Psychosocial interventions for pregnant women in outpatient illicit drug treatment programs compared to other interventions (Review)

Transcription

1 Psychosocial interventions for pregnant women in outpatient illicit drug treatment programs compared to other interventions (Review) Terplan M, Lui S This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2008, Issue 3

2 T A B L E O F C O N T E N T S HEADER ABSTRACT PLAIN LANGUAGE SUMMARY BACKGROUND OBJECTIVES METHODS RESULTS DISCUSSION AUTHORS CONCLUSIONS REFERENCES CHARACTERISTICS OF STUDIES DATA AND ANALYSES Analysis 1.1. Comparison 1 Any Psychosocial Interventions versus Control, Outcome 1 Retention in treatment Analysis 1.2. Comparison 1 Any Psychosocial Interventions versus Control, Outcome 2 Retention at 1 month or more. 25 Analysis 2.1. Comparison 2 Contingency Management vesrus Control, Outcome 1 Retention in treatment Analysis 3.1. Comparison 3 Manual Based Interventions versus Control, Outcome 1 Retention in treatment APPENDICES WHAT S NEW HISTORY CONTRIBUTIONS OF AUTHORS DECLARATIONS OF INTEREST INDEX TERMS i

3 [Intervention Review] Psychosocial interventions for pregnant women in outpatient illicit drug treatment programs compared to other interventions Mishka Terplan 1, Steve Lui 2 1 Department of Obstetrics and Gynecology, The University of Chicago, Chicago, ILLINOIS, USA. 2 Leeds Addiction Unit, University of Leeds, Leeds, UK Contact address: Mishka Terplan, Department of Obstetrics and Gynecology, The University of Chicago, 5841 Maryland Avenue, Chicago, ILLINOIS, IL 60637, USA. meterplan@babies.bsd.uchicago.edu. Editorial group: Cochrane Drugs and Alcohol Group. Publication status and date: Edited (no change to conclusions), published in Issue 3, Review content assessed as up-to-date: 2 August Citation: Terplan M, Lui S. Psychosocial interventions for pregnant women in outpatient illicit drug treatment programs compared to other interventions. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD DOI: / CD pub2. Background A B S T R A C T Illicit drug use in pregnancy is a complex social and public health problem. It is important to develop and evaluate effective treatments. There is evidence for the effectiveness of psychosocial in this population; however, to our knowledge, no systematic review on the subject has been undertaken. Objectives To evaluate the effectiveness of psychosocial interventions in pregnant women enrolled in illicit drug treatment programs on birth and neonatal outcomes, on attendance and retention in treatment, as well as on maternal and neonatal drug abstinence. In short, do psychosocial interventions translate into less illicit drug use, greater abstinence, better birth outcomes, or greater clinic attendance.? Search methods We searched the Cochrane Drugs and Alcohol Group s trial register (May 2006), the Cochrane Central Register of Trials (Central- The Cochrane Library, Issue 3, 2005); MEDLINE ( ); EMBASE ( ); CINAHL ( ), and reference lists of articles. Selection criteria Randomised studies comparing any psychosocial intervention versus pharmacological interventions or placebo or non-intervention or another psychosocial intervention for treating illicit drug use in pregnancy. Data collection and analysis Two reviewers independently assessed trial quality and extracted data. 1

4 Main results Nine trials involving 546 pregnant women were included. Five studies considered contingency management (CM), and four studies considered manual based interventions such as motivational interviewing (MI). The main finding was that contingency management led to better study retention. There was only minimal effect of CM on illicit drug abstinence. In contrast, motivational interviewing led towards poorer study retention, although this did not approach statistical significance. For both, no difference in birth or neonatal outcomes was found, but this was an outcome rarely captured in the studies. Authors conclusions The present evidence suggests that CM strategies are effective in improving retention of pregnant women in illicit drug treatment programs as well as in transiently reducing illicit drug use. There is insufficient evidence to support the use of MI. Overall the available evidence has low numbers and, therefore, it is impossible to accurately assess the effect of psychosocial interventions on obstetrical and neonatal outcomes. It is important to develop a better evidence base to evaluate psychosocial modalities of treatment in this important population. P L A I N L A N G U A G E S U M M A R Y Psychosocial interventions for pregnant women in outpatient illicit drug treatment programs compared to other interventions The effectiveness of psychosocial interventions in pregnant women enrolled in illicit drug treatment programs.women who use illicit drugs while pregnant are more likely to give birth early and have low weight infants that are at risk of neonatal abstinence syndrome and requiring intensive care. A pregnant woman reduces the risk of these complications by undergoing prenatal drug treatment. Maternal concern for the infant can also motivate her. The length of time on treatment is important. Psychosocial interventions may help to overcome the many barriers to staying in a treatment program and reduce the use of illicit drugs.contingency management uses positive, supportive reinforcement with, for example, monetary vouchers or giving work and a salary only when abstaining from drug use or attending treatment to change behaviour. Manual based interventions include motivational interviewing with a directive, counselling style. This systematic review found that contingency management is effective in improving retention of pregnant women in illicit drug treatment programs but with minimal effects on their abstaining from illicit drugs. Motivational interviewing over three to six sessions may, if anything, lead to poorer retention in treatment. These findings are based on nine controlled trials over 14 days to 24 weeks, five studies used contingency management (346 women) and four studies (266 women) that considered motivational interviewing.all but one took place in the United States. Many of the young women were African American, single, never married or divorced, and unemployed. They were receiving methadone maintenance, using cocaine, or opiate dependent and marijuana and alcohol use was also involved in six studies. In two trials, almost all women were nicotine dependent. No difference in birth outcomes or length of hospital detoxification for the newborns was found, from two studies.none of the included studies stated how the women were referred to treatment. Manual based interventions are less likely to be effective among coerced individuals. it is also unlikely to be used on their own in clinical practice. B A C K G R O U N D Illicit drug use among pregnant women is an important and complex public health concern. Since the early 1990s, there has been a gradual increase in the incidence of illicit drug use in the United States, especially among reproductive aged women (http: //oas.samhsa.gov/women.htm). The most current data on illicit drug use in the U.S. is from the 2003 National Survey on Drug Use and Health ( in which 4.3% pregnant women aged reported using illicit drugs. However, the prevalence of illicit drug use in pregnancy varies widely in the literature depending on the populations studied from 1.6% among 2

