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Altered Functional Brain Network Integration, Segregation, and Modularity in Infants Born Very Preterm at Term-Equivalent Age.

ABSTRACT: OBJECTIVES:To determine the functional network organization of the brain in infants born very preterm at term-equivalent age and to relate network alterations to known clinical risk factors for poor neurologic outcomes in prematurity. STUDY DESIGN:Resting-state functional magnetic resonance imaging data from 66 infants born very preterm (gestational age <32 weeks and birth weight <1500 g) and 66 healthy neonates born at full term, acquired as part of a prospective, cross-sectional study, were compared at term age using graph theory. Features of resting-state networks, including integration, segregation, and modularity, were derived from correlated hemodynamic activity arising from 93 cortical and subcortical regions of interest and compared between groups. RESULTS:Despite preserved small-world topology and modular organization, resting-state networks of infants born very preterm at term-equivalent age were less segregated and less integrated than those of infants born full term. Chronic respiratory illness (ie, bronchopulmonary dysplasia and the length of oxygen support) was associated with decreased global efficiency and increased path lengths (P < .05). In both cohorts, 4 functional modules with similar composition were observed (parietal/temporal, frontal, subcortical/limbic, and occipital). The density of connections in 3 of the 4 modules was decreased in the very preterm network (P < .01); however, in the occipital/visual cortex module, connectivity was increased in infants born very preterm relative to control infants (P < .0001). CONCLUSIONS:Early exposure to the ex utero environment is associated with altered resting-state network functional organization in infants born very preterm at term-equivalent age, likely reflecting disrupted brain maturational processes.

SUBMITTER: Bouyssi-Kobar M

PROVIDER: S-EPMC6765421 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Altered Functional Brain Network Integration, Segregation, and Modularity in Infants Born Very Preterm at Term-Equivalent Age.

Bouyssi-Kobar Marine M De Asis-Cruz Josepheen J Murnick Jonathan J Chang Taeun T Limperopoulos Catherine C

The Journal of pediatrics 20190726

<h4>Objectives</h4>To determine the functional network organization of the brain in infants born very preterm at term-equivalent age and to relate network alterations to known clinical risk factors for poor neurologic outcomes in prematurity.<h4>Study design</h4>Resting-state functional magnetic resonance imaging data from 66 infants born very preterm (gestational age <32 weeks and birth weight <1500 g) and 66 healthy neonates born at full term, acquired as part of a prospective, cross-sectional ...[more]

PMID: 31358292

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Project description:BackgroundInfants born at 29-36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA).MethodsPreterm infants (N = 133) born 29-36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBF i ) along with peripheral arterial oxygen saturation (SpO2). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO2i ). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA.ResultsSteeper increases in CBF i (p < 0.0001) and CMRO2i (p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBF i , and CMRO2i from birth to TEA were not associated with neurological examination at TEA.ConclusionIn this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBF i and CMRO2i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants.

Project description:AimThis study aimed to identify early clinical biomarkers from birth to 16 weeks corrected age to predict typical outcome and developmental delay in infants born very preterm or with very low birthweight.MethodA prospective cohort of infants on the Sunshine Coast, Australia, was assessed using the Premie-Neuro Examination, the General Movement Assessment (GMA), the Alberta Infant Motor Scale, and the Infant Sensory Profile 2. At 24 months corrected age, delay was identified using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) and Neurosensory Motor Developmental Assessment (NSMDA).ResultsOne hundred and four infants were recruited; 79 completed outcome assessments (43 females, 36 males; mean gestational age 30 weeks [SD 1 week 6 days], mean birthweight 1346 g [SD 323]). The incidence of developmental delay (motor or cognitive) was 6.3%. Suboptimal quality of fidgety general movements (temporal organization) at 16 weeks corrected age demonstrated the best predictive accuracy (Bayley-III motor: sensitivity 100% [95% confidence interval {CI} 3-100], specificity 75% [95% CI 63-84], area under the curve [AUC] 0.87); Bayley-III cognitive: sensitivity 100% [95% CI 3-100], specificity 75% [95% CI 64-84], AUC 0.88); NSMDA motor: sensitivity 100% [95% CI 40-100], specificity 81% [95% CI 70-90], AUC 0.91 [95% CI 0.86-0.95]). GMA trajectories that combined abnormal writhing general movements at 4 to 5 weeks corrected age with suboptimal quality of fidgety movement at 16 weeks corrected age were strongly predictive of developmental delay, superior to all other clinical tools, and perinatal and demographic variables investigated (p = 0.01, Akaike information criterion method 18.79 [score corrected for small sample size], accounting for 93% of the cumulative weight).InterpretationOnly the GMA had sufficient predictive validity to act as a biomarker for both conditions: typical outcome and developmental delay (motor or cognitive). GMA trajectories that assessed both writhing general movements at 4 to 5 weeks corrected age and quality of fidgety movement at 16 weeks corrected age predicted adverse neurodevelopmental outcome, accurately differentiating between infants with typical outcomes and those at increased risk for motor or cognitive delay.

Dataset Information

Altered Functional Brain Network Integration, Segregation, and Modularity in Infants Born Very Preterm at Term-Equivalent Age.

Publications

Altered Functional Brain Network Integration, Segregation, and Modularity in Infants Born Very Preterm at Term-Equivalent Age.

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