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Peer-reviewedCC BY 4.0JAMA Network Open

Functional Connectivity at Birth and Longitudinal Neurocognitive Development in Very Preterm Infants

  • Junqi Wang1,2
  • Wei Jia1
  • Hailong Li1,2,3,4
  • Zhixiu Lu1
  • Mekibib Altaye2,5,6
  • Kim M. Cecil1,4
  • Leanne Tamm2,6
  • Nehal A. Parikh2,6
  • Lili He1,2,3,4,7
  • Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) Investigators
  • Anita Arnsperger8
  • Traci Beiersdorfer8
30 more authors
  • Kaley Bridgewater8
  • Tanya Cahill8
  • Kim Cecil8
  • Kent Dietrich8
  • Christen Distler8
  • Juanita Dudley8
  • Brianne Georg8
  • Cathy Grisby8
  • Lacey Haas8
  • Karen Harpster8
  • Scott K. Holland8
  • Priyanka VSP Illapani8
  • Kristin Kirker8
  • Julia E. Kline8
  • Beth M. Kline-Fath8
  • Matt Lanier8
  • Stephanie L. Merhar8
  • Greg Muthig8
  • Brenda B. Poindexter8
  • David Russell8
  • Kari Tepe8
  • Julia Thompson8
  • Jean A. Tkach8
  • Hui Wang8
  • Jinghua Wang8
  • Brynne Williams8
  • Kelsey Wineland8
  • Sandra Wuertz8
  • Donna Wuest8
  • Weihong Yuan8
8 affiliations
  1. 1Imaging Research Center, Department of Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
  2. 2Neurodevelopmental Disorders Prevention Center, Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
  3. 3Artificial Intelligence Imaging Research Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
  4. 4Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio
  5. 5Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
  6. 6Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
  7. 7Computer Science, Biomedical Informatics, Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio
  8. 8for the Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) Investigators
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Abstract

Importance: Understanding how neonatal functional connectivity at birth is associated with later cognitive performance in infants born very preterm (VPT) may help identify early neuroimaging markers of neurodevelopment.

Objective: To examine the associations between functional connectivity at birth and cognitive performance at age 2 and 3 years in children born VPT.

Design, Setting, and Participants: This prospective cohort study included infants born VPT (gestational age ≤32 weeks) from 5 level III and IV neonatal intensive care units in the greater Cincinnati, Ohio, area between September 16, 2016, and November 19, 2019. Maternal, pregnancy, delivery, and infant clinical data were collected from birth through discharge from the neonatal intensive care unit. Participants underwent magnetic resonance imaging at full-term–equivalent age at Cincinnati Children’s Hospital using the same scanner. Image preprocessing and statistical analyses for this study were conducted between January 25, 2025, and July 30, 2026.

Main Outcomes and Measures: Cognitive outcomes were assessed at corrected age 2 and 3 years using the Bayley Scales of Infant and Toddler Development, Third Edition and the Differential Ability Scales, Second Edition, respectively. Functional connectivity was measured within and between the default mode network (DMN), somatomotor network (SMN), dorsal attention network (DAN), frontoparietal control network, visual network (VIS), and cingulo-opercular network (CO). Associations between neonatal functional connectivity and longitudinal cognitive outcomes were examined using a bayesian hierarchical linear mixed-effects model.

Results: A total of 257 infants born VPT (mean [SD] gestational age, 29.2 [2.5] weeks; 132 male [51.4%]) were included in the final longitudinal analysis. Stronger neonatal connectivity involving the DMN was positively associated with cognitive performance, including intra-DMN (0.23; 95% credible interval [CrI], 0.06-0.39) and DMN connections with the frontoparietal control network (0.24; 95% CrI, 0.07-0.40), SMN (0.20; 95% CrI, 0.02-0.37), VIS (0.32; 95% CrI, 0.13-0.51), and CO (0.39; 95% CrI, 0.21-0.56). Positive associations were also observed for SMN-VIS (0.27; 95% CrI, 0.12-0.43) and SMN-CO (0.26; 95% CrI, 0.09-0.44) connectivity. The SMN-VIS was the only connection showing a difference between assessments, with a less pronounced association at 3 years than at 2 years (interaction, −0.09; 95% CrI, −0.20 to <0.01).

Conclusions and Relevance: In this cohort study of infants born VPT, neonatal functional network organization was associated with cognitive performance at corrected age 2 and 3 years. The findings highlight the relevance of distributed connectivity involving the DMN and SMN to later cognitive outcomes and support further investigation of neonatal functional connectivity as an early marker of neurodevelopment.

