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Background: Pediatric physical therapy seems to reduce skull deformation in infants with positional preference. However, not all infants show improvement., Objective: The study objective was to determine which infant and parent characteristics were related to responses to pediatric physical therapy in infants who were 2 to 4 months old and had positional preference, skull deformation, or both., Design: This was a prospective cohort study., Methods: Infants who were 2 to 4 months old and had positional preference, skull deformation, or both were recruited by pediatric physical therapists at the start of pediatric physical therapy. The primary outcome was a good response or a poor response (moderate or severe skull deformation) at 4.5 to 6.5 months of age. Potential predictors for responses to pediatric physical therapy were assessed at baseline with questionnaires, plagiocephalometry, and the Alberta Infant Motor Scale. Univariate and multiple logistic regression analyses with a stepwise backward elimination method were performed., Results: A total of 657 infants participated in the study. At follow-up, 364 infants (55.4%) showed a good response to therapy, and 293 infants (44.6%) showed a poor response. Multiple logistic regression analysis resulted in the identification of several significant predictors for a poor response to pediatric physical therapy at baseline: starting therapy after 3 months of age (adjusted odds ratio [aOR]=1.50, 95% confidence interval [95% CI]=1.04-2.17), skull deformation (plagiocephaly [aOR=2.64, 95% CI=1.67-4.17] or brachycephaly [aOR=3.07, 95% CI=2.09-4.52]), and a low parental satisfaction score (aOR=2.64, 95% CI=1.67-4.17). A low parental satisfaction score indicates low parental satisfaction with the infant's head shape., Limitations: Information about pediatric physical therapy was collected retrospectively and included general therapy characteristics. Because data were collected retrospectively, no adjustment in therapy for individual participants could be made., Conclusions: Several predictors for responses to pediatric physical therapy in infants who were 2 to 4 months old and had positional preference, skull deformation, or both were identified. Health care professionals can use these predictors in daily practice to provide infants with more individualized therapy, resulting in a better chance for a good outcome., (© 2014 American Physical Therapy Association.)