5 U.S. military recruits and their spouses (Brunader 1991) to 13% in Alabama public clinics (George 1991). Women who use illicit drugs are more likely to experience adverse obstetrical and perinatal outcomes than women in the general population (Ludlow 2004). Illicit drug use in pregnancy has been associated with preterm deliver, low birth weight infants, placental abruption, neonatal abstinence syndrome (NAS), and Neonatal Intensive Care Unit (NICU) admission. There is conflicting evidence for long term outcomes especially among cocaine exposed infants. Although some studies have shown cognitive deficits at two years of life (Singer 2004), the bulk of the research points to minimal or absent effects in early childhood as summarized well in a systematic review (Frank 2001). Drug treatment in pregnancy has been shown to reduce the maternal and fetal complications associated with illicit drug use (Armstrong 2003; Kukko 1999). Since length of time in treatment is related to positive outcomes (Howell 2000; Grella 2000), it is important to identify modalities of treatment retention that are successful in this specific population. Pregnancy has been considered a window of opportunity for drug treatment intervention (Daley 1998). Maternal concern for the infant has been thought of as a motivator to seek treatment. Although qualitative studies have documented maternal motivation (Murphy 1999; Dakof 2003), they have also described the many structural and social barriers to both receiving and remaining in treatment (Boyd 1999; Murphy 1999) Empiric research to date has failed to demonstrate better adherence rates to treatment among pregnant women compared with other individuals in drug treatment (Hser 1998). In fact, pregnant women may have higher drop out rates (Howell 2000). The purpose of this review is to examine all psychosocial interventions aimed at pregnant women enrolled in outpatient illicit drug treatment programs to assess whether they improve birth outcomes or result in less illicit drug use, increase the likelihood of maternal and neonatal abstinence and/or improve attendance and retention. Given the relatively short time frame of pregnancy, the short term efficacy of such interventions may be particularly beneficial in reducing the known complications of illicit drug use in pregnancy. O B J E C T I V E S This review examined all known randomised controlled trials (RCTs) comparing psychosocial interventions versus pharmacological interventions or placebo or non-intervention or a RCTs comparing two different psychosocial interventions to assess the effectiveness of such interventions in improving birth outcomes and in reducing illicit drug use in pregnant women enrolled in outpatient illicit drug treatment, as well as in improving treatment attendance and increasing retention. M E T H O D S Criteria for considering studies for this review Types of studies Randomised controlled trials Types of participants Pregnant women enrolled in illicit drug treatment programs. Illicit drugs include illegal substances such as cannabis, heroin, cocaine, amphetamines etc. Women on methadone are also included. Types of interventions Experimental Interventions Psychosocial interventions of any kind Control Intervention - Pharmacological intervention or placebo or no intervention or a different psychosocial intervention. Types of outcome measures Primary outcomes: (1) Obstetrical outcomes: -birth weight -gestational age at birth -placental abruption (2) Neonatal outcomes: -neonatal abstinence syndrome (NAS) -admission to and length of time spent in neonatal intensive care unit (NICU) (3) Use of primary substance abuse measured by: -maternal toxicology -maternal self-report -newborn toxicology -any biological marker eventually provided in original studies Secondary outcomes: (4) Retention in treatment measured as number of subjects retained at the end of the study, or (5) Retention in treatment measured as number of subjects retained at the end of one month or greater (6) Treatment attendance (7) Prenatal care attendance 3

6 Search methods for identification of studies (1) Electronic searches We searched the Cochrane Drugs and Alcohol Group Register (May 2006); Cochrane Central Register of Trials (Central- The Cochrane Library, Issue 3, 2005), MEDLINE (1996 to August 2006), EMBASE ( ) and CINAHL ( ).We followed the optimal MEDLINE and EMBASE sensitive search strategies devised by the Cochrane Collaboration Review Group for randomised controlled trials (RCTs) as published in Appendix 5b2 of the Cochrane Reviewers Handbook (Higgins 2007) in order to identify studies relevant to this review, for details see Appendix 1. (2) Additional searches The reference lists of all articles obtained as full reports were reviewed to identify any further studies not retrieved by the electronic search. Personal communication, conference abstracts and unpublished trials from books chapters on treatment of opioid dependence were sought. In addition, we checked the database of Selective Dissemination (SDI) and the National Institute on Health, Bethesda, USA to identify additional studies. We scanned Internet web sites including the National Institute on Drug Abuse (USA), National Institute on Alcohol Abuse and Alcoholism (USA) and National Treatment Agency for Substance Misuse (UK). We identified trials by hand searching a wide range of health care /addiction journals, including those not indexed in the main electronic databases and those published in non-english languages. We did not apply any language restriction to this review. Data collection and analysis (1) Study Selection: Both reviewers screened the abstracts of all identified articles. All relevant studies were assessed for inclusion by both reviewers independently based upon the criteria for inclusion. Conflicts were resolved by consensus. (2) Assessment of the methodological quality: In order to systematically evaluate differences between study designs and limit bias of interpretation, study quality was assessed according to the criteria in the Cochrane Handbook for Systematic Reviews of Interventions (version 4.2.6) (Higgins 2007): Selection bias: Empirical research has shown that lack of adequate allocation concealment is associated with bias. Iindeed, concealment has been found to be most important in preventing bias than other components of allocation, such as the generation of the allocation sequence. Performance bias: Systematic differences in the care provided to the participants in the comparison groups and the placebo effect could take place in the addiction field. Blinding of providers avoids co intervention and ascertainment bias whereas blinding of participants avoids contamination, systematic differences in compliance, systematic differences in the placebo effect and detection bias. Attrition bias: Loss to follow up and drop out from the study is one of the major problem in the field of addiction. Retention in treatment is very often the primary outcome measure in these trials; for this reason the information on people who left the study will not be used as a validity criterion. Detection bias: To keep blind the people who will assess outcomes is particularly important when subjective outcome measures are used. Selection bias, performance bias and detection bias have been assessed and rated as follow: (1) Selection bias: allocation concealment A: adequate allocation concealment, central randomizations (e.g. allocation by a central office unaware of subject characteristics), pre-numbered or coded identical bottles or containers which are administered serially to participants, drug prepared by the pharmacy, serially numbered, opaque, sealed envelopes, on-site computer system combined with allocations kept in a locked unreadable; computer file that can be accessed only after the characteristics of an enrolled participant have been entered or other description that contained elements convincing of concealment.; B: unclear allocation concealment: when the authors either did not report an allocation concealment approach at all or report an approach that did not fall in the category A or C. C: inadequate allocation concealment: alternation or reference to case numbers, dates of birth, day of the week. Any procedure that is entirely transparent before allocation, such as an open list of random numbers or other description that contained elements convincing of not concealment (2) Performance bias: blinding of those providing and receiving the intervention A: double blind B: single blind (blinding of participants) C: unclear D: no blinding (3) Detection bias: blinding of the outcome assessor A) Blind to treatment allocation at outcome assessment B) Unclear C) Not blind to treatment allocation at outcome assessment The methodological quality has not been used as a criterion for inclusion; in order to assess the effect of the low quality studies a sensitivity analysis, either including or excluding the classes C studies from meta-analysis was performed. (3) Data extraction: Both reviewers independently extracted data. All disagreements were discussed and resolved by consensus. 4

