Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada.
Department of Neonatology, Hospital for Sick Children, Toronto, Ontario, Canada.
Early Hum Dev. 2023 Sep;184:105841. doi: 10.1016/j.earlhumdev.2023.105841. Epub 2023 Aug 2.
To investigate whether immediate response to inhaled nitric oxide (iNO) therapy is associated with reduced mortality in preterm infants with hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH).
A systematic review and meta-analysis of observational studies was conducted to examine the association between immediate response (improved oxygenation ≤6 h) compared to non-response, and all-cause mortality among preterm infants <34 weeks gestational age without congenital anomalies or genetic disorders who received iNO treatment. Adjusted and unadjusted odds ratio, were pooled using a random effects meta-analysis Hartung-Knapp-Sidik-Jonkman approach. Subgroup analyses were planned for infants with preterm premature rupture of membranes (PPROM) and those treated within 72 h after birth.
The primary analysis included 5 eligible studies, a total of 400 infants (196 responders; 204 non-responders). The studies were rated as low to moderate risk of bias based on the Quality in Prognostic Studies tool. Immediate iNO responsiveness was associated with reduced odds of mortality [odds ratio (OR) 0.22, 95 % confidence interval (95 % CI) (0.10-0.49)]. Although there was insufficient data for a subgroup analysis of infants with PPROM, infants treated with iNO within 72 h demonstrated consistent findings of reduced mortality [OR 0.21 95 % CI (0.13-0.36)]. Based on the GRADE approach, considering the risk of bias of included studies, the overall strength of evidence was rated as moderate.
There is evidence to suggest that immediate improvement in oxygenation following iNO therapy is associated with reduced odds of mortality before discharge in preterm infants with HRF and clinically suspected or confirmed PH.
探讨急性一氧化氮吸入（iNO）治疗反应与伴有肺动脉高压（PH）的早产儿低氧性呼吸衰竭（HRF）患儿病死率降低的相关性。
通过系统综述和观察性研究的荟萃分析，来检验 iNO 治疗后即刻反应（氧合改善≤6 h）与无反应早产儿（<34 孕周、无先天畸形或遗传疾病）全因病死率之间的相关性。采用随机效应荟萃分析 Hartung-Knapp-Sidik-Jonkman 法来汇总校正和未校正比值比。计划进行亚组分析，包括胎膜早破（PPROM）患儿和出生后 72 h 内接受治疗的患儿。
主要分析纳入 5 项研究，共 400 例患儿（196 例为反应者；204 例为无反应者）。根据预后研究质量工具（Quality in Prognostic Studies tool），这些研究的偏倚风险被评为低至中度。iNO 即刻反应与病死率降低相关[比值比（OR）0.22，95%置信区间（95%CI）（0.10-0.49）]。尽管没有足够的数据进行 PPROM 患儿的亚组分析，但在 72 h 内接受 iNO 治疗的患儿病死率降低的结果一致[OR 0.21，95%CI（0.13-0.36）]。根据 GRADE 方法，考虑到纳入研究的偏倚风险，总的证据强度被评为中度。
有证据表明，在伴有 HRF 和临床疑似或确诊 PH 的早产儿中，iNO 治疗后氧合的即刻改善与出院前病死率降低相关。
