Neonatal brainstem function and 4-month arousal-modulated attention are jointly associated with autism

Abstract

The authors evaluated the contribution of initially abnormal neonatal auditory brainstem responses (ABRs) and 4-month arousal-modulated attention visual preference to later autism spectrum disorder (ASD) behaviors in neonatal intensive care unit (NICU) graduates. A longitudinal study design was used to compare NICU graduates with normal ABRs (n = 28) to those with initially abnormal ABRs (n = 46) that later resolved. At 4 months postterm age, visual preference (measured after feeding) for a random check pattern flashing at 1, 3, or 8 Hz and gestational age (GA) served as additional predictors. Outcome measures were PDD Behavior Inventory (PDDBI) scores at 3.4 years (standard deviation = 1.2), and developmental quotients (DQ) obtained around the same age with the Griffiths Mental Development Scales (GMDS). Preferences for higher rates of stimulation at 4 months were highly correlated with PDDBI scores (all P-values < 0.01) and the GMDS Hearing and Speech DQ, but only in those with initially abnormal ABRs. Effects were strongest for a PDDBI social competence measure most associated with a diagnosis of autism. For those with abnormal ABRs, increases in preference for higher rates of stimulation as infants were linked to nonlinear increases in severity of ASD at 3 years and to an ASD diagnosis. Abnormal ABRs were associated with later reports of repetitive and ritualistic behaviors irrespective of 4-month preference for stimulation. The joint occurrence of initially abnormal neonatal ABRs and preference for more stimulation at 4 months, both indices of early brainstem dysfunction, may be a marker for the development of autism in this cohort.

Figure 1

Shown are the PDDBI Autism Composite T-score (A) and Social Discrepancy difference score (B) versus individual AMA slope values at four months of age and ABR group. Filled circles are ASD cases and open circles are Not-ASD cases. Dotted lines along the ordinates indicate the cut-off scores that best discriminate ASD from non-ASD cases. Fitted curves are based on a LOWESS function with a stiffness of 0.9. Curves for the Abnormal ABR group show a discontinuity near an AMA Slope of 0.1.

Figure 2

Shown are the Griffiths Performance (A) and Hearing and Speech (B) DQs versus the individual AMA slope values at four months of age and ABR group. Filled circles are ASD cases and open circles are Not-ASD cases. Fitted curves are based on a LOWESS function with a stiffness of 0.9. For Hearing and Speech, there is a sharp discontinuity near an AMA Slope of 0.1 for the Abnormal ABR group.