Tox in The Land: Opioid Use Disorder in Pregnancy

Epidemiology

  • 39.4% of Medicaid insured and 27.7% of privately insured women of reproductive age (15-44 years) filled an outpatient prescription for an opioid each year (2008-2012) (1)

    Proportion of pregnant women admitted to substance abuse treatment facilities that reported a history of prescription opioid abuse increased from 2% to 28% between 1992-2012 (2)

  • By 2012, one infant was born, on average, every 30 minutes in the United States having drug withdrawal (NAS), accounting for an estimated $1.5 billion in healthcare expenditures (3)

Medical-Assisted vs Non-Assisted Withdrawal

  • Previously thought medically assisted withdrawal was associated with adverse fetal outcomes such as stillbirth, fetal stress, which has since been disproven (4, 5)

    • Systematic reviews have reported that fetal loss and preterm birth rates were similar among patients who did and did not undergo medically assisted withdrawal (6)

  • Medication for opioid use disorder is now preferred, methadone or buprenorphine.

    • Prevents withdrawal symptoms, reduces or eliminates cravings.

Methadone

  • Daily visits to federally certified opioid treatment program

  • Greater risk of sedation compared to partial agonists

  • 50% exposed neonates treated for NAS

    • Monitor for 4-7 days after delivery (7)

    • Longer NAS duration compared to buprenorphine

  • Safe for breastfeeding (8)

 

Buprenorphine

  • Can be prescribed in office setting with weekly to bi-weekly dispensing

    • Meta-analysis did not detect any statistically significant differences when comparing the groups of women using buprenorphine-naloxone with the groups of women prescribed with other medications as part of the medication-assisted treatment (9)

  • Milder risk of sedations effects compared to methadone (full mu opioid agonists)

  • Decreased risk severity of neonatal withdrawal for patients with OUD (10)

  • Lower risk of preterm birth, higher birth weight, larger head circumference compared to methadone (11)

  • 50% of neonates are treated for NAS

    • May be milder compared to full mu opioid agonists

    • Monitor neonates 4-7 days after delivery (12)

    • Shorter NAS duration compared to methadone

  • Safe for breastfeeding (13)

Neonatal Abstinence Syndrome

  • Symptoms:

    • Sleep & wake cycle disturbances: fragmented sleep, difficulty staying awake

    • Changes in tone: hypertonicity, tremors, jitteriness

    • Autonomic dysfunction: sweating, sneezing, mottling, fever, yawning

    • Easy over-stimulation, sensitivity, hyperarousal: irritability, crying

    • Difficulties with feeding: poor weight gain, tachypnea, GI symptoms

    • Low birth weight 2/2 intrauterine growth restriction

https://www.nature.com/articles/s41572-018-0045-0

 

Prenatal Buprenorphine vs Methadone Exposures & Neonatal Outcomes: Systematic Review & Meta-Analysis

  • Systematic review, meta-analysis from Jan 2000 to Oct 2013 for total of 515 BMT-exposed and 855 MMT-exposed neonates

  • Risk ratio of NAS treatment was 0.90 (95% confidence interval (CI): 0.81, 0.98) in BMT-exposed versus MMT-exposed neonates

  • Average hospital stay was shorter (−7.23 days, 95% CI: −10.64, −3.83) for BMT

  • Length of treatment (−8.46 days, 95% CI: −14.48, −2.44) and the total amount of morphine used (−3.60 mg, 95% CI: −7.26, 0.07) were lower in BMT-exposed versus MMT-exposed neonates

  • Mean differences in gestational age at birth (0.89 weeks, 95% CI: 0.50, 1.29), birth weight (243.63 g, 95% CI: 154.36, 332.91), body length (1.34 cm, 95% CI: 0.69, 1.99), and head circumference (0.87 cm, 95% CI: 0.45, 1.29) were higher in BMT-exposed versus MMT-exposed neonates

  • No difference in the risk of preterm birth (<37 vs. ≥37 weeks’ gestation) by exposure (risk ratio = 0.82, 95% CI: 0.46, 1.45) (14)

