended to replace advice given to you by your health care provider. 
Make sure you discuss any questions you have with your health care provider. 
Document Released: 05/01/2006 Document Revised: 10/06/2017 Document Reviewed: 10/06/2017 
Elsevier Interactive Patient Education © 2018 Elsevier Inc. 
 
 
 
 
 
 
 

 
19 
8.2 Consent Form 
CONSENT FORM TO BE PART OF A RESEARCH STUDY 
 
Title of Research:  
Smoking Reduction In Gravid Women with Substance Use Disorders 
(SIGS): A Randomized Controlled Trial 
 
UAB IRB Protocol #: 
IRB-300004487 
 
Principal Investigator:  
Rubymel Knupp, M.D. 
 
Sponsor: 
UAB Department of OBGYN 
 
For Children (persons under 18 years of age) participating in this study, the term “You” addresses both 
the participant ("you") and the parent or legally authorized representative ("your child"). 
General Information 
You are being asked to take part in a research study. This research study is 
voluntary, meaning you do not have to take part in it. The procedures, 
risks, and benefits are fully described further in the consent form. 
Purpose 
The purpose of this study is determine whether patient knowledge of 
exhaled carbon monoxide levels and the corresponding fetal 
carboxyhemoglobin levels will decrease the number of cigarettes smoked 
by women at the end of the pregnancy.  
Duration & Visits 
You will be in this study from the time of enrollment until up to 5 days 
after you deliver your baby. Each study participation during your prenatal 
visits and/or delivery will take 5 minutes. 
Overview of Procedures This is a study that compared two groups to each other. Each group will 
have different activities and you will be randomized to one of these groups 
by chance (flip of a coin).  
This study may include: 
 
Screening interview to determine interest in smoking cessation 
 
An enrollment interview and record the carbon monoxide levels in 
your breath using the Smokerlyzer device 
 
Resources to quit smoking 
 
Counseling on carbon monoxide levels and its effects 
 
Medical record review for information regarding your pregnancy 
and your infant 
 
Patient satisfaction survey 

 
20 
This study will enroll 74 pregnant women who smoke and their infants at 
UAB. 
Risks 
There are minimal risks to participating in this study. The risks with this 
study are those associated with discomfort from using the Smokerlyzer, 
being assigned to a group that may be less effective than the other and 
loss of confidentiality. 
Benefits 
You may or may not benefit directly from taking part in this study. 
Alternatives 
An alternative to this study is to not participate. 
 
Purpose of the Research Study 
 
We are asking you to take part in a research study. The purpose of this research study is to test whether 
the knowledge of expired carbon monoxide levels and fetal carboxyhemoglobin levels help women quit 
smoking in pregnancy. Smokerlyzer® is a small, handheld device that measures the amount of carbon 
monoxide in your breath. It does not measure any other substances or require any invasive procedures. 
This device is safe to use for pregnant women. Carbon monoxide is a poisonous gas found in cigarette 
smoke. You are being invited to participate because you have been identified as being interested in 
quitting smoking or reducing your smoking. There will be 74 participants enrolled at UAB.  
 
Study Participation & Procedures 
 
If you agree to join the study, and are interested in smoking cessation, you will be randomized (like the 
flip of a coin) to one of two groups. 
 
In the intervention group, we will measure your expired carbon monoxide levels and inform you of how 
it affects the oxygen level of your baby. This procedure will be repeated at every prenatal visit. We will 
also counsel you about what these levels mean in terms of how it affects your pregnancy overall. You 
will also be asked how many cigarettes you are smoking at each visit. Resources to assist you in quitting 
smoking will be provided. 
 
In the standard care group, we will measure your expired carbon monoxide level at your first study visit 
and repeated at every prenatal visit. You will be provided the same resources that can help assist you in 
quitting smoking as the other group but will not be counselled about your levels.  You will also be asked 
about smoking at each visit. 
 

 
21 
At your final visit, we will ask you questions about how satisfied you are with the information received 
about quitting smoking, and about your experiences in trying to quit smoking. 
 
We will review and collect from your medical records information regarding your pregnancy, smoking 
habits, and we will also collect information about your baby’s birth and health. 
 
