Alterations in Brain Structure and Their Association with Umbilical Blood Gases in Neonates with Perinatal Asphyxia

Alterations in Brain Structure and Their Association with Umbilical Blood Gases in Neonates with Perinatal Asphyxia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Alterations in Brain Structure and Their Association with Umbilical Blood Gases in Neonates with Perinatal Asphyxia Chen-Yu Dong, Yuan-Hui Li, Si-Jian Huang, Yu Xuan Ni, Bo-Ya Yin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8863172/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Perinatal asphyxia is a leading cause of neonatal morbidity and can induce central nervous system hypoxia with functional sequelae. Current evidence on associated brain structural changes remains limited. This study aimed to determine whether mild perinatal asphyxia correlates with subtle alterations in neonatal cortical structure. Methods Head MRI data from 115 neonates were collected. Using a 1‑minute Apgar score cutoff of 7, neonates were classified into an asphyxia (AS) group and a non‑asphyxia (non‑AS) group. T2, T2‑FLAIR, and 3D T1 sequences were acquired. Gray matter volume, cortical thickness, surface area, and curvature were computed via the uAI Research Portal. Umbilical artery blood gas parameters (including hydrogen ion concentration index, lactate, and base excess) were recorded. Gender, corrected gestational age, and total brain volume were included as covariates. Group differences in gray matter volume and cortical parameters were compared, and their correlations with umbilical artery blood gas indicators were analyzed. Results Relative to the non‑AS group, the AS group exhibited significantly reduced bilateral amygdala volume, left transverse temporal gyrus thickness, and curvature of the left caudal middle frontal gyrus, pars triangularis, supramarginal gyrus, and right inferior temporal gyrus (corrected p = 0.001–0.046). All these parameters showed significant correlations with umbilical artery blood gas measures ( p < 0.05). Conclusion A low 1‑minute Apgar score is associated with measurable changes in brain structure and correlates with clinical indicators from umbilical artery blood gas analysis. These findings may provide future imaging evidence for the clinical assessment of perinatal asphyxia. perinatal asphyxia magnetic resonance imaging gray matter volume cerebral cortex umbilical artery blood gas analysis Figures Figure 1 Figure 2 Figure 3 1 Background Perinatal asphyxia is a major cause of perinatal mortality and long-term neurodevelopmental impairment, affecting over three million neonates annually worldwide [ 1 ]. It arises from impaired gas exchange during labor, leading to fetal/newborn hypoxia-ischemia [ 2 ]. The Apgar score, assessed immediately after birth, serves as a key pragmatic indicator for early hypoxic insult. Although many infants recover breathing quickly, the transient hypoxic-ischemic exposure can still result in adverse outcomes such as neonatal encephalopathy and cerebral palsy [ 3 ]. Understanding how perinatal asphyxia disrupts early brain development is therefore critical for elucidating mechanisms of later impairment and guiding timely intervention. No unified diagnostic standard for perinatal asphyxia exists [ 4 ]. In clinical practice, the Apgar score remains the primary immediate assessment for newborn status and is commonly used to screen infants at risk of asphyxia[ 5 ]. The core integrates five physiological signs, heart rate, respiratory effort, muscle tone, reflex irritability, and skin color[ 6 ], each rated from 0 to 2, yielding a total score from 0 to 10[ 7 ]. A lower Apgar score indicates a higher risk of intrauterine hypoxia and asphyxia in newborns[ 8 ]. To enhance objectivity, umbilical artery blood gas parameters (pH, base excess) and lactate are increasingly used alongside Apgar scores [ 9 ]. These biomarkers reflect acid-base status and anaerobic metabolism, correlate with neonatal outcomes, and may improve diagnostic and prognostic accuracy [ 10 ]. However, whether neonates with an abnormal 1-minute Apgar score that normalizes by 5 minutes sustain meaningful effects on early brain development remains unclear. Over the past four decades, neuroimaging has become central to the evaluation of brain injury following perinatal asphyxia[ 11 ]. As a noninvasive tool, neonatal neuroimaging enables early detection of tissue injury and provides clinically meaningful information beyond bedside assessments[ 12 ]. MRI provides high spatial resolution and multi-sequence detail for locating and characterizing injury, and its patterns predict neurodevelopmental outcomes [ 13 ]. Studies have shown that perinatal asphyxia can cause long-term damage to the brain regions, and this damage cannot be compensated for by plastic mechanisms[ 14 ]. Injury patterns vary with gith age, involving changes in volume, surface area, and thickness [ 15 , 16 ]. In typical development, cortical surface area increases with age until 8–9 years and then decreases into early adulthood [ 17 ], due to cortical pruning and enhanced myelination [ 18 ]. Extensive cross-sectional applications of new surface-based morphometry methods have been used for measuring cortical surface area and cortical thickness [ 19 , 20 ]. MRI-derived metrics like thickness, area, volume, and curvature can quantify these changes [ 21 – 23 ]. Cortical thickness was lower in the AS group across several regions, including the left postcentral, middle-posterior frontal, middle cingulate, superior temporal, and transverse temporal gyri, and right parahippocampal and parasuperior temporal gyri. Cortical thickness development perinatally remains underexplored due to imaging constraints [ 24 ]. Thinning in asphyxiated neonates may reflect developmental delay[ 25 ], indicating regional vulnerability. Cortical surface area was also reduced in the AS group. Although cortical area expands significantly in early life [ 26 ], its perinatal dynamics are poorly understood [ 27 ]. Early area expansion supports lasting cognitive development [ 28 ] via anatomical connections [ 29 ]. A smaller area in the AS group may signify delayed maturation [ 30 ]. Our findings indicate that the cortical surface area of the aforementioned brain regions may be vulnerable to perinatal asphyxia. The curvature of bilateral orbital regions, etc., is reduced in the AS group. In neonates and infants, studies on cortical development have primarily focused on changes in gray matter volume [ 31 ], gyral maturation of deep sulci [ 32 ], thickness and surface area [ 33 ], as well as cortical folding and fiber organization [ 34 ], with limited investigation into estational age (GA); in term/near-term infants, deep gray matter abnormalities are strongly linked to poor outcomes. Prior research, however, has predominantly examined infants with overt hypoxic-ischemic encephalopathy, leaving subtle gray matter alterations in neonates without clear lesions poorly characterized. The cerebral cortex matures rapidly during the perinatal period and is highly vulnerable to early insults with lasting consequences [ 35 ]. Injury extent depends on gestational age, insult severity, and intervention timing [ 36 ]. MRI-based cortical morphometry quantifies cortical development in vivo. Cortical volume integrates two biologically distinct dimensions—thickness and surface area—which should be assessed jointly [ 37 ]. Metrics such as curvature further complement the evaluation of cortical folding and maturation [ 38 ]. Together, these measures allow multidimensional characterization of cortical development and may detect subtle alterations after hypoxic exposure. This study aimed to determine whether mild perinatal asphyxia is associated with subtle neonatal cortical structural changes. We focused on neonates with an abnormal 1-minute Apgar score (≤ 7) that recovered by 5 minutes (> 7)—a clinically reassuring group seldom examined for brain developmental sequelae. Using MRI morphometry, we assessed cortical volume, thickness, surface area, and curvature and examined their correlations with umbilical artery blood gas parameters. By clarifying whether transient Apgar abnormalities correlate with measurable cortical alterations, this work may aid early risk stratification and inform personalized intervention. 