Heart Rate during Sleep at 1 Month of Age Correlates with ASD Risk Scores at 30 Months

Background: Autism spectrum disorder has been associated with a range of atypical autonomic responses, from pupillary light reflex to cardiac arousal. Heart rate (HR), an easily obtainable biomarker of autonomic function, is frequently found to be elevated at baseline in children with autism (Klusek et al, 2015). Although a few studies in children reported no correlation, this may be attributable to variations in measurement contexts. Only two studies thus far have examined cardiac variables during sleep, with both reporting autonomic dysregulation during non-REM sleep, and one reporting elevated HR in ASD across both non-REM and REM sleep (Pace et al, 2016; Harder et al, 2016). No studies to date have examined autonomic dysregulation during sleep prior to symptom development, despite the evidence of atypical brain development in ASD during this time.

Objectives: To the best of our knowledge, this is the first study to investigate a relationship between autonomic function during sleep in newborns and later autism risk.

Methods: Data was collected from healthy term newborns enrolled in the Prenatal Alcohol and SIDS and Stillbirth Network in the Northern Plains region of South and North Dakota. This cohort includes 352 children (47% male, 53% female). This sample reflects general population risk for ASD. Average heart rates were obtained at a 1-month postnatal follow up visit and calculated across a 10-minute period of quiet sleep (QS) and a 10-minute period of active sleep (AS), reflecting the different autonomic arousal profiles associated with non-REM and REM sleep respectively. Brief Infant-Toddler Social and Emotional Assessments (BITSEA) were obtained between 24-36 months of age (mean age of 30 months) (Briggs-Gowan and Carter, 2006). The BITSEA ASD Total subscale is a validated measure with high sensitivity, specificity, and PPV as a screener for ASD risk (Kiss and Carter, 2017).

Results: There was a moderate positive correlation between average HR during quiet sleep at 1 month of age and BITSEA ASD Total score at 30 months, r=0.311 (p=0.021). During active sleep, there was small positive correlation which approached significance with r=0.138 at p=0.051. Results were calculated controlling for sex, gestational age at birth, and age at BITSEA assessment.

Conclusions: These preliminary results demonstrate a significant correlation between average HR during quiet sleep in newborns and later autism risk. A similar correlation that approached significance was noted during active sleep. These results mirror previous findings of autonomic differences during sleep in ASD and are the first to indicate that this phenomenon may occur prior to symptom development. Replication on an expanded sample with confirmed ASD diagnoses is needed. If this correlation is upheld, it may have important implications for early brain development in autism. Recent research has demonstrated increased extra-axial cerebrospinal fluid (CSF) at 6 months in children who later develop ASD (Shen et al 2017). Autonomic regulation plays a major role in CSF circulation, with enhanced sympathetic tone leading to increased CSF volume (Sakka, 2011). Further research is important to understand what role, if any, autonomic dysfunction may play in brain development in ASD.