Pregnant and high: new treatments?

Many years ago a woman came to OB triage at my hospital.  She was about 28 weeks pregnant and feeling horrible.   As the nurses hooked her up to monitors and started an IV, she clutched a pink, kidney-shaped emesis basin, her boyfriend holding her hair back and away.  A few minutes later, she called for the nurse urgently—she had to go to the bathroom.   The nurse detached her from her IV and her monitors.  The patient shuffled to the bathroom, basin in one hand, purse clutched in the other.  She returned from the bathroom and lay back on the gurney, appearing much more comfortable.  I watched the nurse get her settled back in, and as the patient turned, her purse fell on the floor and a syringe rolled out.

Drug dependence among pregnant women is tough to track. By some reports, about 4% of pregnant women admit to illicit drug use.  I haven’t been able to find statistics on opiate dependence in pregnancy, but opiate misuse is not an uncommon problem.  In addition to heroin, misuse of prescription drugs such as Vicodin and oxycodone has been on the rise among adults.

While drug use has obvious effects on the mother, maternal opiate dependence has health consequences for the newborn as well.  One of these consequences is “neonatal abstinence syndrome” (NAS), basically opiate withdrawal in the newborn.  In addition to increased risk for viral hepatitis and HIV if intravenous drugs are used, babies born to opiate-dependent mothers can be underweight, and can have significant irritability and feeding problems.  They can also have vomiting, diarrhea, dehydration—a wide variety of problems that would be uncomfortable for an adult but can be potentially life-threatening for an infant (although mortality rates are probably quite low).

For many years, methadone has been used to help control opioid dependence in pregnant women.  If patients have safe access to methadone, they are less likely to seek illegal drugs or to inject drugs.   But methadone is a “regular opiate”, strongly binding to and stimulating the mu-opioid receptor, giving us the effects we classically associate with morphine and heroin.  Methadone can lead to NAS, and infants born to methadone-dependent mothers can require long-term use of opioids themselves.  Another drug, buprenorphine, binds opioid receptors differently and among its effects is a reportedly less severe withdrawal syndrome.  Buprenorphine is gaining some acceptance in maintenance therapy for opiate dependence, and a new study in the New England Journal of Medicine examines its potential to reduce the incidence of neonatal abstinence syndrome.

Researchers recruited opiate-dependent pregnant women and randomly assigned them to double-blind use of either methadone or buprenorphine.  A significant number of women dropped out of the study, but study was otherwise pretty good.  The authors looked at five outcomes: number of neonates requiring treatment for NAS, peak NAS score, total amount of morphine needed for treatment of NAS, length of hospital stay, and head circumference.   Infants in both groups were just as likely to require treatment for NAS, and their NAS was equally severe.  But the buprenorphine group required less total morphine and shorter hospitalizations.  While these results are interesting, the authors took a bit of a leap in their conclusions (emphasis mine):

In summary, our findings are consistent with the use of buprenorphine as an alternative to methadone for the treatment of opioid dependency during pregnancy. Although there were no significant differences in overall rates of NAS among infants exposed to buprenorphine and those exposed to methadone, the benefits of buprenorphine in reducing the severity of NAS among neonates with this complication suggest that it should be considered a first-line treatment option in pregnancy.

Here, they seem to be wiggling around with the definition of “severity”.  Be that as it may, it’s an interesting study.  One of the interesting findings was that women more often dropped out of the buprenorphine group, citing dissatisfaction.   It would be useful to investigate the relative risks and benefits of a treatment that may be marginally better but is associated with worse patient adherence.

Working with people with opiate use disorders can be difficult for a variety of reasons.  This study gives us a bit more data, but I don’t see it as dramatically changing the way we practice.

References

Jones, H., Kaltenbach, K., Heil, S., Stine, S., Coyle, M., Arria, A., O’Grady, K., Selby, P., Martin, P., & Fischer, G. (2010). Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure New England Journal of Medicine, 363 (24), 2320-2331 DOI: 10.1056/NEJMoa1005359

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