Sarah H. Heil

Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure

BACKGROUND Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy. METHODS We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference. RESULTS Treatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events. CONCLUSIONS These results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.).

Delay discounting predicts postpartum relapse to cigarette smoking among pregnant women.

Delay discounting (DD), a measure of impulsivity, describes the rate at which rewards lose value as the delay to their receipt increases. Greater discounting has been associated with cigarette smoking and various other types of drug abuse in recent research. The present study examined whether DD predicts treatment outcome among cigarette smokers. More specifically, the authors examined whether baseline discounting for hypothetical monetary rewards predicted smoking status at 24 weeks postpartum among women who discontinued smoking during pregnancy. Participants were 48 pregnant women (10.5 = 4.1 weeks gestational age at study entry) who participated in a clinical trial examining the use of incentives to prevent postpartum relapse. Several sociodemographic characteristics (being younger, being less educated, and reporting a history of depression) assessed at study entry were associated with increased baseline DD, but in multivariate analyses only DD predicted smoking status at 24 weeks postpartum. Greater baseline DD was a significant predictor of smoking status at 24 weeks postpartum. DD was reassessed periodically throughout the study and did not significantly change over time among those who eventually resumed smoking or those who sustained abstinence. The results extend the association of DD with risk for substance abuse to pregnant and recently postpartum cigarette smokers and demonstrate a significant relationship between DD and treatment outcome.

Maternal Smoking and Its Association With Birth Weight

OBJECTIVE: Maternal smoking has been associated with a reduction in newborn birth weight. We sought to estimate how the pattern of maternal smoking throughout pregnancy influences newborn size. METHODS: One hundred sixty pregnant smoking women were enrolled in a prospective study. We collected data on maternal age, education, prepregnancy body mass index, and parity, as well as alcohol and illicit drug use. Cigarette use was defined as self-reported consumption before pregnancy, at the time of study enrollment, and in the third trimester. Statistical analyses were performed based on bivariate correlations and multiple linear regression. RESULTS: Of the smoking parameters examined, maternal third-trimester cigarette consumption was the strongest predictor of birth weight percentile (partial r = –0.23, P < .001). For each additional cigarette per day that a participant smoked in the third trimester, there was an estimated 27 g reduction in birth weight. Prepregnancy smoking volume was not significantly associated with birth weight percentile in bivariate (r = –0.06, P = .47) or multivariable analyses. Additional factors contributing to birth weight include gestational age (partial r = 0.69, P < .001), maternal body mass index (partial r = 0.23, P < .001), and parity (partial r = 0.16, P < .004). In total, these 4 variables explain 61% of the variance in newborn birth weight. CONCLUSION: Maternal third-trimester cigarette consumption is a strong and independent predictor of birth weight percentile. This supports the hypothesis that reductions in maternal cigarette consumption during pregnancy will result in improved birth weight, regardless of the prepregnancy consumption levels. LEVEL OF EVIDENCE: III

Effects of voucher-based incentives on abstinence from cigarette smoking and fetal growth among pregnant women.

AIMS This study examined whether voucher-based reinforcement therapy (VBRT) contingent upon smoking abstinence during pregnancy is an effective method for decreasing maternal smoking during pregnancy and improving fetal growth. DESIGN, SETTING AND PARTICIPANTS A two-condition, parallel-groups, randomized controlled trial was conducted in a university-based research clinic. A total of 82 smokers entering prenatal care participated in the trial. INTERVENTION Participants were assigned randomly to either contingent or non-contingent voucher conditions. Vouchers exchangeable for retail items were available during pregnancy and for 12 weeks postpartum. In the contingent condition, vouchers were earned for biochemically verified smoking abstinence; in the non-contingent condition, vouchers were earned independent of smoking status. MEASUREMENTS Smoking outcomes were evaluated using urine-toxicology testing and self-report. Fetal growth outcomes were evaluated using serial ultrasound examinations performed during the third trimester. FINDINGS Contingent vouchers significantly increased point-prevalence abstinence at the end-of-pregnancy (41% versus 10%) and at the 12-week postpartum assessment (24% versus 3%). Serial ultrasound examinations indicated significantly greater growth in terms of estimated fetal weight, femur length and abdominal circumference in the contingent compared to the non-contingent conditions. CONCLUSIONS These results provide further evidence that VBRT has a substantive contribution to make to efforts to decrease maternal smoking during pregnancy and provide new evidence of positive effects on fetal health.

