Wireless Heart Sensor for Capturing Cardiac Orienting Response for Prediction of Neurodevelopmental Delay in Infants.

Early identification of infants at risk of neurodevelopmental delay is an essential public health aim. Such a diagnosis allows early interventions for infants that maximally take advantage of the neural plasticity in the developing brain. Using standardized physiological developmental tests, such as the assessment of neurophysiological response to environmental events using cardiac orienting responses (CORs), is a promising and effective approach for early recognition of neurodevelopmental delay. Previous CORs have been collected on children using large bulky equipment that would not be feasible for widespread screening in routine clinical visits. We developed a portable wireless electrocardiogram (ECG) system along with a custom application for IOS tablets that, in tandem, can extract CORs with sufficient physiologic and timing accuracy to reflect the well-characterized ECG response to both auditory and visual stimuli. The sensor described here serves as an initial step in determining the extent to which COR tools are cost-effective for the early screening of children to determine who is at risk of developing neurocognitive deficits and may benefit from early interventions. We demonstrated that our approach, based on a wireless heartbeat sensor system and a custom mobile application for stimulus display and data recording, is sufficient to capture CORs from infants. The COR monitoring approach described here with mobile technology is an example of a desired standardized physiologic assessment that is a cost-and-time efficient, scalable method for early recognition of neurodevelopmental delay.

Infant Cardiac Orienting Responses Predict Later FASD in the Preschool Period.

BACKGROUND: Prenatal alcohol exposure (PAE) has been identified as one of the leading preventable causes of developmental disabilities, but early identification of those impacted has been challenging. This study evaluated the use of infant cardiac orienting responses (CORs), which assess neurophysiological encoding of environmental events and are sensitive to the impact of PAE, to predict later fetal alcohol spectrum disorder (FASD) status. METHODS: Mother-infant dyads from Ukraine were recruited during pregnancy based on the mother's use of alcohol. Participants (n = 120) were then seen at 6 and 12 months when CORs were collected and in the preschool period when they were categorized as having (i) fetal alcohol syndrome (FAS), (ii) partial FAS (pFAS), (iii) alcohol-related neurodevelopmental disorder (ARND), (iv) PAE and no diagnosis, or (v) no PAE and no diagnosis. To assess CORs, stimuli (auditory tones and pictures) were presented using a fixed-trial habituation/dishabituation paradigm. Heart rate (HR) responses were aggregated across the first 3 habituation and dishabituation trials and converted to z-scores relative to the sample's mean response at each second by stimuli. Z-scores greater than 1 were then counted by condition (habituation or dishabituation) to compute a total risk index. RESULTS: Significant group differences were found on total deviation scores of the CORs elicited from visual but not auditory stimuli. Those categorized as pFAS/FAS had significantly higher total deviation scores than did those categorized as ARND or as having no alcohol-related diagnosis with or without a history of PAE. Receiver operating characteristic curve analysis of the visual response yielded an area under the curve value of 0.765 for predicting to pFAS/FAS status. CONCLUSIONS: A score reflecting total deviation from typical HR during CORs elicited using visual stimuli in infancy may be useful in identifying individuals who need early intervention as a result of their PAE.

The Use of Cardiac Orienting Responses as an Early and Scalable Biomarker of Alcohol-Related Neurodevelopmental Impairment.

BACKGROUND: Considered the leading cause of developmental disabilities worldwide, fetal alcohol spectrum disorders (FASD) are a global health problem. To take advantage of neural plasticity, early identification of affected infants is critical. The cardiac orienting response (COR) has been shown to be sensitive to the effects of prenatal alcohol exposure and is an inexpensive, easy to administer assessment tool. The purpose of this study was to evaluate the COR effectiveness in assessing individual risk of developmental delay. METHODS: As part of an ongoing longitudinal cohort study in Ukraine, live-born infants of women with some to heavy amounts of alcohol consumption in pregnancy were recruited and compared to infants of women who consumed low or no alcohol. At 6 and 12 months, infants were evaluated with the Bayley Scales of Infant Development-II. CORs were also collected during a habituation/dishabituation learning paradigm. Using a supervised logistic regression classifier, we compared the predictive utility of the COR indices to that of the 6-month Bayley scores for identification of developmental delay based on 12-month Bayley scores. Heart rate collected at each second (Standard COR) was compared to key features (Key COR) extracted from the response. RESULTS: Negative predictive values (NPV) were 85% for Standard COR, 82% for Key COR, and 77% for the Bayley, and positive predictive values (PPV) were 66% for Standard COR, 62% for Key COR, and 43% for the Bayley. CONCLUSIONS: Predictive analysis based on the COR resulted in better NPV and PPV than the 6-month Bayley score. As the resources required to obtain a Bayley score are substantially more than in a COR-based paradigm, the findings are suggestive of its utility as an early scalable screening tool based on the COR. Further work is needed to test its long-term predictive accuracy.

Cardiac Orienting Responses Differentiate the Impact of Prenatal Alcohol Exposure in Ukrainian Toddlers.

BACKGROUND: Prenatal alcohol exposure (PAE) has been found to impact neurophysiological encoding of environmental events negatively in the first year of life but has not been evaluated in older infants or toddlers. Cardiac orienting responses (ORs) collected during a habituation/dishabituation learning paradigm were obtained from 12- to 18-month-olds to assess the impact of PAE beyond the first year of life. METHODS: Participants included women and their toddlers who differed in PAE histories and enrolled in a randomized clinical trial of multivitamin/mineral usage during pregnancy. Those who were randomly assigned to the no intervention group were used for this analysis. The habituation/dishabituation paradigm consisted of 10 habituation and 5 dishabituation trials. Baseline heart rate (HR) was collected for 30 seconds prior to stimulus onset, and responses to the stimuli were assessed by sampling HR for 12 seconds poststimulus onset. RESULTS: The speed of the OR in response to auditory stimuli in the dishabituation condition was found to be altered as a function of maternal alcohol use around conception. For visual stimuli, positive histories of PAE were predictive of the magnitude but not the speed of the response on habituation and dishabituation trials. A history of binge drinking was associated with reduced magnitude of the OR response on visual encoding trials, and level of alcohol exposure at the time of conception was predictive of the magnitude of the response on visual dishabituation trials. CONCLUSIONS: Cardiac ORs collected in the toddler period were sensitive to the effects of PAE. The magnitude of the OR was more sensitive to the impact of PAE than in previous research with younger infants, and this may be a function of brain maturation. Additional research assessing the predictive utility of using ORs in making decisions about individual risk was recommended.