This case report describes a rare instance of heart failure temporally associated with the administration of mydriatic eye drops during routine retinopathy of prematurity screening. A 36-week-old preterm infant developed acute tachypnea, tachycardia, and hepatomegaly shortly after receiving 0.5% tropicamide and 0.5% phenylephrine, and was subsequently diagnosed with heart failure, which responded well to intravenous deslanoside. Cardiac imaging later revealed multiple congenital anomalies, including an atrial septal defect, persistent left superior vena cava, and horseshoe lung, among others. No similar cardiovascular symptoms were observed during a subsequent screening using tropicamide alone, suggesting that phenylephrine may have contributed to the observed hemodynamic instability. This case illustrates the potential for severe cardiovascular complications associated with mydriatic agents in neonates with undiagnosed congenital heart defects. It underscores the need for individualized risk assessment, vigilant monitoring, and cautious application of mydriatic protocols to ensure patient safety in high-risk preterm populations.

Purpose:To investigate the current incidence, risk factors and treatment for severe retinopathy of prematurity (ROP) in very preterm infants in China. Methods:This was a descriptive, retrospective cohort study. The study population was very preterm infants admitted to one of the 70 neonatal intensive care units (NICUs) in the Chinese Neonatal Network who underwent ROP screening between January 2019 and December 2020. The primary outcome was severe ROP, defined as type 1 or type 2 ROP. Potential risk factors were identified based on prior evidence and statistical significance. Adjusted odds ratios with 95% confidence intervals were calculated using a multivariable multinomial logistic regression model. Results:This study included 14,670 very preterm infants, among which 17.3% had low-grade ROP, and 8.5% had severe ROP. Treatment was performed in 1,381 (4.7%) eyes of the infants, among which 1,029 (74.5%), 148 (10.7%), and 124 (9.0%) received intravitreal anti-vascular endothelial growth factor injection only, laser treatment only, and vitreoretinal surgery, respectively. Extremely preterm birth (7.61, 95% CI: 6.12-9.46), small for gestational age (SGA; 2.31, 95% CI: 1.71-3.12), outborn status (1.43, 95% CI: 1.22-1.67), 1-min Apgar score < 7 (1.30, 95% CI: 1.11-1.51), >40 days on oxygen (1.70, 95% CI: 1.37-2.10), >28 days on parenteral nutrition (PN; 1.17, 95% CI: 1-1.35), and any inotropes use (2.12, 95% CI: 1.82-2.46) were associated with increased odds of severe ROP. Antenatal steroid use (0.77, 95% CI: 0.66-0.91), large for gestational age (LGA; 0.62, 95% CI: 0.45-0.85), and surfactant treatment (0.75, 95% CI: 0.64-0.87) were associated with reduced odds of severe ROP. Conclusion:The incidence of severe ROP in very preterm infants in China was high compared to the developed countries, and intravitreal anti-VEGF injection was the preferred treatment for severe ROP.

BACKGROUND:The variety of shocks in neonates, if not recognized and treated immediately, is a major cause for fatality. The use of echocardiography may improve assessment and treatment, but its reference values across gestational age (GA) and birth weight (BW) are lacking. To address the information gap, this study aimed at correlating GA and BW of newborns with nonhemodynamic abnormalities, and at evaluating the usefulness of such reference values in neonates with early onset septic (EOS) -shock. METHODS:A total of 200 normal newborns were enrolled as controls and subdivided into groups based on GA, BW, days of age, and patent ductus arteriosus (PDA). Echocardiography was used to document inferior vena cava diameter (IVC), inferior vena cava collapsibility index (IVC-CI), and inferior vena cava to abdominal aorta ratio (IVC/AO). In addition, 18 neonates with EOS shock were recruited and evaluated using echocardiography. RESULTS:Among the control newborns, IVC and AO were significantly increased with GA and BW (P < 0.05) but IVC-CI and IVC/AO did not correlate with GA, BW, day of age, and PDA. Compared to the control group, the EOS-shock group had significantly decreased IVC and IVC/AO, and increased IVC-CI (P < 0.05). The cut-off values for indicating EOS-shock were > 34.15% for IVC-CI, < 47.58% for IVCmin/AO, and < 66.11% for IVCmax/AO. CONCLUSIONS:The IVC-CI, IVCmin/AO, and IVCmax/AO indices are applicable to all neonates. Although the number of neonates with EOS-shock in our study is small, the cut-off values showed usefulness for diagnosis. Further research is needed to determine the application of the indices in a larger population and among other populations, especially for clinical application in treatment of shock among neonates.

