Bowel Wall Thickness Velocity as a Quantitative Marker of Intestinal Adaptation in Preterm Infants

Bowel Wall Thickness Velocity as a Quantitative Marker of Intestinal Adaptation in Preterm Infants | 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 Article Bowel Wall Thickness Velocity as a Quantitative Marker of Intestinal Adaptation in Preterm Infants Indrani Bhattacharjee, Saharnaz Talebiyan, Terri Williams-Weekes, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8990068/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 Objective To characterize bowel wall thickness velocity (BWTv) across postmenstrual age (PMA) in preterm infants and examine its relationship with somatic growth velocity and feeding exposure. Study Design: Prospective observational pilot study of preterm infants undergoing serial standardized bowel ultrasound examinations. Mean bowel wall thickness (BWT) was measured per scan; BWTv was defined as interval-based change over time. Somatic growth velocity was expressed as interval changes in anthropometric z-scores. Feeding exposures were modeled as time-varying covariates. Regression models with clustering by infant assessed maturity-dependent associations. Results Fourteen infants contributed 260 ultrasounds. BWTv was higher and more heterogeneous at earlier PMA and attenuated with advancing maturity. Weight z-score velocity showed the strongest association with BWTv. Enteral caloric intake was positively associated with BWTv at earlier PMA, with diminishing effects over time. Conclusion BWTv represents a dynamic, maturity-dependent marker of intestinal structural adaptation in preterm infants. Health sciences/Biomarkers/Diagnostic markers Health sciences/Health care/Medical imaging Preterm infants Bowel ultrasound Bowel wall thickness Intestinal growth velocity Enteral nutrition Postmenstrual age Figures Figure 1 Figure 2 Figure 3 Figure 4 INTRODUCTION Early postnatal growth in preterm infants is characterized by rapid and coordinated development across multiple organ systems. In clinical practice, growth velocity, rather than absolute size alone, is widely used to assess somatic and neurodevelopmental health, with anthropometric z-score velocity serving as a sensitive indicator of nutritional adequacy and physiologic adaptation [ 1 – 3 ]. In contrast, despite the intestine’s central role in nutrient absorption, immune maturation, and metabolic regulation, unlike brain and somatic growth, intestinal development is not routinely quantified longitudinally in neonatal practice. The neonatal intestine undergoes marked postnatal remodeling in response to gestational maturity and enteral nutrition, reflecting substantial developmental plasticity [ 1 – 6 ]. Experimental models, particularly the preterm piglet, demonstrate rapid, feeding-responsive intestinal adaptation during early postnatal life and are particularly sensitive to postnatal age and enteral nutrition [ 1 – 6 ]. In neonatal clinical practice, however, commonly used indicators of intestinal health—such as feeding tolerance and abdominal radiography—are indirect markers and often lag behind underlying structural adaptation [ 19 – 22 ]. Moreover, intestinal injury, including necrotizing enterocolitis (NEC), is thought to evolve over days to weeks before clinical diagnosis, suggesting that antecedent structural changes may precede overt disease [ 19 – 22 ]. Bowel ultrasound has emerged as a feasible bedside modality for evaluating neonatal intestinal structure. Prior work has shown that absolute parameters like bowel wall thickness (BWT) vary systematically with gestational age and exhibits consistent regional asymmetry, supporting its role as a structural marker of intestinal maturity [ 15 , 16 ]. Similar principles underpin the use of intestinal ultrasound in pediatric and adult populations, where bowel wall thickness is a validated quantitative parameter for longitudinal monitoring in inflammatory bowel disease [ 7 – 12 ]. Normative pediatric data further demonstrate age-dependent variation in bowel wall thickness [ 14 – 16 ]. Static measurements such as absolute bowel wall thickness do not capture the rate of intestinal change, which is a defining feature of developmental adaptation. Across organ systems, developmental assessment increasingly relies on rate-based metrics to capture physiologic adaptation [ 2 , 17 , 18 ]. Applying a velocity-based framework to intestinal development may therefore provide novel insight into early gut adaptation. The primary aim of this study was to characterize developmental intestinal adaptation by quantifying bowel wall thickness velocity (BWTv) across different postmenstrual ages in preterm infants using serial bowel ultrasound measurements. Secondary aims were to examine its relationship with somatic growth velocity and developmental maturity. METHODS Study Design and Population This was a prospective observational study of preterm infants admitted to a tertiary neonatal intensive care unit who underwent serial bowel ultrasound examinations as part of a standardized intestinal ultrasound protocol. Infants were included if they had at least two bowel ultrasound examinations with corresponding anthropometric and feeding data available for interval-based analysis. Exclusion criteria included major congenital gastrointestinal anomalies or inadequate imaging quality. Institutional Review Board approval was obtained prior to enrollment of subjects. Ethics Approval and Consent to Participate This study was approved by the Institutional Review Board of Tufts Medical Center (HS-IRB reference number 0003864). Written informed consent was obtained from the parents or legal guardians of all participating infants prior to study enrollment. The study was conducted in accordance with the principles of the Declaration of Helsinki Bowel Ultrasound Acquisition and Measurement Bowel ultrasound examinations were performed at the bedside using a high-frequency linear transducer (8-18 MHz) on GE LOGIQ E10 ultrasound system (GE Healthcare, Chicago, IL, USA) according to a standardized acquisition protocol. All examinations were conducted by a senior sonographer with over 10 years of ultrasound experience. The sonographer was blinded to clinical status at the time of measurement. Image acquisition followed predefined criteria to ensure consistency. A random 25% subset of ultrasound examinations (65/260) was independently re-measured from stored raw images by a second reviewer blinded to clinical data and study hypotheses. Agreement for scan-level mean bowel wall thickness was assessed using a two-way random-effects intraclass correlation coefficient (ICC) with absolute agreement (ICC [2,1]). The small and large intestines were systematically evaluated in predefined abdominal quadrants. Bowel wall thickness (BWT) was measured in the transverse plane from the inner echogenic mucosal interface to the outer serosal boundary during periods of minimal peristalsis and without external compression. The standardized measurement approach is illustrated in Figure 1. Measurements were recorded in millimeters; values displayed in centimeters were converted prior to analysis. Quadrant-level measurements were averaged to derive a scan-level mean BWT to quantify within-infant longitudinal change rather than regional variation. Anthropometric Measurements and Somatic Growth Velocity Weight, length, and head circumference were obtained using standardized clinical methods on the day of ultrasound examination. Anthropometric z-scores were calculated using established reference standards. Somatic growth velocity was defined as the interval-based change in anthropometric z-score divided by the number of days between consecutive ultrasound examinations. Definition of bowel wall thickness velocity BWTv was defined as the rate of change in scan-level