Early Alteration of Structural and Functional Brain Development in Premature Infants Born with Intrauterine Growth Restriction

Abstract

Placental insufficiency with fetal intrauterine growth restriction (IUGR) is an important cause of perinatal mortality and morbidity and is subsequently associated with significant neurodevelopmental impairment in cognitive function, attention capacity, and school performance. The underlying biologic cause for this association is unclear. Twenty-eight preterm infants (gestational age 32.5 Ϯ 1.9 wk) were studied by early and term magnetic resonance imaging (MRI). An advanced quantitative volumetric three-dimensional MRI technique was used to measure brain tissue volumes in 14 premature infants with placental insufficiency, defined by abnormal antenatal Doppler measurements and mean birth weights Ͻ10 th percentile (1246 Ϯ 299 g) (IUGR) and in 14 preterm infants matched for gestational age with normal mean birth weights 1843 Ϯ 246 g (control). Functional outcome was measured at term in all infants by a specialized assessment scale of preterm infant behavior. Premature infants with IUGR had a significant reduction in intracranial volume (mean Ϯ SD: 253.7 Ϯ 29.9 versus 300.5 Ϯ 43.5 mL, p Ͻ 0.01) and in cerebral cortical gray matter (mean Ϯ SD: 77.2 Ϯ 16.3 versus 106.8 Ϯ 24.6 mL, p Ͻ 0.01) when measured within the first 2 wk of life compared with control premature infants. These findings persisted at term with intracranial volume (mean Ϯ SD: 429.3 Ϯ 47.9 versus 475.9 Ϯ 53.4 mL, p Ͻ 0.05) and cerebral cortical gray matter (mean Ϯ SD: 149.3 Ϯ 29.2 versus 189 Ϯ 34.2 mL, p Ͻ 0.01). Behavioral assessment at term showed a significantly less mature score in the subsystem of attention-interaction availability in IUGR infants (p Ͻ 0.01). Cerebral cortical gray matter volume at term correlated with attention-interaction capacity measured at term (r ϭ 0.45, p Ͻ 0.05). These results suggest that placental insufficiency with IUGR have specific structural and functional consequences on cerebral cortical brain development. These findings may provide insight into the structural-functional correlate for the developmental deficits associated with IUGR. An increasing number of developmental disorders (1, 2) and diseases (3, 4) in child and adult life are thought to have their origin in the fetal period. Central to this predisposition is fetal growth (5). The fetus receives its nutrients from the maternal/ uterine circulation via the placenta. Any disturbance in the placental-fetal circulation will therefore have severe consequences on the supply of important nutrients such as oxygen, glucose, and amino acids (6). The placenta itself is also an active endocrine organ and, therefore, changes in nutrient availability will also affect placental and, potentially, fetal endocrine function, in particular, the modification of the hypothalamo-pituitary-adrenal axis (7,8). Placental insufficiency, which is the most common cause of IUGR, has further been shown to be associated with a considerable perinatal mortality

Differential effect of intrauterine growth restriction on childhood neurodevelopment: a systematic review

“…44 Early insults in the intrauterine environment may impair the development of neural architecture in the frontal lobes that is necessary for the later development of complex executive functions. 45 IUGR has been demonstrated to lead to a reduction in frontal volume, identifiable through both MRI 46 and sonographic biometric estimation. 47 Not only is frontal volume generally reduced in IUGR fetuses, but it is also reduced relative to total intracranial volume, suggesting specific disturbance of frontal lobe development following IUGR.…”

Mother’s voice and heartbeat sounds elicit auditory plasticity in the human brain before full gestation

“…Exclusion criteria included prenatal diagnosed brain lesions, intracranial hemorrhage, cystic periventricular leukomalacia, prominent extra-axial spaces, and dilated lateral ventricular atria. Additional restrictive exclusion criteria were included to ensure our results would not be skewed by common conditions known to alter brain anatomy, such as small for gestational age (100) and intrauterine growth restriction (101,102). A written informed consent was obtained from parents.…”

Regional Brain Development in Serial Magnetic Resonance Imaging of Low-Risk Preterm Infants

“…13,14,[32][33][34] An expert conducted 5 repeated segmentations of 5 infants' MRI scans to assess the accuracy of the segmentation approach. An algorithm called Simultaneous Truth and Performance Level Estimation (STAPLE) 35 was then applied to estimate for each tissue class the probability of the true segmentation of each voxel based on the repeated segmentations.…”

“…Several conditions, such as periventricular leukomalacia and fetal growth restriction, have been found to affect white and gray matter development in preterm infants when compared with healthy term infants. [10][11][12][13][14][15] Whereas most investigations compare total brain tissue volumes, studies assessing regional changes are few in number. 10,16 Investigations in preterm infants also offer the opportunity for the study of longitudinal brain development.…”