Hippocampal morphometry is altered in infants with congenital heart disease

Barat Gal-Er; Alexandra Bonthrone; Emily Nichols; Andrew Chew; Daniel Cromb; Chiara Casella; Alexia Egloff Collado; Kuberan Pushparajah; John  Simpson; Mary Rutherford; David Edwards; Jo Hajnal; Chiara Nosarti; Jonathan O'Muircheartaigh; Emma Duerden; Serena Counsell

doi:10.1093/braincomms/fcag060

Hippocampal morphometry is altered in infants with congenital heart disease

^*Corresponding author for this work

Western Institute for Neuroscience, Western University
Department of Applied Psychology, Faculty of Education, Western University
Cardiovascular Imaging Department

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Abstract

Congenital heart disease (CHD) is associated with impaired early brain development and an increased risk of adverse neurodevelopmental outcomes. Previous studies have reported smaller hippocampal volumes in infants, children and adolescents with CHD. However, it is unclear whether specific subfields are differentially sensitive as hippocampal subfield morphometry has not been assessed in this population. The aims of this study were to test the hypothesis that infants with CHD deviate from typical hippocampal morphometry, using a normative modelling approach with reference data from 217 typically developing infants, and characterize the relationship between hippocampal morphometric measures and both cerebral oxygen delivery and neurodevelopmental outcomes in infants with CHD. Infants with CHD [60 preoperative and 29 postoperative, gestational age at birth median (range) 38.43 (36.71–40.57) weeks, postmenstrual age at scan 39.86 (37.14–45.71) weeks] and typically developing infants underwent brain MRI on a 3T scanner, and T2-weighted and inversion recovery T1-weighted imaging were acquired. Phase-contrast angiography was acquired in 53 infants with CHD before surgery, and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 52) using the Bayley Scales of Infant and Toddler Development-Third Edition. Volumes of the whole hippocampus, subiculum, cornu ammonis 1–4, dentate gyrus, and stratum radiatum lacunosum and moleculare were obtained by segmenting T1-weighted MRI data using a U-net model trained on infant data using HippUnfold. Normative curves were generated from the typically developing infants using two models: one for relative hippocampal volumes and one for hippocampal gyrification. Models accounted for the infant’s postmenstrual age at scan, postnatal age at scan and sex. The hippocampal gyrification model also accounted for hippocampal subfield volume. Z-scores representing the degree of positive or negative deviation from the normative mean were generated for infants with CHD. Relative volume z-scores were reduced for the bilateral cornu ammonis 4 and dentate gyrus (median Z-scores −0.45 to −0.82) and were increased for the left subiculum (mean Z-scores: preoperative 0.44; postoperative 0.51) in infants with CHD. Hippocampal gyrification was reduced in the bilateral subiculum, cornu ammonis 1–4 and dentate gyrus both pre- and postoperatively (mean Z-scores, −0.50 to −1.33). There was no significant relationship between preoperative hippocampal morphometric Z-scores and cerebral oxygen delivery or neurodevelopmental outcomes. Our findings suggest that hippocampal morphometry is altered in infants with CHD; however these effects are not uniform across the hippocampus.

Original language	English
Article number	fcag060
Number of pages	14
Journal	Brain Communications
Volume	8
Issue number	2
Early online date	26 Feb 2026
DOIs	https://doi.org/10.1093/braincomms/fcag060
Publication status	Published - 2026

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HippocampalMorphometryIsAlteredInInfants_GalEr_GoldVoRFinal published version, 1.47 MBLicence: CC BY

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Gal-Er, B., Bonthrone, A., Nichols, E., Chew, A., Cromb, D., Casella, C., Egloff Collado, A., Pushparajah, K., Simpson, J., Rutherford, M., Edwards, D., Hajnal, J., Nosarti, C., O'Muircheartaigh, J., Duerden, E., & Counsell, S. (2026). Hippocampal morphometry is altered in infants with congenital heart disease. Brain Communications, 8(2), Article fcag060. https://doi.org/10.1093/braincomms/fcag060

