QuestionÌý Do alterations in newborn brain function precede the development of callous-unemotional traits and associate with later symptom severity?

FindingsÌý In this longitudinal cohort study of 283 mother-infant dyads recruited during pregnancy, stronger functional connectivity between the cingulo-opercular network and the medial prefrontal cortex was associated with higher callous-unemotional traits at age 3 years, as well as lower empathy and prosociality at ages 1, 2, and 3 years.

MeaningÌý Frontolimbic brain connectivity in newborns may be associated with the development of callous-unemotional traits in preschoolers and, therefore, precede increased symptom severity.

ImportanceÌý Children with high callous-unemotional traits are more likely to develop severe and persistent conduct problems; however, the newborn neurobiology underlying early callous-unemotional traits remains unknown. Understanding the neural mechanisms that precede the development of callous-unemotional traits could help identify at-risk children and encourage development of novel treatments.

ObjectiveÌý To determine whether newborn brain function is associated with early-emerging empathy, prosociality, and callous-unemotional traits.

Design, Setting, and ParticipantsÌý In this prospective, longitudinal cohort study, pregnant women were recruited from obstetric clinics in St Louis, Missouri, from September 1, 2017, to February 28, 2020, with longitudinal data collected until March 20, 2023. Mothers were recruited during pregnancy. Newborns underwent brain magnetic resonance imaging shortly after birth. Mothers completed longitudinal follow-up when the children were aged 1, 2, and 3 years.

ExposuresÌý The sample was enriched for exposure to socioeconomic disadvantage.

Main Outcome and MeasureÌý Functional connectivity between hypothesized brain regions was assessed using newborn-specific networks and voxel-based connectivity analyses. Children’s callous-unemotional traits were measured using the Inventory of Callous-Unemotional Traits. Empathy and prosociality were assessed using the Infant and Toddler Socio-Emotional Assessment.

ResultsÌý A total of 283 children (mean [SD] gestational age, 38 [2] weeks; 159 male [56.2%]; 2 Asian [0.7%], 171 Black [60%], 7 Hispanic or Latino [2.5%], 106 White [38%], 4 other racial or ethnic group [1.4%]) were included in the analysis. Stronger newborn functional connectivity between the cingulo-opercular network (CO) and medial prefrontal cortex (mPFC) was associated with higher callous-unemotional traits at age 3 years (β = 0.31; 95% CI, 0.17-0.41; P < .001). Results persisted when accounting for parental callous-unemotional traits and child externalizing symptoms. Stronger newborn CO-mPFC connectivity was also associated with lower empathy and lower prosociality at ages 1, 2, and 3 years using multilevel models (β = −0.12; 95% CI, −0.21 to −0.04; P = .004 and β = −0.20; 95% CI, −0.30 to −0.10; P < .001, respectively).

Conclusions and RelevanceÌý Newborn functional connectivity was associated with early-emerging empathy, prosociality, and callous-unemotional traits, even when accounting for parental callous-unemotional traits and child externalizing symptoms. Understanding the neurobiological underpinnings of empathy, prosociality, and callous-unemotional traits at the earliest developmental point may help early risk stratification and novel intervention development.