Products to help you quit smoking are not provided as part of this study (these products are also not 
typically provided during routine pregnancy care). 
 
Your de-identified private information (private information with all identifiers removed) may be used for 
future research studies or distributed to another researcher for future research studies without 
additional informed consent. This is only when there are no identifiers associated with the data. 
 
We would like to contact you in the future for research studies related to women’s health for which you 
may be eligible. 
 
Initial your choice below: 
 
___ I agree to be contacted for future research related to women’s health. 
 
___ I do not agree to be contacted for future research related to women’s health. 
Risks and Discomforts 
 
The Smokerlyzer is a non-invasive device used only to measure the level of carbon monoxide in your 
breath. There may be discomfort with using the Smokerlyzer such as feeling out of breath or having a 
dry mouth from using the mouth piece.  
  
 
You will be assigned to a group by chance, which may prove to be less effective or to have more side 
effects than the other study group or alternatives. If you are assigned to the standard care group, you 
may be at risk for pregnancy and/or neonatal complications associated with smoking. 
 
Benefits 

 
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You may or may not benefit directly from taking part in this study. However, this study may help us 
better understand how smoking affects pregnant women and their unborn babies as well as how to help 
other women quit smoking during pregnancy. You will be assigned to a group by chance, which may 
prove to have more or less benefits than the other study group. 
 
Alternatives 
 
The alternative is to not participate in this study. If you choose not to participate, you will receive 
routine prenatal care, which includes referral to resources to quit smoking. 
 
Confidentiality and Authorization to Use and Disclose Information for Research Purposes 
 
Federal regulations give you certain rights related to your health information. These include the right to 
know who will be able to get the information and why they may be able to get it. The study doctor must 
get your authorization (permission) to use or give out any health information that might identify you. 
 
What protected health information may be used and/or given to others? 
All medical information, including but not limited to information and/or records of any diagnosis or 
treatment of disease or condition, which may include sexually transmitted diseases (e.g., HIV, etc.) or 
communicable diseases, drug/alcohol dependency, etc.; all personal identifiers, including but not limited 
to your name, social security number, medical record number, date of birth, dates of service, etc.; any 
past, present, and future history, examinations, laboratory results, imaging studies and reports and 
treatments of any kind, including but not limited to drug/alcohol treatment, psychiatric/psychological 
treatment; financial/billing information, including but not limited to copies of your medical bills; any 
other information related to or collected for use in the research study, regardless of whether the 
information was collected for research or non-research (e.g., treatment) purposes; records about any 
study drug you received or about study devices used; and consent forms from past studies that might be 
in your medical record. 
 
Your consent form will be placed in your medical record at UAB Health System. This may include either a 
paper medical record or electronic medical record (EMR). An EMR is an electronic version of a paper 
medical record of your care within this health system. Your EMR may indicate that you are on a clinical 
trial and provide the name and contact information for the principal investigator. 
 

 
23 
If you are receiving care or have received care within this health system (outpatient or inpatient), results 
of research tests or procedures (i.e. laboratory tests, imaging studies and clinical procedures) may be 
placed in your existing medical record. 
 
If you have never received care within this health system (outpatient or inpatient), a medical record will 
be created for you to maintain results of research tests or procedures. 
 
Results of research tests or procedures may be placed in your medical record. All information within 
your medical record can be viewed by individuals authorized to access the record. 
 
Who may use and give out information about you? 
Information about your health may be used and given to others by the study doctor and staff. They 
might see the research information during and after the study. 
 
Who might get this information? 
All Individuals/entities listed in the informed consent document(s), including but not limited to, the 
physicians, nurses and staff and others performing services related to the research (whether at UAB or 
elsewhere). Your information may also be given to the sponsor of this research. “Sponsor” includes any 
persons or companies that are working for or with the sponsor, or are owned by the sponsor, or are 
providing support to the sponsor (e.g., contract research organization). 
 
