Antioxidants ; therapeutic use ; Humans ; Infant, Newborn ; Oxygen Inhalation Therapy ; Persistent Fetal Circulation Syndrome ; drug therapy ; metabolism ; Reactive Oxygen Species ; metabolism

OBJECTIVES: To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO). METHODS: A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk. RESULTS: A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO (HR=8.500, 95%CI: 3.024-23.887, P<0.001), 1-minute Apgar score ≤3 points (HR=10.094, 95%CI: 2.577-39.534, P=0.001), a low value of minimum PaO₂/FiO₂ within 12 hours after admission (HR=0.067, 95%CI: 0.009-0.481, P=0.007), and a low value of minimum pH within 12 hours after admission (HR=0.049, 95%CI: 0.004-0.545, P=0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO₂/FiO₂ value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2. CONCLUSIONS Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO₂/FiO₂ value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage.
Administration, Inhalation ; Child ; Humans ; Hypertension, Pulmonary/drug therapy* ; Infant ; Infant, Newborn ; Nitric Oxide ; Persistent Fetal Circulation Syndrome/drug therapy* ; Retrospective Studies ; Risk Factors

Persistent pulmonary hypertension of the newborn infant (PPHN), is a clinical syndrome characterized by elevated pulmonary vascular resistance, resulting from reactive vasoconstriction or structural remodeling of the pulmonary vasculature. Although inhaled nitric oxide (iNO) has emerged as a novel selective treatment of PPHN, responses to iNO are variable according to the etiologies or the clinical situation. A retrospective chart review of 51 newborn infants with PPHN and treated with iNO, was undertaken to evaluate the factors affecting response to iNO. Response to iNO was defined as a reduction in the oxygenation index (OI) of more than 20%, or disappearance of the difference in oxygen saturation between preductal and postductal circulation after iNO therapy. The patients were divided into two groups; the responder group and the non- responder group. Respiratory distress syndrome (RDS) was more commonly associated with PPHN in the responder group than in the non-responder group (p < 0.05), while there were many more patients with congenital diaphragmatic hernia (CDH) in the non-responder group than in the responder group (p < 0.05). Infants with meconium aspiration syndrome (MAS) were similar in both of the two groups. Initial OI, initial mean airway pressure (MAP), and initial and peak NO concentration were significantly lower in the responder group compared to the non-responder group (p < 0.05). Rapid response (response to iNO within the first hour) was shown in 74% of the responder group and 33% of the nonresponder group (p < 0.05). There was no significant differences in the initial chest radiographic findings, such as normal, focal or bilateral diffuse infiltration, with the exception of CDH, between each group. Lower initial OI, lower initial MAP and significant response within the first hour were shown to be favourable factors in response to iNO therapy. Patients with RDS associated with PPHN responded much better to iNO than those with other diseases.
Administration, Inhalation ; Female ; Human ; Infant, Newborn ; Male ; Nitric Oxide/*administration & dosage ; Persistent Fetal Circulation Syndrome/*drug therapy/radiography ; Retrospective Studies ; Treatment Outcome ; Vascular Resistance/drug effects

Combined Modality Therapy ; High-Frequency Ventilation ; methods ; Humans ; Infant, Newborn ; Nitric Oxide ; administration & dosage ; Persistent Fetal Circulation Syndrome ; drug therapy ; Pulmonary Surfactants ; administration & dosage

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*