Background Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. Methods VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. Results Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P -values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (β = 0.6, 95%CI:0.1, 1.0; P = 0.01). Conclusions The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. Trial registration This study was registered on ClinicalTrials.gov (NCT04283799).

Objective We aimed to investigate the relationship between admission hypothermia and outcomes among very preterm infants (VPIs) in neonatal intensive care units (NICUs) in China. We also investigated the frequency of hypothermia in VPIs in China and the variation in hypothermia across Chinese Neonatal Network (CHNN) sites. Study Design This retrospective cohort study enrolled infants with 240/7 to 316/7 weeks of gestation with an admission body temperature ≤37.5 °C who were admitted to CHNN-participating NICUs between January 1 and December 31, 2019. Results A total of 5,913 VPIs were included in this study, of which 4,075 (68.9%) had hypothermia (<36.5 °C) at admission. The incidence of admission hypothermia varied widely across CHNN sites (9–100%). Lower gestational age (GA), lower birth weight, antenatal steroid administration, multiple births, small for GA, Apgar scores <7 at the 5th minute, and intensive resuscitation were significantly associated with admission hypothermia. Compared with infants with normothermia (36.5–37.5 °C), the adjusted odds ratios (ORs) for composite outcome among infants with admission hypothermia <35.5 °C increased to 1.47 (95% confidence interval [CI], 1.15–1.88). The adjusted ORs for mortality among infants with admission hypothermia (36.0–36.4 and <35.5 °C) increased to 1.41 (95% CI, 1.09–1.83) and 1.93 (95% CI, 1.31–2.85), respectively. Admission hypothermia was associated with a higher likelihood of bronchopulmonary dysplasia, but was not associated with necrotizing enterocolitis ≥stage II, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. Conclusion Admission hypothermia remains a common problem for VPIs in a large cohort in China and is associated with adverse outcomes. Continuous quality improvement of admission hypothermia in the future may result in a substantial improvement in the outcomes of VPIs in China. Key Points

The objective of this study was to assess the relationship of ACS with neonatal outcomes among very preterm infants born to mothers with clinical chorioamnionitis in China. This was a multicenter retrospective cohort study. Study participants included infants born at <32 weeks’ gestation with clinical chorioamnionitis and registered in the Chinese Neonatal Network from 1 January 2019 to 31 December 2020. Infants were divided into two groups: any amount of ACS or no administration of ACS. Multivariable generalized linear models using generalized estimating equations were used to assess the association between ACS and neonatal outcomes among the study population. We identified 2193 infants eligible for this study; 1966 (89.6%) infants had received ACS therapy, and 227 (10.4%) had not received any ACS therapy. Among very preterm infants born to mothers with clinical chorioamnionitis, any ACS usage was significantly associated with decreased risks of early death (aRR 0.56, 95% CI 0.32, 0.99) and severe ROP (aRR 0.51, 95% CI 0.28, 0.93) after adjustment for maternal hypertension, gestational age at birth, Caesarean section, being inborn, and administration of systemic antibiotics to the mother within 24 h before birth. In addition, out of the 2193 infants, the placentas of 1931 infants underwent pathological examination with recorded results. Subsequently, 1490 of these cases (77.2%) were diagnosed with histological chorioamnionitis. In 1490 cases of histologic chorioamnionitis, any ACS usage was significantly related to decreased risks of overall mortality (aRR 0.52, 95% CI 0.31, 0.87), severe ROP (aRR 0.47, 95% CI 0.25, 0.97), and respiratory distress syndrome (aRR 0.52, 95% CI 0.31, 0.87). We concluded that any ACS was associated with reduced risks for neonatal early death and severe ROP among very preterm infants born to mothers with clinical chorioamnionitis.

