Neonatal Abstinence Syndrome Severity Index Predicts 18-Month Neurodevelopmental Outcome in Neonates Randomized to Morphine or Methadone

Abstract

To develop an index to determine which opioid-exposed neonates have the most severe neonatal abstinence syndrome (NAS). Full-term neonates with NAS (n=116) from mothers maintained on methadone or buprenorphine were enrolled from 8 sites into a randomized clinical trial of morphine vs methadone. Ninety-nine (85%) were evaluated at hospital discharge using the NICU Network Neurobehavioral Scale (NNNS). At 18months, 83 of 99 (83.8%) were evaluated with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and 77 of 99 (77.7%) were evaluated with the Child Behavior Checklist (CBCL). Cluster analysis was used to define high (n=21) and low (n=77) NAS severity. Compared with infants in the low NAS severity cluster, infants in the high NAS severity cluster had a longer length of stay (P<.001), longer length of stay due to NAS (P<.001), longer duration of treatment due to NAS (P<.001), and higher total dose of the study drug (P<.001) and were more likely to have received phenobarbital (P<.001), to have been treated with morphine (P=.020), and to have an atypical NNNS profile (P=.005). The 2 groups did not differ in terms of maximum Finnegan score. At 18months, in unadjusted analyses, compared with the high-severity cluster, the low-severity cluster had higher scores on the Bayley-III Cognitive (P=.013), Language (P<.001), and Motor (P=.041) composites and less total behavior problems on the CBCL (P=.028). In adjusted analyses, the difference in the Bayley-III Language composite remained (P=.013). Presumptive measures of NAS severity can be aggregated to develop an index that predicts developmental outcomes at age 18months.