Early Brainstem Dysfunction in Preterm Infants Increases Risk for ASD: Findings from Parent Report Measures

Background:   Identifying early indicators for Autism Spectrum Disorders (ASDs) could enhance understanding of the underlying pathways to ASDs, thus contributing to earlier screening and intervention. We have reported abnormalities more prevalent in NICU graduates later diagnosed with ASD that reflect brainstem dysfunction including: (1) a pattern of arousal-modulated-attention (AMA) at 4 months post-term-age (PTA) more typical of newborns (Karmel et al, 2010); (2) abnormal auditory brainstem evoked responses (ABRs), and (3) abnormal AMA conjoined with abnormal ABRs, predicting increased ASD risk in preterm infants (Cohen et al, 2013). To further increase understanding of factors associated with early identification of ASD in preterm infants, we related these to parent report measures associated with autism diagnosis.

Objectives:   To ascertain if these findings of very early neurofunctional associations to ASD are: (1) common to the atypical development associated with high-medical-risk NICU graduates; and (2) related to later parent report measures indicating ASD risk.

Methods:   Two groups of medically at-risk NICU infants recruited as newborns were compared: 1. later-diagnosed ASD (n=50); and 2. non-ASD (n=1985). Various contrasts between ASD and non-ASD groups were performed where the effects of gestational age, birth weight, gender, CNS injury, and ASD were included along with information from: (1) ABRs obtained shortly after birth (after 32wks PCA); (2) AMA at 4 months PTA: Slope of preference function across pairs of stimuli >.1 = looking at higher rate (8Hz>3Hz>1Hz); (3) Parent report measures of ASD risk: Communication and Symbolic Behavior Scales (CSBS) Infant-Toddler Checklist (13 months); Modified Checklist for Autism in Toddlers, (M-CHAT) (18 mo); PDD Behavior Inventory Short Version (PDDBI-SV) (18 mo): Screening to assess PDD/ASD.

Results:   There was a high incidence of abnormal ABRs in ASD compared to non-ASD (72% vs. ~28%). ASD looked more at higher stimulus rates than non-ASD (70% vs. 40 %). The combination of abnormal ABR with AMA slope >.1 predicted ASD, with 60% of ASD having both vs. 17% of non-ASD. Preterm infants showing high abnormality may represent developmental problems not necessarily within criteria for ASD. M-CHAT (> 60%) and CSBS (~26% across 3 composites and total) indicated positive findings for ASD, but a high rate of failures for non-ASD preterms.

Conclusions:   Dysfunction during early brainstem development, indicated by altered neuronal transmission speeds together with deficits in attention regulation observable as early as 4 months of age may represent a potentially important path leading to later ASD, an idea strengthened by their relationship to parent report measures associated with later diagnosis of ASD. Moreover, the high rate of failures found for preterms on parent report measures likely reflect developmental and regulatory issues common to ASD and high-medical-risk. Findings support the conclusion that increased incidence of ASD in preterms may be secondary to the conditions that increase risk for preterm birth, but the consequences of preterm birth are independent. Thus, preterm birth may be correlated, but not causal to ASD.