Spontaneous intestinal perforation among very preterm infants in China: a multicenter cohort study.

Background: Spontaneous intestinal perforation (SIP) is one of the most serious surgical bowel conditions affecting preterm infants. There are limited data on the mortality and morbidities of very preterm infants [VPIs, <32 weeks' gestational age (GA)] with SIP in China. The study aimed to describe the prevalence, treatment, and outcomes of SIP among VPIs in China. Methods: This retrospective cohort study included all infants born at 24+0-31+6 weeks GA from January 1, 2019, to December 31, 2020, and admitted within seven days after birth to the neonatal intensive care units in the Chinese Neonatal Network. The primary outcome was survival without major morbidities. The association between SIP and neonatal outcomes was evaluated using multivariate logistic regression controlling for possible confounders. Results: Out of the 15,814 enrolled infants, 150 (1.0%) developed SIP with a median onset age of four (IQR 2-6) days. Infants with GA 24+0-25+6 weeks had the highest incidence of SIP (13/532, 2.4%), followed by those with GA 26+0-27+6 weeks (22/2,005, 1.1%), 28+0-29+6 weeks (44/5,269, 0.8%) and 30+0-31+6 weeks (71/8,008, 0.9%). Ten SIP cases were lost to follow-up with unknown survival status and 41 (29.3%) of the remaining 140 infants with SIP died during hospitalization. Only 29.3% of infants with SIP survived without major morbidities, significantly lower than those without SIP (59.2%; P<0.01). Multivariate analysis revealed SIP was associated with a higher risk of overall death (adjusted OR 3.36; 95% CI: 1.85 to 6.08), late-onset sepsis (adjusted OR 2.10; 95% CI: 1.02 to 4.31), and bronchopulmonary dysplasia (adjusted OR 2.49; 95% CI: 1.44 to 4.30). Among all infants with SIP, 28 (18.7%) did not receive any surgical intervention. Laparotomy was provided to 113 (92.6%) of the remaining 122 infants, solely (84/122, 68.9%) or following peritoneal drainage (29/122, 23.8%), while nine (7.4%) infants underwent peritoneal drainage only. Conclusions: Around 1% of VPIs in China developed SIP, associated with increased risk of mortality and morbidities. Over 90% of VPIs with SIP underwent laparotomy as initial or subsequent surgical treatment. Effective and evidence-based strategies are needed for the prevention and management of SIP.

Association between Neonatal Outcomes and Admission Hypothermia among Very Preterm Infants in Chinese Neonatal Intensive Care Units: A Multicenter Cohort Study.

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: · Admission hypothermia is common in VPIs.. · The incidence of admission hypothermia in VPIs remains high in China.. · Admission hypothermia is associated with adverse outcomes in VPIs..

Characteristics of red blood cell transfusion among very preterm infants in China.

BACKGROUND AND OBJECTIVES: National-level data on the incidence of red blood cell (RBC) transfusions and outcomes among very preterm infants (VPIs) are lacking in China. This study aims to describe the use and variation of RBC transfusion among VPIs in China. MATERIALS AND METHODS: This cohort study was conducted among 70 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 2019 to 2020 across China. All VPIs admitted to the CHNN neonatal intensive care units (NICUs) were included. RESULTS: A total of 13,447 VPIs were enrolled, of whom 7026 (52.2%) received ≥1 RBC transfusions. The mean number of transfusions per infant was 2 (interquartile range [IQR] 1-4 times) and the median age at first transfusion was 15 days (IQR 3-27 days). The transfusion rate was higher in critically ill infants compared with non-critically ill infants (70.5% vs. 39.3%). The transfusion rate varied widely (13.5%-95.0%) between different NICUs. The prevalence of death, severe intra-ventricular haemorrhage, necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP), sepsis, bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP) and cystic periventricular leukomalacia (cPVL) was significantly higher in the transfused group. Among non-critically ill infants, RBC transfusion was independently associated with BPD, severe ROP and cPVL. CONCLUSION: Our study, providing the first baseline data on RBC transfusions among VPIs in China, shows an alarmingly high RBC transfusion rate with significant site variations. There is an urgent need for national guidelines on RBC transfusions for VPIs in China.

Synergistic effects of achieving perinatal interventions on bronchopulmonary dysplasia in preterm infants.

To investigate the effect of perinatal interventions on the risk of severe BPD (sBPD) and death in extremely preterm infants (EPIs) and their synergistic effects. This was a secondary analysis of the prospective cohort Chinese Neonatal Network (CHNN). Infants with a birth weight of 500 to 1250 g or 24-28 weeks completed gestational age were recruited. The impacts and the synergistic effects of six evidence-based perinatal interventions on the primary outcomes of sBPD and death were assessed by univariate and multivariable logistic regression modeling. Totally, 6568 EPIs were finally enrolled. Antenatal corticosteroid (adjusted OR, aOR, 0.74; 95%CI, 0.65-083), birth in centers with tertiary NICU (aOR, 0.64; 95%CI, 0.57-0.72), preventing intubation in the delivery room (aOR, 0.65; 95%CI, 0.58-0.73), early caffeine therapy (aOR, 0.59; 95%CI, 0.52-0.66), and early extubating (aOR, 0.42; 95%CI 0.37-0.47), were strongly associated with a lower risk of sBPD and death while early surfactant administration was associated with a lower risk of death (aOR, 0.84; 95%CI, 0.72, 0.98). Compared with achieving 0/1 perinatal interventions, achieving more than one intervention was associated with decreased rates (46.6% in 0/1 groups while 38.5%, 29.6%, 22.2%, 16.2%, and 11.7% in 2/3/4/5/6-intervention groups respectively) and reduced risks of sBPD/death with aORs of 0.76(0.60, 0.96), 0.55(0.43, 0.69), 0.38(0.30, 0.48), 0.28(0.22, 0.36), and 0.20(0.15, 0.27) in 2, 3, 4, 5, and 6 intervention groups respectively. Subgroup analyses showed consistent results. CONCLUSION: Six perinatal interventions can effectively reduce the risk of sBPD and death in a synergistic form. WHAT IS KNOWN: • Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease associated with prematurity. The effective management of BPD requires a comprehensive set of interventions. However, the extent to which these interventions can mitigate the risk of severe outcomes, such as severe BPD or mortality, or if they possess synergistic effects remains unknown. WHAT IS NEW: • The implementation of various perinatal interventions, such as prenatal steroids, birth in centers with tertiary NICU, early non-Invasive respiratory support, surfactant administration within 2 hours after birth, early caffeine initiation within 3 days, and early extubation within 7 days after birth has shown promising results in the prevention of severe bronchopulmonary dysplasia (BPD) or mortality in extremely preterm infants. Moreover, these interventions have demonstrated synergistic effects when implemented in combination.

