Preterm birth results in significant neurodevelopmental disability during childhood.^1,2 Depending on the birth weight of the children studied and the years in which they were born, the incidence of major disabilities ranges from 20% to almost 50% in the first several years of life.^3-8 In addition, almost one fifth develop major cognitive disabilities by age 8 years,^9,10 more than 50% are reported to require special assistance in the classroom, 20% are in special education, and 15% have repeated at least 1 grade in elementary school.^10-13 However, recent reports suggest that two thirds of preterm infants require no special assistance in school at ages 14 to 15 years, almost three quarters graduate from high school, and more than 40% are enrolled in college programs. These data suggest change in cognitive function over time in those born preterm.^14-18

OBJECTIVE. Although preterm very low birth weight infants have a high prevalence of neuroanatomical abnormalities when evaluated at term-equivalent age, patterns of brain growth in prematurely born infants during school age and adolescence remain largely unknown. Our goal was to test the hypothesis that preterm birth results in long-term dynamic changes in the developing brain.METHODS. We performed serial volumetric MRI studies at ages 8 and 12 years in 55 preterm infants born weighing 600 to 1250 g and 20 term control children who participated in the follow-up component of a prospective, randomized, placebo-controlled intraventricular hemorrhage prevention study.RESULTS. Total brain volumes increased 2% to 3% between the ages of 8 and 12 years for both preterm and term children. These changes involved reductions in cerebral gray matter while white matter increased. Between 8 and 12 years of age, preterm subjects experienced a 2% decrease in left cerebral gray matter compared with a 10% reduction in left cerebral gray for term controls. For right cerebral gray matter, preterm children experienced a 3% decrease in volume between years 8 and 12, compared with 9% for term controls (group-by-time). In contrast, preterm subjects had a 10% increase in cerebral white matter volumes bilaterally between ages 8 and 12 years, compared with >26% increases for both hemispheres for term controls. Significant differences in regional volume changes between study groups were found in bilateral temporal gray and in parietal white matter.CONCLUSIONS. Preterm birth continues to perturb the trajectory of cerebral development during late childhood and early adolescence with preterm children, showing both lower gray matter reduction and less white matter gain over time compared with term control subjects.

Human neurodevelopment requires the organization of neural elements into complex structural and functional networks called the connectome. Emerging data suggest that prenatal exposure to maternal stress plays a role in the wiring, or miswiring, of the developing connectome. Stress-related symptoms are common in women during pregnancy and are risk factors for neurobehavioral disorders ranging from autism spectrum disorder, attention deficit hyperactivity disorder, and addiction, to major depression and schizophrenia. This review focuses on structural and functional connectivity imaging to assess the impact of changes in women's stress-based physiology on the dynamic development of the human connectome in the fetal brain.