Exposure to prescription opioid analgesics in utero and risk of neonatal abstinence syndrome: population based cohort study.

OBJECTIVE: To provide absolute and relative risk estimates of neonatal abstinence syndrome (NAS) based on duration and timing of prescription opioid use during pregnancy in the presence or absence of additional NAS risk factors of history of opioid misuse or dependence, misuse of other substances, non-opioid psychotropic drug use, and smoking. DESIGN: Observational cohort study. SETTING: Medicaid data from 46 US states. PARTICIPANTS: Pregnant women filling at least one prescription for an opioid analgesic at any time during pregnancy for whom opioid exposure characteristics including duration of therapy: short term (<30 days) or long term (≥ 30 days); timing of use: early use (only in the first two trimesters) or late use (extending into the third trimester); and cumulative dose (in morphine equivalent milligrams) were assessed. MAIN OUTCOME MEASURE: Diagnosis of NAS in liveborn infants. RESULTS: 1705 cases of NAS were identified among 290,605 pregnant women filling opioid prescriptions, corresponding to an absolute risk of 5.9 per 1000 deliveries (95% confidence interval 5.6 to 6.2). Long term opioid use during pregnancy resulted in higher absolute risk of NAS per 1000 deliveries in the presence of additional risk factors of known opioid misuse (220.2 (200.8 to 241.0)), alcohol or other drug misuse (30.8 (26.1 to 36.0)), exposure to other psychotropic medications (13.1 (10.6 to 16.1)), and smoking (6.6 (4.3 to 9.6)) than in the absence of any of these risk factors (4.2 (3.3 to 5.4)). The corresponding risk estimates for short term use were 192.0 (175.8 to 209.3), 7.0 (6.0 to 8.2), 2.0 (1.5 to 2.6), 1.5 (1.0 to 2.0), and 0.7 (0.6 to 0.8) per 1000 deliveries, respectively. In propensity score matched analyses, long term prescription opioid use compared with short term use and late use compared with early use in pregnancy demonstrated greater risk of NAS (risk ratios 2.05 (95% confidence interval 1.81 to 2.33) and 1.24 (1.12 to 1.38), respectively). CONCLUSIONS: Use of prescription opioids during pregnancy is associated with a low absolute risk of NAS in the absence of additional risk factors. Long term use compared with short term use and late use compared with early use of prescription opioids are associated with increased NAS risk independent of additional risk factors.

A comparison of cigarette smoking profiles in opioid-dependent pregnant patients receiving methadone or buprenorphine.

INTRODUCTION: Little is known about the relationship between cigarette smoking and agonist treatment in opioid-dependent pregnant patients. The objective of this study is to examine the extent to which cigarette smoking profiles differentially changed during the course of pregnancy in opioid-dependent patients receiving either double-blind methadone or buprenorphine. Patients were participants in the international, randomized controlled Maternal Opioid Treatment: Human Experimental Research (MOTHER) study. METHODS: A sample of opioid-maintained pregnant patients (18-41 years old) with available smoking data who completed a multisite, double-blind, double-dummy, randomized controlled trial of methadone (n = 67) and buprenorphine (n = 57) between 2005 and 2008. Participants were compared on smoking variables based on opioid agonist treatment condition. RESULTS: Overall, 95% of the sample reported cigarette smoking at treatment entry. Participants in the two medication conditions were similar on pretreatment characteristics including smoking rates and daily cigarette amounts. Over the course of the pregnancy, no meaningful changes in cigarette smoking were observed for either medication condition. The fitted difference in change in adjusted cigarettes per day between the two conditions was small and nonsignificant (ß = -0.08, SE = 0.05, p = .132). CONCLUSIONS: Results support high rates of smoking with little change during pregnancy among opioid-dependent patients, regardless of the type of agonist medication received. These findings are consistent with evidence that suggests nicotine effects, and interactions may be similar for buprenorphine compared with methadone. The outcomes further highlight that aggressive efforts are needed to reduce/eliminate smoking in opioid-dependent pregnant women.