Background Shock is a potentially fatal condition in neonates that requires timely fluid resuscitation and hemodynamic monitoring. Echocardiography may improve assessment and treatment, but reference values across gestational age (GA) and birth weight (BW) are lacking. This study aimed to correlate key indicators with GA and BW of newborns with nonhemodynamic abnormalities, provide corresponding reference ranges, and evaluate them in neonates with early onset septic (EOS) -shock. Methods A total of 200 control group newborns were enrolled, and the inferior vena cava diameter (IVC), inferior vena cava collapse index (IVC-CI), and inferior vena cava to abdominal aorta ratio (IVC/AO) were recorded using echocardiography. Neonates were grouped based on GA, BW, days of age, and patent ductus arteriosus (PDA). 18 cases of neonatal EOS shock were also monitored using echocardiography. Results IVC and AO significantly increased with GA and BW (P < 0.05). IVC-CI and IVC/AO did not correlate with GA, BW, day of age, and PDA. Compared to control group, the EOS-shock group had significantly decreased IVC and IVC/AO and increased IVC-CI (P < 0.05). Cut-off values for indicating EOS-shock were > 34.15% for IVC-CI, < 47.58% for IVCmin/AO, and < 66.11% for IVCmax/AO. Conclusions IVC-CI, IVCmin/AO, and IVCmax/AO are applicable to all neonates. Although the number of neonates with EOS-shock is limited, the cut-off values still show certain diagnostic value. Further research is needed to determine the universality of the population and the role in the diagnosis and treatment of shock in neonates.

BackgroundThe neonatal outcomes across different percentiles of birth weight for gestational age are still unclear.MethodsThis retrospective cohort study was conducted within 57 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 25 provinces throughout China. Infants with gestational age (GA) 24+0-31+6 weeks who were admitted within 7 days after birth were included. The composite outcome was defined as mortality or any one of neonatal major morbidities, including necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (cPVL), severe retinopathy of prematurity (ROP), and sepsis. Multivariable logistic regressions using generalized estimating equation approach were conducted.ResultsA total of 8380 infants were included with a mean GA of 30 (28-31) weeks. Of these, 1373 (16.5%) were born at less than 28 weeks, while 6997 (83.5%) had a GA between 28 and 32 weeks. Our analysis indicated that the risk of composite outcomes was negatively associated with birth weight for gestational age, and compared to the reference group, the multiple-adjusted ORs (95%CI) of composite outcomes were 4.89 (3.51-6.81) and 2.16 (1.77-2.63) for infants with birth weight for gestational less than 10th percentile and 10th -30th percentile, respectively. The ORs (95%CI) of mortality, NEC, BPD, severe ROP, and sepsis in infants with birth weight for gestational age at 10th-30th percentile were 1.94 (1.56-2.41), 1.08 (0.79-1.47), 2.48 (2.03-3.04), 2.35 (1.63-3.39), and 1.39 (1.10-1.77), respectively.ConclusionOur study suggested that the risk of adverse neonatal outcomes increased significantly when the birth weight for gestational age was below the 30th percentile. Regular monitoring and early intervention are crucial for these high-risk infants.

Objective:To analyze the distribution of ages at the interhospital transfer of outborn very preterm infants in China and to compare their perinatal characteristics and outcomes at discharge and neonatal intensive care unit (NICU) treatment.Methods:A total of 3 405 outborn very premature infants with a gestational age of 24-31 +6 weeks who were transferred to the NICUs of the Chinese Neonatal Network (CHNN) in 2019 were included in this retrospective study. According to the age at transfer, they were divided into three groups: early transfer (≤1 d), delayed transfer (>1-7 d) and late transfer (>7 d) groups. Analysis of variance, t-test, Chi-square test (Bonferroni correction), Kruskal-Wallis test and Wilcoxon rank-sum test were used to compare the general clinical condition, treatment, and outcomes at discharge among the three groups. Results:The median gestational age was 29.7 weeks (28.3-31.0 weeks) and the average birth weight was (1 321.0 ± 316.5) g for these 3 405 infants. There were 2 031 patients (59.6%) in the early transfer group, 406 (11.9%) in the delayed transfer group and 968 (28.4%) in the late transfer group. Infants who received continuous positive airway pressure ventilation and tracheal intubation in the delivery room accounted for 8.4% (237/2 806) and 32.9% (924/2 805), respectively. A total of 62.7% (1 569/2 504) of the mothers received antenatal glucocorticoid therapy and the ratio in the early transfer group was 68.7% (1 121/1 631), which was higher than that in the delayed transfer group [56.1% (152/271), χ2=16.78, P<0.017] and the late transfer group [49.2% (296/602), χ2=72.56, P<0.017]. The total mortality rate of very premature infants was 12.7% (431/3 405), and the mortality rates in the early, delayed and late transfer groups were 12.4% (252/2 031), 16.3% (66/406) and 11.7% (113/968), respectively ( χ2=5.72, P=0.057). The incidences of severe intraventricular hemorrhage, late-onset sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge were all higher in the delayed and late transfer groups than in the early transfer group, respectively. The incidences of retinopathy of prematurity, retinopathy of prematurity requiring treatment and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge in the late transfer group were significantly higher than that in the delayed transfer group (Bonferroni correction, all P<0.017). In the late transfer group, the median age of very premature infants at discharge was 66.0 d (51.0-86.0 d), and the corrected gestational age at discharge was 38.9 weeks (37.1-41.2 weeks), and both were greater than those in the early transfer [48.0 d (37.0-64.0 d), Z=260.83; 36.9 weeks (35.7-38.3 weeks), Z=294.32] and delayed transfer groups [52.0 d (41.0-64.0 d), Z=81.49; 37.4 weeks (36.1-38.7 weeks), Z=75.97] (all P<0.017). Conclusions:Many very premature infants need to be transferred to higher-level hospitals after birth. The later the very premature infants are transferred, the higher the incidence of complications will be. It is suggested that intrauterine or early postnatal transport may improve the prognosis of very premature infants.

