OBJECTIVETo characterize recent trends of nosocomial infection (NI) among preterm infants admitted to Canadian Level 3 NICUs during 2008-2012, and its association with neonatal outcomes.

METHODSA retrospective observational cohort study was performed including infants born <33 weeks gestational age and admitted to 24 NICU sites participating in the Canadian Neonatal NetworkTM during 2008-2012. NICU sites were classified into three groups according to their baseline NI rates in 2008 [Low NI group (≤14%), Medium NI group (14.1%-19%) and High NI group (>19%)], and NICU sites were also classified according to their NI trend during 2008-2012 (decreased, null and increased). Trends in NI were further examined for each baseline-NI group. Trends for a composite outcome indicating mortality or severe morbidities (intraventricular hemorrhage grades≥3 or periventricular leukomalacia, retinopathy of prematurity stages≥3, bronchopulmonary dysplasia or necrotizing enterocolitis stages≥2) were examined for each baseline-NI and trend-NI NICU site groups using multivariable logistic regression analyses adjusted for potential confounders.

RESULTSBaseline high NI group showed significantly decreased trends in NI rates, while for with medium or low baseline NI groups showed no significant trends in NI rates. The composite outcome (mortality during NICU stay or any severe neonatal morbidity such as intraventricular hemorrhage grades 3-4, periventricular leukomalacia, retinopathy of prematurity stages 3-5, bronchopulmonary dysplasia and necrotizing enterocolitis stages 2-3) decreased significantly for sites with decreased (OR=0.89, 95% CI=0.85-0.93) or null (OR=0.94, 95% CI=0.90-0.98) NI trends, but no significant trends in the composite outcome were detected for sites with increased NI rates.

CONCLUSIONSThe neonatal outcome is possibly influenced by NI rates and trend. The trend in the mortality and the risk of bronchopulmonary dysplasia, retinopathy of prematurity stage≥3 and intraventricular hemorrhage>2 were significantly decreased for sites with decreased NI trend, suggesting that these improved outcomes may be associated with effort to decrease NI rate.

Real-world evidence has become the basis for approval and regulation of drugs and medical devices. Real-world study has played a more and more important role with the continuous updating and iteration of medical technologies. The diseases and their underlying mechanisms in the neonatal period, the early stage of life, are significantly different from other stages of life and early high-quality clinical management has a profound impact on the long-term outcomes. Therefore, it is necessary to provide robust evidence for clinical diagnosis and treatment through real-world study. This paper explores the access to high-quality medical care in the neonatal period based on the application, challenges, and thinking of the China Neonatal Network (CHNN) in the real world and the integration of the China Neonatal Genome Project and other multi-omics data.

Objective:To analyze the accuracy of lung ultrasound and chest X-ray in the diagnosis of neonatal pulmonary disease.Methods:We prospectively collected newborns that needed chest X-ray examination to diagnose pulmonary disease from twelve neonatal intensive care units across the country between June 2019 and April 2020.Each newborn was examined by lung ultrasound within two hours after chest X-ray examination.All chest X-ray and lung ultrasound images were independently read by a radiologist and a sonographer.When there was a disagreement, a panel of two experienced physicians made a final diagnosis based on the clinical history, chest X-ray and lung ultrasound images.Results:A total of 1 100 newborns were enrolled in our study.The diagnostic agreement between chest X-ray and lung ultrasound(Cohen′s kappa coefficient=0.347) was fair.Lung ultrasound(area under the curve=0.778; 95% CI 0.753-0.803) performed significantly better than chest X-ray(area under the curve=0.513; 95% CI 0.483-0.543) in the diagnosis of transient tachypnea of the newborn( P<0.001). The accuracy of lung ultrasound in diagnosing neonatal respiratory distress syndrome, meconium aspiration syndrome, pneumonia and neonatal pulmonary atelectasis was similar to that of chest X-ray. Conclusion:Lung ultrasound, as a low-cost, simple and radiation-free auxiliary examination method, has a diagnostic accuracy close to or even better than that of chest X-ray, which may replace chest X-ray in the diagnosis of some neonatal lung diseases.It should be noted that both chest X-ray and lung ultrasound can only be used as auxiliary means for the diagnosis of lung diseases, and it is necessary to combine imaging with the clinical history and presentation.

Objective:To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021.Methods:This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results:Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions:With the increasing number of extremely preterm infants at 22-25 weeks′ gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.

Objective: To investigate the incidence and pathogen distribution of ventilator-associated pneumonia (VAP) among preterm infants admitted to level Ⅲ neonatal intensive care units (NICU) in China. Method: A prospective study was conducted in 25 level Ⅲ NICU, enrolling all preterm infants <34 weeks gestational age admitted to the participating NICU within the first 7 days of life from May 2015 to April 2016. Chi-square test, t test and Mann-Whitney U test were used for statistical analysis. Result: A total of 7 918 patients were enrolled, within whom 4 623(58.4%) were males. The birth weight was (1 639±415) g and the gestational age was (31.4±2.0) weeks; 4 654(58.8%) infants required non-invasive mechanical ventilation and 2 154(27.2%) required intubation. Of all the mechanically ventilated patients, VAP occurred in 95 patients. The overall VAP rate was 7.0 episodes per 1 000 ventilator days, varying from 0 to 34.4 episodes per 1 000 ventilator days in different centers. The incidence of VAP was 9.6 and 6.0 per 1 000 ventilator days in children′s hospitals and maternity-infant hospitals respectively, without significant differences (t=1.002, P=0.327). Gram-negative bacilli (76 strains, 91.6%) were the primary VAP microorganisms, mainly Acinetobacter baumannii (24 strains, 28.9%), Klebsiella pneumonia (23 strains, 27.7%), and Pseudomonas aeruginosa (10 strains, 12.0%). Conclusion The incidence of VAP in China is similar to that in developed counties, with substantial variability in different NICU settings. More efforts are needed to monitor and evaluate the preventable factors associated with VAP and conduct interventions that could effectively reduce the occurrence of VAP.