Cigarette smoking in opioid-dependent pregnant women: neonatal and maternal outcomes.

BACKGROUND: The relationship between cigarette smoking and neonatal and maternal clinical outcomes among opioid-agonist-treated pregnant patients is sparse. OBJECTIVES: (1) Is smoking measured at study entry related to neonatal and maternal outcomes in pregnant women receiving opioid-agonist medication? (2) Is it more informative to use a multi-item measure of smoking dependence or a single-item measure of daily smoking? (3) Is the relationship between smoking at study entry and outcomes different between methadone and buprenorphine? METHODS: Secondary analyses examined the ability of the tobacco dependence screener (TDS) and self-reported past 30-day daily average number of cigarettes smoked, both measured at study entry, to predict 12 neonatal and 9 maternal outcomes in 131 opioid-agonist-maintained pregnant participants. RESULTS: Past 30-day daily average number of cigarettes smoked was significantly positively associated with total amount of morphine (mg) needed to treat neonatal abstinence syndrome (NAS), Adjusted Odds Ratio (AOR)=1.06 (95% CI: 1.02, 1.09), number of days medicated for NAS, AOR=1.04 (95% CI: 1.01, 1.06), neonatal length of hospital stay in days, AOR=1.03 (95% CI: 1.01, 1.05), and negatively associated with 1-AOR=.995 (95% CI: .991,.999) and 5-min Apgar scores, AOR=.996 (95% CI: .994,.998). Simple effect tests of the two significant TDS×medication condition effects found TDS was unrelated to non-normal presentation and amount of voucher money earned in the methadone [AORs=.90 (95% CI: .74, 1.08, p>.24) and 1.0 (95% CI: .97, 1.03, p>.9)] but significant in the buprenorphine condition [AORs=1.57 (95% CI: 1.01, 2.45, p<.05) and 1.08 (95% CI: 1.04, 1.12, p<.01)]. CONCLUSIONS: Regardless of prenatal methadone or buprenorphine exposure, heavier cigarette smoking was associated with more compromised birth outcomes.

Predicting treatment for neonatal abstinence syndrome in infants born to women maintained on opioid agonist medication.

AIM: To identify factors that predict the expression of neonatal abstinence syndrome (NAS) in infants exposed to methadone or buprenorphine in utero. DESIGN AND SETTING: Multi-site randomized clinical trial in which infants were observed for a minimum of 10 days following birth, and assessed for NAS symptoms by trained raters. PARTICIPANTS: A total of 131 infants born to opioid dependent mothers, 129 of whom were available for NAS assessment. MEASUREMENTS: Generalized linear modeling was performed using maternal and infant characteristics to predict: peak NAS score prior to treatment, whether an infant required NAS treatment, length of NAS treatment and total dose of morphine required for treatment of NAS symptoms. FINDINGS: Of the sample, 53% (68 infants) required treatment for NAS. Lower maternal weight at delivery, later estimated gestational age (EGA), maternal use of selective serotonin re-uptake inhibitors (SSRIs), vaginal delivery and higher infant birthweight predicted higher peak NAS scores. Higher infant birthweight and greater maternal nicotine use at delivery predicted receipt of NAS treatment for infants. Maternal use of SSRIs, higher nicotine use and fewer days of study medication received also predicted total dose of medication required to treat NAS symptoms. No variables predicted length of treatment for NAS. CONCLUSIONS: Maternal weight at delivery, estimated gestational age, infant birthweight, delivery type, maternal nicotine use and days of maternal study medication received and the use of psychotropic medications in pregnancy may play a role in the expression of neonatal abstinence syndrome severity in infants exposed to either methadone or buprenorphine.

Effectiveness of a smoking cessation intervention for methadone-maintained women: a comparison of pregnant and parenting women.