7 (4) Data synthesis: Data from the trials were tabulated and entered into the Characteristics of included trials and Characteristics of excluded trials. When possible, we analysed the results as dichotomous outcomes (retention in treatment) and reported them as an Odds Ratio (OR) with a 95%confidence interval (CI). The OO from each trial was combined through meta-analysis using a fixed effects model, unless there was significant heterogeneity, in which case a random effects model was used. Heterogeneity of the results was assessed by calculating a statistical test of heterogeneity. A P-value of the chi square test less than 0.05 indicated significant heterogeneity. R E S U L T S Description of studies See: Characteristics of included studies; Characteristics of excluded studies. The search strategies yielded 263 records which were screened by reading both the title and abstract. Forty-four studies were considered eligible and were reviewed as full texts. Nine of these met the inclusion criteria and were included in the review. We didn t retrieve any unpublished study. Thirthy -five studies were excluded from the review.the reasons for exclusion were: study design not in the inclusion criteria of this review (Amato 2006; Ashley 2003; Bolnick 2003; Brady 1993; Chang 1992; Chazotte 1995; Clark 2001; Daley 2005; Day 2003; Egelko 1998; Elk 1997; Elk 1995; Finnegan 2005; Funai 2003; Fundaro 2004; Hulse 2002; Jansson 2003; Jones 2002; Jones 2004; Kastner 2002; Kukko 1999; Rayburn 2004; Seracini 1997; Shieh 2002; Svikis 1998; Sweeney 2000; Weisdorf 1999; Wexler 1998; Winhusen 2003; Zlotnick 1996), study participants were not in the inclusion criteria (Chang 2005; Fundaro 2004; Nishimoto 2001; Ondersman 2005), or intervention was not in the scope of the review (Daley 2005; Fischer 1999; Nishimoto 2001). For substantive descriptions of studies see Characteristics of excluded studies Included studies Nine randomised-controlled trials fulfilled the study inclusion criteria. There was agreement on the inclusion of all of the studies by the two reviewers. Although the search was not restricted to the English language, all of the included studies were in English. For substantive descriptions of studies see Characteristics of included studies. Duration of trials Duration of included trials ranged from 14 days to 24 weeks. Design All the trials were randomised controlled trials. Participants There were a total of 546 participants enrolled in the nine included studies. Age was reported in eight of the studies (Carroll 1995, Haug 2004; Jones 2000; Jones 2001; Mullins 2004; O Neill 1996; Silverman 2001; Svikis 1997) and the mean age for those was 28.3 years. Ethnicity was not reported in two studies (O Neill 1996; Svikis 1997). All but two studies had a majority of African American participants. Carroll 1995 did not report specifics of ethnicity, but a majority of the participants were non-minority (11/ %). Mullins 2004 reported 50% Caucasian and only 33% African American. Averaging the trials that reported ethnicity (Elk 1998; Haug 2004; Jones 2000; Jones 2001 all but O Neill 1996; Carroll 1995 and Svikis 1997), 72% of the participants were African American. All the studies but O Neill 1996 reported marital status. Overall 80% of the participants were single, never married or divorced. Employment status was mentioned for all participants but in O Neill Overall 91% of the study participants were unemployed. Three studies did not report the educational level of participants (Carroll 1995;Jones 2001; Mullins 2004). Of the remaining studies, most of the participants had at least some high school education either measured as a proportion (>50%) (Elk 1998; Jones 2000; Silverman 2001) or greater than 10 mean years of education (O Neill 1996; Svikis 1997). Only Haug 2004 had a majority of participants with a less than high school education (94%). Gestational age was not mentioned in the majority of the studies (Haug 2004; Jones 2000; Mullins 2004; O Neill 1996; Silverman 2001). Of the remaining articles, participants were enrolled, on average, during the second trimester (Elk 1998; Jones 2001; Svikis 1997) with the exception of Carroll 1995 in which the average gestational age was 8 (+/-6) weeks. All but one study (Carroll 1995) used the DSM-III-R criteria for diagnosing substance dependence among the participants. In this article, all participants can be assumed to have had opiate dependence as they were receiving methadone maintenance. Many were also using cocaine (mean days of cocaine = 2.7 in 30 days prior to enrolment). 61% of the participants in the remaining eight studies were cocaine dependent, and 72% were opiate dependent. Only one study had no heroin-using participants (Mullins 2004). Six studies recorded both marijuana and alcohol use (Haug 2004; Jones 2001; Mullins 2004; O Neill 1996; Silverman 2001; Svikis 1997). Within these studies, 25% of the participants were marijuana dependent, and 18% were dependent on alcohol. Only two studies recorded nicotine dependence (Haug 2004; O Neill 1996). In those two trials, 99% were nicotine dependent. Compliance with reporting was high in all studies. Setting and Country of origin All of the included studies took place in the United States except for one (O Neill 1996) which took place in Australia. All of the studies took place in drug treatment facilities that were either academic-based, or hospital-based, or both. All of the studies were predominately outpatient. Two of the studies began in an inpatient setting (Jones 2000; Jones 2001) during which randomisation took place but all of the participants transitioned to outpa- 5

8 tient management after 7 days. The remainder were entirely outpatient. Several study sites provided free transportation and child care to their participants (Elk 1998,; Jones 2000; Jones 2001; Mullins 2004; Silverman 2001). Jones 2000 also included on-site prenatal care as well as psychiatric consultation. Mullins 2004 described their centre as providing gender-specific treatment. Study Size Study sizes ranged between 12 and 142 participants. Types of Interventions Trials fell into two types of interventions: six used contingency management (Carroll 1995; Elk 1998; Jones 2000; Jones 2001; Svikis 1997), and three used manual based interventions that involved motivational approaches (Haug 2004; Mullins 2004; O Neill 1996). Contingency management (CM) treatments are based on the principle of positive reinforcement as a means of operant conditioning that influences behaviour change. It is grounded in the work of Thorndike, especially in his Law of Effect, which states that behavioural responses which produce a satisfying effect are stamped in by the experience and likely to occur more frequently than responses which produce an annoying effect (Thorndike 1898). This theory was elaborated by B.F. Skinner who examined the relationship between positive versus negative reinforcement and positive versus negative punishment in terms of behavioural outcome. Like Thorndike, his research (initially) involved the use of animals (a pigeon in a box rather than a cat in a maze). He demonstrated that punishment, regardless of being positive or negative, decreases behaviour, whereas reinforcement, increases behaviour, and he attempted to describe the psycho-dynamic mechanism by which this behaviour change was affected (Skinner 1947). The premise behind CM is to systematically use reinforcement techniques to modify behaviour in a positive and supportive manner. It has been used in the treatment of substance abuse since the 1970 s (for a good review see Sitzer 2006). The most common form of CM has been the use of monetary vouchers, although prize reinforcers have been used as well. CM was first demonstrated to be efficacious in both treatment retention and substance abstinence in cocaine-dependent individuals (Higgins 1991), but has subsequently been studied in opioids, marijuana, cigarettes, alcohol, benzodiazepines, and multiple drugs. Only recently has it been used in populations of pregnant illicit drugdependent women. With the exception of Silverman 2001, all of the studies applied CM in the form of monetary vouchers. In Silverman 2001, the concept of abstinent reinforcement contingencies were integrated into an employment setting referred to as the Therapeutic Workplace. The participants received work and salary only when they remained abstinent. Overall, the vouchers were tied to negative urine toxicology (Carroll 1995; Silverman 2001), treatment attendance (Svikis 1997), or both (Elk 1998; Jones 2000; Jones 2001). Although the original applications of CM to substance treatment involved a schedule of escalating reinforcement for sustained behaviours (for example Higgins 1991), only Jones 2000 and Jones 2001 used an escalating schedule. Manual based interventions are cognitive-behavioural interventions that are standardized and reproducible. Perhaps the most common is motivational interviewing (MI). MI is a concept that arises from within the field of substance treatment as it developed from the treatment of problem drinkers. Motivational interviewing is a directive, client-centred counselling style for eliciting behaviour change by helping clients to explore and resolve ambivalence (Rollnick 1995). It draws from the trans theoretical model of change (DiClemente 1998) in order to improve treatment readiness and retention. The three included studies each employed a relatively brief MI intervention. In Mullins 2004, participants in the intervention group received three one hour MI sessions. In O Neill 1996, the participants received a total of six session lasting minutes each. The first session was MI, whereas the subsequent sessions addressed strategies for avoiding high risk behaviours including relaxation techniques and problem-solving techniques. In Haug 2004, the most standardized form of MI was employed, motivational enhancement therapy (MET). This involved four sessions each tailored to the individual s stage of change. Types of comparisons considered Any Psychosocial versus Control, nine studies, 546 participants (Carroll 1995; Elk 1998; Haug 2004; Jones 2000; Jones 2001; Mullins 2004; O Neill 1996; Silverman 2001; Svikis 1997) Contingency Management versus Control, five studies, 346 participants (Carroll 1995; Elk 1998; Jones 2000; Jones 2001; Svikis 1997) Manual Based Interventions versus Control, four studies, 266 participants (Haug 2004; Mullins 2004; O Neill 1996; Silverman 2001) Outcomes The outcomes reported in the studies included in the review were the following: Primary outcomes: (1) Obstetrical outcomes such as: (a) Proportion of individuals with preterm labor (b) Proportion of individuals with preterm birth (c) Gestational age at delivery (weeks) (d) Birth Weight (grams) (2) Neonatal outcomes such as: (a) Mean length of hospitalisation (days) (3) Use of illicit drugs measured as: (a) Proportion of positive urine toxicology samples for the following substances (i) cocaine (ii) opiates (iii) both cocaine and opiates (iv) marijuana 6