2 Materials and methods 2.1 Demographic data This prospective cross-sectional study, approved by the Third Affiliated Hospital of Sun Yat-sen University (II2023-003-01), enrolled neonates born between May 2020 and July 2024 presenting with respiratory distress, intrauterine hypoxia, birth asphyxia, abnormal electroencephalogram, or preterm birth. Exclusion criteria were: (i) intracranial hemorrhage of any type; (ii) hydrocephalus; (iii) congenital intracranial malformations. Written informed consent was obtained from all parents. Neonates were categorized into two groups based on 1‑ and 5‑minute Apgar scores: the asphyxia (AS) group (Apgar ≤ 7 at 1 min and > 7 at 5 min) and the non‑asphyxia (non‑AS) group (Apgar > 7 at both timepoints). 2.2 Clinical data A 10–20 cm umbilical cord segment was clamped immediately after delivery. Umbilical artery blood was collected using a heparinized syringe for analysis of pH, lactate (LAC), and base excess (BE). 2.3 MRI acquisition MRI was performed on a 3.0 T scanner (GE SIGNA Architect). Neonates were fed, swaddled, and sedated with oral chloral hydrate (20–30 mg/kg). Pulse oximetry and hearing protection were applied. The three-dimensional magnetization prepared rapid gradient echo sequence was used for 3D T1-weighted bravo acquisition with the following parameters: repetition time = 7.7 ms, echo time = 3.1 ms, flip angle = 12°, field of view = 256×256mm 2 , matrix = 256×256, slice thickness = 1mm, with no slice gap, and slices = 172. The total scanning time was 4 min and 53 s. Additionally, T2-weighted(repetition time = 4043 ms, echo time = 130 ms,, field of view = 160×128mm 2 , matrix = 280×192, slice thickness = 1mm), T2-FLAIR༈repetition time = 9000 ms, echo time = 133 ms, flip angle = 12°, field of view = 60×128mm 2 , matrix = 300×192, slice thickness = 1mm༉images were obtained to exclude subjects with major brain changes, intracerebral hemorrhage, intracerebral malformation, or other lesions, as demonstrated by the above exclusion criteria. 2.4 MRI data processing All images in this study were processed using the uAI Research Portal (United Imaging Intelligence). Preprocessing included skull stripping, bias correction, and resampling to 1 mm isotropic resolution. Subsequently, T1-weighted images were parcellated into 109 regions of interest (ROIs) according to the Desikan–Killiany (DK) atlas using a pre-trained cascaded VB-Net model. Cortical surface reconstruction was performed within the Cortical Flow Framework, whereby cortical vertices were iteratively deformed to delineate the cortical boundaries. The segmentation model employed a two-stage architecture combining coarse anatomical localization with refined segmentation, demonstrating high robustness and accuracy in medical image segmentation tasks (Fig. 1 ). Finally, we obtain gray matter volume, cortical thickness, surface area, and curvature metrics. 2.5 Statistical analysis Statistical analysis was performed using SPSS 27.0 statistical software. Continuous variables were tested for normality; group comparisons employed t‑tests or Wilcoxon rank‑sum tests accordingly. Categorical variables were compared via the chi‑square test. For imaging data, Analysis of Variance (ANOVA) compared AS and non‑AS groups with gender, corrected gestational age (CGA), and total brain volume as covariates. For the results of multiple brain regions within each indicator, Storey’s q -value method was used for multiple comparison correction. A corrected p < 0.05 was considered statistically significant. Correlations between significant regions and clinical indicators were assessed using Pearson or Spearman tests based on data distribution. 3 Results 3.1 Demographic characteristics and clinical data Of 137 initially enrolled subjects, 22 were excluded due to intracerebral hemorrhage (n = 16), hydrocephalus (n = 4), or intracranial vascular malformations (n = 2). The final cohort comprised 115 neonates: 53 in the AS group and 62 in the non-AS group. In the AS group, corrected gestational age (CGA) was 270.14 ± 15.07 days, and total brain volume was 406.16 ± 72.87 cm³. In the non-AS group, CGA was 271.56 ± 18.97 days, and total brain volume was 410.68 ± 61.02 cm³. The AS group had a significantly lower umbilical artery pH (7.14 ± 0.12) and higher LAC (7.36 ± 2.71) and BE (6.88 ± 4.76) compared to the non-AS group (pH: 7.21 ± 0.10; LAC: 5.69 ± 1.68; BE: 5.69 ± 1.67). (Table 1 ) Table 1 Demographic and Clinical Characteristics of the Study Cohort. Characteristic LAS group NAS group T /χ 2 p ( n = 53) ( n = 62) CGA 270.14 ± 15.07 271.56 ± 18.97 −0.442 0.659 Volume 406.16 ± 72.87 410.68 ± 61.02 -0.668 0.505 Sex (male/female) 26/27 33/29 1.792 0.181 GA (preterm/term) 23/30 25/37 0.111 0.739 Laboratory Tests UABG PH 7.14 ± 0.12 7.21 ± 0.10 -3.594 0.001 UABG BE 7.36 ± 2.71 5.69 ± 1.68 2.78 0.008 UABG LAC 6.88 ± 4.76 5.69 ± 1.67 -2.081 0.04 Note: Data are shown as mean ± SD. Abbreviations: LAS = Low Apgar score, NAS = Normal Apgar score, UABGU = Umbilical Artery Blood Gas, PH = Potential of Hydrogen, LAC=Lactic Acid, BE = Base Excess 3.2 Volume Relative to the non-AS group, the AS group showed reduced volume in several brain regions (Supplementary Materials 1). After multiple comparison correction, significantly smaller volumes were observed in the bilateral amygdala and the right transverse temporal gyrus (Table 2 and Fig. 2 A-D). Table 2 Brain Regions Exhibiting Significant Between-Group Differences (Corrected p ≤ 0.05) Character Brain region AS group non-AS group F p value Corrected p-value Volume Amygdala (L) (cm³) 0.676 ± 0.186 0.609 ± 0.176 1.117 < 0.001 0.005 Amygdala (R) (cm³) 0.688 ± 0.207 0.607 ± 0.178 1.361 0.005 0.026 Transverse temporal (R) (cm³) 0.500 ± 0.141 0.443 ± 0.131 1.157 0.005 0.028 Thickness Transverse temporal (L) (cm) 2.013 ± 0.253 2.051 ± 0.223 1.288 0.001 0.013 Curvature Frontal Mid Caudal (L) 0.327 ± 0.081 0.339 ± 0.074 1.196 0.005 0.046 Parstriangularis (L) 0.327 ± 0.082 0.365 ± 0.068 1.460 < 0.001 0.003 Supramarginal (L) 0.300 ± 0.056 0.310 ± 0.063 0.775 0.003 0.031 Temporal Inf (R) 0.305 ± 0.087 0.336 ± 0.054 2.596 0.004 0.037 Note: Data are shown as mean ± SD. Abbreviations: AS = Asphyxia, L = left, R = right, SD = Standard Deviation. 3.3 Cortical Thickness Cortical thickness was lower in the AS group across several regions (Supplementary Materials 2). After multiple comparison correction to calculate the corrected p -values, the left transverse temporal remained statistically significant. (Table 2 and Fig. 2 E) 3.4 Cortical Surface Area Smaller surface areas were noted in the AS group for the left postcentral, caudal middle frontal, middle cingulate, superior temporal, and transverse temporal gyri, and the right medial orbitofrontal gyrus, insular cortex, superior parietal lobule, and temporal pole (Supplementary Materials 3). No regions survived multiple comparison correction. 3.5 Cortical Curvature The AS group exhibited reduced cortical curvature in multiple regions (Supplementary Materials 4). After multiple comparison correction, significant reductions persisted in the left caudal middle frontal gyrus, left pars triangularis, left supramarginal gyrus, and right inferior temporal gyrus (Table 2 and Fig. 2 F-G). 3.6 Correlation results In the AS group, significant correlations were found as follows: There was a significant correlation between the right transverse temporal gyrus and pH value ( r = -0.845, p = 0.014). There was a significant correlation between the right amygdala and LAC ( r = -0.812, p = 0.001). There was a significant correlation between the right transverse temporal gyrus and BE values ( r = -0.627, p = 0.002). In the non-AS group, significant correlations were found as follows: The right amygdala ( r = -0.321, p = 0.003), the left amygdala ( r = -0.304, p = 0.005), and the right transverse temporal gyrus ( r =-0.224, p = 0.043) were each significantly correlated with pH value. The right amygdala ( r = -0.293, p = 0.015) and right transverse temporal gyrus ( r = -0.349, p = 0.003) were each significantly correlated with BE values (Table 3 and Fig. 3 ). Table 3 Correlations Between Brain Structural Measures and Umbilical Artery Blood Gas Parameters Brain region AS group non-AS group PH LAC BE PH LAC BE r p r p r p r p r p r p Amygdala (L) (cm³) 0.028 0.893 0.045 0.045 0.080 0.722 0.582 0.005 0.149 0.274 -0.145 0.235 Amygdala (R) (cm³) 0.030 0.888 -0.812 0.001 -0.006 0.980 0.612 0.003 0.008 0.956 0.465 0.015 Transverse temporal (R) (cm³) -0.845 0.014 0.297 0.297 -0.627 0.002 0.392 0.043 0.207 0.126 0.562 0.003 Transversetemporal (L) (cm) -0.105 0.625 0.052 0.865 -0.337 0.136 -0.125 0.268 0.018 0.898 -0.205 0.094 Frontal Mid Caudal (L) -0.032 0.883 0.184 0.547 0.062 0.790 -0.013 0.907 -0.145 0.286 0.144 0.242 Parstriangularis (L) 0.103 0.633 0.091 0.768 0.253 0.268 0.078 0.491 -0.044 0.750 0.178 0.148 Temporal Inf (R) -0.052 0.810 0.459 0.114 -0.257 0.261 0.047 0.679 -0.241 0.074 -0.025 0.841 Supramarginal (L) 0.026 0.907 0.510 0.109 0.106 0.658 -0.010 0.931 0.114 0.413 -0.171 0.167 Note: Data are shown as mean ± SD. Abbreviations: LAS = Low Apgar score, NAS = Normal Apgar score, UABGU = Umbilical Artery Blood Gas, PH = Potential of Hydrogen, LAC=Lactic Acid, BE = Base Excess 4 Discussion This study found that neonates with low 1-minute Apgar scores exhibited reduced gray matter volume, cortical thickness, and curvature compared to controls. These structural alterations correlated significantly with umbilical artery pH, LAC, and BE, suggesting that early transient hypoxia may impact neonatal gray matter development. Brain volume increases progressively from the neonatal period into adulthood [ 39 ], doubling within the first year [ 40 ]. Gray matter volume rises 108–149% from birth to age 1 [ 41 ]. Despite extensive research on brain developmental trajectories over the past few decades, significant discrepancies remain among existing findings [ 42 ]. In addition, conclusions regarding the timing of brain maturation vary across different studies [ 43 ], hindering our in-depth understanding of this highly complex and multifactorial physiological phenomenon [ 44 ]. Neonates with low Apgar scores showed reduced bilateral amygdala volume, among other regions. Studying early brain development has been limited by imaging challenges. Subcortical structures grow ~ 105% in the first year and ~ 15% in the second [ 45 , 46 ]. Changes in volumetric development are closely correlated with alterations in the number of oligodendrocytes [ 17 , 47 ], increased myelination of axonal projections, and reduced striatal development [ 48 , 49 ]. The amygdala preferentially connects to the dorsal striatum (caudate nucleus, putamen) and medial prefrontal cortex, consistent with the latter’s early, rapid development in the same period. Our findings align with these reports and indicate these regions are vulnerable to perinatal asphyxia, with early hypoxia potentially delaying their development. Cortical surface area, thickness, and curvature were reduced in the AS group. Late gestation involves rapid cortical expansion and folding [ 50 , 51 ]. Cortical complexity increases with cortical curvature. Our results suggest that cortical curvature in the aforementioned regions may represent vulnerable brain areas affected by perinatal asphyxia. Previous research on cortical thickness, surface area, and curvature alterations following early neonatal hypoxia remains scarce. Thus, the alterations identified in our study warrant further validation in future investigations. Neonates with lower 1-minute Apgar scores had more abnormal umbilical blood gas parameters (pH, BE, LAC), even with normalized 5-minute scores. The Apgar score reflects neonatal cardiorespiratory and neurological status, guiding resuscitation [ 52 ]. Intrapartum hypoxia can induce metabolic acidosis and organ risk [ 53 ]. Umbilical artery pH (median ~ 7.25 in normal deliveries [ 54 ]) indicates acidaemia severity [ 55 ]. BE is used as a supplementary indicator to assess the severity and duration of neonatal acidemia [ 56 ]. It should be noted that the introduction of BE aims to reflect the metabolic component (i.e., base deficit) underlying the low pH value [ 57 ]. Variant base deficit formulas and no selection consensus preclude a statistically defined BE reference range. We found that the umbilical artery blood gas pH, BE, and LAC values of infants with perinatal asphyxia were lower than those of the non-asphyxia group, consistent with previous studies. In the AS group, right amygdala volume correlated with LAC, and right transverse temporal gyrus volume correlated with pH and BE. In the non-AS group, bilateral amygdala and right transverse temporal gyrus volumes correlated with pH, and right amygdala and transverse temporal gyrus volumes correlated with BE. These associations suggest that brain regional volumes relate to hypoxic biomarkers, linking imaging indices to physiological markers. We focused on neonates with transiently low Apgar scores (≤ 7 at 1 min, > 7 at 5 min) and found persistent gray matter alterations. Assessing volume, thickness, curvature, and surface area provided a comprehensive structural evaluation. There are several limitations. This was a cross-sectional study without long-term follow-up. Sample size limited subgroup analysis by preterm/term status, though group proportions did not differ significantly. Future studies should stratify by gestational age. 5 Conclusion This study demonstrates that neonates with lower 1‑minute Apgar scores show reductions in brain volume, cortical thickness, surface area, and curvature, with some of these structural alterations correlating with umbilical artery blood gas parameters. These findings indicate that even transiently low Apgar scores, normalizing by 5 minutes, may influence early brain development. The results offer potential neuroimaging evidence to support future clinical assessment of perinatal asphyxia. Declarations Ethics a pproval and consent to participate This study was approved by the Institutional Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-Sen University (II2023-003-01), and written informed consent was obtained from the guardians of all infants. Consent for publication 1. All authors of the manuscript have read and agreed to its content and are accountable for all aspects of the accuracy and integrity of the manuscript in accordance with ICMJE criteria 2. That the article is original, has not already been published in a journal, and is not currently under consideration by another journal Availability of data and materials 1. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. 2. All data generated or analysed during this study are included in this article. Competing interests No conflict of interest or industry support exists in the submission of this manuscript. Funding This study was supported by grants from the National Natural Science Foundation of China (No. 82471567, 81801757), Guangdong Basic and Applied Basic Research Foundation (No. 2024A1515010279, 2023A1515010256). Authors' contributions CY Dong, YH Li, SJ H, YY Liang, and RM Guo: Data curation, Investigation, Software, Writing - original draft BY Yin and YX Ni: Data curation, Formal analysis, Methodology RM Guo: Funding acquisition, Supervision Acknowledgment None. Clinical trial number Not applicable. References Lawn JE, et al. Every Newborn: progress, priorities, and potential beyond survival. Lancet. 2014;384(9938):189–205. Schiariti V, et al. Perinatal characteristics and parents' perspective of health status of NICU graduates born at term. J Perinatol. 2008;28(5):368–76. Lee AC, et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res. 2013;74(Suppl 1):50–72. Cai Y, et al. The value of umbilical artery blood gas analysis in the diagnosis and prognosis evaluation of fetal distress. Am J Transl Res. 2022;14(7):4821–9. Dalili H, et al. 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Wiberg N, et al. Lactate concentration in umbilical cord blood is gestational age-dependent: a population-based study of 17 867 newborns. BJOG. 2008;115(6):704–9. Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterials.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8863172","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":597194790,"identity":"fe5883f1-04da-491e-b691-3e2c58dda835","order_by":0,"name":"Chen-Yu Dong","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Chen-Yu","middleName":"","lastName":"Dong","suffix":""},{"id":597194791,"identity":"a770d6ab-dd69-4713-90f6-805db7f74212","order_by":1,"name":"Yuan-Hui Li","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Yuan-Hui","middleName":"","lastName":"Li","suffix":""},{"id":597194792,"identity":"e52e9da4-34c1-4a3e-88f1-0ac9dad8c645","order_by":2,"name":"Si-Jian Huang","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Si-Jian","middleName":"","lastName":"Huang","suffix":""},{"id":597194796,"identity":"620bd4f2-48f6-4b71-a0dc-47322610c288","order_by":3,"name":"Yu Xuan Ni","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"Xuan","lastName":"Ni","suffix":""},{"id":597194798,"identity":"8627a15e-8e93-48ef-8c6d-141a3e875591","order_by":4,"name":"Bo-Ya Yin","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Bo-Ya","middleName":"","lastName":"Yin","suffix":""},{"id":597194800,"identity":"cbcdc4bf-217c-4bfc-927f-5a6f87ca62f8","order_by":5,"name":"Yayong Liang","email":"","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Yayong","middleName":"","lastName":"Liang","suffix":""},{"id":597194802,"identity":"ba44fbcf-b4b6-4813-bb5a-c2758deec56f","order_by":6,"name":"Ruo-Mi Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEElEQVRIiWNgGAWjYBADHn725gMMDAYWMAFmwloke44lALVIEK+FweCGjwGQIkKLfETysc88FdtkJGfwfN3wo0CCQX5G+jMJhgrrxAb2swewaTG8kZY8m+fMbR5+6d5tN3uADjO4kWMmwXAmPbGBJy8Bq5YZOcbMvG23eSTnnN12gwekRSKHTYKx7XBigwSPAV4tQMOf3fxjAHUY4z/cWuQlEFrYboNsYbiRYCbB2IBbiwHPs2TGOUC/AAPZ7LaMAVDZmTfGFgnH0o3beHKw29KefJjhTcVte2BUPrv55o+NnHx7+sMbH2qsZfvZz2C3BT0ceRgEgOEECio2bOpBtjRgCPGjmzIKRsEoGAUjHQAARJRb3TeGPccAAAAASUVORK5CYII=","orcid":"","institution":"Third Affiliated Hospital of Sun Yat-sen University","correspondingAuthor":true,"prefix":"","firstName":"Ruo-Mi","middleName":"","lastName":"Guo","suffix":""}],"badges":[],"createdAt":"2026-02-12 14:27:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8863172/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8863172/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104399200,"identity":"ca027b0d-ee0b-4a8e-a263-caca465ec10e","added_by":"auto","created_at":"2026-03-11 12:05:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":21452074,"visible":true,"origin":"","legend":"\u003cp\u003eBrain parcellation schematic diagram.\u003c/p\u003e\n\u003cp\u003eA: anterior, P: posterior, L: left, R: right, I: inferior, S: superior\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8863172/v1/5c88eaf3e9a2f84fa6af0912.png"},{"id":103598221,"identity":"dfe980eb-e162-40bc-aac7-dead3b1655b4","added_by":"auto","created_at":"2026-02-27 13:37:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":13401068,"visible":true,"origin":"","legend":"\u003cp\u003eBrain regions showing significant between-group differences after multiple comparison correction.\u003c/p\u003e\n\u003cp\u003eAS: asphyxia group; non-AS: non-asphyxia group.\u003c/p\u003e\n\u003cp\u003e*\u003cem\u003ep\u003c/em\u003e＜0.05; **\u003cem\u003ep\u003c/em\u003e＜0.01; ***\u003cem\u003ep\u003c/em\u003e＜0.001.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8863172/v1/5f0f573334ea412167924a2a.png"},{"id":103598220,"identity":"b851fbaf-1b4a-40e9-a0ba-b3a5ba4a1e15","added_by":"auto","created_at":"2026-02-27 13:37:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":7770636,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelations between alterations in brain regional measures and umbilical artery blood gas parameters.\u003c/p\u003e\n\u003cp\u003eLAC: Lactic Acid, PH: Potential of Hydrogen, BE: Base Excess.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8863172/v1/b81bf73d6e50ebcf1b772d95.png"},{"id":104835104,"identity":"6eb1eeb9-e873-4ecb-92f7-249a702ce6f5","added_by":"auto","created_at":"2026-03-17 17:40:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":41377122,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8863172/v1/710c0b6a-43f1-44c3-aea9-02ab9991673e.pdf"},{"id":103598219,"identity":"66ffcb38-ab0e-4e1f-8546-6055ec503863","added_by":"auto","created_at":"2026-02-27 13:37:49","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":66262,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-8863172/v1/c534a51bef7d2f2043edb7ec.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Alterations in Brain Structure and Their Association with Umbilical Blood Gases in Neonates with Perinatal Asphyxia","fulltext":[{"header":"1 Background","content":"\u003cp\u003ePerinatal asphyxia is a major cause of perinatal mortality and long-term neurodevelopmental impairment, affecting over three million neonates annually worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It arises from impaired gas exchange during labor, leading to fetal/newborn hypoxia-ischemia [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The Apgar score, assessed immediately after birth, serves as a key pragmatic indicator for early hypoxic insult. Although many infants recover breathing quickly, the transient hypoxic-ischemic exposure can still result in adverse outcomes such as neonatal encephalopathy and cerebral palsy [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Understanding how perinatal asphyxia disrupts early brain development is therefore critical for elucidating mechanisms of later impairment and guiding timely intervention.\u003c/p\u003e \u003cp\u003eNo unified diagnostic standard for perinatal asphyxia exists [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In clinical practice, the Apgar score remains the primary immediate assessment for newborn status and is commonly used to screen infants at risk of asphyxia[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The core integrates five physiological signs, heart rate, respiratory effort, muscle tone, reflex irritability, and skin color[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], each rated from 0 to 2, yielding a total score from 0 to 10[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A lower Apgar score indicates a higher risk of intrauterine hypoxia and asphyxia in newborns[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. To enhance objectivity, umbilical artery blood gas parameters (pH, base excess) and lactate are increasingly used alongside Apgar scores [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. These biomarkers reflect acid-base status and anaerobic metabolism, correlate with neonatal outcomes, and may improve diagnostic and prognostic accuracy [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, whether neonates with an abnormal 1-minute Apgar score that normalizes by 5 minutes sustain meaningful effects on early brain development remains unclear.\u003c/p\u003e \u003cp\u003eOver the past four decades, neuroimaging has become central to the evaluation of brain injury following perinatal asphyxia[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. As a noninvasive tool, neonatal neuroimaging enables early detection of tissue injury and provides clinically meaningful information beyond bedside assessments[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. MRI provides high spatial resolution and multi-sequence detail for locating and characterizing injury, and its patterns predict neurodevelopmental outcomes [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Studies have shown that perinatal asphyxia can cause long-term damage to the brain regions, and this damage cannot be compensated for by plastic mechanisms[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Injury patterns vary with gith age, involving changes in volume, surface area, and thickness [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In typical development, cortical surface area increases with age until 8\u0026ndash;9 years and then decreases into early adulthood [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], due to cortical pruning and enhanced myelination [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Extensive cross-sectional applications of new surface-based morphometry methods have been used for measuring cortical surface area and cortical thickness [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. MRI-derived metrics like thickness, area, volume, and curvature can quantify these changes [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCortical thickness was lower in the AS group across several regions, including the left postcentral, middle-posterior frontal, middle cingulate, superior temporal, and transverse temporal gyri, and right parahippocampal and parasuperior temporal gyri. Cortical thickness development perinatally remains underexplored due to imaging constraints [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Thinning in asphyxiated neonates may reflect developmental delay[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], indicating regional vulnerability. Cortical surface area was also reduced in the AS group. Although cortical area expands significantly in early life [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], its perinatal dynamics are poorly understood [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Early area expansion supports lasting