This multicenter retrospective study was conducted to explore the effects of different courses and durations of invasive mechanical ventilation (MV) on the respiratory outcomes of very low birth weight infants (VLBWI) in China. The population for this study consisted of infants with birth weight less than 1500 g needing at least 1 course of invasive MV and admitted to the neonatal intensive care units affiliated with the Chinese Neonatal Network within 6 h of life from January 1st, 2019 to December 31st, 2020. Univariate and multivariate logistic regression analyses were performed to evaluate associations between invasive MV and respiratory outcomes. Adjusted odds ratios (ORs) were computed with the effects of potential confounders. (1) Among the 3183 VLBWs with a history of at least one course of invasive MV, 3155 (99.1%) met inclusion criteria and were assessed for the primary outcome. Most infants received one course (76.8%) and a shorter duration of invasive MV (62.16% with ventilation for 7 days or less). (2) In terms of the incidence of all bronchopulmonary dysplasia (BPD) (mild, moderate, and severe BPD), there were no significant differences between different invasive MV courses [For 2 courses, adjusted OR = 1.11 (0.88, 1.39); For 3 courses or more, adjusted OR = 1.07 (0.72, 1.60)]. But, with the duration of invasive MV prolonging, the OR of BPD increased [8–21 days, adjusted OR = 1.98 (1.59, 2.45); 22–35 days, adjusted OR = 4.37 (3.17, 6.03); ≥ 36 days, adjusted OR = 18.44 (10.98, 30.99)]. Concerning severe BPD, the OR increased not only with the course of invasive MV but also with the duration of invasive MV [For 2 courses, adjusted OR = 2.17 (1.07, 4.40); For 3 courses or more, adjusted OR = 2.59 (1.02, 6.61). 8–21 days, adjusted OR = 8.42 (3.22, 22.01); 22–35 days, adjusted OR = 27.82 (9.08, 85.22); ≥ 36 days, adjusted OR = 616.45 (195.79, > 999.999)]. (3) When the interaction effect between invasive MV duration and invasive MV course was considered, it was found that there were no interactive effects in BPD and severe BPD. Greater than or equal to three courses would increase the chance of severe BPD, death, and the requirement of home oxygen therapy. Compared with distinct courses of invasive MV, a longer duration of invasive MV (> 7 days) has a greater effect on the risk of BPD, severe BPD, death, and the requirement of home oxygen therapy.

