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  • Clinical Research Article
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Association between the risk of necrotizing enterocolitis and intrauterine growth: a multicenter cohort study

Pediatric Research (2025)Cite this article

Abstract

Background

Despite the established correlation between small for gestational age (SGA) and heightened necrotizing enterocolitis (NEC) risk, the relationship between intrauterine growth, including SGA, and the occurrence of NEC remains ambiguous.

Methods

This study utilized data of very preterm infants (VPIs) with a gestational age <32 weeks from the Chinese Neonatal Network cohort study. Intrauterine growth status was categorized through birthweight (BW) percentile delineated by the Fenton growth chart.

Results

The cohort comprised 23,702 VPIs containing 1186 cases of NEC. A non-linear relationship between BW percentiles and death or NEC was identified. Infants with a BW percentile ≤23rd showed an increased risk of death or NEC. The multivariate analysis indicated a significantly higher risk of death or NEC in infants categorized between the 10th and 23rd percentiles (adjusted odds ratio [aOR] = 1.41; 95% confidence interval [CI], 1.22–1.63) and those below 10th percentile (aOR = 2.09; 95% CI, 1.74–2.52), comparing with infants in the above 23rd percentile group. Subgroup analyses yielded analogous results.

Conclusions

Intrauterine growth restriction significantly increases the risk of mortality or NEC among VPIs. The increased risk also extends to infants, particularly those within the 10th to 23rd percentile range, emphasizing the need for heightened surveillance and care.

Impact

  • This study explores the relationship between intrauterine growth and the occurrence of necrotizing enterocolitis (NEC).

  • In this multicenter cohort study that included 23,702 very preterm infants (VPIs), a non-linear relationship between birth weight percentiles and death or NEC was identified. Infants with a birth weight percentile at or below 23rd showed an increased risk of death or NEC.

  • Intrauterine growth restriction significantly increases mortality or NEC risk among VPIs with birth weight at or below the 23rd percentile. This risk extends to infants, particularly within the 10th to 23rd percentile range, highlighting the need for heightened surveillance and care.

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Fig. 1: Flow chart of study population.
Fig. 2: Smooth curve fitting detected a nonlinear positive relationship between birthweight percentile and death or NEC.
Fig. 3: Multiple logistic regression: outcome of SGA and infants within the 10th and 23rd BW percentiles compared with infants with birthweight percentile >23%.
Fig. 4: Outcome of SGA and infants within the 10th and 23rd BW percentiles in subgroups.

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Data availability

The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files.

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Funding

National Natural Science Foundation of China (82301952, 82271737); Jilin Provincial Department of Science and Technology (YDZJ202301ZYTS070); National Key Research and Development Program of China (2021YFC2701800, 2021YFC2701801); Shanghai Science and Technology Commission’s Scientific and Technological Innovation Action Plan (21Y21900800); Canadian Institutes of Health Research (CTP87518).

Author information

Authors and Affiliations

  1. Department of Neonatology, Children’s Medical Center, The First Hospital of Jilin University, Changchun, Jilin, China

    Dan Dang & Hui Wu

  2. Department of Neonatology, Children’s Hospital of Fudan University, Shanghai, China

    Siyuan Jiang, Xinyue Gu, Wenhao Zhou, Yun Cao & Jianguo Zhou

  3. Division of Neonatal-Perinatal Care, Department of Pediatrics, Women and Children’s Health Research Institute, University of Alberta, Edmonton, AB, Canada

    Joseph Y. Ting

  4. Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China

    Xiaoping Lei

  5. Neonatal Intensive Care Unit, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

    Lizhong Du

  6. National Clinical Research Center for Child Health, National Children’s Regional Medical Center, Hangzhou, Zhejiang, China

    Lizhong Du

  7. Maternal-Infant Care Research Centre and Department of Pediatrics, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

