Risk of neonatal drug withdrawal after intrauterine co-exposure to opioids and psychotropic medications: cohort study

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.

Prevalence of Maternal‐Risk Factors Related to Neonatal Abstinence Syndrome in a Commercial Claims Database: 2011‐2015

“…This finding is consistent with other literature showing that in the absence of other non–opioid‐related NAS risk factors, the absolute risk for NAS is low in mothers exposed to prescription opioids. However, this risk increases with concurrent maternal exposures of opioids and other psychotropic medications such as antidepressants, benzodiazepines, or antipsychotics . This study found high rates of co‐prescriptions for opioids and other psychotropic medications; 18% of NAS deliveries exposed to an opioid were also exposed to SSRIs.…”

“…Prior large database studies evaluating NAS‐related risk factors focused primarily on mothers exposed to an opioid prescription during pregnancy . However, due to an increased scrutiny over prescribing opioids and their subsequent role in the opioid crisis, rates of prescription opioids in the United States decreased after plateauing in 2012 .…”

Drug Dosing in Pregnant Women: Challenges and Opportunities in Using Physiologically Based Pharmacokinetic Modeling and Simulations

“…Fetal drug exposure in later trimesters may also lead to complications, as drugs may interfere with fetal growth or result in the acute interference of key homeostatic processes in the unborn child. Examples include intra‐uterine exposure to opioid analgesics, resulting in postpartum withdrawal symptoms and respiratory depression in the newborn . There are also cases in which maternal drug treatment is prescribed to treat or prevent disease in the unborn child.…”

Neonatal abstinence syndrome: an update

“…Huybrechts et al (15)** used a national sample of over 200,000 publically insured pregnant women to investigate the impact of in utero co-exposure to psychotropic medications and opioids on the incidence and severity of neonatal drug withdrawal. They observed that the risk of neonatal abstinence syndrome increased 30-60% in with co-exposure to antidepressants, benzodiazepines, and gabapentin.…”