Although problem crying in the first three to four months of life is usually self-limiting, it is not a trivial condition. Early intervention is important, yet families receive conflicting advice from health professionals. The past decade has seen significant advances in neuroscience, lactation science, and developmental psychology, including new insights into the significance of developmentally sensitive windows. We propose a neurobiological model to explain the mechanisms of cry-fuss problems in the first months of life, and the mechanisms which underlie effective intervention, with a view to facilitating research collaboration and consistency of advice across health disciplines. We hypothesise that crying in the first three to four neurodevelopmentally sensitive months signals activation of the hypothalamic-pituitary-adrenal axis and adrenergic neuronal circuitry in response to perceptions of discomfort or threat. Susceptible infants may be conditioned by early stress, for example, by unidentified feeding difficulties, into a sensitised stress response, which usually settles at three to four months of age with neurodevelopmental maturity. Bouts of prolonged and unsoothable crying result from positive feedback loops in the hypothalamic-pituitary-adrenal and adrenergic systems. Importantly, epigenetic modulation of the infant's limbic neuronal circuitry may explain correlations between regulatory problems in the first months of life, and behavioural problems including feeding problems in later childhood.
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