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Infantile colic is characterized by persistent crying, diminished soothability, and excessive activity or restlessness. The purpose of this study was to explore the processes underlying the persistent, recurrent irritability by investigating behavioral and interactional differences in irritable and nonirritable infants. In this two-group longitudinal study, 40 infants and their mothers were followed over the first 4 months of life. Statistically significant differences between the two groups were found, with the irritable infants demonstrating an increase in the amount and intensity of crying, more disruption in sleep-wake states, and less synchrony in mother-infant interaction.