Association between the risk of necrotizing enterocolitis and intrauterine growth: a multicenter cohort study

Dan Dang; Siyuan Jiang; Joseph Y Ting; Xiaoping Lei; Xinyue Gu; Wenhao Zhou; Lizhong Du; Yun Cao; Shoo Kim Lee; Hui Wu; Jianguo Zhou; Chinese Neonatal Network (CHNN)

doi:10.1038/s41390-025-04039-4

Association between the risk of necrotizing enterocolitis and intrauterine growth: a multicenter cohort study

Pediatr Res. 2025 Jun 13. doi: 10.1038/s41390-025-04039-4. Online ahead of print.

Authors

Dan Dang¹, Siyuan Jiang², Joseph Y Ting³, Xiaoping Lei⁴, Xinyue Gu², Wenhao Zhou², Lizhong Du^{5

6}, Yun Cao², Shoo Kim Lee⁷, Hui Wu⁸, Jianguo Zhou⁹; Chinese Neonatal Network (CHNN)

Collaborators

Chinese Neonatal Network (CHNN):
Shoo K Lee, Chao Chen, Lizhong Du, Wenhao Zhou, 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, Joseph Ting

Affiliations

¹ Department of Neonatology, Children's Medical Center, The First Hospital of Jilin University, Changchun, Jilin, China.
² Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China.
³ Division of Neonatal-Perinatal Care, Department of Pediatrics, Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, Canada.
⁴ Division of Neonatology, Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
⁵ Neonatal Intensive Care Unit, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁶ National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, Zhejiang, China.
⁷ Maternal-Infant Care Research Centre and Department of Pediatrics, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.
⁸ Department of Neonatology, Children's Medical Center, The First Hospital of Jilin University, Changchun, Jilin, China. wuhui@jlu.edu.cn.
⁹ Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China. joezhou@fudan.edu.cn.

PMID: 40514414
DOI: 10.1038/s41390-025-04039-4

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.

Abstract

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