Outcomes associated with the use of medications for opioid use disorder during pregnancy

Abstract

Aim: To test the effect of the duration of medication for opioid use disorder (MOUD) use during pregnancy on maternal, perinatal and neonatal outcomes.

Design: Retrospective cohort analysis of claims, encounter and pharmacy data.

Setting: Pennsylvania, USA.

Participants: We analyzed 13 320 pregnancies among 10 741 women with opioid use disorder aged 15-44 years enrolled in Pennsylvania Medicaid between 2009 and 2017.

Measurements: We examined five outcomes during pregnancy and for 12 weeks postpartum: (1) overdose, (2) postpartum MOUD continuation, (3) preterm birth (< 37 weeks gestation), (4) term low birth weight (< 2500 g at ≥ 37 weeks) and (5) neonatal abstinence syndrome (NAS). Our primary exposure was the duration (count of weeks) of any MOUD use, including methadone or buprenorphine, during pregnancy.

Findings: Among 13 320 pregnancies, 306 (2.3%) were complicated by an overdose, 1753 (13.2%) resulted in a preterm birth and 6787 (50.9%) continued MOUD postpartum. Among infants, 874 (7.6%) were low birth weight at term and 7706 (57.9%) were diagnosed with NAS. As the duration of MOUD use increased, we found a statistically significant decrease in the rate of overdose and preterm birth, a statistically significant increase in the rate of postpartum MOUD continuation and NAS and a decline in term low birth weight. Specifically, for each additional week of MOUD, the adjusted odds of overdose decreased by 2% [adjusted odds ratio (aOR) = 0.98; 95% confidence interval (CI) = 0.97, 0.99], preterm birth decreased by 1% (aOR = 0.99; 95% CI = 0.99, 1.00), postpartum MOUD continuation increased by 95% (aOR = 1.95; 95% CI = 1.87, 2.04) and NAS increased by 41% (aOR = 1.41; 95% CI = 1.35, 1.47). The odds of term low birth weight did not change (aOR = 1.00; 95% CI = 0.99, 1.00), although the rate declined with a longer duration of MOUD use during pregnancy.

Conclusions: Longer duration of medication for opioid use disorder use during pregnancy appears to be associated with improved maternal and perinatal outcomes.

Keywords: Low birthweight; NAS; medication for opioid use disorder; neonatal abstinence syndrome; opioid use disorder; overdose; postpartum; pregnancy; preterm birth; substance use disorder.

Figure 1

(a,b), Maternal outcomes associated with medications for opioid use disorder (MOUD) use during pregnancy. Association between duration of MOUD in pregnancy and (a), overdose and (b) postpartum MOUD continuation. Average predicted probabilities and 95% confidence intervals (CIs) were derived using marginal standardization from multivariable logistic regression models (log-binomial model for overdose) adjusted for age, race/ethnicity, psychiatric disorders, non-OUD substance use disorders, tobacco use disorder, alcohol use disorder, maternal HIV or hepatitis C virus (HCV) infection, and any prescription use of either selective serotonin re-uptake inhibitors (SSRIs), gabapentins or benzodiazepines. Robust sandwich estimator was used to account for non-independence of observations within each person. Weeks’ duration of MOUD in pregnancy is modeled as a continuous exposure for overdose and as a restricted cubic spline term for postpartum MOUD continuation. Overdose defined as any overdose event in pregnancy or within 12 weeks after delivery; postpartum MOUD utilization is any utilization in first 12 weeks after delivery.

Figure 1

(a,b), Maternal outcomes associated with medications for opioid use disorder (MOUD) use during pregnancy. Association between duration of MOUD in pregnancy and (a), overdose and (b) postpartum MOUD continuation. Average predicted probabilities and 95% confidence intervals (CIs) were derived using marginal standardization from multivariable logistic regression models (log-binomial model for overdose) adjusted for age, race/ethnicity, psychiatric disorders, non-OUD substance use disorders, tobacco use disorder, alcohol use disorder, maternal HIV or hepatitis C virus (HCV) infection, and any prescription use of either selective serotonin re-uptake inhibitors (SSRIs), gabapentins or benzodiazepines. Robust sandwich estimator was used to account for non-independence of observations within each person. Weeks’ duration of MOUD in pregnancy is modeled as a continuous exposure for overdose and as a restricted cubic spline term for postpartum MOUD continuation. Overdose defined as any overdose event in pregnancy or within 12 weeks after delivery; postpartum MOUD utilization is any utilization in first 12 weeks after delivery.