Conclusions

  • Medication-assisted withdrawal is preferred

  • Can use buprenorphine or methadone, no change in fetal or maternal outcomes

  • May reduce hospital duration or treatment of NAS for buprenorphine compared to methadone

  • Monitor for NAS and treat as needed

AUTHORED BY: AUBREY STICKLAND, MS4

FACULTY EDITING BY: LAUREN PORTER, DO


References

  1. Ailes EC, Dawson AL, Lind JN, Gilboa SM, Frey MT, Broussard CS, Honein MA. Opioid Prescription Claims Among Women of Reproductive Age - United States, 2008-2012. MMWR Morb Mortal Wkly Rep. 2015;64(2):1–41.

  2. Martin CE, Longinaker N, Terplan M. Recent trends in treatment admissions for prescription opioid abuse during pregnancy. J of Subst Abuse Treat. 2015;48(1):37–42.

  3. Patrick SW, Davis MM, Lehmann CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 2009 to 2012. J Perinatol. 2015;35(8):650–655.

  4. Rementeriá JL, Nunag NN. Narcotic withdrawal in pregnancy: stillbirth incidence with a case report. Am J Obstet Gynecol. 1973 Aug 15;116(8):1152-6.

  5. Zuspan FP, Gumpel JA, Mejia-Zelaya A, Madden J, Davis R. Fetal stress from methadone withdrawal. Am J Obstet Gynecol. 1975 May 1;122(1):43-6. doi: 10.1016/0002-9378(75)90613-4. PMID: 1130446. Zuspan FP, Gumpel JA, Mejia-Zelaya A, Madden J, Davis R. Fetal stress from methadone withdrawal. Am J Obstet Gynecol. 1975 May 1;122(1):43-6.

  6. Terplan M, Laird HJ, Hand DJ, Wright TE, Premkumar A, Martin CE, Meyer MC, Jones HE, Krans EE. Opioid Detoxification During Pregnancy: A Systematic Review. Obstet Gynecol. 2018 May;131(5):803-814.

  7. Hudak ML, Tan RC, American Academy of Pediatrics (AAP) Committee on Drugs, AAP Committee on Fetus and Newborn. Neonatal drug withdrawal. Pediatrics 2012; 129:e540.

  8. Reece-Stremtan S, Marinelli KA. AMB clinical protocol #21: Guidelines for breastfeeding and substance use disorder, revised 2015. Breastfeed Med 2015; 10:135.

  9. Link HM, Jones H, Miller L, Kaltenbach K, Seligman N. Buprenorphine-naloxone use in pregnancy: a systematic review and metaanalysis. Am J Obstet Gynecol MFM. 2020 Aug;2(3):100179.

  10. Nanda S, Brant R, Regier M, Yossuck P. Buprenorphine: a new player in neonatal withdrawal syndrome. W V Med J. 2015 Jan-Feb;111(1):16-21. PMID: 25665273.

  11. Zedler BK, Mann AL, Kim MM, Amick HR, Joyce AR, Murrelle EL, Jones HE. Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child. Addiction. 2016 Dec;111(12):2115-2128.

  12. Hudak ML, Tan RC, American Academy of Pediatrics (AAP) Committee on Drugs, AAP Committee on Fetus and Newborn. Neonatal drug withdrawal. Pediatrics 2012; 129:e540.

  13. Reece-Stremtan S, Marinelli KA. AMB clinical protocol #21: Guidelines for breastfeeding and substance use disorder, revised 2015. Breastfeed Med 2015; 10:135.

  14. Brogly, S. B., Saia, K. A., Walley, A. Y., Du, H. M., & Sebastiani, P. (2014). Prenatal buprenorphine versus methadone exposure and neonatal outcomes: Systematic review and metaanalysis.American Journal of Epidemiology, 180(7), 673–686.

ToxLauren McCaffertytoxicology, medtox, tox, opioid, pregnancy