mean BWT between consecutive ultrasound examinations for the same infant. Velocity was calculated using a forward-difference approach: where ΔBWT represents the change in scan-level mean BWT between two consecutive scans and Δtime represents the corresponding time interval. The midpoint PMA between consecutive scans was used for analyses involving maturational trends. Intervals with non-positive time differences were excluded. Velocity estimates were evaluated using graphical diagnostics, including individual-level longitudinal plots and scatterplots against postmenstrual age, to confirm that high-magnitude values reflected coherent within-infant trajectories over clinically meaningful time intervals rather than isolated measurement artifact. Feeding Exposure Variables Enteral feeding exposure was quantified using scan-day enteral caloric intake, expressed as kilocalories per kilogram per day (kcal/kg/day), derived from daily feeding records corresponding to each ultrasound assessment. Additional feeding variables included total enteral feeding volume (mL/kg/day) and the percentage of human milk, defined as the proportion of enteral intake provided as mother’s or donor human milk on the day of scan. Feeding variables reflected scan-day exposure and were modeled as time-varying covariates; interval-level feeding variability could not be fully captured. This approach parallels standard clinical growth velocity assessments and was selected to preserve temporal alignment with ultrasound measurements. Statistical Analysis Descriptive statistics were used to summarize baseline demographic and clinical characteristics. Bowel wall thickness velocity (BWTv) was modeled as the dependent variable. Postmenstrual age (PMA) was treated as a continuous variable to evaluate maturational trends. Because multiple ultrasound examinations were obtained per infant, linear mixed-effects regression models with a random intercept for infant were used to account for within-infant correlation from repeated measures . Associations between BWTv and somatic growth velocities (weight, length, and head circumference z-score velocities) were examined using multivariable models including interaction terms between PMA and growth velocity to assess maturity-dependent effects. Feeding variables (enteral caloric intake, feeding volume, and percentage of human milk) were incorporated as time-varying covariates; interval-level feeding variability between scans could not be fully captured. Adjusted models evaluated the independent and modifying associations of feeding exposure with BWTv after accounting for somatic growth and PMA. All analyses were performed using R (R Foundation for Statistical Computing, Vienna, Austria) and Python (Python Software Foundation, Wilmington, DE). Statistical significance was defined as a two-sided p-value < 0.05. Table 1 . Baseline demographic and clinical characteristics of the study cohort. Characteristic Value Number of infants, n 14 Total bowel ultrasound examinations, n 260 Male sex, n (%) 8 (54%) Gestational age at birth, weeks, mean ± SD 29.7 (2.9) Birth weight, g, mean ± SD 1,371(571) Post menstrual age at ultrasound, weeks, range 26.4–37.2 Cesarean delivery, n (%) 12 (86%) Non-White race, n (%) 9 (64.2%) Antenatal steroid exposure, n (%) 11 (82%) Day of life at feed initiation, mean ± SD 1.1 (0.7) Day of life at full enteral feeds, mean ± SD 9.9 (3.2) Data are presented as mean (SD) , range , or number (percentage) as indicated. RESULTS Fourteen preterm infants (54% male) with a mean gestational age of 29.7 ± 2.9 weeks and mean birth weight of 1,371 ± 571 g were enrolled, contributing 260 serial bowel ultrasound scans across a post menstrual age range of 26.4–37.2 weeks . Baseline demographic and clinical characteristics are shown in Table 1. Inter-observer agreement for scan-level mean bowel wall thickness demonstrated good reliability (ICC [2,1] = 0.82; 95% CI 0.72–0.89; n = 65 scans) Developmental trajectory of bowel wall thickness velocity Serial bowel ultrasound measurements demonstrated that BWTv varied systematically with postmenstrual age (PMA), revealing a clear developmental trajectory. At earlier PMA, BWT velocity was higher and exhibited greater inter-individual variability, whereas with advancing maturity, BWT velocity progressively attenuated and approached zero, consistent with structural stabilization of the intestinal wall (Figure 2). Somatic growth and intestinal growth velocity We first examined associations between BWTv and somatic growth velocities, including weight, length, and head circumference z-score velocities across postmenstrual age (PMA) (Supplementary Figure 1). Weight z-score velocity showed the strongest and most consistent association with BWT velocity, particularly at earlier PMA. Length z-score velocity demonstrated a weaker association, while head circumference z-score velocity showed minimal or inverse associations, especially at later maturity. These findings indicate that intestinal growth velocity preferentially tracks with somatic mass accretion rather than linear or neurocranial growth. Maturity-dependent coupling between weight growth and intestinal growth velocity Given the dominant association for weight z-score velocity, we next evaluated its maturity-dependent relationship with intestinal growth velocity. Feeding-adjusted response surface analysis demonstrated strong positive coupling at earlier PMA, with progressive attenuation as maturity advanced (Figure 3). At later PMA, BWT velocity showed limited responsiveness to variation in weight z-score velocity, consistent with increasing structural stabilization of the intestine. Feeding modulation of intestinal growth velocity Finally, we assessed whether feeding exposure independently modulated intestinal growth velocity after accounting for somatic growth and maturity. Enteral caloric intake was positively associated with BWT velocity at earlier PMA, whereas this relationship weakened substantially with advancing maturity when weight z-score velocity was held constant (Figure 4). These findings suggest that feeding exerts its strongest influence on intestinal growth velocity during early developmental windows, with diminishing effects as maturity progresses. DISCUSSION In this prospective ultrasound-based study, we demonstrate that bowel wall thickness velocity (BWTv) captures maturity-dependent variation in intestinal structural adaptation in preterm infants. Unlike static structural measurements, velocity-based metrics capture dynamic physiologic adaptation by integrating recent developmental and nutritional influences, allowing transient accelerations or attenuations in intestinal growth to be detected even when absolute thickness values appear normal. The velocity-based approach revealed substantial temporal heterogeneity, with higher and more variable growth rates at earlier postmenstrual ages followed by progressive attenuation as intestinal maturation advanced. Similar developmental nonlinearity has been described in experimental models of prematurity, where intestinal structure and function adapt rapidly during early postnatal life and stabilize with advancing maturity [1,2]. BWT velocity was associated with somatic growth velocity and recent feeding exposure; however, these relationships varied by developmental stage, supporting a framework of developmentally gated intestinal plasticity. Intestinal growth as a dynamic and maturity-dependent process Our findings indicate that intestinal structural growth during early life is nonlinear and temporally regulated, rather than steady or monotonic. In preterm piglet models, Hansen et al. demonstrated rapid postnatal intestinal growth accompanied by delayed functional maturation, highlighting dissociation between structural expansion and digestive capacity during early development [1]. Similarly, Ren et al. showed that postnatal age, rather than birth weight alone, governs intestinal and immune maturation in preterm piglets, underscoring the importance of developmental timings [2]. The higher and more variable BWT velocities observed at earlier PMA in our cohort align closely with these experimental observations. As PMA increased, BWT velocity approached zero, suggesting a transition toward relative structural stabilization, consistent with the progressive consolidation of intestinal architecture described in animal models [1–6]. These findings emphasize the limitations of relying on single time-point bowel wall thickness measurements and highlight the added value of velocity-based metrics for characterizing real-time intestinal development. Coupling between intestinal growth and somatic growth We observed a significant association between weight z-score velocity and BWT velocity, particularly at earlier PMA, indicating coordinated growth between the intestine and the overall somatic compartment. This relationship weakened with advancing maturity, suggesting reduced intestinal responsiveness to short-term systemic growth signals as developmental programs consolidate. In contrast, length and head circumference growth velocities demonstrated weaker and less consistent associations with BWT velocity, supporting the interpretation that intestinal structural adaptation preferentially aligns with somatic mass accretion rather than linear or neurocranial growth alone. Similar preferential coupling between intestinal growth and body mass accretion has been reported in piglet studies, where nutrient-driven somatic growth closely parallels intestinal tissue expansion during early postnatal life [4,6]. These findings extend prior work on organ-specific growth trajectories by demonstrating that intestinal growth can be quantified as a rate-based process with biologically meaningful coupling to somatic growth that evolves across developmental time. A comparable velocity-based framework underlies intestinal ultrasound monitoring in pediatric and adult populations, where longitudinal changes in bowel wall thickness are used to track disease activity and therapeutic response in inflammatory bowel disease [7,8]. Our results suggest that similar dynamic principles apply to intestinal development in early life. Role of feeding exposure and intestinal plasticity Incorporation of time-varying feeding variables revealed that enteral caloric exposure was independently associated with variation in BWT velocity, particularly at earlier PMA. Experimental studies in preterm piglets have shown that early enteral nutrition exerts disproportionate effects on intestinal structure, vascularization, and immune signaling during narrow developmental windows [1,5]. The attenuation of feeding effects observed at later PMA in our cohort mirrors these findings, suggesting that nutritional modulation of intestinal structure is most pronounced during periods of immaturity. Notably, adjustment for feeding exposure only partially attenuated the association between weight z-score velocity and BWT velocity, indicating that intestinal growth velocity reflects integration of recent feeding exposure, systemic growth state, and intrinsic maturational factor s , rather than nutrient delivery alone. This observation aligns with experimental data demonstrating that intestinal growth trajectories are shaped by both environmental inputs and developmentally programmed constraints [2,6]. Implications for intestinal vulnerability and disease risk Although this study was not designed to evaluate clinical outcomes, the observed heterogeneity in BWT velocity—particularly periods of accelerated or attenuated growth—raises important hypotheses regarding intestinal adaptation during early life. In neonatal bowel ultrasound literature, particularly in the context of NEC, emphasis has traditionally been placed on categorical findings such as bowel wall thickening, thinning, or perfusion abnormalities [19,20]. More recent neonatal ultrasound studies similarly focus on threshold-based markers of bowel viability rather than longitudinal structural change [21,22]. A velocity-based framework may offer a complementary approach by capturing early structural dynamics preceding clinically apparent disease, warranting further investigation in outcome-focused studies. STRENGTHS AND LIMITATIONS Strengths of this study include its longitudinal design, standardized ultrasound imaging acquisition, interval-based velocity modeling, and integration of somatic growth and feeding data as time-varying covariates. Several limitations merit consideration. Feeding exposure was summarized using scan-day values as proxies for interval exposure, which may not fully capture daily variability. The cohort size limited formal outcome analyses, and causality cannot be inferred from observational associations. However, the high density of longitudinal measurements (260 scans) enabled robust within-infant trajectory modeling despite the modest cohort size. Additionally, ultrasound-derived bowel wall thickness reflects a composite structural measure and does not directly assess mucosal or cellular composition. Although inter-observer reliability was assessed in a subset of examinations, intra-observer variability was not formally quantified and will be evaluated in future multicenter studies. CONCLUSION Bowel wall thickness velocity is a dynamic, maturity-dependent measure of intestinal structural adaptation in preterm infants, with strongest coupling to somatic growth and feeding exposure at earlier postmenstrual ages and gradual attenuation with advancing maturation. These findings support a framework of developmentally gated intestinal plasticity. If validated in larger multicenter cohorts, velocity-based intestinal ultrasound metrics may inform future risk-stratified nutritional and monitoring strategies in preterm infants. Declarations AUTHORS CONTRIBUTIONS Conceptualization: Indrani Bhattacharjee, Michael Todd Dolinger Methodology: Indrani Bhattacharjee, Saharnaz Talebiyan Data Acquisition: Saharnaz Talebiyan, Indrani Bhattacharjee Ultrasound Supervision and Validation: Terri Williams-Weekes , Indrani Bhattacharjee Formal Analysis: Indrani Bhattacharjee Investigation: Indrani Bhattacharjee, Saharnaz Talebiyan Writing – Original Draft: Indrani Bhattacharjee Writing – Review & Editing: All authors Supervision: Rachana Singh, Yogen Singh, Micheal Todd Dolinger All authors have read and approved the final manuscript and agree to be accountable for all aspects of the work. Funding Dr. Bhattacharjee was supported by the Natalie Zucker Grant for Women Scholars at Tufts University. The authors received no additional specific funding for this study. Conflict of Interest The authors declare no competing interests. Data Availability The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. Acknowledgments The authors acknowledge the Biostatistics, Epidemiology, and Research Design (BERD) Center at the Tufts Clinical and Translational Science Institute for statistical consultation and analytical support. References Hansen CF, Thymann T, Andersen AD, et al. Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs. Am J Physiol Gastrointest Liver Physiol. 2016;310(8):G550–G560. Ren S, Hui Y, Goericke-Pesch S, et al. Neonatal gut and immune maturation is determined more by postnatal age than by birth weight in preterm pigs. Am J Physiol Gastrointest Liver Physiol. 2018;315(5):G889–G901. Eiby YA, Wright LL, Kalanjati VP, et al. A pig model of the preterm neonate: anthropometric and physiological characteristics. PLoS One. 2013;8(7):e68763. Buddington RK, Sangild PT, Hance B, et al. Organ growth and intestinal functions of preterm pigs fed milk replacers. Front Nutr. 2021;8:641928. Modina SC, Bosi P, Trevisi P. Stages of gut development as a tool to prevent gastrointestinal disorders in pigs. Animals (Basel). 