cognitive development [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] via anatomical connections [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. A smaller area in the AS group may signify delayed maturation [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Our findings indicate that the cortical surface area of the aforementioned brain regions may be vulnerable to perinatal asphyxia. The curvature of bilateral orbital regions, etc., is reduced in the AS group. In neonates and infants, studies on cortical development have primarily focused on changes in gray matter volume [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], gyral maturation of deep sulci [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], thickness and surface area [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], as well as cortical folding and fiber organization [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], with limited investigation into estational age (GA); in term/near-term infants, deep gray matter abnormalities are strongly linked to poor outcomes. Prior research, however, has predominantly examined infants with overt hypoxic-ischemic encephalopathy, leaving subtle gray matter alterations in neonates without clear lesions poorly characterized.\u003c/p\u003e \u003cp\u003eThe cerebral cortex matures rapidly during the perinatal period and is highly vulnerable to early insults with lasting consequences [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Injury extent depends on gestational age, insult severity, and intervention timing [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. MRI-based cortical morphometry quantifies cortical development in vivo. Cortical volume integrates two biologically distinct dimensions\u0026mdash;thickness and surface area\u0026mdash;which should be assessed jointly [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Metrics such as curvature further complement the evaluation of cortical folding and maturation [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Together, these measures allow multidimensional characterization of cortical development and may detect subtle alterations after hypoxic exposure.\u003c/p\u003e \u003cp\u003eThis study aimed to determine whether mild perinatal asphyxia is associated with subtle neonatal cortical structural changes. We focused on neonates with an abnormal 1-minute Apgar score (\u0026le;\u0026thinsp;7) that recovered by 5 minutes (\u0026gt;\u0026thinsp;7)\u0026mdash;a clinically reassuring group seldom examined for brain developmental sequelae. Using MRI morphometry, we assessed cortical volume, thickness, surface area, and curvature and examined their correlations with umbilical artery blood gas parameters. By clarifying whether transient Apgar abnormalities correlate with measurable cortical alterations, this work may aid early risk stratification and inform personalized intervention.\u003c/p\u003e"},{"header":"2 Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Demographic data\u003c/h2\u003e \u003cp\u003e This prospective cross-sectional study, approved by the Third Affiliated Hospital of Sun Yat-sen University (II2023-003-01), enrolled neonates born between May 2020 and July 2024 presenting with respiratory distress, intrauterine hypoxia, birth asphyxia, abnormal electroencephalogram, or preterm birth. Exclusion criteria were: (i) intracranial hemorrhage of any type; (ii) hydrocephalus; (iii) congenital intracranial malformations. Written informed consent was obtained from all parents. Neonates were categorized into two groups based on 1‑ and 5‑minute Apgar scores: the asphyxia (AS) group (Apgar\u0026thinsp;\u0026le;\u0026thinsp;7 at 1 min and \u0026gt;\u0026thinsp;7 at 5 min) and the non‑asphyxia (non‑AS) group (Apgar\u0026thinsp;\u0026gt;\u0026thinsp;7 at both timepoints).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Clinical data\u003c/h2\u003e \u003cp\u003eA 10\u0026ndash;20 cm umbilical cord segment was clamped immediately after delivery. Umbilical artery blood was collected using a heparinized syringe for analysis of pH, lactate (LAC), and base excess (BE).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 MRI acquisition\u003c/h2\u003e \u003cp\u003eMRI was performed on a 3.0 T scanner (GE SIGNA Architect). Neonates were fed, swaddled, and sedated with oral chloral hydrate (20\u0026ndash;30 mg/kg). Pulse oximetry and hearing protection were applied. The three-dimensional magnetization prepared rapid gradient echo sequence was used for 3D T1-weighted bravo acquisition with the following parameters: repetition time\u0026thinsp;=\u0026thinsp;7.7 ms, echo time\u0026thinsp;=\u0026thinsp;3.1 ms, flip angle\u0026thinsp;=\u0026thinsp;12\u0026deg;, field of view\u0026thinsp;=\u0026thinsp;256\u0026times;256mm\u003csup\u003e2\u003c/sup\u003e, matrix\u0026thinsp;=\u0026thinsp;256\u0026times;256, slice thickness\u0026thinsp;=\u0026thinsp;1mm, with no slice gap, and slices\u0026thinsp;=\u0026thinsp;172. The total scanning time was 4 min and 53 s. Additionally, T2-weighted(repetition time\u0026thinsp;=\u0026thinsp;4043 ms, echo time\u0026thinsp;=\u0026thinsp;130 ms,, field of view\u0026thinsp;=\u0026thinsp;160\u0026times;128mm\u003csup\u003e2\u003c/sup\u003e, matrix\u0026thinsp;=\u0026thinsp;280\u0026times;192, slice thickness\u0026thinsp;=\u0026thinsp;1mm), T2-FLAIR༈repetition time\u0026thinsp;=\u0026thinsp;9000 ms, echo time\u0026thinsp;=\u0026thinsp;133 ms, flip angle\u0026thinsp;=\u0026thinsp;12\u0026deg;, field of view\u0026thinsp;=\u0026thinsp;60\u0026times;128mm\u003csup\u003e2\u003c/sup\u003e, matrix\u0026thinsp;=\u0026thinsp;300\u0026times;192, slice thickness\u0026thinsp;=\u0026thinsp;1mm༉images were obtained to exclude subjects with major brain changes, intracerebral hemorrhage, intracerebral malformation, or other lesions, as demonstrated by the above exclusion criteria.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 MRI data processing\u003c/h2\u003e \u003cp\u003eAll images in this study were processed using the uAI Research Portal (United Imaging Intelligence). Preprocessing included skull stripping, bias correction, and resampling to 1 mm isotropic resolution. Subsequently, T1-weighted images were parcellated into 109 regions of interest (ROIs) according to the Desikan\u0026ndash;Killiany (DK) atlas using a pre-trained cascaded VB-Net model. Cortical surface reconstruction was performed within the Cortical Flow Framework, whereby cortical vertices were iteratively deformed to delineate the cortical boundaries. The segmentation model employed a two-stage architecture combining coarse anatomical localization with refined segmentation, demonstrating high robustness and accuracy in medical image segmentation tasks (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Finally, we obtain gray matter volume, cortical thickness, surface area, and curvature metrics.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS 27.0 statistical software. Continuous variables were tested for normality; group comparisons employed t‑tests or Wilcoxon rank‑sum tests accordingly. Categorical variables were compared via the chi‑square test. For imaging data, Analysis of Variance (ANOVA) compared AS and non‑AS groups with gender, corrected gestational age (CGA), and total brain volume as covariates. For the results of multiple brain regions within each indicator, Storey\u0026rsquo;s \u003cem\u003eq\u003c/em\u003e-value method was used for multiple comparison correction. A corrected \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Correlations between significant regions and clinical indicators were assessed using Pearson or Spearman tests based on data distribution.\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Demographic characteristics and clinical data\u003c/h2\u003e \u003cp\u003eOf 137 initially enrolled subjects, 22 were excluded due to intracerebral hemorrhage (n\u0026thinsp;=\u0026thinsp;16), hydrocephalus (n\u0026thinsp;=\u0026thinsp;4), or intracranial vascular malformations (n\u0026thinsp;=\u0026thinsp;2). The final cohort comprised 115 neonates: 53 in the AS group and 62 in the non-AS group. In the AS group, corrected gestational age (CGA) was 270.14\u0026thinsp;\u0026plusmn;\u0026thinsp;15.07 days, and total brain volume was 406.16\u0026thinsp;\u0026plusmn;\u0026thinsp;72.87 cm\u0026sup3;. In the non-AS group, CGA was 271.56\u0026thinsp;\u0026plusmn;\u0026thinsp;18.97 days, and total brain volume was 410.68\u0026thinsp;\u0026plusmn;\u0026thinsp;61.02 cm\u0026sup3;. The AS group had a significantly lower umbilical artery pH (7.