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Brain functional connectivity and growth measurements in near-term and term-born neonates: an fNIRS study.

Donga, C.; Tang, L.; Samaan, K.; Stubbs, K.; Vahidi, H.; Bhattacharya, S.; Grafe, C.; De Ribaupierre, S.; St. Lawrence, K.; Duerden, E. G.

2026-05-18 pediatrics
10.64898/2026.05.14.26349878 medRxiv
Show abstract

Resting state networks RSNs measured through functional connectivity FC emerge in utero and are detectable within hours of birth. Although neonatal growth metrics predict later neurodevelopmental outcomes and structural brain maturation their relationship to early functional network organization remains poorly understood. We examined associations between anthropometric growth metrics and resting state FC in a cohort of healthy near term and term born neonates using functional near infrared spectroscopy fNIRS acquired during the first few days of life. Task free fNIRS data were recorded in 121 neonates 67 males 55 percent mean postnatal age equals 25.6 hours mean gestational age equals 38.63 weeks. Based on birthweight percentiles 12 9 percent newborns were small for gestational age SGA and 13 11 percent were large for gestational age LGA. Growth metrics included birth weight for gestational age z score BGZ head circumference for gestational age z score HGZ birth weight for length z score BLZ and z scored Ponderal Index PIz. Whole brain FC was calculated as the mean Fisher Z transformed correlation across valid channel pairs. Channel wise associations were examined using general linear and linear mixed effects models controlling for gestational age postnatal age and sex. Linear and quadratic terms were tested and multiple comparisons were controlled using the false discovery rate. None of the anthropometric measures were associated with global FC however significant nonlinear quadratic relationships emerged at the channel pair level. BGZ B range equals negative 0.102 to negative 0.074 FDR corrected p less than 0.005 and PIz B range equals negative 0.088 to negative 0.074 FDR corrected p less than 0.001 demonstrated negative quadratic associations with inter and intra hemispheric connectivity such that newborns with both lower SGA and higher LGA growth values showed reduced FC relative to those with average growth. In contrast HGZ demonstrated positive quadratic associations B range equals 0.051 to 0.074 FDR corrected p less than 0.001 with infants at the lower and higher ends of the head size distribution exhibiting increased FC relative to infants near the mean. BLZ showed no significant associations after correction. Results indicate that early somatic growth is reflected in the organization of neonatal functional brain networks and that deviations from average growth whether smaller or larger are associated with altered regional connectivity. Findings suggest that neonatal growth metrics may provide an accessible marker of early brain health reflected in regionally specific functional connectivity patterns.

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