    Shoo Kim Lee

  8. Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

    Shoo K Lee

  9. Children’s Hospital of Fudan University, Shanghai, China

    Chao Chen, Wenhao Zhou & Yun Cao

  10. Children’s Hospital of Zhejiang University School of Medicine, Zhejiang, China

    Lizhong Du

  11. The Third Affiliated Hospital of Zhengzhou University, Henan, China

    Xiuyong Cheng

  12. Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, China

    Huayan Zhang

  13. Tianjin Obstetrics & Gynecology Hospital, Tianjin, China

    Xiuying Tian

  14. Gansu Provincial Maternity and Child Care Hospital, Gansu, China

    Jingyun Shi

  15. Northwest Women’s and Children’s Hospital, Shaanxi, China

    Zhankui Li

  16. Shenzhen Maternity and Child Health Care Hospital, Guangdong, China

    Chuanzhong Yang

  17. Guizhou Women and Children’s Hospital, Guizhou, China

    Ling Liu

  18. Suzhou Municipal Hospital affiliated to Nanjing Medical University, Jiangsu, China

    Zuming Yang

  19. Shengjing Hospital of China Medical University, Liaoning, China

    Jianhua Fu

  20. Children’s Hospital of Shanxi, Shanxi, China

    Yong Ji

  21. Quanzhou Women and Children’s Hospital, Fujian, China

    Dongmei Chen

  22. Fujian Women and Children’s Medical Center, Fujian, China

    Changyi Yang

  23. Children’s Hospital of Nanjing Medical University, Jiangsu, China

    Rui Cheng

  24. Hunan Children’s Hospital, Hunan, China

    Xiaoming Peng

  25. Qingdao Women and Children’s Hospital, Shandong, China

    Ruobing Shan

  26. Nanjing Maternity and Child Health Care Hospital, Jiangsu, China

    Shuping Han

  27. The First Hospital of Jilin University, Jilin, China

    Hui Wu

  28. The First Affiliated Hospital of Anhui Medical University, Anhui, China

    Lili Wang

  29. Women and Children’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi, China

    Qiufen Wei

  30. The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China

    Mingxia Li

  31. Foshan Women and Children’s Hospital, Guangdong, China

    Yiheng Dai

  32. The Affiliated Hospital of Qingdao University, Shandong, China

    Hong Jiang

  33. Henan Children’s Hospital, Henan, China

    Wenqing Kang

  34. Children’s Hospital of Shanghai, Shanghai, China

    Xiaohui Gong

  35. Chongqing Health Care Center for Women and Children, Chongqing, China

    Xiaoyun Zhong

  36. Children’s Hospital of Chongqing Medical University, Chongqing, China

    Yuan Shi

  37. Wuxi Maternity and Child Healthcare Hospital, Jiangsu, China

    Shanyu Jiang

  38. Children’s Hospital of Soochow University, Jiangsu, China

    Bing Sun

  39. People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, China

    Long Li

  40. Yuying Children’s Hospital Affiliated to Wenzhou Medical University, Zhejiang, China

    Zhenlang Lin

  41. Shanghai First Maternity and Infant Hospital, Shanghai, China

    Jiangqin Liu

  42. Anhui Provincial Hospital, Anhui, China

    Jiahua Pan

  43. Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China

    Hongping Xia

  44. Qilu Children’s Hospital of Shandong University, Shandong, China

    Xiaoying Li

  45. The First Affiliated Hospital of Zhengzhou University, Henan, China

    Falin Xu

  46. General Hospital of Ningxia Medical University, Ningxia, China

    Yinping Qiu

  47. Hebei Children’s Hospital, Hebei, China

    Li Ma

  48. Hainan Women and Children’s Hospital, Hainan, China

    Ling Yang

  49. The Second Xiangya Hospital of Central South University, Hunan, China

    Xiaori He

  50. Ningbo Women & Children Hospital, Zhejiang, China

    Yanhong Li

  51. Xiamen Children’s Hospital, Fujian, China

    Deyi Zhuang

  52. Shaanxi Provincial People’s Hospital, Shaanxi, China

    Qin Zhang

  53. The Affiliated Hospital of Southwest Medical University, Sichuan, China

    Wenbin Dong

  54. Shanghai Children’s Medical Center affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China

    Jianhua Sun

  55. First Affiliated Hospital of Kunming Medical University, Yunnan, China

    Kun Liang

  56. Changzhou Maternal and Children Health Care Hospital, Jiangsu, China

    Huaiyan Wang

  57. Shenzhen Children’s Hospital, Guangdong, China

    Jinxing Feng

  58. Jiangxi Provincial Children’s Hospital, Jiangxi, China

    Liping Chen

  59. Xiamen Maternity and Child Health Care Hospital, Fujian, China

    Xinzhu Lin

  60. Zhuhai Center for Maternal and Child Health Care, Guangdong, China

    Chunming Jiang

  61. Guangdong Women and Children’s Hospital, Guangdong, China

    Chuan Nie

  62. Wuhan Children’s Hospital, Hubei, China

    Linkong Zeng

  63. Beijing Children’s Hospital of Capital Medical University, Beijing, China

    Mingyan Hei

  64. Maternal and Children Hospital of Shaoxing, Zhejiang, China

    Hongdan Zhu

  65. The First People’s Hospital of Yunnan Province, Yunnan, China

    Hongying Mi

  66. Dehong People’s Hospital of Yunnan Province, Yunnan, China

    Zhaoqing Yin

  67. First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi, China

    Hongxia Song

  68. Inner Mongolia Maternal and Child Health Care Hospital, Inner Mongolia, China

    Hongyun Wang

  69. Dalian Municipal Women and Children’s Medical Center, Liaoning, China

    Dong Li

  70. Lianyungang Maternal and Children Health Hospital, Jiangsu, China

    Yan Gao

  71. Children’s Hospital Affiliated to Capital Institute of Pediatrics, Beijing, China

    Yajuan Wang

  72. Anhui Children’s Hospital, Anhui, China

    Liying Dai

  73. Fuzhou Children’s Hospital of Fujian Province, Fujian, China

    Liyan Zhang

  74. Kunming Children’s Hospital, Yunnan, China

    Yangfang Li

  75. Shenzhen Hospital of Hong Kong University, Guangdong, China

    Qianshen Zhang

  76. Peking Union Medical College Hospital, Beijing, China

    Guofang Ding

  77. Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China

    Jimei Wang

  78. The Affiliated Hospital of Guizhou Medical University, Guizhou, China

    Xiaoxia Chen

  79. Qinghai Women and Children Hospital, Qinghai, China

    Zhen Wang

  80. The International Peace Maternity & Child Health Hospital of China Welfare Institute, Shanghai, China

    Zheng Tang

  81. Children’s Hospital, Zhejiang University School of Medicine, Zhejiang, China

    Xiaolu Ma

  82. Inner Mongolia People’s Hospital, Inner Mongolia, China

    Xiaomei Zhang

  83. Xiamen Humanity Hospital, Fujian, China

    Xiaolan Zhang

  84. Shanghai General Hospital, Shanghai, China

    Fang Wu

  85. The First People’s Hospital of Yinchuan, Ningxia, China

    Yanxiang Chen

  86. The Third Hospital of Nanchang, Jiangxi, China

    Ying Wu

  87. University of Alberta, Edmonton, AB, Canada

    Joseph Ting

Authors
  1. Dan Dang
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  2. Siyuan Jiang
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  3. Joseph Y. Ting
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  4. Xiaoping Lei
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  5. Xinyue Gu
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  6. Wenhao Zhou
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  7. Lizhong Du
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  8. Yun Cao
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  9. Shoo Kim Lee
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  10. Hui Wu
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  11. Jianguo Zhou
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Consortia

Chinese Neonatal Network (CHNN)

  • Group Information of the Chinese Neonatal Network:Chairmen

    • Shoo K Lee
    •  & Chao Chen

  • Vice-Chairmen

    • Lizhong Du
    •  & Wenhao Zhou

  • Site principal investigators of the Chinese Neonatal Network

    • Yun Cao
    • , Xiuyong Cheng
    • , Huayan Zhang
    • , Xiuying Tian
    • , Jingyun Shi
    • , Zhankui Li
    • , Chuanzhong Yang
    • , Ling Liu
    • , Zuming Yang
    • , Jianhua Fu
    • , Yong Ji
    • , Dongmei Chen
    • , Changyi Yang
    • , Rui Cheng
    • , Xiaoming Peng
    • , Ruobing Shan
    • , Shuping Han
    • , Hui Wu
    • , Lili Wang
    • , Qiufen Wei
    • , Mingxia Li
    • , Yiheng Dai
    • , Hong Jiang
    • , Wenqing Kang
    • , Xiaohui Gong
    • , Xiaoyun Zhong
    • , Yuan Shi
    • , Shanyu Jiang
    • , Bing Sun
    • , Long Li
    • , Zhenlang Lin
    • , Jiangqin Liu
    • , Jiahua Pan
    • , Hongping Xia
    • , Xiaoying Li
    • , Falin Xu
    • , Yinping Qiu
    • , Li Ma
    • , Ling Yang
    • , Xiaori He
    • , Yanhong Li
    • , Deyi Zhuang
    • , Qin Zhang
    • , Wenbin Dong
    • , Jianhua Sun
    • , Kun Liang
    • , Huaiyan Wang
    • , Jinxing Feng
    • , Liping Chen
    • , Xinzhu Lin
    • , Chunming Jiang
    • , Chuan Nie
    • , Linkong Zeng
    • , Mingyan Hei
    • , Hongdan Zhu
    • , Hongying Mi
    • , Zhaoqing Yin
    • , Hongxia Song
    • , Hongyun Wang
    • , Dong Li
    • , Yan Gao
    • , Yajuan Wang
    • , Liying Dai
    • , Liyan Zhang
    • , Yangfang Li
    • , Qianshen Zhang
    • , Guofang Ding
    • , Jimei Wang
    • , Xiaoxia Chen
    • , Zhen Wang
    • , Zheng Tang
    • , Xiaolu Ma
    • , Xiaomei Zhang
    • , Xiaolan Zhang
    • , Fang Wu
    • , Yanxiang Chen
    •  & Ying Wu

  • Advisor

    • Joseph Ting

Contributions

Dan Dang: performed study concept and design, performed development of methodology, analysis and interpretation of data, writing—original draft, read and approved the final paper. Siyuan Jiang: performed study concept and design, provided technical and material support, read and approved the final paper. Joseph Y. Ting: language polishing, review & editing, read and approved the final paper. Xiaoping Lei: provided technical support, read and approved the final paper. Xinyue Gu: analysis and interpretation of data, statistical analysis, read and approved the final paper. Wenhao Zhou, Lizhong Du, Yun Cao and Shoo Kim Lee: create and maintain CHNN data platform, read and approved the final paper. Hui Wu and Jianguo Zhou: performed study concept and design, project administration, writing—review & editing, read and approved the final paper.

Corresponding authors

Correspondence to Hui Wu or Jianguo Zhou.

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Dang, D., Jiang, S., Ting, J.Y. et al. Association between the risk of necrotizing enterocolitis and intrauterine growth: a multicenter cohort study. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04039-4

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