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12) and higher LAC (7.36\u0026thinsp;\u0026plusmn;\u0026thinsp;2.71) and BE (6.88\u0026thinsp;\u0026plusmn;\u0026thinsp;4.76) compared to the non-AS group (pH: 7.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10; LAC: 5.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.68; BE: 5.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67). (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and Clinical Characteristics of the Study Cohort.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLAS group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNAS group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT /χ 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e270.14\u0026thinsp;\u0026plusmn;\u0026thinsp;15.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e271.56\u0026thinsp;\u0026plusmn;\u0026thinsp;18.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;0.442\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.659\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVolume\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e406.16\u0026thinsp;\u0026plusmn;\u0026thinsp;72.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e410.68\u0026thinsp;\u0026plusmn;\u0026thinsp;61.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.668\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.505\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male/female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26/27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33/29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.792\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.181\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGA (preterm/term)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23/30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25/37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.739\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory Tests\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUABG PH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-3.594\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUABG BE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.36\u0026thinsp;\u0026plusmn;\u0026thinsp;2.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUABG LAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.88\u0026thinsp;\u0026plusmn;\u0026thinsp;4.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-2.081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.04\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: Data are shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. Abbreviations: LAS\u0026thinsp;=\u0026thinsp;Low Apgar score, NAS\u0026thinsp;=\u0026thinsp;Normal Apgar score, UABGU\u0026thinsp;=\u0026thinsp;Umbilical Artery Blood Gas, PH\u0026thinsp;=\u0026thinsp;Potential of Hydrogen, LAC=Lactic Acid, BE\u0026thinsp;=\u0026thinsp;Base Excess\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Volume\u003c/h2\u003e \u003cp\u003eRelative to the non-AS group, the AS group showed reduced volume in several brain regions (Supplementary Materials 1). After multiple comparison correction, significantly smaller volumes were observed in the bilateral amygdala and the right transverse temporal gyrus (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-D).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBrain Regions Exhibiting Significant Between-Group Differences (Corrected \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrain region\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAS group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003enon-AS group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCorrected \u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eVolume\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmygdala (L) (cm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.676\u0026thinsp;\u0026plusmn;\u0026thinsp;0.186\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.609\u0026thinsp;\u0026plusmn;\u0026thinsp;0.176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmygdala (R) (cm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.688\u0026thinsp;\u0026plusmn;\u0026thinsp;0.207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.607\u0026thinsp;\u0026plusmn;\u0026thinsp;0.178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.361\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTransverse temporal (R) (cm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.500\u0026thinsp;\u0026plusmn;\u0026thinsp;0.141\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.443\u0026thinsp;\u0026plusmn;\u0026thinsp;0.131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.157\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTransverse temporal (L) (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.013\u0026thinsp;\u0026plusmn;\u0026thinsp;0.253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.051\u0026thinsp;\u0026plusmn;\u0026thinsp;0.223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eCurvature\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrontal Mid Caudal (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.327\u0026thinsp;\u0026plusmn;\u0026thinsp;0.081\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.339\u0026thinsp;\u0026plusmn;\u0026thinsp;0.074\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.196\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParstriangularis (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.327\u0026thinsp;\u0026plusmn;\u0026thinsp;0.082\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.365\u0026thinsp;\u0026plusmn;\u0026thinsp;0.068\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.460\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSupramarginal (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.300\u0026thinsp;\u0026plusmn;\u0026thinsp;0.056\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.310\u0026thinsp;\u0026plusmn;\u0026thinsp;0.063\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.775\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal Inf (R)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.305\u0026thinsp;\u0026plusmn;\u0026thinsp;0.087\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e0.336\u0026thinsp;\u0026plusmn;\u0026thinsp;0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eNote: Data are shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. Abbreviations: AS\u0026thinsp;=\u0026thinsp;Asphyxia, L\u0026thinsp;=\u0026thinsp;left, R\u0026thinsp;=\u0026thinsp;right, SD\u0026thinsp;=\u0026thinsp;Standard Deviation.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Cortical Thickness\u003c/h2\u003e \u003cp\u003eCortical thickness was lower in the AS group across several regions (Supplementary Materials 2). After multiple comparison correction to calculate the corrected \u003cem\u003ep\u003c/em\u003e-values, the left transverse temporal remained statistically significant. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Cortical Surface Area\u003c/h2\u003e \u003cp\u003eSmaller surface areas were noted in the AS group for the left postcentral, caudal middle frontal, middle cingulate, superior temporal, and transverse temporal gyri, and the right medial orbitofrontal gyrus, insular cortex, superior parietal lobule, and temporal pole (Supplementary Materials 3). No regions survived multiple comparison correction.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Cortical Curvature\u003c/h2\u003e \u003cp\u003eThe AS group exhibited reduced cortical curvature in multiple regions (Supplementary Materials 4). After multiple comparison correction, significant reductions persisted in the left caudal middle frontal gyrus, left pars triangularis, left supramarginal gyrus, and right inferior temporal gyrus (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF-G).