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Cite

BibTeXRIS
BibTeX
@article{wang2026functional,
  title = {{Functional Connectivity at Birth and Longitudinal Neurocognitive Development in Very Preterm Infants}},
  author = {Junqi Wang and Wei Jia and Hailong Li and Zhixiu Lu and Mekibib Altaye and Kim M. Cecil and Leanne Tamm and Nehal A. Parikh and Lili He and Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) Investigators and Anita Arnsperger and Traci Beiersdorfer and Kaley Bridgewater and Tanya Cahill and Kim Cecil and Kent Dietrich and Christen Distler and Juanita Dudley and Brianne Georg and Cathy Grisby and Lacey Haas and Karen Harpster and Scott K. Holland and Priyanka VSP Illapani and Kristin Kirker and Julia E. Kline and Beth M. Kline-Fath and Matt Lanier and Stephanie L. Merhar and Greg Muthig and Brenda B. Poindexter and David Russell and Kari Tepe and Julia Thompson and Jean A. Tkach and Hui Wang and Jinghua Wang and Brynne Williams and Kelsey Wineland and Sandra Wuertz and Donna Wuest and Weihong Yuan},
  journal = {JAMA Network Open},
  year = {2026},
  month = nov,
  doi = {10.1001/jamanetworkopen.2026.41840},
  url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2856145},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Functional Connectivity at Birth and Longitudinal Neurocognitive Development in Very Preterm Infants
AU  - Junqi Wang
AU  - Wei Jia
AU  - Hailong Li
AU  - Zhixiu Lu
AU  - Mekibib Altaye
AU  - Kim M. Cecil
AU  - Leanne Tamm
AU  - Nehal A. Parikh
AU  - Lili He
AU  - Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS) Investigators
AU  - Anita Arnsperger
AU  - Traci Beiersdorfer
AU  - Kaley Bridgewater
AU  - Tanya Cahill
AU  - Kim Cecil
AU  - Kent Dietrich
AU  - Christen Distler
AU  - Juanita Dudley
AU  - Brianne Georg
AU  - Cathy Grisby
AU  - Lacey Haas
AU  - Karen Harpster
AU  - Scott K. Holland
AU  - Priyanka VSP Illapani
AU  - Kristin Kirker
AU  - Julia E. Kline
AU  - Beth M. Kline-Fath
AU  - Matt Lanier
AU  - Stephanie L. Merhar
AU  - Greg Muthig
AU  - Brenda B. Poindexter
AU  - David Russell
AU  - Kari Tepe
AU  - Julia Thompson
AU  - Jean A. Tkach
AU  - Hui Wang
AU  - Jinghua Wang
AU  - Brynne Williams
AU  - Kelsey Wineland
AU  - Sandra Wuertz
AU  - Donna Wuest
AU  - Weihong Yuan
PY  - 2026
DA  - 2026/11/02
JO  - JAMA Network Open
DO  - 10.1001/jamanetworkopen.2026.41840
UR  - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2856145
AB  - Importance: Understanding how neonatal functional connectivity at birth is associated with later cognitive performance in infants born very preterm (VPT) may help identify early neuroimaging markers of neurodevelopment.  Objective: To examine the associations between functional connectivity at birth and cognitive performance at age 2 and 3 years in children born VPT.  Design, Setting, and Participants: This prospective cohort study included infants born VPT (gestational age ≤32 weeks) from 5 level III and IV neonatal intensive care units in the greater Cincinnati, Ohio, area between September 16, 2016, and November 19, 2019. Maternal, pregnancy, delivery, and infant clinical data were collected from birth through discharge from the neonatal intensive care unit. Participants underwent magnetic resonance imaging at full-term–equivalent age at Cincinnati Children’s Hospital using the same scanner. Image preprocessing and statistical analyses for this study were conducted between January 25, 2025, and July 30, 2026.  Main Outcomes and Measures: Cognitive outcomes were assessed at corrected age 2 and 3 years using the Bayley Scales of Infant and Toddler Development, Third Edition and the Differential Ability Scales, Second Edition, respectively. Functional connectivity was measured within and between the default mode network (DMN), somatomotor network (SMN), dorsal attention network (DAN), frontoparietal control network, visual network (VIS), and cingulo-opercular network (CO). Associations between neonatal functional connectivity and longitudinal cognitive outcomes were examined using a bayesian hierarchical linear mixed-effects model.  Results: A total of 257 infants born VPT (mean [SD] gestational age, 29.2 [2.5] weeks; 132 male [51.4%]) were included in the final longitudinal analysis. Stronger neonatal connectivity involving the DMN was positively associated with cognitive performance, including intra-DMN (0.23; 95% credible interval [CrI], 0.06-0.39) and DMN connections with the frontoparietal control network (0.24; 95% CrI, 0.07-0.40), SMN (0.20; 95% CrI, 0.02-0.37), VIS (0.32; 95% CrI, 0.13-0.51), and CO (0.39; 95% CrI, 0.21-0.56). Positive associations were also observed for SMN-VIS (0.27; 95% CrI, 0.12-0.43) and SMN-CO (0.26; 95% CrI, 0.09-0.44) connectivity. The SMN-VIS was the only connection showing a difference between assessments, with a less pronounced association at 3 years than at 2 years (interaction, −0.09; 95% CrI, −0.20 to <0.01).  Conclusions and Relevance: In this cohort study of infants born VPT, neonatal functional network organization was associated with cognitive performance at corrected age 2 and 3 years. The findings highlight the relevance of distributed connectivity involving the DMN and SMN to later cognitive outcomes and support further investigation of neonatal functional connectivity as an early marker of neurodevelopment.
SN  - 2574-3805
ER  -