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All infants are at risk for adverse outcomes, but the risk is far higher for infants that require neonatal intensive care. Many of the highest risk infants require neonatal intensive care. Most of the conditions that place a neonate at risk of dying (eg, preterm birth, sepsis, organ injury or malformation) also increase the risk of subsequent health and neurodevelopmental problems. Over the last half century, major advances in high-risk obstetrics and neonatal intensive care have yielded dramatic reductions in neonatal mortality at all gestational ages.1,2 There has been no concomitant dramatic reduction in frequency of health problems or neurodevelopmental disabilities. Since no one can foresee the future for an individual infant, prediction of outcome relies on assessment of the infant’s current status (eg, neuroimaging and examination findings) as well as prenatal, perinatal, and neonatal risk factors, illnesses, and treatments.3,4

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Maturation of the central nervous system (CNS) is a dynamic process. Successive stages of neuromaturation have been described in the fetus, preterm infant in a neonatal intensive care unit, preterm infant at term, full-term neonate, infant, toddler, and child.5-7 Our genome drives neuromaturation, but continuous gene-environmental interactions make us who we are. Structural development of the central nervous system is continuously modified by first the intrauterine, then the extrauterine, environment. Just as fetal breathing movements of amniotic fluid are necessary for lung development, sensory input and fetal movement help shape the central nervous system. Patterns of electrical activity associated with movement and sensory input shape neural networks during synaptogenesis and later determine which pathways are pruned.

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While most infants are born near term (ie, 40 weeks’ gestation), with no major difficulties, and grow up without any impairments, the challenge for prediction of outcomes is to recognize those processes that alter or interfere with neuromaturation. The greater challenge is to understand the mechanisms of unfavorable processes and to develop strategies to prevent or promote recovery from them.

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We focus on risk factors because it is not possible to make a diagnosis of neurodevelopmental disability in the neonatal period, even with evidence of brain injury from neuroimaging studies.1,3,4 In infants with birth weights below 1000 g and either intraparenchymal hemorrhage or white matter injury on ultrasound, 28% to 30% had no neurodevelopmental impairment at 18 to 22 months.8 Neurodevelopmental diagnoses require assessment of neuromaturation with sequential attainment of motor, cognitive, and adaptive skills during infancy and childhood.3,5 The major disabilities (ie, cerebral palsy, intellectual disability) generally can be diagnosed within the first 3 years, but learning disability, attention deficit, and minor neuromotor dysfunction require follow-up to the preschool and school years.3,9,10

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The absence of risk factors does not guarantee a normal outcome. In the general population, 1% develop intellectual disability and 0.1% to 0.4% develop intellectual disability as shown in Table 62-1.3 Up to ...

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