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title = "Hippocampal morphometry is altered in infants with congenital heart disease",

abstract = "Congenital heart disease (CHD) is associated with impaired early brain development and an increased risk of adverse neurodevelopmental outcomes. Previous studies have reported smaller hippocampal volumes in infants, children and adolescents with CHD. However, it is unclear whether specific subfields are differentially sensitive as hippocampal subfield morphometry has not been assessed in this population. The aims of this study were to test the hypothesis that infants with CHD deviate from typical hippocampal morphometry, using a normative modelling approach with reference data from 217 typically developing infants, and characterize the relationship between hippocampal morphometric measures and both cerebral oxygen delivery and neurodevelopmental outcomes in infants with CHD. Infants with CHD [60 preoperative and 29 postoperative, gestational age at birth median (range) 38.43 (36.71–40.57) weeks, postmenstrual age at scan 39.86 (37.14–45.71) weeks] and typically developing infants underwent brain MRI on a 3T scanner, and T2-weighted and inversion recovery T1-weighted imaging were acquired. Phase-contrast angiography was acquired in 53 infants with CHD before surgery, and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 52) using the Bayley Scales of Infant and Toddler Development-Third Edition. Volumes of the whole hippocampus, subiculum, cornu ammonis 1–4, dentate gyrus, and stratum radiatum lacunosum and moleculare were obtained by segmenting T1-weighted MRI data using a U-net model trained on infant data using HippUnfold. Normative curves were generated from the typically developing infants using two models: one for relative hippocampal volumes and one for hippocampal gyrification. Models accounted for the infant{\textquoteright}s postmenstrual age at scan, postnatal age at scan and sex. The hippocampal gyrification model also accounted for hippocampal subfield volume. Z-scores representing the degree of positive or negative deviation from the normative mean were generated for infants with CHD. Relative volume z-scores were reduced for the bilateral cornu ammonis 4 and dentate gyrus (median Z-scores −0.45 to −0.82) and were increased for the left subiculum (mean Z-scores: preoperative 0.44; postoperative 0.51) in infants with CHD. Hippocampal gyrification was reduced in the bilateral subiculum, cornu ammonis 1–4 and dentate gyrus both pre- and postoperatively (mean Z-scores, −0.50 to −1.33). There was no significant relationship between preoperative hippocampal morphometric Z-scores and cerebral oxygen delivery or neurodevelopmental outcomes. Our findings suggest that hippocampal morphometry is altered in infants with CHD; however these effects are not uniform across the hippocampus.",

author = "Barat Gal-Er and Alexandra Bonthrone and Emily Nichols and Andrew Chew and Daniel Cromb and Chiara Casella and \{Egloff Collado\}, Alexia and Kuberan Pushparajah and John Simpson and Mary Rutherford and David Edwards and Jo Hajnal and Chiara Nosarti and Jonathan O'Muircheartaigh and Emma Duerden and Serena Counsell",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026. Published by Oxford University Press on behalf of the Guarantors of Brain.",

year = "2026",

doi = "10.1093/braincomms/fcag060",

language = "English",

volume = "8",

journal = "Brain Communications",

issn = "2632-1297",

publisher = "Oxford University Press",

number = "2",

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Gal-Er, B , Bonthrone, A, Nichols, E, Chew, A , Cromb, D , Casella, C , Egloff Collado, A , Pushparajah, K, Simpson, J, Rutherford, M , Edwards, D , Hajnal, J , Nosarti, C , O'Muircheartaigh, J, Duerden, E & Counsell, S 2026, 'Hippocampal morphometry is altered in infants with congenital heart disease', Brain Communications, vol. 8, no. 2, fcag060. https://doi.org/10.1093/braincomms/fcag060