2021;11(5):1412. Ahnfeldt AM, Sangild PT, Petersen YM, et al. Nutrient restriction has limited short-term effects on gut structure and function in neonatal pigs. J Nutr. 2020;150(10):2664–2674. Maaser C, Petersen F, Helwig U, et al. Intestinal ultrasound for monitoring therapeutic response in inflammatory bowel disease: results from a prospective multicenter study. Gut. 2020;69(9):1629–1639. Kucharzik T, Wittig BM, Helwig U, et al. Use of intestinal ultrasound to monitor Crohn’s disease activity. Clin Gastroenterol Hepatol. 2017;15(4):535–542.e2. Mayer D, Reinshagen M, Bouchard R, et al. Sonographic measurement of bowel wall thickness as a quantitative parameter of inflammatory bowel disease activity. Ultraschall Med. 2000;21(6):241–246. 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Transabdominal ultrasound for standardized measurement of bowel wall thickness in normal children and those with Crohn’s disease. Med Ultrason. 2014;16(4):319–324. Haber HP, Stern M. Intestinal ultrasonography in children and young adults: bowel wall thickness is age dependent. J Ultrasound Med. 2000;19(5):315–321. Albshesh A, Novak KL, Panaccione R, et al. Intestinal ultrasound measurement of bowel wall thickness as a predictor of treatment failure in Crohn’s disease. Ther Adv Gastroenterol. 2025;18:1756284824123456. Räisänen L, Puylaert C, Nylund K, et al. Bowel wall thickness cutoff values for assessing intestinal inflammation: adult and pediatric perspectives. Inflamm Bowel Dis. 2025;31(2):245–254. Epelman M, Daneman A, Navarro OM, et al. Necrotizing enterocolitis: review of state-of-the-art imaging findings with pathologic correlation. Radiographics. 2007;27(2):285–305. Silva CT, Daneman A, Navarro OM, et al. Correlation of sonographic findings and outcome in necrotizing enterocolitis. Pediatr Radiol. 2007;37(3):274–282. Bhattacharjee I, Dolinger MT, Singh R, Singh Y. Ultrasound for the early detection and diagnosis of necrotizing enterocolitis: a scoping review of emerging evidence. Diagnostics (Basel). 2025;15(15):1852. Singh Y, Kempley ST, Jhaveri R, et al. Abdominal ultrasound as an adjunct to clinical and radiographic evaluation in neonatal intestinal injury, including necrotizing enterocolitis. Pediatr Radiol. 2024;54(6):921–930. Additional Declarations There is NO conflict of interest to disclose. Supplementary Files SupplementaryFigure1SomaticGrowthVelocities.png 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. 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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-8990068","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":600010852,"identity":"8b50b656-0377-439b-b5db-1969d2c0adad","order_by":0,"name":"Indrani Bhattacharjee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABf0lEQVRIie2RwUvCUBzHf2PwvMy6vlDbv7AhiCf9V/YY6GUUIYgHkwfCuqzOE8P+BSOQDkFPgnlZnhUvSmSnYF7CKKM3h8s0OgftA2/b+7334ft+ewAREX8QmYLCXxjyOChowagAxKg/RxjQd4VPA0W1QaAsVFwFJOdXhT8HXwqAYIbK1sFQot7xXq+zoDbrTw9eNXew22ST8az1Tiz55LHtlbPyTqLOYHZzvFKSTqlx6vJeko5KmaOXcF/T1UZHIRaSMkO7j1Uz6WiCPe2tFGykIW76vWhcQYxQFwqJOFdukYRGfEnjexRRYs6aIiy4ogyKM8o+GLlwofi2OPdTYtPRYqkcehuKGF8qhkq7JiNtniIK1FcgMxKCFOBKNVQKJTFlYkm1jSP7/kwnly7oe5aTTlvIyAwtvxdcULo2Y6urtPUr4dms7edxse1VXnKk5UrEm1f3U5bYmw7m5ZrM90zGHqtt/Gxp/VvbugvgEXfb1ZAY+7G8mRIRERHxb/gEFHKRysXTtf0AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-6815-8555","institution":"Tufts University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Indrani","middleName":"","lastName":"Bhattacharjee","suffix":""},{"id":600010853,"identity":"ca89e53f-5759-4b70-8df6-84b9dd11cb81","order_by":1,"name":"Saharnaz Talebiyan","email":"","orcid":"","institution":"Tufts University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Saharnaz","middleName":"","lastName":"Talebiyan","suffix":""},{"id":600010854,"identity":"221b1a22-9b19-4a8e-8eeb-6e50879173f4","order_by":2,"name":"Terri Williams-Weekes","email":"","orcid":"","institution":"Tufts University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Terri","middleName":"","lastName":"Williams-Weekes","suffix":""},{"id":600010855,"identity":"e1a8ddb1-8f9a-4851-b5dd-bddc0fc8a990","order_by":3,"name":"Yogen Singh","email":"","orcid":"https://orcid.org/0000-0002-5207-9019","institution":"UC Davis Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yogen","middleName":"","lastName":"Singh","suffix":""},{"id":600010856,"identity":"5c08e4d1-93ad-46a9-a3ec-2decb513a718","order_by":4,"name":"Rachana Singh","email":"","orcid":"","institution":"Tufts University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Rachana","middleName":"","lastName":"Singh","suffix":""},{"id":600010857,"identity":"be7191b4-63ca-4700-a3e7-8725d7e47738","order_by":5,"name":"Michael Dolinger","email":"","orcid":"","institution":"NYU Grossman School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Dolinger","suffix":""}],"badges":[],"createdAt":"2026-02-27 16:21:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8990068/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8990068/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104404670,"identity":"c441c77d-0b61-4293-831e-1ee1bd5ffc6e","added_by":"auto","created_at":"2026-03-11 12:20:47","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":25264340,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStandardized measurement of bowel wall thickness using neonatal ultrasound.\u003c/strong\u003e\u003cbr\u003e\n Representative transverse bowel ultrasound image demonstrating measurement of bowel wall thickness (BWT). BWT was measured from the inner echogenic mucosal interface to the outer serosal boundary during minimal peristalsis without external compression. Measurements from predefined abdominal quadrants were averaged to derive scan-level mean BWT.\u003c/p\u003e","description":"","filename":"Figure1BWTMeasurement.png","url":"https://assets-eu.researchsquare.com/files/rs-8990068/v1/2aa2f089ce33b502cf5503f2.png"},{"id":104204550,"identity":"23705e39-e286-40b1-a567-0b9fa8af296f","added_by":"auto","created_at":"2026-03-09 06:37:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":169846,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDevelopmental trajectory of bowel wall thickness velocity across post menstrual age.\u003c/strong\u003eEach point represents an interval-based bowel wall thickness velocity (BWTv) derived from consecutive ultrasound examinations (n = 246 intervals from 14 infants). The solid line represents mixed-effects model–based predicted values across postmenstrual age (PMA), and the shaded region indicates the 95% confidence interval.\u003c/p\u003e","description":"","filename":"Figure2BWTvvsPMA.png","url":"https://assets-eu.researchsquare.com/files/rs-8990068/v1/20388696b1620b0ccaecdacf.png"},{"id":104204547,"identity":"5b7262f2-86c9-41b7-b4e8-c00eb3456fd6","added_by":"auto","created_at":"2026-03-09 06:37:35","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":187882,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMaturity-dependent coupling of somatic and intestinal growth.\u003c/strong\u003e\u003cbr\u003e\n Response surface derived from mixed-effects modeling illustrating the interaction between weight z-score velocity and post menstrual age (PMA) in relation to predicted bowel wall thickness velocity (BWTv). The color gradient represents predicted BWTv magnitude (mm/day). Points represent observed interval-based measurements (n = 246 intervals).\u003c/p\u003e","description":"","filename":"Figure3BWTvWeightPMA.png","url":"https://assets-eu.researchsquare.com/files/rs-8990068/v1/f5d166c098e7e1b0d833c8d3.png"},{"id":104404447,"identity":"d9fb2048-14e7-450f-a577-6d23ca66909c","added_by":"auto","created_at":"2026-03-11 12:20:18","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":196874,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFeeding-related modulation of bowel wall thickness velocity across postmenstrual age.