BACKGROUND

Despite the rising incidence of neonatal abstinence syndrome (NAS), data evaluating trends in maternal risk factors associated with NAS have not been available for recent years, a period characterized by declining opioid prescriptions. The objective of this study was to examine the prevalence of opioid- and non-opioid-related factors associated with NAS, and by mutually exclusive subgroups of deliveries without prescription-opioid use, with prescription-opioid use, and with opioid-use disorder (OUD).

METHODS

A cohort of pregnancies resulting in live births in a commercial claims data base in 2011-2015 was identified. Examples of maternal risk factors of interest included antepartum prescription-drug use (e.g., opioids, selective serotonin reuptake inhibitors [SSRIs], antipsychotics) and nonprescription-related factors (e.g., smoking, OUD).

RESULTS

A total of 659 cases of NAS among 621,940 deliveries was identified. Among NAS deliveries, prescription opioids were the most commonly used drug-class (39.0%). Adjusted relative risk (RR) for NAS was 5.43 (95% confidence interval [CI] 4.25-6.95), followed by SSRIs (20.9%; RR 3.16, CI 2.43-4.11); OUD was noted in 36.3% of the deliveries (RR 40.74, CI 22.64-73.32). In the subgroup of deliveries without a prescription opioid (33% of overall NAS deliveries), the absolute incidence of NAS was low (0.3 cases/1000 deliveries), and SSRIs were the most commonly used medication class (32.7%; RR 10.21, CI 7.28-14.31). In the subgroup of deliveries with an opioid prescription, the absolute incidence of NAS was 7.7/1000 (29% of all overall NAS deliveries), and 22.7% of these deliveries were exposed to one other psychotropic agent in addition to the opioid, most commonly an SSRI (18.0%). In the subgroup of deliveries with a diagnosis of OUD, the NAS incidence was high (214.3/1000 [36% of all NAS cases]).

CONCLUSION

A third of NAS deliveries did not have evidence of prescription opioids. Other psychotropic medications, especially SSRIs, were strong predictors of NAS in this stratum but had no relevance among deliveries with OUD, suggesting varying etiologies and the need for tailored preventive approaches to reduce NAS effectively.