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The most prevalent musculoskeletal disorder of childhood with unclear aetiology is growing pains (GPs). Anatomic deformities and factors that change bone turnover are implicated in GP pathophysiology. Perinatal risk factors alter the bone metabolism affecting the bone mineral density and content. The aim of our study was to analyze the relationship between GPs, knock knees and perinatal factors. The examined population consisted of 276 children aged 3–7 years. Among them, ten pairs of dizygotic twins were evaluated. The data were collected by using a combination of semi-structured questionnaires, clinical examinations and medical charts of the children and the obstetric history of the mothers. A total of 78 children presenting GPs met Peterson’s criteria. Genu valgum severity was a significant factor for GP manifestation and for their increased frequency and intensity. Subsequently, perinatal factors regarding gestational age, Apgar score, head circumference (lower than 33 cm) and birth length or weight (smaller than 50 cm and 3000 g, respectively) made a remarkable contribution to the development of GPs. Conversely, antenatal corticosteroid treatment, increased maternal age and maternal smoking during pregnancy were not predictive of the disorder. Our data are potentially supportive for the “bone strength” theory and for the contribution of anatomical disturbances in GP appearance.