\u003c/strong\u003e\u003cbr\u003e\n Model-based predictions from mixed-effects regression illustrating the association between enteral caloric intake (kcal/kg/day) and bowel wall thickness velocity (BWTv), adjusted for weight z-score velocity. Shaded regions indicate 95% confidence intervals (n = 246 intervals).\u003c/p\u003e","description":"","filename":"Figure4BWTvFeedingPMA.png","url":"https://assets-eu.researchsquare.com/files/rs-8990068/v1/a5a81a8a7ac247e5b5909209.png"},{"id":105034172,"identity":"00a907fa-820c-4191-92a1-3775c1e28101","added_by":"auto","created_at":"2026-03-20 07:22:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":20462871,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8990068/v1/e5440421-3927-42c8-bdad-5fd438603c88.pdf"},{"id":104204551,"identity":"d2a7ad5f-c587-4451-9043-b650e284d718","added_by":"auto","created_at":"2026-03-09 06:37:36","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":296478,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure1SomaticGrowthVelocities.png","url":"https://assets-eu.researchsquare.com/files/rs-8990068/v1/758224d524f3b771b1d843a2.png"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Bowel Wall Thickness Velocity as a Quantitative Marker of Intestinal Adaptation in Preterm Infants","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eEarly postnatal growth in preterm infants is characterized by rapid and coordinated development across multiple organ systems. In clinical practice, growth velocity, rather than absolute size alone, is widely used to assess somatic and neurodevelopmental health, with anthropometric z-score velocity serving as a sensitive indicator of nutritional adequacy and physiologic adaptation [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In contrast, despite the intestine\u0026rsquo;s central role in nutrient absorption, immune maturation, and metabolic regulation, unlike brain and somatic growth, intestinal development is not routinely quantified longitudinally in neonatal practice.\u003c/p\u003e \u003cp\u003eThe neonatal intestine undergoes marked postnatal remodeling in response to gestational maturity and enteral nutrition, reflecting substantial developmental plasticity [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Experimental models, particularly the preterm piglet, demonstrate rapid, feeding-responsive intestinal adaptation during early postnatal life and are particularly sensitive to postnatal age and enteral nutrition [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In neonatal clinical practice, however, commonly used indicators of intestinal health\u0026mdash;such as feeding tolerance and abdominal radiography\u0026mdash;are indirect markers and often lag behind underlying structural adaptation [\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Moreover, intestinal injury, including necrotizing enterocolitis (NEC), is thought to evolve over days to weeks before clinical diagnosis, suggesting that antecedent structural changes may precede overt disease [\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBowel ultrasound has emerged as a feasible bedside modality for evaluating neonatal intestinal structure. Prior work has shown that absolute parameters like bowel wall thickness (BWT) vary systematically with gestational age and exhibits consistent regional asymmetry, supporting its role as a structural marker of intestinal maturity [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Similar principles underpin the use of intestinal ultrasound in pediatric and adult populations, where bowel wall thickness is a validated quantitative parameter for longitudinal monitoring in inflammatory bowel disease [\u003cspan additionalcitationids=\"CR8 CR9 CR10 CR11\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Normative pediatric data further demonstrate age-dependent variation in bowel wall thickness [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStatic measurements such as absolute bowel wall thickness do not capture the rate of intestinal change, which is a defining feature of developmental adaptation. Across organ systems, developmental assessment increasingly relies on rate-based metrics to capture physiologic adaptation [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Applying a velocity-based framework to intestinal development may therefore provide novel insight into early gut adaptation.\u003c/p\u003e \u003cp\u003eThe primary aim of this study was to characterize developmental intestinal adaptation by quantifying bowel wall thickness velocity (BWTv) across different postmenstrual ages in preterm infants using serial bowel ultrasound measurements. Secondary aims were to examine its relationship with somatic growth velocity and developmental maturity.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cem\u003eStudy Design and Population\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis was a prospective observational study of preterm infants admitted to a tertiary neonatal intensive care unit who underwent serial bowel ultrasound examinations as part of a standardized intestinal ultrasound protocol. Infants were included if they had at least two bowel ultrasound examinations with corresponding anthropometric and feeding data available for interval-based analysis. Exclusion criteria included major congenital gastrointestinal anomalies or inadequate imaging quality. Institutional Review Board approval was obtained prior to enrollment of subjects.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics Approval and Consent to Participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board of Tufts Medical Center (HS-IRB reference number 0003864). Written informed consent was obtained from the parents or legal guardians of all participating infants prior to study enrollment. The study was conducted in accordance with the principles of the Declaration of Helsinki\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBowel Ultrasound Acquisition and Measurement\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBowel ultrasound examinations were performed at the bedside using a high-frequency linear transducer (8-18 MHz) on GE LOGIQ E10 ultrasound system (GE Healthcare, Chicago, IL, USA) according to a standardized acquisition protocol. All examinations were conducted by a senior sonographer with over 10 years of ultrasound experience. The sonographer was blinded to clinical status at the time of measurement. Image acquisition followed predefined criteria to ensure consistency. A random 25% subset of ultrasound examinations (65/260) was independently re-measured from stored raw images by a second reviewer blinded to clinical data and study hypotheses. Agreement for scan-level mean bowel wall thickness was assessed using a two-way random-effects intraclass correlation coefficient (ICC) with absolute agreement (ICC [2,1]).\u003c/p\u003e\n\u003cp\u003eThe small and large intestines were systematically evaluated in predefined abdominal quadrants. Bowel wall thickness (BWT) was measured in the transverse plane from the inner echogenic mucosal interface to the outer serosal boundary during periods of minimal peristalsis and without external compression. The standardized measurement approach is illustrated in Figure 1. Measurements were recorded in millimeters; values displayed in centimeters were converted prior to analysis. Quadrant-level measurements were averaged to derive a scan-level mean BWT to quantify within-infant longitudinal change rather than regional variation.