AbstractBackgroundThe prevalence of preterm birth has been rising, and there is a paucity of nationwide data on the perinatal characteristics and neonatal outcomes of twin deliveries of very preterm infants (VPIs) in China. This study compared the perinatal characteristics and outcomes of singletons and twins admitted to neonatal intensive care units (NICUs) in China.MethodsThe study population comprised all infants born before 32 weeks in the Chinese Neonatal Network (CHNN) between January 2019 and December 2019. Three-level and population-average generalized estimating equation (GEE)/alternating logistic regression (ALR) models were used to determine the association of twins with neonatal morbidities and the use of NICU resources.ResultsDuring the study period, there were 6634 (71.2%) singletons and 2680 (28.8%) twins, with mean birth weights of 1333.70 g and 1294.63 g, respectively. Twins were significantly more likely to be delivered by caesarean section (p < 0.01), have antenatal steroid usage (p = 0.048), have been conceived by assisted reproductive technology (ART) (p < 0.01), have a higher prevalence of maternal diabetes (p < 0.01) and be inborn (p < 0.01) than singletons. In addition, twins had a lower prevalence of small for gestational age, maternal hypertension, and primigravida mothers than singletons (allp < 0.01). After adjusting for potential confounders, twins had higher mortality rates (adjusted odds ratio [AOR] 1.28, 95% confidence interval [CI] 1.10–1.49), higher incidences of short-term composite outcomes (AOR 1.28, 95% CI 1.09–1.50), respiratory distress syndrome (RDS) (AOR 1.30, 95% CI 1.12–1.50), and bronchopulmonary dysplasia (BPD) (AOR 1.10, 95% CI 1.01–1.21), more surfactant usage (AOR 1.22, 95% CI 1.05–1.41) and prolonged hospital stays (adjusted mean ratio 1.03, 95% CI 1.00–1.06), compared to singletons.ConclusionOur work suggests that twins have a greater risk of mortality, a higher incidence of RDS and BPD, more surfactant usage, and longer NICU stays than singletons among VPIs in China.

F-box and WD repeat domain containing 10 (FBXW10) is a member of the FBXW subgroup that contains the WD40 domain. FBXW10 has been rarely reported in colorectal cancer (CRC) and its mechanism is unclear. To investigate the role of FBXW10 in CRC, we conducted in vitro and in vivo experiments. Through the database and our clinical samples, we found that FBXW10 expression was up-regulated in CRC, and it was positively correlated with CD31 expression. CRC patients with high FBXW10 expression levels had a poor prognosis. Overexpression of FBXW10 up-regulated cell proliferation, migration and vascular formation, while knockdown of FBXW10 had the opposite effects. Studies on the mechanism of FBXW10 in CRC showed that FBXW10 could ubiquitinate large tumor suppressor kinase 2 (LATS2) and promote its degradation with the Fbox region of FBXW10 played an essential role in this process. In vivo studies demonstrated that knockout of FBXW10 inhibited tumor proliferation and reduced liver metastasis. In conclusion, our study proved that FBXW10 was significantly overexpressed in CRC and was involved in the pathogenesis of CRC by affecting angiogenesis and liver metastasis. Mechanistically, FBXW10 degraded LATS2 through ubiquitination. Therefore, FBXW10-LATS2 can be used as a therapeutic target for CRC in subsequent studies.

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.

Background Maternal systemic lupus erythematosus (SLE) is at greater risk of pregnancy complications and is associated with increased risk of preterm delivery. However hardly any study has looked at the influence of SLE on the outcomes of preterm infants. This study aimed to explore the influence of SLE on the outcomes of preterm infants. Methods In this retrospective cohort study, preterm infants born to mothers with SLE from Shanghai Children’s Medical Center during 2012 to 2021 were enrolled. Infants were excluded if they were died during hospitalization or has major congenital anomalies and neonatal lupus. Exposure was defined as mother diagnosed SLE before or during pregnancy. Maternal SLE group was matched with Non-SLE group by gestational age, birth weight and gender. Clinical data has been extracted from patients’ records and registered. Major morbidities of premature and biochemical parameters in the two groups were compared using multiple logistic regression. Results One hundred preterm infants born to 95 mothers with SLE were finally enrolled. The mean (standard deviation) of gestational age and birth weight were 33.09 (7.28) weeks and 1768.50 (423.56) g respectively. There was no significant difference in major morbidities between SLE group and non-SLE group. Compared with non-SLE group, SLE off-spring had significantly lower leukocytes, neutrophiles after birth, neutrophils and platlet in one week (mean difference: -2.825, -2.001, -0.842, -45.469, respectively). Among SLE group, lower birth weight and smaller gestational age were observed in SLE mothers with disease active during pregnancy, kidney involved, blood system involved and not taking Aspirin during pregnancy. In the multivariable logistic regression analysis, exposure to aspirin during pregnancy reduced the risk of very preterm birth and increased the incidence of survive without major morbidities among preterm infants born to SLE mothers. Conclusion Born to mothers with SLE may not increase the risk of major premature morbidities, but the hematologic profile of SLE preterm infants may be different from preterm infants born to women without SLE. The outcome of SLE preterm infants is associated with maternal SLE status and may benefit from maternal aspirin administration.

Lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) is a transcription factor that activates the transcription of TNF-α and regulates the inflammatory response. LITAF has been found to have potential anti-cancer effects of in several tumors. However, the role of LITAF in colorectal cancer (CRC) remains unclear. Through a comprehensive pan-cancer analysis of the Cancer Genome Atlas (TCGA), LITAF was identified as a differentially downregulated gene in CRC. We hypothesized that LITAF may participate in the modulation of CRC progression. The present study was aimed to investigate the expression profile of LITAF in CRC and its effect on metastatic behavior and stemness as well as the underlying molecular mechanism. The expression profile of LITAF in CRC, and its relationship with the prognosis of CRC were explored using public databases. LITAF expression was detected by quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry. Furthermore, the effects of overexpression or knockdown of LITAF on cell proliferation, apoptosis, migration, invasion, and stemness of CRC cells were investigated in vitro. The regulatory effect of LITAF on forkhead Box O 1 (FOXO1)-sirtuin 1 (SIRT1) signaling axis was also explored. In addition, a xenograft mouse model was used to investigate the in-vivo role of LITAF. LITAF was downregulated in tumor tissues and its expression was associated with the prognosis, pathological stage and liver metastasis. In-vitro experiments confirmed that LITAF inhibited tumor cell proliferation, migration, invasion and stemness, and induced cell apoptosis. In vivo experiments demonstrated that LITAF inhibited the tumorigenicity and liver metastasis in tumor-bearing mice. Additionally, LITAF promoted FOXO1-mediated SIRT1 inhibition, thus regulating cancer stemness and malignant phenotypes. LITAF was silenced in CRC and it participated in the progression of CRC by inhibiting CRC cell stemness, and malignant phenotypes. Therefore, LITAF may serve as a novel biomarker of CRC prognosis.

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.

Background The aim of this study was to review current delivery room (DR) resuscitation intensity in Chinese tertiary neonatal intensive care units and to investigate the association between DR resuscitation intensity and short-term outcomes in preterm infants born at 24 +0 –31 +6 weeks’ gestation age (GA). Methods This was a retrospective cross-sectional study. The source population was infants born at 24 +0 –31 +6 weeks’ GA who were enrolled in the Chinese Neonatal Network 2019 cohort. Eligible infants were categorized into five groups: (1) regular care; (2) oxygen supplementation and/or continuous positive airway pressure (O 2 /CPAP); (3) mask ventilation; (4) endotracheal intubation; and (5) cardiopulmonary resuscitation (CPR). The association between DR resuscitation and short-term outcomes was evaluated by inverse propensity score-weighted logistic regression. Results Of 7939 infants included in this cohort, 2419 (30.5%) received regular care, 1994 (25.1%) received O 2 /CPAP, 1436 (18.1%) received mask ventilation, 1769 (22.3%) received endotracheal intubation, and 321 (4.0%) received CPR in the DR. Advanced maternal age and maternal hypertension correlated with a higher need for resuscitation, and antenatal steroid use tended to be associated with a lower need for resuscitation ( P < 0.001). Severe brain impairment increased significantly with increasing amounts of resuscitation in DR after adjusting for perinatal factors. Resuscitation strategies vary widely between centers, with over 50% of preterm infants in eight centers requiring higher intensity resuscitation. Conclusions Increased intensity of DR interventions was associated with increased mortality and morbidities in very preterm infants in China. There is wide variation in resuscitative approaches across delivery centers, and ongoing quality improvement to standardize resuscitation practices is needed.

