Cigarette smoking in opioid-dependent pregnant women: Neonatal and maternal outcomes
Introduction
Approximately 21% of U.S. women of childbearing age are current cigarette smokers (Center for Disease Control, 2011). Approximately 20% of these smokers quit upon learning of their pregnancy, but the vast majority, especially heavier smokers, continue smoking throughout their pregnancy (Solomon and Quinn, 2004). Smoking is the leading preventable cause of poor pregnancy outcomes, increased risk for infertility, catastrophic pregnancy complications, intrauterine growth restriction, birth defects, infant death, and later-in-life metabolic diseases (Cohen et al., 2010, Dietz et al., 2010, Guerrero-Preston et al., 2010, Hackshaw et al., 2011, Rogers, 2009).
Among pregnant opioid agonist-maintained women, the rate of smoking (e.g., 88%; Jones et al., 2009, Haug et al., 2001) is four times higher than in the general population of pregnant women. Consistent with the larger literature on smoking and poor pregnancy outcomes, one study on this topic reported that heavier smoking among opioid-maintained pregnant women was associated with lower neonatal birth weight and smaller birth length (Winklbaur et al., 2009).
One factor unique to in utero opioid-exposed neonates is neonatal abstinence syndrome (NAS). NAS is characterized by hyperirritability of the central nervous system and dysfunction in the autonomic nervous system, gastrointestinal tract, and respiratory system (Kaltenbach et al., 1998). Heavier cigarette smoking has been found to be related to peak NAS score and amount of time to reach peak NAS score in neonates of 29 methadone-maintained women (Choo et al., 2004), and higher NAS severity scores in the neonates of 139 opioid-maintained (methadone, buprenorphine, or slow-release morphine) pregnant women (Winklbaur et al., 2009). Heavy cigarette smoking has also been associated with longer duration of NAS treatment in 26 neonates of methadone-maintained pregnant women. However, this association was not found in 12 neonates of buprenorphine-maintained pregnant women (Bakstad et al., 2009). Lastly, heavy cigarette smoking was associated with increased number of NAS symptoms, but not duration of hospitalization, in 64 neonates of methadone-maintained women (Jansson et al., 2010).
The purpose of the present secondary analysis study was to determine the relationship between cigarette smoking and neonatal and maternal outcomes in a sample of 131 opioid-dependent pregnant women who were participants in the MOTHER (Maternal Opioid Treatment: Human Experimental Research) study, a randomized clinical trial comparing buprenorphine and methadone (Jones et al., 2010). The MOTHER study sample is ideal for examining the relationship between maternal cigarette smoking at study entry and neonatal and maternal outcomes due to limited concomitant illicit drug use. Current alcohol and/or benzodiazepine regular use, abuse or dependence were exclusion criteria in the study. Furthermore, patients earned monetary vouchers for providing urine samples negative for opioids and other illicit drug use to minimize use of these substances. This intervention produced a low level of illicit drug use throughout the study: 73% and 81% of urine samples were opioid- and cocaine-negative, respectively, throughout the period of thrice-weekly prenatal testing, and only 13% of the samples were positive for opioids other than their respective study medication at delivery.
This study was intended to answer three specific questions: (1) is smoking measured at study entry related to neonatal and maternal outcomes in opioid-dependent pregnant women receiving opioid agonist medication? (2) is it more informative to use a multi-item measure of smoking dependence or a single-item self-report measure of recent daily smoking to determine the relationship between smoking at study entry and neonatal and maternal outcomes? and (3) does it make a difference in the relationship between smoking at study entry and neonatal and maternal outcomes if the medication is methadone or buprenorphine?
Section snippets
The MOTHER study
The MOTHER (Maternal Opioid Treatment: Human Experimental Research) study (Jones et al., 2010, Jones et al., 2012) was a double-blind, double-dummy, flexible-dosing, two-group randomized clinical trial comparing methadone and buprenorphine pharmacotherapy for opioid-dependent women within the context of comprehensive care. Findings supported the comparative efficacy of buprenorphine, revealing that, on average, neonates exposed to buprenorphine in utero needed 89% less morphine to treat NAS,
Participant characteristics
The 131 MOTHER participants were, on average, in their mid-20s, white, had less than a high school education, unmarried, and unemployed. Table 1 in Jones et al. (2010) contains more complete details regarding this sample.
In terms of cigarette smoking, 127/131 (97%) of the sample smoked cigarettes at study entry, the average age at first cigarette use was 14.4 years old (SD = 2.8), and lifetime months of regular cigarette use was 128.2 (SD = 76.5). Mean TDS scores were 7.2 (SD = 3.7) and 7.3 (SD = 3.7)
Discussion
Findings from the present study clearly support three conclusions. First, the failure to find an interaction between medication condition and past 30-day daily average number of cigarettes smoked indicates that the choice of agonist medication for treating opioid dependence in pregnant women does not need to take into consideration information regarding level of cigarette smoking at treatment entry.
Second, there is little support for the utility of a tobacco dependence measure in predicting
Role of funding source
The MOTHER clinical trial was registered with ClinicalTrials.gov (Identifier: NCT00271219; Title: RCT Comparing Methadone and Buprenorphine in Pregnant Women).
All MOTHER grants are from the National Institute on Drug Abuse (NIDA) unless noted otherwise: Brown University, R01 DA015778; Johns Hopkins University, R01 DA015764; Medical University of Vienna, R01 DA018417; Thomas Jefferson University, R01 DA015738; University of Toronto, R01 DA015741; University of Vermont, R01 DA018410 and M01
Contributors
HEJ planned this secondary analysis study, and wrote the initial draft of the manuscript. SHH, MT, MSC, and KK provided substantive revisions to the initial draft. JMM conducted the literature searches. KEO’G conducted the statistical analyses. All authors discussed the results and implications and commented on the final versions of the manuscript.
All authors have approved the final manuscript.
The authors alone are responsible for the content and writing of this article.
No honorarium, grant, or
Conflict of interest
H.E.J. discloses that she has received reimbursement for time and travel from Reckitt Benckiser. K.E.O’G. discloses that he has received reimbursement for time from Reckitt Benckiser. The remaining authors report no conflicts of interest.
Acknowledgements
We thank Brown University (R01 DA 015778) and Drs Barry Lester, Amy Salisbury, Suzanne Caron, Jeff Michaud, and Lawrence Novo, Kathleen Hawes, Danielle Finch, Marissa Cerrone, and the staff of the Level II Nursery at St. Luke's Hospital; Wayne State University (R01 DA 15832) and co-Investigators Drs Carl Christenson, Virginia Delaney-Black, Robert Sokol, Charles Schuster, Eugene Cepeda, and the assistance of Darlene Tansil and Mea Ebenbichler; Johns Hopkins University (R01 DA 015764) and the
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