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAnthropometric Measurements and Somatic Growth Velocity\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWeight, length, and head circumference were obtained using standardized clinical methods on the day of ultrasound examination. Anthropometric z-scores were calculated using established reference standards. Somatic growth velocity was defined as the interval-based change in anthropometric z-score divided by the number of days between consecutive ultrasound examinations.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDefinition of bowel wall thickness velocity\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBWTv was defined as the rate of change in scan-level mean BWT between consecutive ultrasound examinations for the same infant. Velocity was calculated using a forward-difference approach:\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003ewhere \u0026Delta;BWT represents the change in scan-level mean BWT between two consecutive scans and \u0026Delta;time represents the corresponding time interval. The midpoint PMA between consecutive scans was used for analyses involving maturational trends. Intervals with non-positive time differences were excluded. Velocity estimates were evaluated using graphical diagnostics, including individual-level longitudinal plots and scatterplots against postmenstrual age, to confirm that high-magnitude values reflected coherent within-infant trajectories over clinically meaningful time intervals rather than isolated measurement artifact.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFeeding Exposure Variables\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEnteral feeding exposure was quantified using scan-day enteral caloric intake, expressed as kilocalories per kilogram per day (kcal/kg/day), derived from daily feeding records corresponding to each ultrasound assessment. Additional feeding variables included total enteral feeding volume (mL/kg/day) and the percentage of human milk, defined as the proportion of enteral intake provided as mother\u0026rsquo;s or donor human milk on the day of scan. Feeding variables reflected scan-day exposure and were modeled as time-varying covariates; interval-level feeding variability could not be fully captured. This approach parallels standard clinical growth velocity assessments and was selected to preserve temporal alignment with ultrasound measurements.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical Analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDescriptive statistics were used to summarize baseline demographic and clinical characteristics. Bowel wall thickness velocity (BWTv) was modeled as the dependent variable. Postmenstrual age (PMA) was treated as a continuous variable to evaluate maturational trends. \u003cstrong\u003eBecause multiple ultrasound examinations were obtained per infant,\u0026nbsp;\u003c/strong\u003elinear mixed-effects regression models with a random intercept for infant were used to account for within-infant correlation from repeated measures\u003cstrong\u003e.\u003c/strong\u003e Associations between BWTv and somatic growth velocities (weight, length, and head circumference z-score velocities) were examined using multivariable models including interaction terms between PMA and growth velocity to assess maturity-dependent effects. Feeding variables (enteral caloric intake, feeding volume, and percentage of human milk) were incorporated as time-varying covariates; interval-level feeding variability between scans could not be fully captured. Adjusted models evaluated the independent and modifying associations of feeding exposure with BWTv after accounting for somatic growth and PMA. All analyses were performed using R (R Foundation for Statistical Computing, Vienna, Austria) and Python (Python Software Foundation, Wilmington, DE). Statistical significance was defined as a two-sided p-value \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Baseline demographic and clinical characteristics of the study cohort.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"567\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003eValue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003eNumber of infants, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003eTotal bowel ultrasound examinations, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e260\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003eMale sex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e8 (54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003eGestational age at birth, weeks, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e29.7 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003eBirth weight, g, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e1,371(571)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003ePost menstrual age at ultrasound, weeks, range\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e26.4\u0026ndash;37.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003eCesarean delivery, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e12 (86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003eNon-White race, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e9 (64.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003eAntenatal steroid exposure, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e11 (82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003eDay of life at feed initiation, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e1.1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 390px;\"\u003e\n \u003cp\u003eDay of life at full enteral feeds, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 177px;\"\u003e\n \u003cp\u003e9.9 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as \u003cem\u003emean (SD)\u003c/em\u003e, \u003cem\u003erange\u003c/em\u003e, or \u003cem\u003enumber (percentage)\u003c/em\u003e as indicated.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eFourteen preterm infants (54% male) with a mean gestational age of \u003cstrong\u003e29.7 ± 2.9 weeks\u003c/strong\u003e and mean birth weight of \u003cstrong\u003e1,371 ± 571 g\u003c/strong\u003e were enrolled, contributing \u003cstrong\u003e260 serial bowel ultrasound scans\u003c/strong\u003e across a post menstrual age range of \u003cstrong\u003e26.4–37.2 weeks\u003c/strong\u003e. Baseline demographic and clinical characteristics are shown in \u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eInter-observer agreement for scan-level mean bowel wall thickness demonstrated good reliability (ICC [2,1] = 0.82; 95% CI 0.72–0.89; n = 65 scans)\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eDevelopmental trajectory of bowel wall thickness velocity\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eSerial bowel ultrasound measurements demonstrated that BWTv varied systematically with postmenstrual age (PMA), revealing a clear developmental trajectory. At earlier PMA, BWT velocity was higher and exhibited greater inter-individual variability, whereas with advancing maturity, BWT velocity progressively attenuated and approached zero, consistent with structural stabilization of the intestinal wall (Figure 2).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSomatic growth and intestinal growth velocity\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe first examined associations between BWTv and somatic growth velocities, including weight, length, and head circumference z-score velocities across postmenstrual age (PMA) (Supplementary Figure 1). Weight z-score velocity showed the strongest and most consistent association with BWT velocity, particularly at earlier PMA. Length z-score velocity demonstrated a weaker association, while head circumference z-score velocity showed minimal or inverse associations, especially at later maturity. These findings indicate that intestinal growth velocity preferentially tracks with somatic mass accretion rather than linear or neurocranial growth.