Early Antibiotic Exposure and Bronchopulmonary Dysplasia in Very Preterm Infants at Low Risk of Early-Onset Sepsis
Authors: Shi Wei , Chen Zheng , Shi Liping , Jiang Siyuan , Zhou Jianguo , Gu Xinyue , Lei Xiaoping , Xiao Tiantian , Zhu Yanping , Qian Aimin , Zhou Wenhao , Lee Shoo K. , Du Lizhong , Yang Jie , Ma Xiaolu , Hu Liyuan ,   Chinese Neonatal Network, Chen Chao , Cao Yun , Chen Xiuyong , Zhang Huyan , Tian Xiuying , Shi Jingyun , Li Zhankui , Yang Chuanzhong , Liu Ling , Yang Zuming , Fu Jianhua , Ji Yong , Chen Dongmei , Yang Changyi , Chen Rui , Peng Xiaoming , Shan Ruobing , Han Shuping , Wu Hui , Wang Lili , Wei Qiufen , Li Mingxia , Dai Yiheng , Jiang Hong , Kang Wenqing , Gong Xiaohui , Zhong Xiaoyun , Shi Yuan , Jiang Shanyu , Sun Bing , Li Long , Lin Zhenlang , Liu Jiangqin , Pan Jiahua , Xia Hongping , Li Xiaoying , Xu Falin , Qiu Yinping , Ma Li , Yang Ling , He Xiaori , Li Yanhong , Zhuang Deyi , Zhang Qin , Dong Wenbin , Sun Jianhua , Liang Kun , Wang Huaiyan , Feng Jinxing , Chen Liping , Lin Xinzhu , Jiang Chunming , Nie Chuan , Zeng Linkong , Hei Mingyan , Zhu Hongdan , Mi Hongying , Yin Zhaoqing , Song Hongxia , Wang Hongyun , Li Dong , Gao Yan , Wang Yajuan , Dai Liying , Zhang Liyan , Li Yangfang , Zhang Qianshen , Ding Guofang , Wang Jimei , Chen Xiaoxia , Wang Zhen , Tang Zheng , Zhang Xiaomei , Zhang Xiaolan , Wu Fang , Chen Yanxiang , Wu Ying , Ting Joseph 
Published: June 2024

Importance

The overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities. Nevertheless, the association of early antibiotic exposure with bronchopulmonary dysplasia (BPD) remains equivocal.

Objective

To evaluate the association of varying durations and types of early antibiotic exposure with the incidence of BPD in VPIs at low risk of EOS.

Design, Setting, and Participants

This national multicenter cohort study utilized data from the Chinese Neonatal Network (CHNN) which prospectively collected data from January 1, 2019, to December 31, 2021. VPIs less than 32 weeks’ gestational age or with birth weight less than 1500 g at low risk of EOS, defined as those born via cesarean delivery, without labor or rupture of membranes, and no clinical evidence of chorioamnionitis, were included. Data analysis was conducted from October 2022 to December 2023.

Exposure

Early antibiotic exposure was defined as the total number of calendar days antibiotics were administered within the first week of life, which were further categorized as no exposure, 1 to 4 days of exposure, and 5 to 7 days of exposure.

Main Outcomes and Measures

The primary outcome was the composite of moderate to severe BPD or mortality at 36 weeks’ post menstrual age (PMA). Logistic regression was employed to assess factors associated with BPD or mortality using 2 different models.

Results

Of the 27 176 VPIs included in the CHNN during the study period (14 874 male [54.7%] and 12 302 female [45.3%]), 6510 (23.9%; 3373 male [51.8%] and 3137 female [48.2.%]) were categorized as low risk for EOS. Among them, 1324 (20.3%) had no antibiotic exposure, 1134 (17.4%) received 1 to 4 days of antibiotics treatment, and 4052 (62.2%) received 5 to 7 days of antibiotics treatment. Of the 5186 VPIs who received antibiotics, 4098 (79.0%) received broad-spectrum antibiotics, 888 (17.1%) received narrow-spectrum antibiotics, and 200 (3.9%) received antifungals or other antibiotics. Prolonged exposure (5-7 days) was associated with increased likelihood of moderate to severe BPD or death (adjusted odds ratio [aOR], 1.23; 95% CI, 1.01-1.50). The use of broad-spectrum antibiotics (1-7 days) was also associated with a higher risk of moderate to severe BPD or death (aOR, 1.27; 95% CI, 1.04-1.55).

Conclusions and Relevance

In this cohort study of VPIs at low risk for EOS, exposure to prolonged or broad-spectrum antibiotics was associated with increased risk of developing moderate to severe BPD or mortality. These findings suggest that VPIs exposed to prolonged or broad-spectrum antibiotics early in life should be monitored for adverse outcomes.