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.6 Correlation results\u003c/h2\u003e \u003cp\u003eIn the AS group, significant correlations were found as follows: There was a significant correlation between the right transverse temporal gyrus and pH value (\u003cem\u003er\u003c/em\u003e = -0.845, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014). There was a significant correlation between the right amygdala and LAC (\u003cem\u003er\u003c/em\u003e = -0.812, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). There was a significant correlation between the right transverse temporal gyrus and BE values (\u003cem\u003er\u003c/em\u003e = -0.627, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). In the non-AS group, significant correlations were found as follows: The right amygdala (\u003cem\u003er\u003c/em\u003e = -0.321, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), the left amygdala (\u003cem\u003er\u003c/em\u003e = -0.304, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005), and the right transverse temporal gyrus (\u003cem\u003er\u003c/em\u003e =-0.224, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.043) were each significantly correlated with pH value. The right amygdala (\u003cem\u003er\u003c/em\u003e = -0.293, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015) and right transverse temporal gyrus (\u003cem\u003er\u003c/em\u003e = -0.349, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) were each significantly correlated with BE values (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelations Between Brain Structural Measures and Umbilical Artery Blood Gas Parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"13\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eBrain region\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c7\" namest=\"c2\"\u003e \u003cp\u003eAS group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c13\" namest=\"c8\"\u003e \u003cp\u003enon-AS group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePH\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eLAC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eBE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003ePH\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003eLAC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003eBE\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003er\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003er\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003er\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003er\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e\u003cem\u003er\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cem\u003er\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmygdala (L) (cm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.893\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.080\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.722\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.582\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.149\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0.274\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e-0.145\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e0.235\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmygdala (R) (cm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.888\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.812\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.980\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.612\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0.956\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0.465\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e0.015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransverse temporal (R) (cm\u0026sup3;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.845\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.014\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.297\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.297\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.627\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.392\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.043\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0.126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0.562\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransversetemporal (L) (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.865\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.337\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e-0.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0.898\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e-0.205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e0.094\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrontal Mid Caudal (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.883\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.547\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.790\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e-0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.907\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-0.145\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0.286\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e0.242\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParstriangularis (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.633\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.768\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.491\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0.750\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e0.148\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemporal Inf (R)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.810\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.459\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.261\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.679\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e-0.241\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0.074\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e-0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e0.841\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSupramarginal (L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.907\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.510\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.658\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e-0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.931\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e0.413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e-0.171\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"13\"\u003eNote: Data are shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. Abbreviations: LAS\u0026thinsp;=\u0026thinsp;Low Apgar score, NAS\u0026thinsp;=\u0026thinsp;Normal Apgar score, UABGU\u0026thinsp;=\u0026thinsp;Umbilical Artery Blood Gas, PH\u0026thinsp;=\u0026thinsp;Potential of Hydrogen, LAC=Lactic Acid, BE\u0026thinsp;=\u0026thinsp;Base Excess\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThis study found that neonates with low 1-minute Apgar scores exhibited reduced gray matter volume, cortical thickness, and curvature compared to controls. These structural alterations correlated significantly with umbilical artery pH, LAC, and BE, suggesting that early transient hypoxia may impact neonatal gray matter development.\u003c/p\u003e \u003cp\u003eBrain volume increases progressively from the neonatal period into adulthood [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], doubling within the first year [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Gray matter volume rises 108\u0026ndash;149% from birth to age 1 [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Despite extensive research on brain developmental trajectories over the past few decades, significant discrepancies remain among existing findings [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. In addition, conclusions regarding the timing of brain maturation vary across different studies [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e], hindering our in-depth understanding of this highly complex and multifactorial physiological phenomenon [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeonates with low Apgar scores showed reduced bilateral amygdala volume, among other regions. Studying early brain development has been limited by imaging challenges. Subcortical structures grow\u0026thinsp;~\u0026thinsp;105% in the first year and ~\u0026thinsp;15% in the second [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Changes in volumetric development are closely correlated with alterations in the number of oligodendrocytes [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e], increased myelination of axonal projections, and reduced striatal development [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. The amygdala preferentially connects to the dorsal striatum (caudate nucleus, putamen) and medial prefrontal cortex, consistent with the latter\u0026rsquo;s early, rapid development in the same period. Our findings align with these reports and indicate these regions are vulnerable to perinatal asphyxia, with early hypoxia potentially delaying their development.