9 Secondary outcomes: (4) Retention in treatment measured as number of subjects retained at the end of the study, or (5) Retention in treatment measured as number of subjects retained at the end of one month or greater (6) Compliance with prenatal care measured as: (a) Number of prenatal care visits attended Risk of bias in included studies All of the included studies were randomised controlled trials, however, only two (Jones 2001, Silverman 2001) reported the method of randomisation. In Jones 2001, randomisation was performed via coloured chip selection from a hat (with replacement of the chip following each selection). In Silverman 2001 a modified dynamic balanced randomisation (Signorini 1993) was used to randomise patients sequentially to the treatment conditions. All the other studies simply report that the groups were randomised. None of the trials adequately described any methods of allocation concealment. All were therefore evaluated with a Cochrane quality criteria (Schulz 1995) rating of a B. Given the type of interventions reviewed here, it was impossible for there to have been blinding for the study participants. There was, however, no mention in any of the studies as to whether the outcomes were assessed in a blinded fashion. Baseline characteristics such as demographic data were collected and reported in all the trials. This allowed for the comparison of the study sample between intervention and control groups in all but one trial. In Svikis 1997 the information was stratified by methadone maintenance groups, and it was therefore impossible to evaluate differences between intervention and control groups. In the remaining studies, the groups were judged to be similar in terms of baseline drug use. With the exception of Haug 2004 demographic data between the groups was similar. In Haug 2004 the groups differed with respect to race; there was a higher proportion of Caucasians in the intervention group (23% versus 6%). In terms of statistical analyses, only one study (Haug 2004) reported a power calculation in the assessment of sample size. Although most of the studies reported the results of significance testing, only one (Elk 1998) made appropriate adjustment for multiple testing. Few studies reported on missing data and only one (Jones 2001) explicitly included an analysis of the missing data in its summary calculations. Effects of interventions The results were summarized and compared quantitatively when possible. Overall, it was only for the outcome of treatment retention that it was possible to provide meta-analytic synthesis. For the other outcomes, the data was either not reported or not reported in a manner that allowed for extraction. All of the authors were contacted. Two responded. H. E. Jones is no longer at the institution where the studies she authored were done and attempts to contact individuals at the original institution were without success. N. A. Huag responded as well, and she did send the original data on urine toxicology. However, since hers was the only data we received, meta-analysis of abstinence was not possible. Conparison 01: Any psychosocial intervention versus Control (1) Obstetrical outcomes Only two studies reported obstetrical outcomes (Carroll 1995, Elk 1998). Given the difference in both the outcome reported as well as method of reporting, statistical comparison of the results between the two studies was impossible. Carroll 1995 compared median gestational age at delivery as well as median birth weight between the control and intervention groups. Women in the intervention group had slightly longer gestations (40 versus 38 weeks) as well as heavier infants (3,348 gm versus 2,951 gm). Null hypothesis testing was not provided. Elk 1998 described adverse events between the intervention and the control group (although exactly what constituted an adverse perinatal event was not defined). None of the individuals in the intervention group had an adverse event, whereas 80% of the control group did: two had preterm labor and two delivered pre-term (prior to 37 weeks). This difference, however, was not statistically significant (p=0.22). Neither study had performed an a priori power calculation and, given the small sample sizes, it is unlikely that either were powered to detect differences in obstetrical or neonatal outcomes between the groups. (2) Neonatal outcomes Only one study reported neonatal outcomes. Elk 1998 stated that there was no difference in length of hospital detoxification for the newborns between the intervention and control groups, although mean days or any other summary statistic were not reported. (3) Substance use All but one article (Svikis 1997) analysed urine toxicology as an outcome. Given the heterogeneity of both the definitions of abstinence as well as the methods of reporting study results, a summary meta-analysis was not possible. All of the study authors were contacted, but only one, Huag, responded with the raw data. Unfortunately, it was not possible to construct a meta-analysis from the data. All but two studies reported no difference in illicit drug use between groups. Both of these studies employed forms of CM. In Silverman 2001, the overall correlation between therapeutic workplace attendance and drug abstinence for Therapeutic Workplace participants was statistically significant (R(18) = 0.99, p < 0.01), however individual calculations of difference between control and Workplace participants in terms of cocaine, opiates, and cocaine and opiates revealed no statistically significant difference. In Jones 2001 individuals randomised to the intervention group had fewer cocaine and opiate positive urine samples, although the number of consecutive negative samples did not differ between the groups. Interestingly, when the vouchers were no longer available, rates of positive urine samples became identical between the groups. Al- 7

10 though both articles employed significance testing, neither mentioned adjusting the results due to repeated measures. This may have led to a spurious generation of statistically significant p-values. In Carroll 1995, both control and intervention groups had similar number of urine collected (42.7 versus 46.2) with a similar proportion of positive tests (for cocaine 39.8% versus 39.4%; for opiates 25.3% versus 30.9%; for both cocaine and opiates 12.9% versus 16.9%). In Elk 1998, individuals provided three urine samples per week. Compliance with sampling, however, was not reported. The rate of cocaine-free urine samples was very high (100% in the intervention group versus 98% in the control group, p=0.34), most likely reflecting the fact that study participants had to be at least 30 days abstinent from cocaine prior to enrolment. The only other illicit drug mentioned was marijuana. More individuals used marijuana in the intervention group compared with the control (3 versus 1), although this was not statistically significant (p=0.11). The statistical methods of this study were unique in that they adjusted for multiple measures by use of the Bonferoni adjustment in the generation of the chi-squared p-values. In Haug 2004, there was no difference between groups. At 10 weeks 45% of total participants tested positive for either cocaine or opiates (28% for opiates, 26% for cocaine, and 6% for marijuana). Jones 2000 had a similar study design to Jones In both, the attainment of cash incentives was tied to negative urine samples. However, unlike Jones 2001, there was no significant difference between weekly urinalysis results and control versus intervention group affiliation. Mullins 2004 also concluded that there was no large association between urine toxicology and treatment intervention. The mean proportion of negative urine screens was 0.51 for the intervention group compared with 0.45 for the control group. Yet, both had large standard deviations (0.40 versus 0.36). In O Neill 1996 there was no change in self-report of drug use or in reported frequency of drug injection. There was, however, a decrease in self-report of sharing injection equipment in the intervention group. (4) Retention in treatment Seven studies (Elk 1998; Elk 1998; Jones 2000; Jones 2001; Mullins 2004; O Neill 1996; Svikis 1997) with a total of 439 participants, RR 1.02 (95% CI 0.92 to 1.13), the difference is not statistically significant. See Analysis 1.1. (5) retention in treatment at 1 month or greater Three studies (Mullins 2004; O Neill 1996; Svikis 1997), including 239 participants; RR 1.07 (95% CI 0.87 to 1.33, the difference is not statistically significant. See Analysis 1.2. Comparison 02: Contingency Management interventions versus Control (4) Retention in treatment Four studies (Elk 1998; Jones 2001; Silverman 2001; Svikis 1997) with 213 participants; none of the four single studies showed significant differences, results were not pooled because the high heterogeneity. See Analysis 2.1. (6) Compliance with prenatal care Only two studies reported attendance in prenatal care as an outcome (Carroll 1995; Elk 1998). Both of these used CM as an intervention. Carroll 1995 reported that individuals in the intervention group attended more prenatal care visits (14.7 +/-3.6 versus 5.1 +/-5.9). Elk 1998 reported that individuals in the intervention group had a higher rate of attendance at prenatal visits although they do not report the number of visits. Instead they reported a p- value of for this comparison. Comparison 03: Manual Based Interventions versus Control (4) Retention in treatment Three studies (Haug 2004, Mullins 2004, O Neill 1996) with a total of 226 participants; RR 0.93 (95% CI 0.81 to 1.06), the difference is not statistically significant. See Analysis 3.1. D I S C U S S I O N The purpose of this systematic review was to assess the effectiveness of psychosocial interventions in the outpatient treatment of illicit drug use for pregnant women. A total of nine trials were identified, six which employed a form of CM and three which used a manual based intervention namely MI. All of the interventions were compared with a control; therefore it was not possible to compare the modalities with each other. Our main interest was in both obstetrical and neonatal outcomes of treatment. Illicit drug use is associated with a myriad of complications for both the pregnant woman and her newborn. These complications are costly and a means of reducing their prevalence would be very beneficial to identify. Unfortunately, obstetrical or neonatal outcomes were rarely included in the studies. Furthermore, obstetrical events such as miscarriage were even a criteria for exclusion in one study (Svikis 1997). Birth outcomes were reported in only two studies (Carroll 1995; Elk 1998). Both studies showed a benefit with contingency management treatment; however neither performed a power calculation. Given that these two studies had a combined total of 26 participants, one can safely surmise that neither was powered to detect any difference in obstetrical outcomes. There is also inconsistency between the studies in regards to which obstetrical outcomes were measured. Carroll 1995 measured both mean gestational age and mean birth weight. Elk 1998, on the other hand, counted adverse perinatal events, a category that included both preterm delivery, a serious obstetrical event, as well as preterm labor, a clinical event of far less significance. Continued illicit drug use, as measured primarily by urine toxicology, was a reported outcome in eight of the studies. Abstinence was a goal of treatment in all of the studies with the exception of O Neill 1996 which employed a harm reduction model. This was 8