A pilot study on voucher-based incentives to promote abstinence from cigarette smoking during pregnancy and postpartum

We report results from a pilot study examining the use of vouchers redeemable for retail items as incentives for smoking cessation during pregnancy and postpartum. Of 100 study-eligible women who were still smoking upon entering prenatal care, 58 were recruited from university-based and community obstetric practices to participate in a smoking cessation study. Participants were assigned to either contingent or noncontingent voucher conditions. Vouchers were available during pregnancy and for 12 weeks postpartum. In the contingent condition, vouchers were earned for biochemically verified smoking abstinence. In the noncontingent condition, vouchers were earned independent of smoking status. Abstinence monitoring and associated voucher delivery was conducted daily during the initial 5 days of the cessation effort, gradually decreased to every other week antepartum, increased to once weekly during the initial 4 weeks postpartum, and then decreased again to every other week for the remaining 8 weeks of the postpartum intervention period. Contingent vouchers increased 7-day point-prevalence abstinence at the end-of-pregnancy (37% vs. 9%) and 12-week postpartum (33% vs. 0%) assessments. That effect was sustained through the 24-week postpartum assessment (27% vs. 0%), which was 12 weeks after discontinuation of the voucher program. Total mean voucher earnings across antepartum and postpartum were 397 US dollars (SD=414 US dollars) and 313 US dollars (SD=142 dollars) in the contingent and noncontingent conditions, respectively. The magnitude of these treatment effects exceed levels typically observed with pregnant and recently postpartum smokers, and the maintenance of effects through 24 weeks postpartum extends the duration beyond those reported previously.

Treatment of opioid-dependent pregnant women: clinical and research issues.

This article addresses common questions that clinicians face when treating pregnant women with opioid dependence. Guidance, based on both research evidence and the collective clinical experience of the authors, which include investigators in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, is provided to aid clinical decision making. The MOTHER project is a double-blind, double-dummy, flexible-dosing, parallel-group clinical trial examining the comparative safety and efficacy of methadone and buprenorphine for the treatment of opioid dependence in pregnant women and their neonates. The article begins with a discussion of appropriate assessment during pregnancy and then addresses clinical management stages including maintenance medication selection, induction, and stabilization; opioid agonist medication management before, during, and after delivery; pain management; breast-feeding; and transfer to aftercare. Lastly, other important clinical issues including managing co-occurring psychiatric disorders and medication interactions are discussed.

Financial Incentives for Smoking Cessation Among Pregnant and Newly Postpartum Women

OBJECTIVE Smoking during pregnancy is the leading preventable cause of poor pregnancy outcomes in the U.S., causing serious immediate and longer-term adverse effects for mothers and offspring. In this report we provide a narrative review of research on the use of financial incentives to promote abstinence from cigarette smoking during pregnancy, an intervention wherein women earn vouchers exchangeable for retail items contingent on biochemically-verified abstinence from recent smoking. METHODS Published reports based on controlled trials are reviewed. All of the reviewed research was conducted by one of two research groups who have investigated this treatment approach. RESULTS Results from six controlled trials with economically disadvantaged pregnant smokers support the efficacy of financial incentives for increasing smoking abstinence rates antepartum and early postpartum. Results from three trials provide evidence that the intervention improves sonographically estimated fetal growth, mean birth weight, percent of low-birth-weight deliveries, and breastfeeding duration. CONCLUSIONS The systematic use of financial incentives has promise as an efficacious intervention for promoting smoking cessation among economically disadvantaged pregnant and recently postpartum women and improving birth outcomes. Additional trials in larger and more diverse samples are warranted to further evaluate the merits of this treatment approach.