Objectives: Exposure to air pollution is associated with increased risks of several adverse conditions in newborns, such as preterm birth. Whether air pollution is associated with neonatal hyperbilirubinemia remains unclear. We aimed to develop and validate an air-quality-based model to better predict neonatal hyperbilirubinemia. Methods: A multicenter, population-based cohort of neonates with a gestational age (GA) >= 35 weeks and birth weight >= 2000 g was enrolled in the study. The study was conducted in Shanghai, China, from July 2017 to December 2018. The daily average concentrations of particulate matter (PM) with aerodynamic diameters <= 2.5 mu m (PM2.5) and <= 10 mu m (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2) and carbon monoxide (CO) were measured. Neonatal hyperbilirubinemia was diagnosed according to the American Academy of Pediatrics (AAP) guidelines by trained neonatologists. We used logistic least absolute shrinkage and selection operator (LASSO) regression to screen air pollutant indicators related to neonatal hyperbilirubinemia and build an air-quality signature for each patient. An air-quality-based nomogram was then established to predict the risk of neonatal hyperbilirubinemia. Results: A total of 11196 neonates were evaluated. Prenatal PM10, CO and NO2 exposure and postpartum SO2 exposure were significantly associated with neonatal hyperbilirubinemia. The air-quality score was calculated according to the hyperbilirubinemia-related pollutants. The air-quality score of the hyperbilirubinemia group was significantly higher than that of the nonhyperbilirubinemia group (P < .01, odds ratio = 2.97). An airquality-based logistic regression model was built and showed good discrimination (C-statistic of 0.675 [95% CI (confidence interval), 0.658 to 0.692]) and good calibration. Decision curve analysis showed that the air-quality-based model was better than the traditional clinical model in predicting neonatal hyperbilirubinemia. Conclusions: The findings of this study suggest that ambient air pollution exposure is associated with an increased risk of neonatal hyperbilirubinemia. Our results encourage further exploration of this possibility in future studies.

Background This study aimed to describe length of stay (LOS) to discharge and site variations among very preterm infants (VPIs) admitted to 57 Chinese neonatal intensive care units (NICUs) and to investigate factors associated with LOS for VPIs. Methods This retrospective multicenter cohort study enrolled all infants < 32 weeks’ gestation and admitted to 57 NICUs which had participated in the Chinese Neonatal Network, within 7 days after birth in 2019. Exclusion criteria included major congenital anomalies, NICU deaths, discharge against medical advice, transfer to non-participating hospitals, and missing discharge date. Two multivariable linear models were used to estimate the association of infant characteristics and LOS. Results A total of 6580 infants were included in our study. The overall median LOS was 46 days [interquartile range (IQR): 35–60], and the median corrected gestational age at discharge was 36 weeks (IQR: 35–38). LOS and corrected gestational age at discharge increased with decreasing gestational age. The median corrected gestational age at discharge for infants at 24 weeks, 25 weeks, 26 weeks, 27–28 weeks, and 29–31 weeks were 41 weeks, 39 weeks, 38 weeks, 37 weeks and 36 weeks, respectively. Significant site variation of LOS was identified with observed median LOS from 33 to 71 days in different hospitals. Conclusions The study provided concurrent estimates of LOS for VPIs which survived in Chinese NICUs that could be used as references for medical staff and parents. Large variation of LOS independent of infant characteristics existed, indicating variation of care practices requiring further investigation and quality improvement.

Background: The population of China represents about one sixth of the global population. It is important to create a national database with a large sample size and a sustained collaborative platform. The objective of this study was to introduce the Chinese Neonatal Network (CHNN), a new platform of national collaboration on quality improvement (QI) for short and long-term health outcomes of preterm infants. Methods: The background, participating centers, data collection, and objectives are described. Specific objectives are to: (I) Establish a standardized database of very preterm infants (VPI) with gestational age <32 weeks or birth weight (BW) <1,500 grams. (II) Assess, benchmark and monitor major outcomes of VPI and their risk determinants, as well as inter-institutional variations. (III) Implement the Evidencebased Practice for Improving Quality (EPIQ) program to improve quality of care and outcomes. (IV) Conduct collaborative research, including epidemiologic, clinical and health services studies and randomized controlled trials. This study is collaboratively funded by Canadian Institute of Health Research and the Children's Hospital of Fudan University. Results: The CHNN collaboration acts as a platform that member neonatal intensive care units (NICUs) can access for evidence on implementing practice improvements, learning activities, and research collaborations. There were 58 participating centers in 2018, which was expanded to be 79 in 2021. CHNN has published 2 annual reports to describe the outcomes and care practices of VPI in 2019 and 2020, and conducted an internal audit of data quality. Conclusions: The knowledge generated will be available nationally and worldwide with a definite national impact and a likely global impact.