Intrauterine Exposure to Methadone or Buprenorphine: Incidence and Severity of Neonatal Abstinence Syndrome

Abstract

Background: Opioid maintenance treatment (OMT) has been the standard of care for opioid dependent pregnant women and is associated with positive outcomes for the mother and the infant. However, intrauterine exposure to methadone or buprenorphine is associated with a significant risk of neonatal abstinence syndrome (NAS). The Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a comprehensive, multi-centre, randomized clinical trial has found that the infants born to women who received buprenorphine had milder symptoms of NAS than those born to women who received methadone. Buprenorphine treatment is also more accessible in primary care settings especially to the patients with a prescription opioid dependence which is an increasing problem in USA and many other developed countries. The primary aim of this study is to examine the relationship between maternal methadone or buprenorphine dose at the time of delivery and, incidence and severity of neonatal abstinence syndrome. Methods: This is a retrospective observational study of pregnant women on methadone or buprenorphine treatment and their babies (N ¼ 218: Methadone 194; Buprenorphine 24) who were delivered at The Canberra Hospital between January 2001 and December 2016. This study was conducted with ethics approval of ACT Health Human Research Ethics Committee. Neonates were divided into two groups based on exposure to methadone or buprenorphine and were compared in terms of NAS and other 298 June 2018 neonatal outcomes. A modified Finnegan score was used to monitor the neonates for NAS. The primary outcome was NAS reaching threshold for treatment- neonates scoring 8 or more on three consecutive scores or 12 or more on two consecutive scores. Neonates in the methadone group were further divided into two groups based on mother’s methadone dose at delivery Low dose (7.5–50 mg) vs High dose (51 170 mg). Receiver operating characteristic (ROC) curve was used to determine the cut off for low dose and high dose groups. The cut-off dose of 50 mg provides a sensitivity of 84% and specificity of 62%. Statistical analysis was performed using SPSS v24. Results: A total of 118 (54%) of neonates reached the threshold for NAS requiring treatment, comprised of 56% (n ¼ 109) in the methadone exposure group and 37% (n ¼ 9) in the buprenorphine exposure group. A total of 109 (56%) of neonates in the methadone group reached the threshold for NAS requiring treatment, comprised of 36% (n ¼ 20) of neonates in the low dose group and 64% (n ¼ 89) of neonates in the high dose group. Logistical regression model showed a significant three-fold increase in incidence of NAS in the high dose exposure group (Exp(B) 3.125; p ¼.001). There were no statistically significant differences between the two dose exposure groups in relation to maternal heroin use during pregnancy, gestational age, preterm delivery, birth weight or head circumference. There was no association between maternal buprenorphine dose and incidence of NAS in this study, There was also no association between maternal buprenorphine or methadone dose and severity of NAS as defined by length of treatment with morphine, total morphine in mg, length of hospital stay and peak Finnegan score. Conclusions: Intrauterine exposure to methadone or buprenorphine is associated with a significant risk of NAS. We found a significant positive correlation between maternal methadone dose and NAS in this study. We also came to the conclusion that the watershed dose of methadone for NAS is 50 mg. Infants exposed to more than 50 mg of maternal methadone dose in intrauterine life are three times more likely to develop NAS compared to exposure less than 50 mg in this study. Rest of the findings of this study are consistent with current research and we came to similar conclusions as in MOTHER study. There was no association between NAS severity and maternal buprenorphine or methadone dose. Currently methadone is the gold standard of treatment for opioid dependent pregnant women. However, there is growing evidence for the use of buprenorphine as a safe and effective treatment in pregnancy. Considering that prescription opioid abuse is a major public health problem, physicians need to consider buprenorphine as a treatment option for pregnant women as it is more accessible in outpatient and primary care setting where they can access antenatal care as well. Treating physician has to consider the implications of NAS for the baby, the mother, and healthcare resources. Summary: This poster will provide an understanding of what is neonatal abstinence syndrome (NAS), current literature review of treatment options (methadone and buprenorphine) for opioid dependent pregnant women and implications of NAS both in terms of incidence and severity of NAS. Although methadone remains the gold standard treatment for opioid dependent pregnant women, it is important to assess the needs of each patient and balance the risks of stability on treatment of the mother and risk of NAS in the neonate. There is growing evidence for the use of buprenorphine as a first line treatment of opioid dependent pregnant women. Considering that prescription opioid abuse is a major public health problem, physicians need to consider buprenorphine as a treatment option for pregnant women as it is more accessible in outpatient and primary care setting where they can access antenatal care as well. Show more