11 also the only study which relied on client self-report to assess continued drug use. The frequency or urine sampling varied between studies as did the methods of reporting the results. It was often unclear how the summary proportions had been generated and, with the exception of Elk 1998, none made mention of statistical adjustment for multiple testing. Overall there appears to be little evidence that psychosocial interventions reduce continued illicit drug use in pregnant women enrolled in drug treatment. None of the articles that employed manual based interventions reported an effect of the intervention on drug abstinence. Of the two studies that reported an effect, both employed CM. The magnitude of the reduction; however, was small (Silverman 2001) and its effect, was temporary (Jones 2001). A primary goal of CM is to alter, if not to eliminate, drug use behaviours. Over the last decade, the clinical evidence demonstrating the efficacy of CM in reinforcing drug abstinence has been established (for a good summary see Sitzer 2006). This review is the first to specifically address drug treatment in pregnancy. It appears that the benefits of CM on drug abstinence are not as profound in pregnant women as in the general population of individuals in drug treatment. MI, in contradistinction, has not been shown to have consistent effects on subsequent abstinence (Miller 2003) in drug treatment. Similarly, our results show no benefit of MI in pregnancy, with a trend towards a negative effect. Our primary concern was with obstetrical and neonatal clinical outcomes. Unfortunately, the heterogeneity of results limited our conclusions. Retention in treatment was the outcome most consistently reported in the studies. As with any surrogate outcome, its clinical utility is dependent upon the evidence of it as an intermediary to the important clinical outcome (Grimes 2005). In pregnancy, attendance in drug treatment has been shown to lead to increase birth weight, increase in one minute Apgars, and overall lower costs (Hubbard 1989, Svikis 1998, McCaul 1996). In terms of retention in treatment, women randomized to CM had greater retention whereas those randomised to MI had less retention compared with controls. This finding is consistent with some of the critical literature on MI which notes that actively engaging an individual before she is ready to change may be detrimental, especially when manual-guided (Hettema 2005). It is important to acknowledge the fact that many pregnant women are referred into drug treatment from the criminal justice system. Unfortunately, none of the included articles discussed the referral pattern of their respective patient populations. Manual based interventions such as MI are likely less effective among coerced individuals. In fact, they may be counter productive. This can be seen in our review, where individuals randomized to MI had worse retention compared to controls (and no difference in drug abstinence rates). It is also important to note the characteristics of the patient population included in these studies. The patients were overwhelmingly unemployed, poor, African American, and with low levels of education. This limits the generalisability of the study results. The population of women who use illicit drugs in pregnancy is different from those enrolled in drug treatment, which is different from the population of women in treatment who participate in experimental trials. The efficacy of psychosocial interventions in general, may vary between these different sub sets of patients. There were several limitations of the studies. Overall they were heterogeneous, differing in the details of the both the intervention and the control and employing different lengths of treatment. Some of the studies were quite small leaving them likely underpowered, especially for obstetrical outcomes. The study settings were all similar, academic specialist drug dependence units primarily in the United States, as were the participants. Although this decreases heterogeneity between studies, the results may not be generalisable to other settings. One of the limitations to CM is the cost. On average, CM participants in the included trials cost up to $600 per client (Jones 2001). Clearly this limits the applicability of CM on a large scale. For this reason, non cash incentives such as vouchers have been used. Silverman 2001 extended this concept to include job training. Overall, our review identified few experimental studies of psychosocial interventions in pregnancy for illicit drug use. This is surprising given the wide use of such interventions in clinical treatment. Furthermore, it is unlikely that manual based interventions such as MI are used in isolation in clinical practice. Counsellors most likely use different parts of multiple modalities simultaneously. Even if a particular psychosocial intervention is found to be beneficial, its application may be limited by the realities of drug treatment. In conclusion, there is insufficient evidence to evaluate whether psychosocial interventions are effective in treating pregnant illicit drug using women. Certainly there is no evidence to evaluate whether they improve birth or neonatal outcomes. Nor is there strong evidence to support a benefit of either intervention in terms of drug abstinence. Whereas CM may increase treatment retention, MI reduces retention, however the literature is sparse and there is great heterogeneity between the studies. Further randomised controlled trials are needed to better evaluate whether psychosocial interventions are a useful and cost effective intervention for pregnant illicit drug using women. A U T H O R S C O N C L U S I O N S Implications for practice Psychosocial interventions, when taken together, do not translate into better neonatal or obstetrical outcomes, nor are they associated with greater illicit drug abstinence among pregnant women. When contingency management is considered alone, there is an 9

12 overall improvement in treatment retention. When manual based interventions were considered alone, there was a trend toward a decrease in retention. There is no data on cost benefit. It is important that future studies include both neonatal and obstetrical outcomes, although this will certainly change the study size required. Implications for research Large randomised trials with obstetrically meaningful endpoints as well as with longer follow ups to examine whether psychosocial interventions help pregnant women with illicit drug dependence are required. Poor obstetrical outcomes should not be an exclusion criteria to study participation, as these events are essential to capture. Ideally these studies would have multiple sites in order to capture a greater diversity of study patients, and thereby avoid potential confounding. The reporting of criminal justice referral into treatment is especially important, as the efficacy of psychosocial interventions may be different between individuals have been coerced into treatment and those who enter voluntarily. Questions that should be considered include the following: Is one psychosocial intervention more effective than another? What covariate, such as, drug use history, time in treatment, or gestational age upon enrolment, are associated with treatment effectiveness? What is the optimal reimbursement for CM and what is its overall cost effectiveness? Overall the trials should state clearly the method of randomisation and allocation concealment. Although blinding of participants is impossible, those performing the analysis should be blinded (and this should be clearly stated). Intention to treat analysis should be performed and power calculations used a priori. R E F E R E N C E S References to studies included in this review Carroll 1995 {published data only} Carrol M, Chang G, Behr H, Clinton B, Kosten T. Improving Tratment Outcome in Pregnant, MEthadone- Maintained WOmen. American Journal on Addictions 1995; 4(1):56 9. Elk 1998 {published data only} Elk R, Mangus L, Rhoades H, Andres R, Grabowski J. Cessation of cocaine use during pregnancy: effects of contingency management interventions on maintaining abstinence and complying with prenatal care. Addictive Behaviors 1998;23(1): Haug 2004 {published data only} Haug N, Svikis D, DiClemente C. Motivational enhancement therapy for nicotine dependence in methadone- maintained pregnant women. Psychology of Addictive Behaviors 2004;18(3): Jones 2000 {published data only} Jones HE, Stitzer M, Svikis D. Improving treatment outcomes for pregnant drug-dependent women using lowmagnitude voucher incentives. Addictive Behaviors 2000;25 (2): Jones 2001 {published data only} Jones HE, Haug N, Silverman K, Stitzer M, Svikis D. The effectiveness of incentives in enhancing treatment attendance and drug abstinence in methadone-maintained pregnant women. Drug and Alcohol Dependence 2001;61 (3): Mullins 2004 {published data only} Mullins SM, Suarez M, Ondersman SJ, Page MC. The impact of motivational interviewing on substance abuse treatment retention: A randomised control trial of women involved with child welfare. Journal of Substance Abuse Treatment 2004;27(1):51 8. O Neill 1996 {published data only} O Neill K, Baker A, Cooke M, Collins E, Heather N, Wodak A. Evaluation of a cognitive-behavioural intervention for pregnant injecting drug users at risk of HIV infection. Addiction 1996;91(8): Silverman 2001 {published data only} Silverman K, Svikis D, Eobles E, Stitzer M, Bigelow GE. A reinforcement-based therapeutic workplace for the treatment of drug abuse: six-month abstinence outcomes. Experimental and clinical psychopharmacology 2001;9(1): Svikis 1997 {published data only} Svikis D, Lee JH, Haug N, Stitzer M. Attendance incentives for outpatient treatment: effects in methadoneand non methadone-maintained pregnant drug dependent women. Drug and Alcohol Dependence 1997;48(1): References to studies excluded from this review Amato 2006 {published data only} Amato L, Minozzi S, Davoli M, Vecchi S, Ferri M, Mayet S. Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: / ] Ashley 2003 {published data only} Ashley OS, Marsden ME, Brady TM. Effectiveness of substance abuse treatment programming for women: A review. American Journal of Drug and Alcohol Abuse 2003; 29(1): Bolnick 2003 {published data only} Bolnick JM, Rayburn WF. Substance use disorders in women: Special considerations during pregnancy. Obstetrics and Gynecology Clinics of North America 2003;30(3):