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMaturity-dependent coupling between weight growth and intestinal growth velocity\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eGiven the dominant association for weight z-score velocity, we next evaluated its maturity-dependent relationship with intestinal growth velocity. Feeding-adjusted response surface analysis demonstrated strong positive coupling at earlier PMA, with progressive attenuation as maturity advanced (Figure 3). At later PMA, BWT velocity showed limited responsiveness to variation in weight z-score velocity, consistent with increasing structural stabilization of the intestine.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFeeding modulation of intestinal growth velocity\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFinally, we assessed whether feeding exposure independently modulated intestinal growth velocity after accounting for somatic growth and maturity. Enteral caloric intake was positively associated with BWT velocity at earlier PMA, whereas this relationship weakened substantially with advancing maturity when weight z-score velocity was held constant (Figure 4). These findings suggest that feeding exerts its strongest influence on intestinal growth velocity during early developmental windows, with diminishing effects as maturity progresses.\u003c/p\u003e"},{"header":"DISCUSSION ","content":"\u003cp\u003eIn this prospective ultrasound-based study, we demonstrate that bowel wall thickness velocity (BWTv) captures maturity-dependent variation in intestinal structural adaptation in preterm infants. Unlike static structural measurements, velocity-based metrics capture dynamic physiologic adaptation by integrating recent developmental and nutritional influences, allowing transient accelerations or attenuations in intestinal growth to be detected even when absolute thickness values appear normal. The velocity-based approach revealed substantial temporal heterogeneity, with higher and more variable growth rates at earlier postmenstrual ages followed by progressive attenuation as intestinal maturation advanced. Similar developmental nonlinearity has been described in experimental models of prematurity, where intestinal structure and function adapt rapidly during early postnatal life and stabilize with advancing maturity [1,2]. BWT velocity was associated with somatic growth velocity and recent feeding exposure; however, these relationships varied by developmental stage, supporting a framework of developmentally gated intestinal plasticity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIntestinal growth as a dynamic and maturity-dependent process\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eOur findings indicate that intestinal structural growth during early life is nonlinear and temporally regulated, rather than steady or monotonic. In preterm piglet models, Hansen et al. demonstrated rapid postnatal intestinal growth accompanied by delayed functional maturation, highlighting dissociation between structural expansion and digestive capacity during early development [1]. Similarly, Ren et al. showed that postnatal age, rather than birth weight alone, governs intestinal and immune maturation in preterm piglets, underscoring the importance of developmental timings [2]. The higher and more variable BWT velocities observed at earlier PMA in our cohort align closely with these experimental observations. As PMA increased, BWT velocity approached zero, suggesting a transition toward relative structural stabilization, consistent with the progressive consolidation of intestinal architecture described in animal models [1–6]. These findings emphasize the limitations of relying on single time-point bowel wall thickness measurements and highlight the added value of velocity-based metrics for characterizing real-time intestinal development.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCoupling between intestinal growth and somatic growth\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe observed a significant association between weight z-score velocity and BWT velocity, particularly at earlier PMA, indicating coordinated growth between the intestine and the overall somatic compartment. This relationship weakened with advancing maturity, suggesting reduced intestinal responsiveness to short-term systemic growth signals as developmental programs consolidate. In contrast, length and head circumference growth velocities demonstrated weaker and less consistent associations with BWT velocity, supporting the interpretation that intestinal structural adaptation preferentially aligns with somatic mass accretion rather than linear or neurocranial growth alone. Similar preferential coupling between intestinal growth and body mass accretion has been reported in piglet studies, where nutrient-driven somatic growth closely parallels intestinal tissue expansion during early postnatal life [4,6].\u003c/p\u003e\n\u003cp\u003eThese findings extend prior work on organ-specific growth trajectories by demonstrating that intestinal growth can be quantified as a rate-based process with biologically meaningful coupling to somatic growth that evolves across developmental time. A comparable velocity-based framework underlies intestinal ultrasound monitoring in pediatric and adult populations, where longitudinal changes in bowel wall thickness are used to track disease activity and therapeutic response in inflammatory bowel disease [7,8]. Our results suggest that similar dynamic principles apply to intestinal development in early life.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eRole of feeding exposure and intestinal plasticity\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIncorporation of time-varying feeding variables revealed that enteral caloric exposure was independently associated with variation in BWT velocity, particularly at earlier PMA. Experimental studies in preterm piglets have shown that early enteral nutrition exerts disproportionate effects on intestinal structure, vascularization, and immune signaling during narrow developmental windows [1,5]. The attenuation of feeding effects observed at later PMA in our cohort mirrors these findings, suggesting that nutritional modulation of intestinal structure is most pronounced during periods of immaturity.\u003c/p\u003e\n\u003cp\u003eNotably, adjustment for feeding exposure only partially attenuated the association between weight z-score velocity and BWT velocity, indicating that intestinal growth velocity reflects integration of recent feeding exposure, systemic growth state, and intrinsic maturational factor\u003cstrong\u003es\u003c/strong\u003e, rather than nutrient delivery alone. This observation aligns with experimental data demonstrating that intestinal growth trajectories are shaped by both environmental inputs and developmentally programmed constraints [2,6].