Women in substance abuse programs have high rates of smoking. Pregnancy represents a unique opportunity for intervention, but few data exist to guide tailoring of effective interventions. In this study, 44 pregnant and 47 nonpregnant opioid-dependent women enrolled in comprehensive substance abuse treatment received a 6-week smoking cessation intervention based on the 5A's counseling model. The number of daily cigarettes decreased by 49% for pregnant patients and 32% for nonpregnant patients at the 3-month followup. Length of time in substance abuse treatment did not correlate with smoking cessation or reduction for either group. Factors predicting reduction of cigarette smoking differed for pregnant versus nonpregnant patients. For pregnant patients, lower levels of nicotine use prior to intervention and self-reported cigarette cravings predicted successful reduction in smoking. For nonpregnant patients, lower affiliative attachment to cigarettes, reliance on cigarettes for cognitive enhancement, and greater sense of control predicted more successful outcomes.

Cigarette Smoking and Neonatal Outcomes in Depressed and Non-Depressed Opioid-Dependent Agonist-Maintained Pregnant Patients.

AIMS: To investigate whether cigarette smoking and/or depression contribute to neonatal abstinence syndrome (NAS) severity. DESIGN: Cohort study analyzing data from a randomized, controlled trial of methadone versus buprenorphine. SETTING: Seven study sites that randomized patients to study conditions and provided comprehensive addiction treatment to pregnant patients. PARTICIPANTS: 119 of 131 opioid-dependent pregnant patients who completed the MOTHER study. MEASUREMENTS: Smoking data and depression status were obtained from the Addiction Severity Index and Mini International Neuropsychiatric Interview, respectively. Neonatal outcomes (birth weight, preterm delivery and NAS pharmacologic treatment) were collected from the medical charts. Study site was a fixed-effect factor in all analyses. FINDINGS: Cigarette smoking was reported by 94% of participants and depression identified in 35%. Smoking was associated with low birth weight, preterm delivery, and NAS pharmacologic treatment in both depressed and non-depressed participants. The association between smoking and NAS treatment differed significantly between depressed and non-depressed participants. Among non-depressed participants, adjusting for site and illicit drug use, each additional average cigarette per day (CPD) increased the odds of NAS treatment by 12% [95%CI: (1.02-1.23), p=0.02]. Among depressed participants, each additional average CPD did not statistically increase the odds of NAS treatment [OR: 0.94, 95% CI: (0.84-1.04), p=0.23]. CONCLUSIONS: These results are consistent with the hypothesis that NAS expression is influenced by many factors. The relationship between CPD and NAS pharmacologic treatment is attenuated among depressed women in this study for reasons currently unknown. Further investigations are needed to clarify the complex relationships among maternal smoking, depression, and NAS.

Maternal methadone dose and neonatal withdrawal.

OBJECTIVE: The purpose of this study was to determine whether maternal methadone dosage correlates with neonatal withdrawal in a large heroin-addicted pregnant population. STUDY DESIGN: A retrospective review of all maternal/neonatal records of pregnancies that were maintained on methadone therapy in our institution was conducted. After in-hospital stabilization, women were given daily methadone therapy under direct surveillance, with liberal dosage increases according to maternal withdrawal symptoms. Neonatal withdrawal was assessed objectively by the neonatal abstinence score. The average methadone dose in the last 12 weeks of pregnancy and the last methadone dose before delivery (cutoffs of 40, 60, or 80 mg) were correlated to various objective measures of neonatal withdrawal. RESULTS: One hundred mother/neonate pairs on methadone therapy were identified. Women who received an average methadone dose of <80 mg (n=50 women) had a trend toward a higher incidence of illicit drug abuse before delivery than women who received doses of >/=80 mg (n=50 women; 48% vs 32%; P=.1). Women who received an average methadone dose of <80 mg had similar highest neonatal abstinence score, need for neonatal treatment for withdrawal, and duration of withdrawal compared with women whose condition was maintained with dosages of >/=80 mg (score, 11.1 vs 11.5; 68% vs 66%; and 13.3 vs 13.6 days, respectively; all P>.5). For all cutoffs that were used for high versus low dose and for both the average and last methadone dosage analyses, neonatal withdrawal was similar. CONCLUSION: The maternal methadone dosage does not correlate with neonatal withdrawal; therefore, maternal benefits of effective methadone dosing are not offset by neonatal harm.