\u003c/p\u003e \u003cp\u003eCortical surface area, thickness, and curvature were reduced in the AS group. Late gestation involves rapid cortical expansion and folding [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. Cortical complexity increases with cortical curvature. Our results suggest that cortical curvature in the aforementioned regions may represent vulnerable brain areas affected by perinatal asphyxia. Previous research on cortical thickness, surface area, and curvature alterations following early neonatal hypoxia remains scarce. Thus, the alterations identified in our study warrant further validation in future investigations.\u003c/p\u003e \u003cp\u003eNeonates with lower 1-minute Apgar scores had more abnormal umbilical blood gas parameters (pH, BE, LAC), even with normalized 5-minute scores. The Apgar score reflects neonatal cardiorespiratory and neurological status, guiding resuscitation [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. Intrapartum hypoxia can induce metabolic acidosis and organ risk [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Umbilical artery pH (median\u0026thinsp;~\u0026thinsp;7.25 in normal deliveries [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]) indicates acidaemia severity [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e]. BE is used as a supplementary indicator to assess the severity and duration of neonatal acidemia [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e]. It should be noted that the introduction of BE aims to reflect the metabolic component (i.e., base deficit) underlying the low pH value [\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. Variant base deficit formulas and no selection consensus preclude a statistically defined BE reference range. We found that the umbilical artery blood gas pH, BE, and LAC values of infants with perinatal asphyxia were lower than those of the non-asphyxia group, consistent with previous studies.\u003c/p\u003e \u003cp\u003eIn the AS group, right amygdala volume correlated with LAC, and right transverse temporal gyrus volume correlated with pH and BE. In the non-AS group, bilateral amygdala and right transverse temporal gyrus volumes correlated with pH, and right amygdala and transverse temporal gyrus volumes correlated with BE. These associations suggest that brain regional volumes relate to hypoxic biomarkers, linking imaging indices to physiological markers. We focused on neonates with transiently low Apgar scores (\u0026le;\u0026thinsp;7 at 1 min, \u0026gt;\u0026thinsp;7 at 5 min) and found persistent gray matter alterations. Assessing volume, thickness, curvature, and surface area provided a comprehensive structural evaluation.\u003c/p\u003e \u003cp\u003eThere are several limitations. This was a cross-sectional study without long-term follow-up. Sample size limited subgroup analysis by preterm/term status, though group proportions did not differ significantly. Future studies should stratify by gestational age.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eThis study demonstrates that neonates with lower 1‑minute Apgar scores show reductions in brain volume, cortical thickness, surface area, and curvature, with some of these structural alterations correlating with umbilical artery blood gas parameters. These findings indicate that even transiently low Apgar scores, normalizing by 5 minutes, may influence early brain development. The results offer potential neuroimaging evidence to support future clinical assessment of perinatal asphyxia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics\u0026nbsp;\u003c/strong\u003ea\u003cstrong\u003epproval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-Sen University (II2023-003-01), and written informed consent was obtained from the guardians of all infants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. All authors of the manuscript have read and agreed to its content and are accountable for all aspects of the accuracy and integrity of the manuscript in accordance with ICMJE criteria\u003c/p\u003e\n\u003cp\u003e2. That the article is original, has not already been published in a journal, and is not currently under consideration by another journal\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e2. All data generated or analysed during this study are included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo conflict of interest or industry support exists in the submission of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by grants from the National Natural Science Foundation of China (No. 82471567, 81801757), Guangdong Basic and Applied Basic Research Foundation (No. 2024A1515010279, 2023A1515010256).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCY Dong, YH Li, SJ H, YY Liang, and RM\u0026nbsp;Guo: Data curation, Investigation, Software, Writing - original draft\u003c/p\u003e\n\u003cp\u003eBY Yin and YX Ni: Data curation, Formal analysis, Methodology\u003c/p\u003e\n\u003cp\u003eRM\u0026nbsp;Guo: Funding acquisition, Supervision\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLawn JE, et al. 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BJOG. 2008;115(6):704\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"perinatal asphyxia, magnetic resonance imaging, gray matter volume, cerebral cortex, umbilical artery blood gas analysis","lastPublishedDoi":"10.21203/rs.3.rs-8863172/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8863172/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePerinatal asphyxia is a leading cause of neonatal morbidity and can induce central nervous system hypoxia with functional sequelae. Current evidence on associated brain structural changes remains limited. This study aimed to determine whether mild perinatal asphyxia correlates with subtle alterations in neonatal cortical structure.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eHead MRI data from 115 neonates were collected. Using a 1‑minute Apgar score cutoff of 7, neonates were classified into an asphyxia (AS) group and a non‑asphyxia (non‑AS) group. T2, T2‑FLAIR, and 3D T1 sequences were acquired. Gray matter volume, cortical thickness, surface area, and curvature were computed via the uAI Research Portal. Umbilical artery blood gas parameters (including hydrogen ion concentration index, lactate, and base excess) were recorded. Gender, corrected gestational age, and total brain volume were included as covariates. Group differences in gray matter volume and cortical parameters were compared, and their correlations with umbilical artery blood gas indicators were analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eRelative to the non‑AS group, the AS group exhibited significantly reduced bilateral amygdala volume, left transverse temporal gyrus thickness, and curvature of the left caudal middle frontal gyrus, pars triangularis, supramarginal gyrus, and right inferior temporal gyrus (corrected \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001\u0026ndash;0.046). All these parameters showed significant correlations with umbilical artery blood gas measures (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eA low 1‑minute Apgar score is associated with measurable changes in brain structure and correlates with clinical indicators from umbilical artery blood gas analysis. These findings may provide future imaging evidence for the clinical assessment of perinatal asphyxia.\u003c/p\u003e","manuscriptTitle":"Alterations in Brain Structure and Their Association with Umbilical Blood Gases in Neonates with Perinatal Asphyxia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-27 13:37:44","doi":"10.21203/rs.3.rs-8863172/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cceb7e41-8125-4ad8-a44f-600f7a64a23c","owner":[],"postedDate":"February 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-04T06:41:48+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-27 13:37:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8863172","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8863172","identity":"rs-8863172","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}