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eImplications for intestinal vulnerability and disease risk\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAlthough this study was not designed to evaluate clinical outcomes, the observed heterogeneity in BWT velocity—particularly periods of accelerated or attenuated growth—raises important hypotheses regarding intestinal adaptation during early life. In neonatal bowel ultrasound literature, particularly in the context of NEC, emphasis has traditionally been placed on categorical findings such as bowel wall thickening, thinning, or perfusion abnormalities [19,20]. More recent neonatal ultrasound studies similarly focus on threshold-based markers of bowel viability rather than longitudinal structural change [21,22]. A velocity-based framework may offer a complementary approach by capturing early structural dynamics preceding clinically apparent disease, warranting further investigation in outcome-focused studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSTRENGTHS AND LIMITATIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStrengths of this study include its longitudinal design, standardized ultrasound imaging acquisition, interval-based velocity modeling, and integration of somatic growth and feeding data as time-varying covariates. Several limitations merit consideration. Feeding exposure was summarized using scan-day values as proxies for interval exposure, which may not fully capture daily variability. The cohort size limited formal outcome analyses, and causality cannot be inferred from observational associations. However, the high density of longitudinal measurements (260 scans) enabled robust within-infant trajectory modeling despite the modest cohort size. Additionally, ultrasound-derived bowel wall thickness reflects a composite structural measure and does not directly assess mucosal or cellular composition. Although inter-observer reliability was assessed in a subset of examinations, intra-observer variability was not formally quantified and will be evaluated in future multicenter studies.\u0026nbsp;\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eBowel wall thickness velocity is a dynamic, maturity-dependent measure of intestinal structural adaptation in preterm infants, with strongest coupling to somatic growth and feeding exposure at earlier postmenstrual ages and gradual attenuation with advancing maturation. These findings support a framework of developmentally gated intestinal plasticity. If validated in larger multicenter cohorts, velocity-based intestinal ultrasound metrics may inform future risk-stratified nutritional and monitoring strategies in preterm infants.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAUTHORS CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConceptualization:\u003c/strong\u003e Indrani Bhattacharjee, Michael Todd Dolinger\u003cbr\u003e\u003cstrong\u003eMethodology:\u003c/strong\u003e Indrani Bhattacharjee, Saharnaz Talebiyan\u003cbr\u003e\u003cstrong\u003eData Acquisition:\u003c/strong\u003e Saharnaz Talebiyan, Indrani Bhattacharjee\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eUltrasound Supervision and Validation:\u003c/strong\u003e Terri Williams-Weekes , Indrani Bhattacharjee\u0026nbsp;\u003cbr\u003e\u003cstrong\u003eFormal Analysis:\u003c/strong\u003e Indrani Bhattacharjee\u003cbr\u003e\u003cstrong\u003eInvestigation:\u003c/strong\u003e Indrani Bhattacharjee, Saharnaz Talebiyan\u003cbr\u003e\u003cstrong\u003eWriting – Original Draft:\u003c/strong\u003e Indrani Bhattacharjee\u003cbr\u003e\u003cstrong\u003eWriting – Review \u0026amp; Editing:\u003c/strong\u003e All authors\u003cbr\u003e\u003cstrong\u003eSupervision:\u003c/strong\u003e Rachana Singh, Yogen Singh, Micheal Todd Dolinger\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the final manuscript and agree to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Bhattacharjee was supported by the Natalie Zucker Grant for Women Scholars at Tufts University. The authors received no additional specific funding for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge the Biostatistics, Epidemiology, and Research Design (BERD) Center at the Tufts Clinical and Translational Science Institute for statistical consultation and analytical support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHansen CF, Thymann T, Andersen AD, et al. 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Intestinal ultrasonography in children and young adults: bowel wall thickness is age dependent. \u003cem\u003eJ Ultrasound Med.\u003c/em\u003e 2000;19(5):315\u0026ndash;321.\u003c/li\u003e\n\u003cli\u003eAlbshesh A, Novak KL, Panaccione R, et al. Intestinal ultrasound measurement of bowel wall thickness as a predictor of treatment failure in Crohn\u0026rsquo;s disease. \u003cem\u003eTher Adv Gastroenterol.\u003c/em\u003e 2025;18:1756284824123456.\u003c/li\u003e\n\u003cli\u003eR\u0026auml;is\u0026auml;nen L, Puylaert C, Nylund K, et al. Bowel wall thickness cutoff values for assessing intestinal inflammation: adult and pediatric perspectives. \u003cem\u003eInflamm Bowel Dis.\u003c/em\u003e 2025;31(2):245\u0026ndash;254.\u003c/li\u003e\n\u003cli\u003eEpelman M, Daneman A, Navarro OM, et al. Necrotizing enterocolitis: review of state-of-the-art imaging findings with pathologic correlation. \u003cem\u003eRadiographics.\u003c/em\u003e 2007;27(2):285\u0026ndash;305.\u003c/li\u003e\n\u003cli\u003eSilva CT, Daneman A, Navarro OM, et al. Correlation of sonographic findings and outcome in necrotizing enterocolitis. \u003cem\u003ePediatr Radiol.\u003c/em\u003e 2007;37(3):274\u0026ndash;282.\u003c/li\u003e\n\u003cli\u003eBhattacharjee I, Dolinger MT, Singh R, Singh Y. Ultrasound for the early detection and diagnosis of necrotizing enterocolitis: a scoping review of emerging evidence. \u003cem\u003eDiagnostics (Basel).\u003c/em\u003e 2025;15(15):1852.\u003c/li\u003e\n\u003cli\u003eSingh Y, Kempley ST, Jhaveri R, et al. Abdominal ultrasound as an adjunct to clinical and radiographic evaluation in neonatal intestinal injury, including necrotizing enterocolitis. \u003cem\u003ePediatr Radiol.\u003c/em\u003e 2024;54(6):921\u0026ndash;930.\u003c/li\u003e\n\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":"Preterm infants, Bowel ultrasound, Bowel wall thickness, Intestinal growth velocity, Enteral nutrition, Postmenstrual age","lastPublishedDoi":"10.21203/rs.3.rs-8990068/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8990068/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eObjective\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTo characterize bowel wall thickness velocity (BWTv) across postmenstrual age (PMA) in preterm infants and examine its relationship with somatic growth velocity and feeding exposure.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStudy Design:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eProspective observational pilot study of preterm infants undergoing serial standardized bowel ultrasound examinations. Mean bowel wall thickness (BWT) was measured per scan; BWTv was defined as interval-based change over time. Somatic growth velocity was expressed as interval changes in anthropometric z-scores. Feeding exposures were modeled as time-varying covariates. Regression models with clustering by infant assessed maturity-dependent associations.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eFourteen infants contributed 260 ultrasounds. BWTv was higher and more heterogeneous at earlier PMA and attenuated with advancing maturity. Weight z-score velocity showed the strongest association with BWTv. Enteral caloric intake was positively associated with BWTv at earlier PMA, with diminishing effects over time.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eBWTv represents a dynamic, maturity-dependent marker of intestinal structural adaptation in preterm infants.\u003c/p\u003e","manuscriptTitle":"Bowel Wall Thickness Velocity as a Quantitative Marker of Intestinal Adaptation in Preterm Infants","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-09 06:37:31","doi":"10.21203/rs.3.rs-8990068/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":"b17b4d98-d892-44dd-99a6-98ae301db43c","owner":[],"postedDate":"March 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":63848454,"name":"Health sciences/Biomarkers/Diagnostic markers"},{"id":63848455,"name":"Health sciences/Health care/Medical imaging"}],"tags":[],"updatedAt":"2026-03-18T10:04:02+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-09 06:37:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8990068","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8990068","identity":"rs-8990068","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}