Acoustic Cry Characteristics in Preterm Infants and Developmental and Behavioral Outcomes at 2 Years of Age.

Importance: Acoustic cry characteristics have been associated with severe medical problems in newborns. However, little is known about the utility of neonatal acoustic cry characteristics in the prediction of long-term outcomes of very preterm infants. Objectives: To evaluate whether acoustic characteristics of infant cry at neonatal intensive care unit (NICU) discharge are associated with behavioral and developmental outcomes at age 2 years in infants born very preterm. Design, Setting, and Participants: Infants born less than 30 weeks postmenstrual age (PMA) were enrolled from April 2014 through June 2016 as part of a multicenter (9 US university affiliated NICUs) cohort study and followed to adjusted age 2 years. Reported analyses began on September 2021. Data were analyzed from September 2021 to September 2022. Exposures: The primary exposure was premature birth (<30 weeks PMA). Main Outcomes and Measures: Cries were recorded during a neurobehavioral examination administered during the week of NICU discharge. Cry episodes were analyzed using a previously published computerized system to characterize cry acoustics. Year-2 outcomes included the Bayley-III Composite scores, Child Behavior Checklist (CBCL) and the Modified Checklist for Autism in Toddlers (M-CHAT R/F), dichotomized using clinically significant cutoffs (<85 on Bayley Language, Cognitive and/or Motor Composite scores, T-score >63 on the CBCL Internalizing, Externalizing and/or Total Problem Scales and total M-CHAT R/F score >2). Results: Analyzed infants (363 participants) were primarily male (202 participants [55.65%]) and had a mean [SD] gestational age of 27.08 [1.95] weeks). Cross-validated random forest models revealed that cry acoustics were associated with 2-year outcomes. Tests of diagnostic odds ratios (DOR) revealed that infants who exhibited total problem behavior CBCL scores greater than 63 at age 2 years were 3.3 times more likely (95% CI, 1.44-7.49) to be identified as so by random forest model estimates relative to other infants (scores ≤63); this association was robust to adjustment for family-wise type-I error rates and covariate measures. Similar associations were observed for internalizing (DOR, 2.39; 95% CI, 1.04-5.47) and externalizing (DOR, 2.25; 95% CI, 1.12-4.54) scores on the CBCL, clinically significant language (DOR, 1.71; 95% CI, 1.10-2.67) and cognitive (DOR, 1.70; 95% CI, 1.00-2.88) scores on the Bayley-III, and a positive autism screen on the M-CHAT (DOR, 1.91; 95% CI, 1.05-3.44). Conclusions and Relevance: In this cohort study of preterm infants, findings pointed to the potential use of acoustic cry characteristics in the early identification of risk for long-term developmental and behavioral deficits.