The Chinese Neonatal Network(CHNN) was established in 2018 with the mission of establishing a national collaboration platform, conducting high-quality and collaborative research, and ultimately improving the quality of neonatal-perinatal care and health in China.At present, 112 hospitals across the country have joined CHNN.CHNN has established a national standardized cohort of very premature infants/very low birth weight infants with >10 000 enrollments each year, has been leading data-driven collaborative quality improvement initiatives, conducting multicenter clinical studies, and performing multi-level training programs.Guided by the principles of collaboration and sharing, data-driven, continuous improvement, and international integration, CHNN has become an important platform for clinical and research collaboration in neonatal medicine in China.

Objective: To describe the use of non-erythrocyte blood products transfusion in very preterm and extremely preterm infants in the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) in 2019, to explore the disparity between different centers, and to further investigate the rationality and standardability of non-erythrocyte blood products transfusion. Methods: This was a cross-sectional study based on the CHNN cohort of very preterm and extremely preterm infants. All 6 598 infants with gestational age (GA)<32 weeks and admitted to the 57 NICU of CHNN within 24 h of life in 2019 were enrolled. Non-erythrocyte blood products included platelet, plasma, albumin, immunoglobulin, cryoprecipitate and prothrombin complex. Infants who received at least one type of non-erythrocyte blood products were defined in transfusion group. The comparison between infants with and without transfusion was done by t-test, rank-sum test or χ² test as appropriate. Linear regression model was used to generate adjusted transfusion rate of each center, and to investigate the correlation between adjusted rate and center-level characteristics. Results: A total of 6 598 infants were enrolled in the study, with gestational age of 30.0 (28.7, 31.0) weeks and birth weight of (1 353±312) g, and 43.6 % (2 877) of them were female. Among them, 42.7% (2 816) infants were enrolled in transfusion group, with the times of transfusion as 3 (1, 6) times. Compared to the infants without any transfusion of non-erythrocyte blood products, those infants received transfusion had lower gestational age (Z=17.62, P<0.01), lower birth weight (t=18.64, P<0.01), higher proportion of small-for-gestation age (χ²=31.06, P<0.01), multiple birth (χ²=12.82, P<0.01) and intensive resuscitation in delivery room (χ²=287.52, P<0.01), as well as lower proportion of females (χ²=10.68, P<0.01) and even lower proportion of infants born in this hospital (χ²=78.23, P<0.01). Among the entire study population, albumin (25.4%, 1 674 cases), immunoglobulin (21.5%, 1 417 cases) and plasma (18.9%, 1 245 cases) were the most commonly used non-erythrocyte blood products. Overall, 60.4% (544/901) infants with gestational age <28 weeks received transfusion 4 (2, 8) times. A total of 39.9% (2 272/5 697) infants between 28-31weeks received non-erythrocyte blood products 3 (1, 6) times. The non-erythrocyte blood products transfusion rates of critically-ill and non-critically-ill infants were 62.2% (1 693/2 723) and 29.0% (1 123/3 875) respectively, and the transfusion times were 4 (2,7) and 2 (1,4) times. The transfusion rates varied significantly among different NICU, and the disparities remained obvious after adjustment (adjusted χ²=153.48, P<0.01). Conclusion: Near half of very preterm and extremely preterm infants admitted to Chinese NICU in 2019 receive non-erythrocyte blood products during hospitalization with significant disparities among different hospitals.
China ; Cross-Sectional Studies ; Female ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Infant, Premature, Diseases ; Intensive Care Units, Neonatal

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*

BACKGROUND: Antenatal corticosteroids (ACS) can significantly improve the outcomes of preterm infants. This study aimed to describe the ACS use rates among preterm infants admitted to Chinese neonatal intensive care units (NICU) and to explore perinatal factors associated with ACS use, using the largest contemporary cohort of very preterm infants in China. METHODS: This cross-sectional study enrolled all infants born at 24 +0 to 31 +6 weeks and admitted to 57 NICUs of the Chinese Neonatal Network from January 1st, 2019 to December 30th, 2019. The ACS administration was defined as at least one dose of dexamethasone and betamethasone given before delivery. Multiple logistic regressions were applied to determine the association between perinatal factors and ACS usage. RESULTS: A total of 7828 infants were enrolled, among which 6103 (78.0%) infants received ACS. ACS use rates increased with increasing gestational age (GA), from 177/259 (68.3%) at 24 to 25 weeks' gestation to 3120/3960 (78.8%) at 30 to 31 weeks' gestation. Among infants exposed to ACS, 2999 of 6103 (49.1%) infants received a single complete course, and 33.4% (2039/6103) infants received a partial course. ACS use rates varied from 30.2% to 100% among different hospitals. Multivariate regression showed that increasing GA, born in hospital (inborn), increasing maternal age, maternal hypertension and premature rupture of membranes were associated with higher likelihood to receive ACS. CONCLUSIONS The use rate of ACS remained low for infants at 24 to 31 weeks' gestation admitted to Chinese NICUs, with fewer infants receiving a complete course. The use rates varied significantly among different hospitals. Efforts are urgently needed to propose improvement measures and thus improve the usage of ACS.
Humans ; Infant, Newborn ; Infant ; Pregnancy ; Female ; Gestational Age ; Infant, Premature ; Intensive Care Units, Neonatal ; Cross-Sectional Studies ; Adrenal Cortex Hormones/therapeutic use*