TY - JOUR

T1 - Hippocampal morphometry is altered in infants with congenital heart disease

AU - Gal-Er, Barat

AU - Bonthrone, Alexandra

AU - Nichols, Emily

AU - Chew, Andrew

AU - Cromb, Daniel

AU - Casella, Chiara

AU - Egloff Collado, Alexia

AU - Pushparajah, Kuberan

AU - Simpson, John

AU - Rutherford, Mary

AU - Edwards, David

AU - Hajnal, Jo

AU - Nosarti, Chiara

AU - O'Muircheartaigh, Jonathan

AU - Duerden, Emma

AU - Counsell, Serena

PY - 2026

Y1 - 2026

N2 - Congenital heart disease (CHD) is associated with impaired early brain development and an increased risk of adverse neurodevelopmental outcomes. Previous studies have reported smaller hippocampal volumes in infants, children and adolescents with CHD. However, it is unclear whether specific subfields are differentially sensitive as hippocampal subfield morphometry has not been assessed in this population. The aims of this study were to test the hypothesis that infants with CHD deviate from typical hippocampal morphometry, using a normative modelling approach with reference data from 217 typically developing infants, and characterize the relationship between hippocampal morphometric measures and both cerebral oxygen delivery and neurodevelopmental outcomes in infants with CHD. Infants with CHD [60 preoperative and 29 postoperative, gestational age at birth median (range) 38.43 (36.71–40.57) weeks, postmenstrual age at scan 39.86 (37.14–45.71) weeks] and typically developing infants underwent brain MRI on a 3T scanner, and T2-weighted and inversion recovery T1-weighted imaging were acquired. Phase-contrast angiography was acquired in 53 infants with CHD before surgery, and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 52) using the Bayley Scales of Infant and Toddler Development-Third Edition. Volumes of the whole hippocampus, subiculum, cornu ammonis 1–4, dentate gyrus, and stratum radiatum lacunosum and moleculare were obtained by segmenting T1-weighted MRI data using a U-net model trained on infant data using HippUnfold. Normative curves were generated from the typically developing infants using two models: one for relative hippocampal volumes and one for hippocampal gyrification. Models accounted for the infant’s postmenstrual age at scan, postnatal age at scan and sex. The hippocampal gyrification model also accounted for hippocampal subfield volume. Z-scores representing the degree of positive or negative deviation from the normative mean were generated for infants with CHD. Relative volume z-scores were reduced for the bilateral cornu ammonis 4 and dentate gyrus (median Z-scores −0.45 to −0.82) and were increased for the left subiculum (mean Z-scores: preoperative 0.44; postoperative 0.51) in infants with CHD. Hippocampal gyrification was reduced in the bilateral subiculum, cornu ammonis 1–4 and dentate gyrus both pre- and postoperatively (mean Z-scores, −0.50 to −1.33). There was no significant relationship between preoperative hippocampal morphometric Z-scores and cerebral oxygen delivery or neurodevelopmental outcomes. Our findings suggest that hippocampal morphometry is altered in infants with CHD; however these effects are not uniform across the hippocampus.

AB - Congenital heart disease (CHD) is associated with impaired early brain development and an increased risk of adverse neurodevelopmental outcomes. Previous studies have reported smaller hippocampal volumes in infants, children and adolescents with CHD. However, it is unclear whether specific subfields are differentially sensitive as hippocampal subfield morphometry has not been assessed in this population. The aims of this study were to test the hypothesis that infants with CHD deviate from typical hippocampal morphometry, using a normative modelling approach with reference data from 217 typically developing infants, and characterize the relationship between hippocampal morphometric measures and both cerebral oxygen delivery and neurodevelopmental outcomes in infants with CHD. Infants with CHD [60 preoperative and 29 postoperative, gestational age at birth median (range) 38.43 (36.71–40.57) weeks, postmenstrual age at scan 39.86 (37.14–45.71) weeks] and typically developing infants underwent brain MRI on a 3T scanner, and T2-weighted and inversion recovery T1-weighted imaging were acquired. Phase-contrast angiography was acquired in 53 infants with CHD before surgery, and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 52) using the Bayley Scales of Infant and Toddler Development-Third Edition. Volumes of the whole hippocampus, subiculum, cornu ammonis 1–4, dentate gyrus, and stratum radiatum lacunosum and moleculare were obtained by segmenting T1-weighted MRI data using a U-net model trained on infant data using HippUnfold. Normative curves were generated from the typically developing infants using two models: one for relative hippocampal volumes and one for hippocampal gyrification. Models accounted for the infant’s postmenstrual age at scan, postnatal age at scan and sex. The hippocampal gyrification model also accounted for hippocampal subfield volume. Z-scores representing the degree of positive or negative deviation from the normative mean were generated for infants with CHD. Relative volume z-scores were reduced for the bilateral cornu ammonis 4 and dentate gyrus (median Z-scores −0.45 to −0.82) and were increased for the left subiculum (mean Z-scores: preoperative 0.44; postoperative 0.51) in infants with CHD. Hippocampal gyrification was reduced in the bilateral subiculum, cornu ammonis 1–4 and dentate gyrus both pre- and postoperatively (mean Z-scores, −0.50 to −1.33). There was no significant relationship between preoperative hippocampal morphometric Z-scores and cerebral oxygen delivery or neurodevelopmental outcomes. Our findings suggest that hippocampal morphometry is altered in infants with CHD; however these effects are not uniform across the hippocampus.

UR - https://www.scopus.com/pages/publications/105032454652

U2 - 10.1093/braincomms/fcag060

DO - 10.1093/braincomms/fcag060

M3 - Article

SN - 2632-1297

VL - 8

JO - Brain Communications

JF - Brain Communications

IS - 2

M1 - fcag060

ER -

Hippocampal morphometry is altered in infants with congenital heart disease

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