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Objectives: Successful development during the first year of life is dependent on the infant's ability to regulate behavioral and physiological state in response to unpredictable environmental challenges. Although most infants develop skills to self-soothe and regulate behavior, a subset lacks these skills and develops regulatory disorders (RD). The purpose of this study was to evaluate the component features of RD by determining if infants with RD differ from typically developing infants on measures of temperament, respiratory sinus arrhythmia, heart rate, and mother-infant interactions. Methods: Parents of 50 9-month-old infants completed behavioral questionnaires that provided information necessary to complete the Regulatory Disorders Checklist, which evaluates for difficulties in self-regulation and hypersensitivities. Infants with difficulties in both domains were assigned to the RD group. Mothers and their infants were videotaped interacting for 10 minutes. Infant heart rate was monitored before and during the mental development test. Results: The RD group (n = 10) was more temperamentally difficult and exhibited atypical physiological regulation relative to infants with difficulties in either self-regulation or hypersensitivity (n = 25) or infants with no difficulties (n = 15). During the mother-infant interactions, the RD group exhibited more high-level withdrawal behaviors, including verbal and physical protests, although there were no differences in the quantity and quality of the maternal approaches. Conclusion: Infants with RD have both temperamental and physiological regulation difficulties and may be in a physiological state that makes it difficult to moderate behavior in response to social demands. Mothers of RD infants might be taught to modify their behavior to help their infants to regulate behavioral and physiological state. (J Dev Behav Pediatr 32:216-224, 2011)