1. Krista F Huybrechts, assistant professor of medicine1,
  2. Brian T Bateman, associate professor of anesthesiology2,
  3. Rishi J Desai, instructor in medicine1,
  4. Sonia Hernandez-Diaz, professor of epidemiology3,
  5. Kathryn Rough, postdoctoral research fellow3,
  6. Helen Mogun, analyst1,
  7. Leslie S Kerzner, assistant professor of pediatrics4,
  8. Jonathan M Davis, professor of pediatrics5,
  9. Megan Stover, fellow in maternal-fetal medicine and genetics6,
  10. Devan Bartels, resident physician7,
  11. Jennifer Cottral, resident physician7,
  12. Elisabetta Patorno, assistant professor of medicine1

Author affiliations

  1. Correspondence to: K F Huybrechts


Objectives To assess the impact of in utero co-exposure to psychotropic medications and opioids on the incidence and severity of neonatal drug withdrawal.

Design Observational cohort study.

Setting Nationwide sample of pregnancies in publicly insured women in the US, nested in the Medicaid Analytic eXtract (2000-10).

Participants 201 275 pregnant women with public insurance who were exposed to opioids around the time of delivery and their liveborn infants.

Interventions In utero exposure to psychotropic medications, in particular antidepressants, atypical antipsychotics, benzodiazepines, gabapentin, and non-benzodiazepine hypnotics (Z drugs), with prescriptions filled within the same time window as prescriptions for opioids.

Main outcome measure Diagnosis of neonatal drug withdrawal in infants exposed in utero to opioids and psychotropic medications compared with opioids alone.

Results The absolute risk for neonatal drug withdrawal ranged from 1.0% in infants exposed in utero to prescription opioids alone to 11.4% for those exposed to opioids co-prescribed with gabapentin. Among neonates exposed in utero to prescription opioids, the relative risk adjusted for propensity score was 1.34 (95% confidence interval 1.22 to 1.47) with concomitant exposure to antidepressants, 1.49 (1.35 to 1.63) with benzodiazepines, 1.61 (1.26 to 2.06) with gabapentin, 1.20 (0.95 to 1.51) with antipsychotics, and 1.01 (0.88 to 1.15) with Z drugs. In utero exposure to two or more psychotropic medications along with opioids was associated with a twofold increased risk of withdrawal (2.05, 1.77 to 2.37). The severity of the withdrawal seemed increased in neonates exposed to both opioids and psychotropic medications compared with opioids alone.

Conclusions During pregnancy, the use of psychotropic medications in addition to prescription opioids is common, despite a lack of safety data. The current findings suggest that these drugs could further increase the risk and severity of neonatal drug withdrawal.


This is a useful paper; how likely are we to see neonatal abstinence after use of various types of psychotrophic medication?  Now we have some answers that are useful to guiding our patients who become pregnant while on these meds.  We can determine if the risk/benefit ratio is great enough to maintain or stop some of the meds.  I was personally surprised at the toll of gabapentin, which I prescribe frequently (but more to men as they tend to have more severe injuries, and more to post-menopausal women and older folks in general).


Dr. Raymond Oenbrink
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