Analysis of early risk factors of death in preterm infants treated with iNO: a national multicentre retrospective study.

Objective: To analyse early risk factors for mortality in preterm infants treated with inhaled nitric oxide (iNO) in China.

Design: A retrospective observational case-control study.

Setting: 8 tertiary hospitals in 5 regions of China.

Patients: 726 preterm infants treated with iNO for hypoxic respiratory failure or persistent pulmonary hypertension of newborns.

Interventions: None.

Measurements: The primary outcome was survival status at discharge.

Main results: (1) The mortality rate was 27.1% (197/726), and which significantly reduced with increasing gestational age (GA) and birth weight. (2) Compared with the survival group, the death group had significantly greater use of assisted reproductive technology, higher multiple pregnancy rates and lower caesarean section rates. Infants in the death group had a significantly higher incidence of small for GA (SGA), Apgar score ≤3 at 1 min after birth, pneumorrhagia, sepsis and shock. In the death group, the utilisation rate of a pulmonary surfactant (PS) was significantly lower, whereas the oxygenation index (OI) before iNO treatment was significantly higher. The maximum dose of iNO in the death group was significantly higher than that in the survival group. (3) The Cox proportional hazard model showed that SGA (HR 1.800, 95% CI (1.113 to 2.911)), sepsis (HR 1.488, 95% CI (1.093 to 2.027)), shock (HR 1.473, 95% CI (1.033 to 2.100)), OI before iNO treatment (HR 1.016, 95% CI (1.006 to 1.026)) and the maximum dose of iNO treatment (HR 1.070, 95% CI (1.035 to 1.105)) were risk factors for death in preterm infants treated with iNO. Furthermore, GA (HR 0.876, 95% CI (0.831 to 0.924)), PS (HR 0.433, 95% CI (0.296 to 0.633)) and a higher initial dose of iNO (HR 0.926, 95% CI (0.891 to 0.962)) were identified as protective factors. (4) Stratified analysis and sensitivity analysis determined the stability of the core results in preterm infants with GA between 28 and 36⁺⁶ weeks.

Conclusion: Premature infants treated with iNO had a high mortality rate. SGA, sepsis, shock and higher OI before iNO treatment increased the mortality risk in infants with GA between 28 and 36⁺⁶ weeks. A higher GA the use of PS, and a higher initial iNO dose could improve the survival outcome of these babies.

Trial registration number: The study was registered in the Chinese Clinical Trials Registry (http://www.chictr.org.cn; registration number: ChiCTR2200066935).