Figure 2

(a-c) Perinatal and neonatal outcomes associated with medications for opioid use disorder (MOUD) use during pregnancy. Association between duration of MOUD in pregnancy and (a) preterm birth, (b), term low birth weight and (c), neonatal abstinence syndrome (NAS). Average predicted probabilities and 95% confidence intervals (CIs) were derived using marginal standardization from multivariable logistic regression models (log-binomial model for overdose) adjusted for age, race/ethnicity, psychiatric disorders, non-OUD substance use disorders, tobacco use disorder, alcohol use disorder, maternal HIV or hepatitis C virus (HCV) infection, chronic hypertension, diabetes mellitus, gestational diabetes mellitus, gestational hypertensive disorder and any prescription use of either SSRIs, gabapentinoids or benzodiazepines. Robust sandwich estimator was used to account for non-independence of observations within each person. Weeks’ duration of MOUD in pregnancy is modeled as a continuous exposure for term low birth weight and preterm birth and as a restricted cubic spline term for NAS. Term low birth weight is < 2500 g among infants born at ≥ 37 weeks’ gestation; preterm birth is < 37 weeks’ gestation; NAS is based on diagnoses in the first 90 days of life, excluding codes indicating iatrogenic withdrawal.

Figure 2

(a-c) Perinatal and neonatal outcomes associated with medications for opioid use disorder (MOUD) use during pregnancy. Association between duration of MOUD in pregnancy and (a) preterm birth, (b), term low birth weight and (c), neonatal abstinence syndrome (NAS). Average predicted probabilities and 95% confidence intervals (CIs) were derived using marginal standardization from multivariable logistic regression models (log-binomial model for overdose) adjusted for age, race/ethnicity, psychiatric disorders, non-OUD substance use disorders, tobacco use disorder, alcohol use disorder, maternal HIV or hepatitis C virus (HCV) infection, chronic hypertension, diabetes mellitus, gestational diabetes mellitus, gestational hypertensive disorder and any prescription use of either SSRIs, gabapentinoids or benzodiazepines. Robust sandwich estimator was used to account for non-independence of observations within each person. Weeks’ duration of MOUD in pregnancy is modeled as a continuous exposure for term low birth weight and preterm birth and as a restricted cubic spline term for NAS. Term low birth weight is < 2500 g among infants born at ≥ 37 weeks’ gestation; preterm birth is < 37 weeks’ gestation; NAS is based on diagnoses in the first 90 days of life, excluding codes indicating iatrogenic withdrawal.

Figure 2

(a-c) Perinatal and neonatal outcomes associated with medications for opioid use disorder (MOUD) use during pregnancy. Association between duration of MOUD in pregnancy and (a) preterm birth, (b), term low birth weight and (c), neonatal abstinence syndrome (NAS). Average predicted probabilities and 95% confidence intervals (CIs) were derived using marginal standardization from multivariable logistic regression models (log-binomial model for overdose) adjusted for age, race/ethnicity, psychiatric disorders, non-OUD substance use disorders, tobacco use disorder, alcohol use disorder, maternal HIV or hepatitis C virus (HCV) infection, chronic hypertension, diabetes mellitus, gestational diabetes mellitus, gestational hypertensive disorder and any prescription use of either SSRIs, gabapentinoids or benzodiazepines. Robust sandwich estimator was used to account for non-independence of observations within each person. Weeks’ duration of MOUD in pregnancy is modeled as a continuous exposure for term low birth weight and preterm birth and as a restricted cubic spline term for NAS. Term low birth weight is < 2500 g among infants born at ≥ 37 weeks’ gestation; preterm birth is < 37 weeks’ gestation; NAS is based on diagnoses in the first 90 days of life, excluding codes indicating iatrogenic withdrawal.