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Review
. 2025 Jan;97(1):99-106.
doi: 10.1038/s41390-024-03353-7. Epub 2024 Jun 21.

Evidence for neurobehavioral risk phenotypes at birth

Affiliations
Review

Evidence for neurobehavioral risk phenotypes at birth

Elisabeth Conradt et al. Pediatr Res. 2025 Jan.

Abstract

Observations of newborn behavior provide clinicians and researchers with a first description of the neurobehavioral organization of the newborn that is largely independent of the postnatal environment. The Neonatal Network Neurobehavioral Scale (NNNS) was developed in 2004 to evaluate how prenatal exposure to substances such as cocaine is related to neurobehavioral outcomes. There are now 156 empirical articles published using the NNNS, which we review and summarize. Z-scores from published studies using the NNNS were compiled and aggregated supporting the replicability of three newborn neurobehavioral phenotypes: one typical and two that are predictive of later cognitive and behavioral delay; hyper- and hypo-dysregulated newborns. These phenotypes emerged from independent samples and research groups and were identified in a variety of populations, including infants with prenatal substance exposure, preterm infants, and healthy term infants. Our findings show that newborn neurobehavior can be measured in a reliable and valid manner and that certain behavioral phenotypes, identifiable at birth, can predict neurodevelopmental challenges. These findings have important clinical utility. Intervening early with infants exhibiting these risk phenotypes may prevent later neurodevelopmental delay. IMPACT: We reviewed all empirical studies published using the Neonatal Network Neurobehavioral Scale and found evidence for two replicable stress phenotypes that predict later behavioral outcomes. This study highlights the utility of the Neonatal Network Neurobehavioral Scale for early identification of newborn neurodevelopmental risk phenotypes. Early identification of neurodevelopmental risk, when neuroplasticity is high, may ultimately reduce the burden of subsequent neurobehavioral problems through early intervention.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Consent statement:: Patient consent was not required as this was a review paper

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