Risk of Neonatal Drug Withdrawal after Intrauterine Coexposure to Opioids and Psychotropic Medications: Cohort Study

Abstract

OBJECTIVESTo assess the impact of in utero co-exposure to psychotropic medications and opioids on the incidence and severity of neonatal drug withdrawal. DESIGNObservational cohort study. SETTINGNationwide sample of pregnancies in publicly insured women in the US, nested in the Medicaid Analytic eXtract .PARTICIPANTS 201 275 pregnant women with public insurance who were exposed to opioids around the time of delivery and their liveborn infants. INTERVENTIONSIn 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 MEASUREDiagnosis of neonatal drug withdrawal in infants exposed in utero to opioids and psychotropic medications compared with opioids alone. RESULTSThe 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. CONCLUSIONSDuring 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 and duration of prescribed opioid use during pregnancy: a cohort study from the Quebec Pregnancy Cohort

“…In the context of pregnancy, associations between prenatal opioid exposure and neonatal abstinence syndrome [16][17][18][19], as well as certain congenital malformations [10,20,21,45] have been reported in recent studies. Bateman et al [24], using the Medicaid Analytic eXtract (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014) and MarketScan (2003MarketScan ( -2015 databases, have shown an increased risk of oral clefts associated with hydrocodone (RR 1.39, 95%CI 1.06-1.83) and oxycodone (RR 1.34, 95%CI 0.72-2.50) use in early pregnancy, but not with codeine (RR 0.74, 95%CI 0.40-1.37, 11 exposed cases), which is a weaker opioid.…”

“…With the rise in the prevalence of opioid use during pregnancy, we can also note a sharp increase in the rate of infants with neonatal abstinence syndrome [16][17][18]. Of note, two in three infants with neonatal abstinence syndrome was exposed to prescribed opioids during gestation [17,19].…”

Identifying Co-Exposure to Opiates and Gabapentin During Pregnancy

“…An analysis of 2000-2010 Medicaid prescription data for pregnant women with at least 1 outpatient prescription filled for an opioid medication showed that only 0.3% also filled a prescription for gabapentin, but the prevalence of co-exposure from illicit sources or for those with OUD is unknown. 6 Implementation of universal gabapentin toxicology screening at other institutions with high prevalence of OUD among pregnant women or other approaches to increase detection of co-exposure may improve pediatric care of affected infants.…”

Opioid crisis: a public health concern in Colorado, United States

“…Among 201,275 pregnant women with public insurance who were exposed to opioids around the time of delivery, prescriptions for other psychotropic medication in particular antidepressants, atypical antipsychotics, benzodiazepines, gabapentin, and non-benzodiazepine hypnotics with opioid, were filed at about the same time. 10 Studies showed that some children tend to experience cognitive, behavioral, developmental and educational challenges following recovery from NAS, which is particularly important in the long-term management of such children. 11 Post NAS children are more likely to experience poor performance in school, low self-esteem, emotional and behavioral problems.…”