Baud Olivier, Lehert Philippe
Department of Neonatal Medicine, Cochin-Port Royal Hospital, University Paris Cité, Paris, France.
University of Geneva, Geneva, Switzerland.
Pediatr Res. 2024 Oct 24. doi: 10.1038/s41390-024-03601-w.
Bronchopulmonary dysplasia (BPD) in extremely low gestational age neonates (ELGANs) was associated with neurodevelopmental impairment (NDI). However, the best endpoint of BPD assessment to predict subsequent NDI remains unclear.
We re-analyzed the PREMILOC trial, previously designed to test the effect of prophylactic hydrocortisone on survival without BPD at 36 weeks of postmenstrual age (BPD) in ELGANs, to compare predictive models of NDI considering baseline characteristics, respiratory course up to and BPD status at 36 or 40 weeks of postmenstrual age (BPD/BPD).
Among 404/519 (77.8%) infants enrolled in the trial alive at 2 years of age, all neurocognitive scores were available for 302 (74.8%) patients. Gestational diabetes and sex were identified as the only statistically significant baseline predictors of NDI. Adding BPD to this baseline model was found to be superior to predict NDI compared to BPD, leading to a mean difference of the developmental quotient of -6.7 points (95% confidence interval: -10.0 to -3.50, P < 0.001). The prophylactic hydrocortisone treatment effect on survival without BPD was found to be highly significant (OR = 2.08 [95% confidence interval: 1.36 to 3.17], P < 0.001).
These data suggest a better accuracy of BPD to predict NDI in ELGANs, an important finding for future clinical trials and research in drug development.
EudraCT number 2007-002041-20, ClinicalTrial.gov number, NCT00623740.
The best endpoint to assess BPD as a surrogate to predict neurocognitive impairment in infants born extremely preterm remains unclear. This study strongly suggests a better discriminative value of BPD as assessed at 40 weeks of postmenstrual age (instead of 36 weeks) to predict neurocognitive impairments at 2 years of age in children born extremely preterm. This study supports the switch up to 40 weeks of the primary outcome chosen in future clinical trials designed to prevent BPD. Our data also provide evidence of the beneficial effect of HC on preventing BPD at full-term equivalent age.
极早早产儿（ELGANs）的支气管肺发育不良（BPD）与神经发育障碍（NDI）相关。然而，用于预测后续NDI的BPD评估的最佳终点仍不明确。
我们重新分析了PREMILOC试验，该试验先前旨在测试预防性氢化可的松对ELGANs在月经龄36周时无BPD存活的影响，以比较考虑基线特征、直至月经龄36或40周时的呼吸过程及BPD状态（BPD/无BPD）的NDI预测模型。
在试验中登记的404/519名（77.8%）2岁时存活的婴儿中，302名（74.8%）患者的所有神经认知评分均可用。妊娠期糖尿病和性别被确定为NDI仅有的具有统计学意义的基线预测因素。与无BPD相比，在该基线模型中加入BPD被发现更能预测NDI，导致发育商平均差异为-6.7分（95%置信区间：-10.0至-3.50，P<0.001）。预防性氢化可的松治疗对无BPD存活的效果被发现具有高度显著性（OR=2.08[95%置信区间：1.36至3.17]，P<0.001）。
这些数据表明BPD在预测ELGANs的NDI方面具有更高的准确性，这对未来临床试验和药物研发研究是一项重要发现。
欧洲药品管理局临床试验注册号2007-002041-20，美国国立医学图书馆临床试验注册号NCT00623740。
评估BPD作为预测极早早产儿神经认知障碍替代指标的最佳终点仍不明确。本研究强烈表明，月经龄40周（而非36周）时评估的BPD对预测极早早产儿2岁时的神经认知障碍具有更好的判别价值。本研究支持在未来旨在预防BPD的临床试验中，将主要结局改为40周。我们的数据还提供了氢化可的松在足月等效年龄预防BPD有益作用的证据。