13 Brady 1993 {published data only} Brady KT, Grice DE, Dustan L, Malcom R, Killeen T. Characteristics of pregnant cocaine abusers. NIDA Research Monograph 1993;132:114. Chang 1992 {published data only} Chang G, Carroll KM, Behr HM, Kosten TR. Improving treatment outcome in pregnant opiate dependent women. Journal of Substance Abuse Treatment 1992;9: Chang 2005 {published data only} Chang G, McNamara TK, Orav EJ, Koby D, Ludman B, Haug LW. Brief intervention for prenatal alcohol use: a randomized trial. Obstetrics and Gynecology 2005;105(5): Chazotte 1995 {published data only} Chazotte C, Youchah J, Freda MC. Cocaine use during pregnancy and low birth weight: The impact of prenatal care and drug treatment. Seminars in Perinatology 1995;19 (4): [MEDLINE: 22] Clark 2001 {published data only} Clark KA, Dee DL, Bale PL, Martin SL. Treatment compliance among prenatal care patients with substance abuse problems. American Journal of Drug and Alcohol Abuse 2001;27(1): Daley 2005 {published data only} Daley M, Shepard D, Maynard DB. Changes in quality of life for pregnant women in substance user treatment: Developing a quality of life index for the addictions. Substance Use and Misuse 2005;40(3): Day 2003 {published data only} Day E, Porter L, Clarke A, Allen D, Moselhy H, Copello A. Drug misuse in pregnancy: The impact of a specialist treatment service. Psychiatric Bulletin 2003;27(3): Drozdick 2002 {published data only} Drozdick J, Berghella V, Hill M, Kaltenbach K. Methadone trough levels in pregnancy. American Journal of Obstetrics and Gynecology 2002;187(5): Egelko 1998 {published data only} Egelko S, Galanter M, Dermatis H, DeMaio C. Evaluation of a multisystems model for treating perinantal cocaine addiction. Journal of Substance Abuse Treatment 1998;15(3): Elk 1997 {published data only} Elk R, Mangus LG, LaSoya RJ, Rhoades HM, Andres RL, Grabowski J. Behavioral Interventions: Effectuve and adaptable for the treatment of pregnant cocaine-dependent women. Journal of Drug Issues 1997;27(3): Elk 1995 {published data only} Elk R, Schmitz J, Spiga R, Rhoades H, Andres R, Grabowski J. Behavioral treatment of cocaine-dependent pregnant women and TB-exposed patients. Addictive Behaviors 1995; 20(4): Finnegan 2005 {published data only} Finnegan LP, Amass L, Jones HE, Kaltenbach K. Addiction and Pregnancy. Heroin Addiction and Related Clinical Problems 2005;7(4):5 22. Fischer 1999 {published data only} Fischer G, Jagsch R, Eder H, Gombas W, Etzersdorfer P, Schmidl-Mohl K, et al.comparison of methadone and slow-release morphine maintenance in pregnant addicts. Addiction 1999;94(2): Funai 2003 {published data only} Funai EF, White J, Lee MJ, Allen M, Kuczynski E. Compliance with prenatal care visits in substance abusers. Journal of Maternal-Fetal and Neonatal Medicine 2003;14 (5): Fundaro 2004 {published data only} Fundaro C, Genovese O, Baldieri F, Miccinesi N. Longterm neurodevelopmental outcome of children exposed to illicit substances during pregnancy: The role of home environmental factors. Italian Journal of Pediatrics 2004;30 (2): Hulse 2002 {published data only} Hulse G, O Neil G. Using naltrexone implants in the management of the pregnant heroin user. Australian and New Zealand Journal of Obstetrics and Gynaecology 2002;42 (5): Jansson 2003 {published data only} Jansson L, Svikis D, Beilenson P. Effectiveness of Child Case Management Services for Offspring of Drug- Dependent Women. Substance Use and Misuse 2003;38(14): Jones 2002 {published data only} Jones HE, Svikis D, Tran G. Patient compliance and maternal/infant outcomes in pregnant drug-using women. Substance Use and Misuse 2002;37(11): Jones 2004 {published data only} Jones HE, Svikis D, Rosado J, Tuten M, Kulstad JL. What if they do not want treatment?: Lessons learned from intervention studies of non-treatment-seeking, drug-using pregnant women. American Journal on Addictions 2004;13 (4): Kastner 2002 {published data only} Kastner R, Hartl K, Lieber A, Hahlweg BC, Knobbe A, Grubert T, et al.opiate addiction during pregnancy: Results of a psychosomatic treatment strategy with replacement therapy.. Geburtshilfe und Frauenheilkunde 2002;32(1): Kukko 1999 {published data only} Kukko H, Halmesmaki E. Prenatal care and counselingof female drug abusers: effcets on drug abuse and perinatal outcomes. Acta Obstetricia et Gynecologica Scandinavica 1999;78:22 6. Nishimoto 2001 {published data only} Nishimoto RH, Roberts AC. Coercion and drug treatment for postpartum women. American Journal of Drug and Alcohol Abuse 2001;27(1): Ondersman 2005 {published data only} Ondersman SJ, Chase SK, Svikis D, Schuster CR. Computer-based brief motivational intervention for perinatal drug use.. Journal of Substance Abuse Treatment 2005;28(4):

