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Neonatal Pain and Developmental Outcomes in Children Born Preterm: A Systematic Review

Valeri, Beatriz O. MSc*; Holsti, Liisa PhD; Linhares, Maria B.M. PhD*

doi: 10.1097/AJP.0000000000000114
Review Articles

Background: Neonates cared for in neonatal intensive care units are exposed to many painful and stressful procedures that, cumulatively, could impact later neurodevelopmental outcomes. However, a systematic analysis of these effects is yet to be reported.

Objectives: The aim of this research was to review empirical studies examining the association between early neonatal pain experiences of preterm infants and the subsequent developmental outcomes of these children across different ages.

Methods: The literature search was performed using the PubMed, PsycINFO, Lilacs, and SciELO databases and included the following key words: “pain,” “preterm,” and “development.” In addition, a complementary search was performed in online journals that published pain and developmental studies to ensure all of the target studies had been found. The data were extracted according to predefined inclusion and exclusion criteria.

Results: Thirteen studies were analyzed. In infants born extremely preterm (gestational age ≤29 wk) greater numbers of painful procedures were associated with delayed postnatal growth, with poor early neurodevelopment, high cortical activation, and with altered brain development. In toddlers born very preterm (gestational age ≤32 wk) biobehavioral pain reactivity-recovery scores were associated with negative affectivity temperament. Furthermore, greater numbers of neonatal painful experiences were associated with a poor quality of cognitive and motor development at 1 year of age and changes in cortical rhythmicity and cortical thickness in children at 7 years of age.

Conclusions: For infants born preterm, neonatal pain-related stress was associated with alterations in both early and in later developmental outcomes. Few longitudinal studies examined the impact of neonatal pain in the long-term development of children born preterm.

*Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil

Department of Occupational Science and Occupational Therapy, University of British Columbia and Child and Family Research Institute, Vancouver, BC, Canada

Supported, in part, by the São Paulo Research Foundation, São Paulo, SP, Brazil (FAPESP: 2011/50788-8) (for B.O.V.) and the National Council for Development Science and Technology, Brasília, DF, Brazil (CNPq: 301247/2010-2) (for M.B.M.L.). L.H. holds a Canadian Institutes of Health Research Canada Research Chair in Neonatal Health and Development. The authors declare no conflict of interest.

Reprints: Maria B.M. Linhares, PhD, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Tenente Catão Roxo, 2650 (Prédio da Saúde Mental, salas 52/53), Campus Universitário Monte Alegre, CEP: 14.051-140, Ribeirão Preto, São Paulo, Brazil (e-mail:

Received April 8, 2013

Received in revised form May 14, 2014

Accepted April 24, 2014

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