Supplementary Material for: Validation of a New Classification for Severe Bronchopulmonary Dysplasia in Extremely Preterm Infants: Insights from a Large Japanese Cohort

Introduction: A recent scoping review identified histological chorioamnionitis (HCA), small for gestational age (SGA), and bubbly/cystic appearance on chest X-ray (bubbly/cystic CXR) as risk factors for severe bronchopulmonary dysplasia (BPD). To further validate these results, a large-scale database was analyzed.
Methods: This retrospective multicenter cohort study included infants born at <28 weeks' gestational age between 2003 and 2016. The validated risk factors identified from the scoping review were analyzed for independent associations with severe BPD using multivariable logistic regression. Additionally, the association of these factors with long-term outcomes at 3 years, including home oxygen therapy (HOT) and neurodevelopmental impairments (NDIs), were analyzed.
Results: Among 15,834 extremely preterm infants, HCA, SGA, and bubbly/cystic CXR on postnatal day 28 were significantly and independently associated with severe BPD (adjusted odds ratio, 1.20; 95% confidence interval, 1.06–1.36) (1.73; 1.51–1.98) (1.79; 1.60–2.01), respectively. These three factors were also linked to HOT at 3 years (1.54; 1.14–2.08) (1.70; 1.21–2.39) (2.63; 1.94–3.56), respectively. Their combination significantly increased the prevalence of severe BPD and HOT at 3 years, particularly with bubbly/cystic CXR. Only SGA was independently associated with NDIs in BPD infants (1.55; 1.32–1.83).
Conclusions: HCA, SGA, and bubbly/cystic CXR on postnatal day 28 were identified as important risk factors for severe BPD and long-term respiratory outcomes. While further research is needed to validate their role in endotype-specific classification of BPD, these findings may contribute to early prognostic strategies and targeted interventions before 36 weeks' postmenstrual age.

引言：近期一项范围综述（scoping review）鉴定出，组织学绒毛膜羊膜炎（histological chorioamnionitis, HCA）、小于胎龄儿（small for gestational age, SGA）以及胸部X线检查可见泡状/囊性表现（bubbly/cystic CXR）是重症支气管肺发育不良（severe bronchopulmonary dysplasia, BPD）的危险因素。为进一步验证上述结论，本研究对大规模数据库展开分析。
方法：本研究为回顾性多中心队列研究，纳入2003年至2016年间胎龄小于28周的早产儿。采用多变量logistic回归分析，探究该范围综述所鉴定的经验证的危险因素与重症支气管肺发育不良的独立相关性。此外，本研究还分析了上述因素与3年随访长期结局的关联，包括家庭氧疗（home oxygen therapy, HOT）及神经发育障碍（neurodevelopmental impairments, NDIs）。
结果：在15834名极早早产儿中，产后第28天的组织学绒毛膜羊膜炎、小于胎龄儿以及泡状/囊性胸部X线表现均与重症支气管肺发育不良存在显著独立相关性（校正比值比分别为1.20；95%置信区间1.06~1.36）、（1.73；1.51~1.98）、（1.79；1.60~2.01）。上述三种危险因素同样与3年家庭氧疗存在相关性（校正比值比分别为1.54；1.14~2.08）、（1.70；1.21~2.39）、（2.63；1.94~3.56）。三种危险因素联合可显著升高重症支气管肺发育不良及3年家庭氧疗的患病率，尤以泡状/囊性胸部X线表现为著。仅小于胎龄儿与支气管肺发育不良患儿的神经发育障碍存在独立相关性（校正比值比1.55；95%置信区间1.32~1.83）。
结论：本研究证实，产后第28天的组织学绒毛膜羊膜炎、小于胎龄儿以及泡状/囊性胸部X线表现是重症支气管肺发育不良及长期呼吸结局的重要危险因素。尽管仍需进一步研究以验证其在支气管肺发育不良内表型特异性分类中的作用，但上述发现可为妊娠36周月经后龄前的早期预后策略及靶向干预提供参考。