Information about you and your health which might identify you may be given to: 
 
the Office for Human Research Protections (OHRP) 
 
the U.S. Food and Drug Administration (FDA) 
 
Department of Health and Human Services (DHHS) agencies 
 
Governmental agencies in other countries 
 
Governmental agencies to whom certain diseases (reportable diseases) must be reported 
 
the University of Alabama at Birmingham - the physicians, nurses and staff working on the research 
study (whether at UAB or elsewhere); other operating units of UAB, UAB Hospital, UAB Highlands 
Hospital, University of Alabama Health Services Foundation, Children’s of Alabama, Eye Foundation 
Hospital, and the Jefferson County Department of Health, as necessary for their operations; the UAB 
IRB and its staff 
 
the billing offices of UAB and UAB Health Systems affiliates and/or Children’s of Alabama and its billing 
agents 
 
Why will this information be used and/or given to others? 

 
24 
Information about you and your health that might identify you may be given to others to carry out the 
research study. The sponsor will analyze and evaluate the results of the study. In addition, people from 
the sponsor and its consultants will be visiting the research site. They will follow how the study is done, 
and they will be reviewing your information for this purpose. 
 
What if I decide not to give permission to use and give out my health information? 
By signing this consent form, you are giving permission to use and give out the health information listed 
above for the purposes described above. If you refuse to give permission, you will not be able to be in 
this research. 
 
May I review or copy the information obtained from me or created about me? 
You have the right to review and copy your health information. However, if you decide to be in this 
study and sign this permission form, you will not be allowed to look at or copy your information until 
after the research is completed. 
 
May I withdraw or revoke (cancel) my permission? 
Yes, but this permission will not stop automatically. The use of your personal health information will 
continue until you cancel your permission. 
 
You may withdraw or take away your permission to use and disclose your health information at any 
time. You do this by sending written notice to the study doctor. If you withdraw your permission, you 
will not be able to continue being in this study. 
 
When you withdraw your permission, no new health information which might identify you will be 
gathered after that date. Information that has already been gathered may still be used and given to 
others. This would be done if it were necessary for the research to be reliable. 
 
Is my health information protected after it has been given to others? 
If you give permission to give your identifiable health information to a person or business, the 
information may no longer be protected. There is a risk that your information will be released to others. 
Including others outside of UAB, without your permission. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This website will not include information that can identify you. At most, the website will include a 
summary of the results. You can search this website at any time. 

 
25 
 
Voluntary Participation and Withdrawal 
Whether or not you take part in this study is your choice. There will be no penalty if you decide not to be 
in the study. If you decide not to be in the study, you will not lose any benefits you are otherwise owed. 
 
You are free to withdraw from this research study at any time. Your choice to leave the study will not 
affect your relationship with this institution. Contact the study doctor if you want to withdraw from the 
study. 
 
If you are a UAB student or employee, taking part in this research is not a part of your UAB class work or 
duties. You can refuse to enroll or withdraw after enrolling at any time before the study is over, with no 
effect on your class standing, grades, or job at UAB. You will not be offered or receive any special 
consideration if you take part in this research. 
 
Cost of Participation 
 
There will be no cost to you for taking part in this study. The cost of your standard medical care will be 
billed to you and/or your insurance company in the usual manner. 
 
Payment for Participation  
 
You will receive $10 at the enrollment visit. You will also receive another $20 after your last carbon 
monoxide level is measured at greater than 36 weeks pregnant or at delivery, whichever comes first. Ask 
the study staff about the method of payment that will be used for this study (e.g., check, cash, gift card, 
direct deposit). 
 
Payment for Research-Related Injuries 
 
UAB has not provided for any payment if you are harmed as a result of taking part in this study. If such 
harm occurs, treatment will be provided. However, this treatment will not be provided free of charge. 
 
New Findings 
 
You will be told by the study doctor or the study staff if new information becomes available that might 
affect your choice to stay in the study. 

 
26 
 
Questions 
If you have any questions, concerns, or complaints about the research or a research-related injury 
including available treatments, please contact the study doctor. You may contact Dr. Rubymel Knupp at 
(205)-934-2565 or after hours by paging her at (205)-934-4966. 
 
If you have questions about your rights as a research participant, or concerns or complaints about the 
research, you may contact the UAB Office of the IRB (OIRB) at (205) 934-3789 or toll free at 1-855-860-
3789. Regular hours for the OIRB are 8:00 a.m. to 5:00 p.m. CT, Monday through Friday. 
 
