Prescription opioid epidemic and infant outcomes

Abstract

Background and objectives: Although opioid pain relievers are commonly prescribed in pregnancy, their association with neonatal outcomes is poorly described. Our objectives were to identify neonatal complications associated with antenatal opioid pain reliever exposure and to establish predictors of neonatal abstinence syndrome (NAS).

Methods: We used prescription and administrative data linked to vital statistics for mothers and infants enrolled in the Tennessee Medicaid program between 2009 and 2011. A random sample of NAS cases was validated by medical record review. The association of antenatal exposures with NAS was evaluated by using multivariable logistic regression, controlling for maternal and infant characteristics.

Results: Of 112,029 pregnant women, 31,354 (28%) filled ≥ 1 opioid prescription. Women prescribed opioid pain relievers were more likely than those not prescribed opioids (P < .001) to have depression (5.3% vs 2.7%), anxiety disorder (4.3% vs 1.6%) and to smoke tobacco (41.8% vs 25.8%). Infants with NAS and opioid-exposed infants were more likely than unexposed infants to be born at a low birth weight (21.2% vs 11.8% vs 9.9%; P < .001). In a multivariable model, higher cumulative opioid exposure for short-acting preparations (P < .001), opioid type (P < .001), number of daily cigarettes smoked (P < .001), and selective serotonin reuptake inhibitor use (odds ratio: 2.08 [95% confidence interval: 1.67-2.60]) were associated with greater risk of developing NAS.

Conclusions: Prescription opioid use in pregnancy is common and strongly associated with neonatal complications. Antenatal cumulative prescription opioid exposure, opioid type, tobacco use, and selective serotonin reuptake inhibitor use increase the risk of NAS.

Keywords: neonatal abstinence syndrome; neonatal drug withdrawal syndrome; neonatal opioid withdrawal syndrome; opioid pain reliever.

FIGURE 1

Rate of NAS in Tennessee Medicaid according to quarter, 2009 through 2011. P < .001.

FIGURE 2

Probability of NAS. A, Opioid type and cumulative morphine milligram equivalents (MMEs). B, Number of cigarettes smoked per day and cumulative MMEs after adjusting for maternal characteristics, infant characteristics, and birth characteristics. Graph A: Cumulative MMEs and risk of NAS for short-acting opioid preparations (P < .001) and long-acting/maintenance opioid preparations (P = .16). Graph B: An increasing number of cigarettes raised the risk of NAS among women with 0 cumulative MME (ie, receiving no legal opioids; P < .001) receiving a cumulative total of 8400 MMEs, which equals oxycodone 10 mg q6h × 20 weeks (P < .001), and 42 000 MMEs, which equals buprenorphine 24 mg daily × 25 weeks (P < .001). The absolute risk and 95% CIs of NAS have been adjusted for cumulative opioid dose in MMEs, maternal age, maternal education, birth number, infant birth weight, year of birth, maternal race, infant gender, multiple gestations, and interaction effects of drug type × cumulative opioid dose (P = .002), number of cigarettes smoked per day × cumulative opioid dose (P < .001), and drug type × number of cigarettes smoked per day. Total sample = 112 029 mother–infant dyads, 30 651 mothers with OPR use, and 1086 infants with NAS.