14 Rayburn 2004 {published data only} Rayburn WF, Bogenschutz MP. Pharmacotherapy for pregnant women with addictions.. American Journal of Obstetrics and Gynecology 2004;191(6): Seracini 1997 {published data only} Seracini AM, Nunes E, Tross S, Spano C. Achieving cocaine abstinence in preinatal cocaine-dependent women: A contingency management approach. Problems of Drug Dependence 1996: Proceedings of the 58th Annual Scientific Meeting. Washington DC: NIH , 1996: 261. Shieh 2002 {published data only} Shieh C, Kravitz M. Maternal-fetal attachment in pregnant women who use illicit drugs. Journal of Obstetric, Gynecologic and Neonatal Nursing 2002;31(2): Svikis 1998 {published data only} Svikis D, McCaul M, Feng T, Stuart M, Fox M, Stokes E. Drug Dependence During Pregnancy: Effect of an on-site support group. Journal of Reproductive Medicine 1998;49: Sweeney 2000 {published data only} Sweeney PJ, Schwartz RM, Mattis NG, Vohr B. The effect of integrating substance abuse treatment with prenatal care on birth outcome. Journal of Perinatology 2000;4: Weisdorf 1999 {published data only} Weisdorf T, Parran TV, Graam A, Snyder C. Comparison of pregnancy-specific interventions to a traditional treatment program for cocaine-addicted pregnant women. Journal of Substance Abuse Treatment 1999;16(1): Wexler 1998 {published data only} Wexler HK, Cuadrado M, Stevens SJ. Residential Treatment for Women: Behavioral and Psychological Outcomes. In: Stevens S, Wexler HK editor(s). Women and Substance Abuse. NY: The Hawthorne Medical Press, 1998: Winhusen 2003 {published data only} Winhusen TM, Kropp F. Psychosocial treatments for women with substance use disorders. Obstetrics and Gynecology Clinics of North America 2003;30(3): Zlotnick 1996 {published data only} Zlotnick C, Franchio K, Claire N, Cox K, John M. The impact of outpatient drug services on abstinence among pregnant and parenting women. Journal of Substance Abuse Treatment 1996;13(3): Additional references Armstrong 2003 Armstrong MA, Gonzales Osejo V, Lieberman L, Carpenter DM, Pantoja PM, Escobar GJ. Perinatal Substance Abuse Intervention in Obstetric Clinics Decreases Adverse Neonatal Outcomes. Journal of Perinatology 2003;23:3 9. Boyd 1999 Boyd SC. Mothers and illicit drugs: transcending the myths. Toronto: University of Toronto Press, Brunader 1991 Brunader RE, Brunader JA, Kugler JP. Prevalence of cocaine and marijuana use among pregnant women in a military health care setting. Journal of the American Board of Family Practice 1991;4(6): Dakof 2003 Dakof GA, Quille TJ, Tejeda MJ, Alberga LR, Bandstra E, Szapocznik J. Enrolling and retaining mothers of substanceexposed infants in drug abuse treatment. Journal of Consilting and Clinical Psychology 2003;71(4): Daley 1998 Daley M, Argeriouu M, McCarty D. Substance abuse treatment for pregnant women: A window of opportunity?. Addictive Behaviors 1998;23(2): DiClemente 1998 DiClemente CC, Prochaska JO. Towards a comprehensive, trans theoretical model of change: Stages of change and addictive behaviours. In: Miller WR, Heather N editor(s). Treating Addictive Behaviours. 2. New York: Plenum Press, 1998:3 24. Frank 2001 Frank DA, Augustyn M, Knight WG, Pell T, Zuckerman B. Growth, development, and behavior in early childhood following prenatal cocaine exposure. Journal of the American Medical Association 20011;285(12): George 1991 George SK, Price J, Hauth JC, Barnette DM, Preston P. Drug abuse screening of childbearing-age women in ALabama public health clinics. American Journal of Obstetrics and Gynecology 1991;165(4): Grella 2000 Grella CE, Joshi V, Hser Y. Program variation in treatment outcomes among women in residential drug treatment. Evaluation Reviewss 2000;24: Grimes 2005 Grimes DA, Schulz KF. Surrogate end points in clinical research: hazardous to your health. Obstetrics and Gynecology 2005;105(5): Hettema 2005 Hettema J, Steele J, Miller WR. Motivational Interviewing. Annual Review of Clinical Psychology 2005;1: Higgins 1991 Higgins ST, Delaney DD, Budney EJ, Bickel WK, Hughes JR, Foerg F, et al.a behavioral approach to achieving initial cocaine abstinence. American Journal of Psychiatry 1991; 148(9): Higgins 2007 Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions [updated May 2005]. The Cochrane Library 2007, issue 3. Howell 2000 Howell EM, Heiser N, Cherlow A, Mason M, Ewell D, Potwein S. Identifying pregnant substance abusers and studying their treatment using birth certificates, Medicaid 12

15 claims, and state substance abuse treatment data. NIDA Research Monograph 2000;1: Hser 1998 Hser Y, Maglione M, Polinsky ML, Anglin MD. Predicting drug treatment entry among treatment-seeking individuals. Journal of Substance Abuse Treatment 1998;15: Hubbard 1989 Hubbard RL, Mardsen ME, Rachal JV, Harwood HJ, Cavanaugh ER, Ginzburg HM. Drug Abuse Treatment: A national study of effectiveness. Chapel Hill: University of North Carolina Press, Ludlow 2004 Ludlow, Joanne P, Sharon F Evans, Gary Hulse. Obstetrical and perinatal outcomes in pregnancies associated with illicit substance abuse. Australian and New Zealand Journal of Obstetrics and Gynaecology 2004;44: McCaul 1996 McCaul ME, Svikis DS. Service Utilization measures in drug treatment research. In: Rahdert E editor(s). Treatment for drug exposed women and their children: Advances in research methodology. Washington DC: U.S. Government Printing Office, 1996: Miller 2003 Miller WR, Yahne CE, Tonigan JS. Motivational Interviewing in Drug Abuse Services: A Randomized Trial. Journal of Consulting and CLinical Psychology 2003;71(4): Murphy 1999 Murphy S, Rosennbaum M. Pregnant women on drugs: combating stereotypes and stigma. New Brunswick: Rutgers University Press, Rollnick 1995 Rollnick S, Miller WR. What is Moticational Interviewing?. Behavioural and Cognitive Psychotherapy 1995;23: Schulz 1995 Schulz, KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias: Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.. JAMA 1995;273(5): Signorini 1993 Signorini SF, Leung O, Simes RJ, Beller E, Gebski VJ, Callaghan T. Dynamic balanced randomisation for clinical trials. Statistics in Medicine 1993;12: Singer 2004 Singer LT, Minnes S, Short E, Arendt R, Farkas K, Lewis B, et al.cognitive outcomes of preschool children with prenatal cocaine exposure. JAMA 2004;291(20): Sitzer 2006 Sitzer M, Nancy P. Contingency Management for Treatment of Substance Abuse. Annual Revew of Clinical Psychology 2006;2: Skinner 1947 Skinner BF. Superstition in the Pidgeon. Journal of Experimental Psychology 1947;38: Thorndike 1898 Thorndike EL. Animal intelligence: An experimental study of the associative processes in animals. Psychological Review Monograph Supplement 1898;2(4):109. Indicates the major publication for the study 13

16 C H A R A C T E R I S T I C S O F S T U D I E S Characteristics of included studies [ordered by study ID] Carroll 1995 Methods Participants Interventions Outcomes Allocation: Randomised controlled trial. Randomisation: method not reported. Blindness: not possible. No difference between groups on baseline drug use or demographic characteristics 14 pregnant women enrolled in methadone maintenance. (1)7 (2)7. Mean age 27.6; 78.6% non-minority (11/14); 78.6% single; 100% unemployed; 8(+/-6) weeks gestational age upon entry into MMT; 2.7 mean days cocaine use in past 30 days. Exclusion: > 28 weeks pregnant For all daily MMT, weekly group counselling, three times/week urine toxicology screening. (1) weekly prenatal classes, weekly relapse-prevention groups, childcare during treatment visits, and CM awards - $15/ week for three consecutive negative urine screens. (2) MMT and weekly group counselling. No difference between groups in terms of MMT dose (mean 50mg). Duration : average 23 weeks (range weeks). Attendance was measured in terms of % number of groups attended. Infant outcomes measured as mean gestational age at delivery, mean weight, and mean number of days in the hospital. Urine toxicology was measure as % positive for cocaine, opiates, or other drugs Notes Unable to measure retention as not reported, however, 20 patients randomised and only 14 analysed. 6 dropouts (unclear from which randomised groups) -- one for delivery, one for sedative detox, and 4 for noncompliance with group therapy. Attempted to contact authors - no answer Risk of bias Item Authors judgement Description Allocation concealment? Unclear B - Unclear Elk 1998 Methods Participants Allocation: randomised controlled trial. Randomisation: method not reported. Blindness: not possible. Groups similar on baseline drug use 12 cocaine dependent pregnant women. (1)6 (2)6. 58% African American, 8% Hispanic, 33% White; 92% never married or separated/widowed/divorced; 75% high school; 83% unemployed; 67% gravida 5 or more, 25% gravida 3-4; 75% in second trimester; DSM-III-R: 92% (10/11) cocaine primary drug of abuse, 8% (1/11) both heroin and cocaine dependent. Exclusion: Cessation of cocaine use greater than 30 days prior to enrolment 14

