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Randomized Controlled Trial
. 2020 Dec:227:101-107.e1.
doi: 10.1016/j.jpeds.2020.08.034. Epub 2020 Aug 14.

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

Tess Flannery  1 , Jonathan M Davis  2 , Adam J Czynski  3 , Lynne M Dansereau  1 , Erica L Oliveira  1 , Samantha A Camardo  1 , Barry M Lester  4
Affiliations
Randomized Controlled Trial

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

Tess Flannery et al. J Pediatr. 2020 Dec.

Abstract

Objective: To develop an index to determine which opioid-exposed neonates have the most severe neonatal abstinence syndrome (NAS).

Study design: 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 18 months, 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).

Results: 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 18 months, 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).

Conclusions: Presumptive measures of NAS severity can be aggregated to develop an index that predicts developmental outcomes at age 18 months.

Keywords: NAS; NAS severity; neonatal abstinence syndrome; neurodevelopmental outcome; prenatal opioid exposure.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
CONSORT flow diagram for ClinicalTrials.gov NCT01958476.
Figure 2.
Figure 2.
NNNS profiles at hospital discharge. (Reprinted from Czynski AJ, Davis JM, Dansereau LM, Engelhardt B, Marro P, Bogen DL, et al. Neurodevelopmental outcomes of neonates randomized to morphine or methadone for treatment of neonatal abstinence syndrome. J Pediatr 2020;219:146–51.e1.).
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