Delay Discounting is Associated with Treatment Response among Cocaine-Dependent Outpatients

Delay discounting (DD) describes the rate at which reinforcers lose value as the temporal delay to their receipt increases. Steeper discounting has been positively associated with vulnerability to substance use disorders, including cocaine use disorders. In the present study, we examined whether DD of hypothetical monetary reinforcers is associated with the duration of cocaine abstinence achieved among cocaine-dependent outpatients. Participants were 36 adults who were participating in a randomized controlled trial examining the efficacy of voucher-based contingency management (CM) using low-magnitude (N = 18) or high-magnitude (N = 18) voucher monetary values. DD was associated with the number of continuous weeks of cocaine abstinence achieved, even after adjusting for treatment condition during the initial 12-week, t(33) = 2.48, p = .045 and entire recommended 24-week of treatment, t(33) = 2.40, p = .022. Participants who exhibited steeper discounting functions achieved shorter periods of abstinence in the Low-magnitude voucher condition (12-week: t(16) = 2.48, p = .025; 24-week: t(16) = 2.68, p = .017), but not in the High-magnitude voucher condition (12-week: t(16) = 0.51, p = .618; 24-week: t(16) = 1.08, p = .298), although the interaction between DD and treatment condition was not significant (12-week: t(32) = -1.12, p = .271; 24-week: t(32) = -0.37, p = .712). These results provide further evidence on associations between DD and treatment response and extend those observations to a new clinical population (i.e., cocaine-dependent outpatients), while also suggesting that a more intensive intervention like the High-magnitude CM condition may diminish this negative relationship between DD and treatment response.

Buprenorphine treatment of opioid‐dependent pregnant women: a comprehensive review

AIMS This paper reviews the published literature regarding outcomes following maternal treatment with buprenorphine in five areas: maternal efficacy, fetal effects, neonatal effects, effects on breast milk and longer-term developmental effects. METHODS Within each outcome area, findings are summarized first for the three randomized clinical trials and then for the 44 non-randomized studies (i.e. prospective studies, case reports and series and retrospective chart reviews), only 28 of which involve independent samples. RESULTS Results indicate that maternal treatment with buprenorphine has comparable efficacy to methadone, although difficulties may exist with current buprenorphine induction methods. The available fetal data suggest buprenorphine results in less physiological suppression of fetal heart rate and movements than methadone. Regarding neonatal effects, perhaps the single definitive conclusion is that prenatal buprenorphine treatment results in a clinically significant less severe neonatal abstinence syndrome (NAS) than treatment with methadone. The limited research suggests that, like methadone, buprenorphine is compatible with breastfeeding. Data available thus far suggest that there are no deleterious effects of in utero buprenorphine exposure on infant development. CONCLUSIONS While buprenorphine produces a less severe neonatal abstinence syndrome than methadone, both methadone and buprenorphine are important parts of a complete comprehensive treatment approach for opioid-dependent pregnant women.

Unintended pregnancy in opioid-abusing women

The aim of this study was to estimate the prevalence of unintended pregnancy and its three subtypes (mistimed, unwanted, and ambivalent) among opioid-abusing women. In the general population, 31%-47% of pregnancies are unintended; data on unintended pregnancy in opioid- and other drug-abusing women are lacking. Pregnant opioid-abusing women (N = 946) screened for possible enrollment in a multisite randomized controlled trial comparing opioid maintenance medications completed a standardized interview assessing sociodemographic characteristics, current and past drug use, and pregnancy intention. Almost 9 of every 10 pregnancies were unintended (86%), with comparable percentages mistimed (34%), unwanted (27%), and ambivalent (26%). Irrespective of pregnancy intention, more than 90% of the total sample had a history of drug abuse treatment, averaging more than three treatment episodes. Interventions are sorely needed to address the extremely high rate of unintended pregnancy among opioid-abusing women. Drug treatment programs are likely to be an important setting for such interventions.