17 Elk 1998 (Continued) Interventions Outcomes Notes All received prenatal care, behaviorally based drug counselling, nutritional education, and HIV counselling. (1) Contingency management, $18 for each cocaine-free urine sample, $20 weekly bonus if all 3 samples negative and perfect attendance (including prenatal care [PNC]). (2) Routine care. Duration unclear (at least 4 weeks) Retention in treatment as number remaining in treatment. Abstinence as average of individual %. Attendance in prenatal care as number of visits. Perinatal outcomes as number of preterm labor and/or preterm delivery. ASI composite scores presented as a bar graph. All outcomes reported as chi square with p-value only when significant Treatment facility provided free transportation and child care. Attempted to contact authors -- no answer Risk of bias Item Authors judgement Description Allocation concealment? Unclear B - Unclear Haug 2004 Methods Participants Interventions Outcomes Notes Allocation: randomised controlled trial. Randomisation: method not reported. Blindness: not possible. Groups significantly different for race. No difference in drug use and psychiatric comorbidity 63 pregnant opioid-dependent women, <= 26 weeks gestational age, receiving MMT and >=5 cigarettes/ day. (1)30 (2)36. Mean age 29.7; 84% African American; 79% single or never married; 97% unemployed; 94% less than high school education. DSM-III-R: all heroin dependent (100%), 41 (35%) cocaine dependent, 10 (16%) marijuana dependent, 17 (27%) alcohol dependent, all (100%) nicotine dependent. Exclusion: not stated For all MMT, no information on urine monitoring, or counselling/therapy. All received $10 voucher after initial battery and $20 when 10-week interview completed. Mean MMT dose 65.2 mg. All received PNC and substance abuse counselling - no details described. (1) four MET sessions using a modification of the Project MATCH MET manual (Miller et al., 1995). Visit 1 - rapport building; visit 2 (1 week later) - personalized feedback on positive behaviours, negative consequences of smoking, and stage of change; visit 3 (week 4) - commitment and plan for change developed; visit 4 (week 6) - barriers to long-term change addressed. (2) not detailed what received. Duration 10 weeks. Retention in treatment as % attrition. Stage of change and stage movement. Urine toxicology done at the 10-week follow-up Randomisation occurred during residential treatment 14 disqualified post randomisation for spontaneous abortion. 21 excluded for reasons not stated. Author contacts -- raw data for urine toxicology received. 15

18 Haug 2004 (Continued) Risk of bias Item Authors judgement Description Allocation concealment? Unclear B - Unclear Jones 2000 Methods Participants Interventions Outcomes Notes Allocation: randomised controlled trial. Randomisation: method not reported. Blindness: possible but not described. No difference between groups on baseline drug use. 93 pregnant women enrolled in substance use treatment, 18 years or older, meeting DSM-III-R criteria. (1)53 (2)40. Average age 28.9; 88% African American; 75% single; 50% less than HS education; 97% unemployed; DSM-III-R: 75% cocaine dependence, 74% opiate dependence, 50% both; 25 individuals (27%) received MMT. Exclusion: not stated For all participants, treatment services included a 7-day residential stay followed by a 30-day intensive treatment (7 days/week, 6.5 hours/day). For individuals receiving MMT, no information on doses. (1) 5$ incentives given out during the first 7 days of outpatient treatment. (2) 0$ incentives given. For MMT subgroup: could receive $5 for each negative urine and $25 or $50 bonus for 5 or 7 days drug-free urine, and additional $20 if completed all urine samplings and or attendance card monitoring. For non MMT: $5 each day attended at least 4 hours treatment, $25 or $50 bonus for attending 5-6 or 7 days. Duration 37 days. Attendance was measured in days and hours. Urine toxicology was not reported. Retention or loss to follow up was not reported Transportation and childcare provided. Although randomised to incentive versus no incentive, the nature of the disbursement of the incentives varied between MMT and not MMT subgroups. Author contacted -- unable to provide original data. Risk of bias Item Authors judgement Description Allocation concealment? Unclear B - Unclear 16

19 Jones 2001 Methods Participants Allocation: randomised controlled trial. Randomisation: by coloured chip. Blindness: not possible. No difference between groups on baseline drug use or demographic characteristics 85 pregnant women on MMT, greater than age 18, meeting DSM-II-R criteria for opiate dependence with cocaine abuse, admitted for first time for substance abuse treatment. (1)47 (2)38. Mean age 28; mean gestational age 23.4; 96% unemployed; 85% single/never married; 76% African American; 20% chronic medical conditions (HTN, DM, HIV); DSM-III-R: 100% opiate dependent, 69% cocaine, 5% marijuana, 10% alcohol Interventions For all participants treatment consisted of a 7-day residential followed by 7 days of intensive outpatient (7 days/week, 6.5 hours/day). Treatment consisted of group counselling and at least once a week individual psychotherapy. All received MMT, mean dose 42. (1) Money vouchers could be earned for specific target behavior: attend at least 4 hours counselling and (days 8-14) provide a cocaine negative urine sample. (2) no voucher incentives. Duration 14 days. Outcomes Notes Attendance was measured as mean full day attendance as well as perfect treatment attendance defined as attendance on at least 13 or 14 full days of treatment. Retention was measured as the % drop out. Urine samples were collected daily from days 8-14 and reported as % positive Transportation, child care, on site PNC and psychiatric consultation provided. Author contacted -- unable to provide raw data. Risk of bias Item Authors judgement Description Allocation concealment? Unclear B - Unclear Mullins 2004 Methods Participants Allocation: randomised controlled trial. Randomisation: not mentioned. Blindness: not possible. No difference between groups in baseline drug use. 71 pregnant women who used illicit drugs in pregnancy, 18 years or older. (1)35 (2)36. Average age 27.1; 73% single/never married; 88% unemployed; 82% receiving government income; 32% African American, 50% Caucasian; DSM-III-R: 49% cocaine dependent, 28% marijuana, 4% alcohol. Exclusion: no obvious impairment (acute psychosis or organic illness) Interventions For all participants, substance treatment counselling provided. Nature of counselling not elaborated. (1) 3 MI sessions (at the time of intake, 1 week following, and 2 months after completion). No manual was used. Session done by four mental health providers all with formal training in MI. (2) Educational control group received 30 minute educational video at intake and at one week and 60 minute home-visit at 2 months. 17

20 Mullins 2004 (Continued) Duration of study 2 months. Outcomes Notes Attendance reported as number and % attended. Urine was screened at intake and then randomly once per week and were reported as a mean proportion of negative screens Gender-specific treatment centre. Transportation and childcare included. Treatment integrity and MI proficiency were evaluated. Likert scores used to asses inter-rater reliability. Attempted to contact author - no answer. Risk of bias Item Authors judgement Description Allocation concealment? Unclear B - Unclear O Neill 1996 Methods Participants Allocation: randomised controlled trial. Randomisation: method not reported. Blindness: not possible. 92 pregnant women enrolled in MMT who injected drugs. (1)47 (2)45. Mean age 26.2; mean years education 10.2; 53% ever sex worker; mean gestational age 22 weeks; DSM-III-R: 85% opiate dependent, 15% cocaine, 59% marijuana, 32% alcohol, 98% nicotine Interventions All participants received MMT (mean methadone dose 49 mg) and counselling about HIV risk. (1) 6 session of manual based CBT lasting minutes, the first being more of a MI. (2) No intervention. Duration 9 months. Outcomes Notes Retention was measured as a proportion. Attendance was measured as the average number of missed appointments Researchers attempted to contact patients lost to follow up through the Department of Social Security and Department of Health. Attempted to contact author -- no answer. Risk of bias Item Authors judgement Description Allocation concealment? Unclear B - Unclear 18