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OBJECTIVE: This study examined the NICU Network Neurobehavioral Scale (NNNS) as a predictor of negative medical and behavioral findings at 1 month to 4.5 years of age. METHODS: The sample included 1248 mother–infant dyads (42% born at <37 weeks' gestational age [GA]) who were participating in a longitudinal study of the effects of prenatal substance exposure on child development. Mothers were recruited at 4 urban university-based centers and were mostly black and on public assistance. At 1 month of age, infants were tested with the NNNS. Latent profile analysis was conducted on NNNS summary scales to identify discrete behavioral profiles. The validity of the NNNS was examined by using logistic regression to predict prenatal drug exposure and medical and developmental outcomes through 4.5 years of age including adjustment for GA and socioeconomic status. RESULTS: Five discrete behavioral profiles were reliably identified; the most extreme negative profile was found in 5.8% of the infants. The profiles showed statistically significant associations with prenatal drug exposure; GA and birth weight; head ultrasound; neurologic and brain disease findings; and abnormal scores on measures of behavior problems, school readiness, and IQ through 4.5 years of age. CONCLUSIONS: The NNNS may be useful to identify infant behavioral needs to be targeted in well-infant pediatric care, as well as for referrals to community-based early intervention services.