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Observational Study
. 2017 Aug 2;358:j3326.
doi: 10.1136/bmj.j3326.

Risk of Neonatal Drug Withdrawal After Intrauterine Co-Exposure to Opioids and Psychotropic Medications: Cohort Study

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Free PMC article
Observational Study

Risk of Neonatal Drug Withdrawal After Intrauterine Co-Exposure to Opioids and Psychotropic Medications: Cohort Study

Krista F Huybrechts et al. BMJ. .
Free PMC article

Abstract

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.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: SHD has consulted for AstraZeneca and UCB for unrelated topics and is co-investigator of a study funded by Eli Lilly and Pfizer, unrelated to the topic of this manuscript; KFH and BTB are co-investigators of a study funded by Eli Lilly and Pfizer, unrelated to the topic of this manuscript; BTB is the principal investigator of a study funded by Baxalta, unrelated to the topic of this manuscript; EP is co-principal investigator of a study funded by Boehringer Ingelheim and site principal investigator of a study funded by GlaxoSmithKline, both unrelated to the topic of this manuscript; no financial relationships with any companies that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Absolute standardized mean difference illustrating balance in baseline characteristics before and after adjustment for high dimensional propensity score. SMD <0.1 indicates characteristics are well balanced
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Fig 2 Adjusted relative risk of neonatal drug withdrawal according to maternal exposure to psychotropic medications in addition to prescription opioids, according to level of adjustment for confounding. Medicaid Analytic eXtract, 2000-10

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