Legal Rights 
 
You are not waiving any of your legal rights by signing this consent form. 
 
Signatures 
 
Your signature below indicates that you have read (or been read) the information provided above and 
that you agree to participate in this study. You will receive a copy of this signed consent form. 
 
__________________________________________________________________________ 
Signature of Participant  
 
 
 
 
 
Date  
 
__________________________________________________________________________ 
Signature of Person Obtaining Consent   
 
 
 
Date  
 
Waiver of Assent 
 
The assent of ______________________________ (name of child/minor) was waived because of age. 
 
 
 

 
27 
8.3 Study Flyer
 
 
 
 
 
 
 
 

 
28 
8.4 Smokerlyzer chart interpretation  
 

 
29 
8.5 Patient Questionnaire 
Smoking Reduction In Gravid Women with Substance Use Disorders (SIGS): A Randomized 
Controlled Trial  
 
Positive and Negative Affect Schedule (PANAS-SF) 
 
Indicate the extent 
you have felt this way 
over the past week 
 
 
 
Very 
slightly 
or not 
at all 
 
 
   
 A 
little 
 
 
Moderately 
 
 
 
 
Quite 
a bit 
 
 
 
Extremely 
 
PANAS 
1 
Interested 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
2 
Distressed 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
3 
Excited 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
4 
Upset 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
5 
Strong 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
6 
Guilty 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
7 
Scared 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
8 
Hostile 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
9 
Enthusiastic 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
10 
Proud 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
11 
Irritable 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
12 
Alert 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
13 
Ashamed 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
14 
Inspired 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
15 
Nervous 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
16 
Determined 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
17 
Attentive 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 

 
30 
PANAS 
18 
Jittery 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
19 
Active 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
PANAS 
20 
Afraid 
⃝ 1 
⃝ 2 
⃝ 3 
⃝ 4 
⃝ 5 
 
 
 
 

 
31 
8.6 Patient Survey 
Smoking Reduction In Gravid Women with Substance Use Disorders (SIGS): 
A Randomized Controlled Trial  
Patient Survey* 
Name: ____________________ 
MRN: _____________________ 
Study ID #:_________________  
The final part of your participation in the research study is to complete this short survey. This should take 
a total of 15 minutes of your time. 
Please circle the appropriate number for each question: 
1. Overall, how satisfied are you with the support you have received to stop smoking? 
 
 Very Unsatisfied 
Unsatisfied 
Unsure  
Satisfied 
Very Satisfied 
          
  1 
 
         2   
      3 
       
       4 
 
           5  
 
2. Would you recommend using the carbon monoxide reading device (Smokerlyzer) to other smokers 
who a want to stop smoking? 
No      Unsure 
 Yes 
 
1 
        2              3 
      
 
 
3. In the event that you started smoking again would you use the Smokerlyzer device to help with 
stopping smoking? 
No      Unsure 
 Yes 
 
1 
         2            3 
 
4. If you were to become pregnant again and were still smoking, would you participate in the study 
again? 
 No      Unsure  Yes 
 
 
 
 
 
 
   
 
 
 
  1             2            3 
5. Have you smoked since your last prenatal appointment? 
No      Unsure 
 Yes 
 
  
 
 
 
 1             2            3 
 
6. How satisfied are you with how the supportive staff has been? 
Very UnsatisfiedUnsatisfied 
Unsure  
Satisfied 
Very Satisfied 
     
1 
 
         2   
      3 
       
       4 
 
           5  
 
7. How helpful has the information and advice that staff have given to you during your appointment 
been? 
Very UnsatisfiedUnsatisfied 
Unsure  
Satisfied 
Very Satisfied 
               1 
 
         2   
      3 
       
       4 
 
           5  
 
8. How helpful has the written information that staff have given to you been? 
No      Unsure 
 Yes 
 
  1             2            3 
 
9. Do you find having your carbon monoxide (CO) reading helpful? 
 
No      Unsure 
 Yes 
 
  1             2            3 
If there are any changes that you would like to see to the SIGS Trial, or if there was anything they did 
particularly well, then please write them here: