752 - Improved survival but increasing bronchopulmonary dysplasia among infants born at 22–23 weeks’ gestation: A 20-year large cohort study

Publication Number: 2733.752

Hidehiko Nakanishi, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan; Masayo Kokubo, Nagano Children's Hospital, Azumino, Nagano, Japan; Tetsuya Isayama, National Center for Child Health and Development, Setagaya-ku, Tokyo, Japan; Shinya Hirano, Osaka Women's and Children's Hospital, Izumi, Osaka, Japan; Kusuda Satoshi, Neonatal Research Network of Japan, Taito, Tokyo, Japan

Background: Advances in neonatal care have improved survival of infants born at 22-23 wk, but bronchopulmonary dysplasia (BPD) remains increasing. Recent studies (Ito 2023; Nakanishi 2025) identified histologic chorioamnionitis (HCA), small for gestational age (SGA), and bubbly/cystic appearance on chest X-ray (bubbly/cystic CXR) as key risk factors for BPD in extremely preterm infants.

Objective: To clarify 20-year trends in BPD incidence, respiratory management, and perinatal background among infants born < 28 wk-particularly those at 22-23 wk-using data from the Neonatal Research Network Japan (NRNJ).

Design/Methods: A retrospective cohort of infants born < 28 wk registered in the NRNJ (2003-2022) was analyzed. Approvals were obtained from Osaka Women's and Children's Hospital (IRB 1104) and all participating centers (C20-040). Temporal trends in survival and BPD outcomes were examined using the Cochran-Armitage test, and multivariable logistic regression was applied to identify risk factors for severe BPD.

Results: A total of 22,486 infants born < 28 wk were analyzed, including 3,198 at 22-23 wk. Among infants born at 22-23 wk, survival improved from 58.1% in 2003 to 76.0% in 2022, accompanied by increased antenatal corticosteroid use (from 21.0% to 69.5%) and cesarean delivery (from 29.8% to 69.8%). In this periviable group, invasive ventilation >56 days declined from 79.7% to 63.7%, while non-invasive support >28 days increased from 18.8% to 65.3% (Figure 1). Despite these advances, the incidence of BPD-36 wk rose from 66.7% to 80.4%, and severe BPD from 40.6% to 49.0% (Figure 2). In the overall cohort ( < 28 wk), risk factors for severe BPD were HCA (AOR 1.17, 95% CI 1.08-1.27), SGA (1.98, 1.81-2.16), and bubbly/cystic CXR (3.25, 3.02-3.50). Among 22-23 wk infants, the prevalence of SGA increased from 7.2% to 13.1%, HCA from 51.9% to 65.3%, and bubbly/cystic CXR from 50.0% to 54.6% (Figure 3). The proportion of mothers aged >35 years doubled from 17.5% to 41.9% and was significantly associated with SGA (1.57, 1.46-1.68).

Conclusion(s): Between 2003 and 2022, survival improved even at 22-23 weeks, but both BPD-36 wk and severe BPD increased. The concurrent rise in advanced maternal age, HCA, SGA, and bubbly/cystic CXR indicates a shift in BPD pathogenesis toward antenatal, growth- and inflammation-related factors. Comprehensive post-discharge care and phenotype-based preventive strategies are needed, and future studies should develop targeted interventions for these phenotypes.

Figure 1. Changes in Respiratory Support Duration by Gestational Age
Temporal trends in the duration of invasive (upper panels) and non-invasive (lower panels) respiratory support by gestational age from 2003 to 2022.
Across all gestational age groups, the duration of invasive ventilation markedly decreased, whereas that of non-invasive support steadily increased.
P-values were calculated using the Cochrane-Armitage χ² test.
*p < 0.05, significant decrease in infants requiring invasive ventilation >56 days (2003-2022).
**p < 0.05, significant increase in infants requiring non-invasive support >28 days (2003-2022).


Figure 2. Trends in Survival and BPD Incidence by Gestational Age ( <28 weeks)
Temporal trends in (a) survival, (b) bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age, and (c) severe BPD among infants born before 28 weeks' gestation from 2003 to 2022.
Across all gestational age subgroups, survival, BPD-36 wk, and severe BPD significantly increased over time. The magnitude of increase was most pronounced among infants born at 22-23 weeks, showing marked improvements in survival accompanied by substantial rises in both BPD and severe BPD rates.
P-values were calculated using the Cochrane-Armitage χ² test.
*p < 0.05, significant trend from 2003 to 2022.
BPD, bronchopulmonary dysplasia; GA, gestational age.


Figure 3. Trends in HCA, SGA, and Bubbly/Cystic CXR by Gestational Age ( <28 weeks)
Temporal trends in the prevalence of (a) histological chorioamnionitis (HCA), (b) small for gestational age (SGA), and (c) bubbly/cystic chest X-ray (CXR) findings among infants born before 28 weeks' gestation from 2003 to 2022.
In all gestational age subgroups (22-23, 24-25, and 26-27 weeks), the prevalence of HCA, SGA, and bubbly/cystic CXR significantly increased over time.
P-values were calculated using the Cochrane-Armitage χ² test.
*p < 0.05, significant increase from 2003 to 2022.
HCA, histological chorioamnionitis; SGA, small for gestational age; CXR, chest X-ray; GA, gestational age.