Treating Pregnant and Parenting Women for Substance Use Disorders: Behavioral and Medication Strategies



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  • MOTHER provided the first randomized controlled trial data to support the safety and efficacy of methadone.
  • Maternal outcomes are similar between medications.
  • Pain management and breastfeeding recommendations are similar between medications.
  • In terms of NAS severity, buprenorphine should be a front-line medication option for managing opioid use disorder in pregnant women who are new to treatment or maintained on buprenorphine pre-pregnancy.
  • NAS, its treatment and elucidating factors that exacerbate and minimize it, remains a significant clinical concern for prenatally opioid-exposed neonates.
  • Currently there is great variation in terms of medications and use of tools.
  • Methadone and Buprenorphine: Summary

Neonatal Opioid Withdrawal: Early History

  • 1875 to 1900 multiple reports of congenital morphinism – most died, no specific treatment offered
  • 1903 report about congenital morphinism –treated infant with morphine
  • JAMA, 1903
  • Jones & Fielder, Preventive Medicine 2015

Timeline of Neonatal Opioid Withdrawal History

  • 1964 Methadone introduced as pharmacotherapy
  • 1965 Goodfriend et al. report neonatal withdrawal signs
  • 1971 Zelson et al reported frequency of signs on neonatal withdrawal in 259 of 384 infants born to drug-abusing mothers
  • 1975 Desmond and Wilson publish Neonatal Abstinence Syndrome: Recognition and Diagnosis
  • 1975 Finnegan et. al. publish a neonatal abstinence syndrome tool

NOWS: Signs and Symptoms

  • Signs of withdrawal typically start after 24-96 hours after birth depending upon the specific opioid exposure
  • Central nervous system signs
    • Tremors
    • Irritability, high-pitched crying
    • Sleep disturbances
    • Tight muscles tone, hyperactive reflexes
    • Myoclonic jerks (sometimes misinterpreted as seizures), seizures - rare
  • Autonomic signs
    • Sweating, fever, yawning and sneezing
    • Rapid breathing, nasal congestion
  • Gastrointestinal signs

NOWS: Untreated

  • What would happen if NOWS is untreated?
  • Depends upon the severity
  • There are many infants who do not receive medication for NOWS and their outcome is good.
  • However, an irritable, crying baby who does not sleep and cannot feed will be at risk for:
  • Excessive irritability and dehydration are very likely to lead the caregiver to seek medical attention.
  • An infant may die without treatment – however, in an extensive literature search, the only reported deaths occurred over 100 years ago.
  • NOWS does not necessarily lead to poor neurodevelopmental outcomes.

NOWS: Increasing in the USA

  • Patrick et al, J of Perinatology 2015
  • 2012:
  • 21,732 newborns
  • ~$1.5 billion
  • 81.5% Medicaid
  • ↑ complications

Tolia et al., N Engl J Med 2015

  • NOWS: Increasing Admissions
  • Other factors that contribute to severity of NAS in neonates exposed to opioid agonists in utero:
  • Genetics
  • Other Substances
    • Cigarette smoking
    • Benzodiazepines
    • SSRIs
  • Hospital Protocols
    • - The NAS assessment and medication
    • initiation and weaning protocols
    • Not breastfeeding
    • Rooming in or separating mother and baby
  • Image Credits: “Woman Smoking E-cigarette” by patrisyu; “Embryonic Development” by dream designs
  • Jansson & Velez, Curr Opin Pediatrics 2012
  • NAS: Factors
  • Pathophysiology of Neonatal Opioid Withdrawal
  • Adapted from Kocherlakota, Pediatrics 2014
  • Credit: Anne Johnston, MD
  • To determine whether concurrent in utero exposure to buprenorphine and antidepressants impacts the course of neonatal abstinence syndrome (NAS) in infants.
  • A retrospective cohort study of 148 infants who were exposed to buprenorphine during pregnancy. Univariate and bivariate analyses were used to examine associations between concurrent maternal use of buprenorphine and antidepressants as compared to maternal use of buprenorphine alone.
  • The time to onset of NAS resolution was significantly longer in infants exposed to both buprenorphine and antidepressants during pregnancy when compared to infants exposed to buprenorphine alone (129.8 h v. 70.2 h, p = .042).
  • Women who are prescribed both antidepressants and buprenorphine during pregnancy should be counseled about the possibility of a prolonged course of neonatal abstinence syndrome.
  • O'Connor et al., J Matern Fetal Neonatal Med 2014
  • NAS: Factors
  • MOTHER Study: Cigarette Smoking NAS
  • RESULTS
  • Average number of cigarettes smoked in the past 30 days was significantly positively related to:
  • Total amount of morphine needed to treat NAS
  • Number of days neonate was medicated for NAS
  • Neonatal length of hospital stay
  • OLS and Poisson regression analyses were used to test average number of cigarettes smoked in the past 30 days at α= .05, adjusting for both Medication Condition and Site. Below-average cigarette smoking was defined as 6 cigarettes/day (-1 SD), average cigarette smoking as 14 cigarettes/day (Mean), and above-average cigarette smoking as 21 cigarettes/day (+1 SD).
  • Jones et al., Drug Alc Depend 2012
  • RESULTS
  • Average number of cigarettes smoked in the past 30 days was significantly negatively related to:
  • Neonatal weight at birth
  • Apgar score at 1 minute
  • Apgar score at 5 minutes
  • Maternal weight gain, study entry to delivery
  • OLS and Poisson regression analyses were used to test average number of cigarettes smoked in the past 30 days at α= .05, adjusting for both Medication Condition and Site. Below-average cigarette smoking was defined as 6 cigarettes/day (-1 SD), average cigarette smoking as 14 cigarettes/day (Mean), and above-average cigarette smoking as 21 cigarettes/day (+1 SD).
  • MOTHER Study: Other Outcomes
  • Jones et al., Drug Alc Depend 2012
  • A Practical Viewpoint on the Results
  • Relative to a pregnant woman in opioid agonist treatment who didn’t smoke during her pregnancy, a pregnant woman in opioid agonist treatment who smokes a pack of cigarettes a day on average during her pregnancy would likely face:
  • More than triple the total amount of morphine needed to treat her neonate’s NAS
  • More than double the number of days required to treat her neonate’s NAS
  • Almost double the length of hospital stay for her neonate
  • A more than 8% decrease in her neonate’s birth weight
  • A decrease of almost 1 point in her neonate’s Apgar scores at 1 minute
  • A more than ½ point decrease in her neonate’s Apgar scores at 5 minutes
  • A more than 3 kg (more than 7 lbs.) decrease in her own weight gain during pregnancy
  • Jones et al., Drug Alc Depend 2012
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