Treatment of patent ductus arteriosus and short-term outcomes among extremely preterm infants: a multicentre cohort study.

Background: The optimal treatment strategy for patent ductus arteriosus (PDA) in extremely preterm infants is currently highly controversial. This study aimed to evaluate the association between PDA treatment and short-term outcomes among extremely preterm infants. Methods: This cohort study included all extremely preterm infants (≤27 and 6/7 weeks) who were admitted to hospitals participating in the Chinese Neonatal Network from January 2019 to December 2021, and were diagnosed to have PDA by echocardiogram. PDA treatment was defined as medical treatment and/or surgical ligation of PDA during hospitalization. Short-term outcomes included death, bronchopulmonary dysplasia (BPD), death/BPD, retinopathy of prematurity, necrotizing enterocolitis, and severe brain injury. Multivariate logistic regression was used to evaluate the association between PDA treatment and outcomes. Subgroup analysis were performed among infants with different respiratory support on 3 and 7 days of life. Findings: A total of 2494 extremely preterm infants with the diagnosis of PDA were enrolled, of which 1299 (52.1%) received PDA treatment. PDA treatment was significantly associated with lower risk of death (adjusted odds ratio, 0.48; 95% confidence interval, 0.38-0.60). The decreased risk of death was accompanied by increased risk of BPD and death/BPD. In subgroup analysis according to respiratory support, PDA treatment was associated with lower risk of death among infants who required invasive ventilation. However, the beneficial effect on death was not significant among infants who did not require invasive ventilation. Interpretation: PDA treatment was associated with reduced mortality in extremely preterm infants, but this beneficial effect was mainly present among infants who required invasive ventilation. Funding: This study was funded by the Shanghai Science and Technology Commission's Scientific and Technological Innovation Action Plan (21Y21900800) and the Canadian Institutes of Health Research (CTP87518).

Effect of different courses and durations of invasive mechanical ventilation on respiratory outcomes in very low birth weight 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.

Impact of Maternal Diabetes Mellitus on Neonatal Outcomes among Infants <32 Weeks of Gestation in China: A Multicenter Cohort Study.

OBJECTIVE: Our study aimed to determine the relationship between maternal diabetes mellitus (MDM) and mortality and major morbidities for very preterm infants, as well as the effects of insulin-treated MDM, in the Chinese population. STUDY DESIGN: This retrospective cohort study included all preterm infants born at 240/7 to 316/7 weeks of gestation and admitted to 57 tertiary neonatal intensive care units participating in the Chinese Neonatal Network in 2019. All infants were followed up until discharging from the hospitals. RESULTS: A total of 9,244 very preterm infants were enrolled, with 1,584 (17.1%) born to mothers with MDM. The rates of mortality or any major morbidity in the MDM and non-MDM groups were 45.9% (727/1,584) and 48.1% (3,682/7,660), respectively. After adjustment, the risk of mortality or any morbidity was not significantly increased in the MDM group (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], 0.94-1.22) compared with the non-MDM group. Among MDM mothers with treatment data, 18.0% (256/1,420) were treated with insulin. Insulin-treated MDM was not independently associated with the risk of mortality or any morbidity (aOR, 1.01; 95% CI, 0.76-1.34) among very preterm infants, but it was associated with an elevated risk of severe retinopathy of prematurity (aOR, 2.39; 95% CI, 1.13-5.04). CONCLUSION: While the MDM diagnostic rate for mothers of very preterm infants was high in China, MDM was not associated with mortality or major morbidities for very preterm infants. KEY POINTS: · A total of 17% of very preterm infants in Chinese neonatal intensive care units were born to mothers with MDM.. · MDM was not related to mortality or major morbidities in very preterm infants.. · MDM treated by insulin was associated with severe retinopathy of prematurity..

Use of narcotics and sedatives among very preterm infants in neonatal intensive care units in China: an observational cohort study.

Background: Narcotics and sedatives are widely used in neonatal intensive care units for very preterm infants. This study aimed to describe the current use of narcotics and/or sedatives among very preterm infants in Chinese neonatal intensive care units, with an emphasis on infants on invasive mechanical ventilation, and to investigate the association of exposure to narcotics and/or sedatives with neonatal outcomes. Methods: This was a retrospective observational cohort study that enrolled all infants born at 24+0-31+6 weeks and admitted to 57 tertiary neonatal intensive care units in the Chinese Neonatal Network in 2019. A multivariate logistic regression model was used to assess the association between narcotics and/or sedatives exposure and major neonatal outcomes. Results: Among 9,442 very preterm infants enrolled, 1,566 (16.6%) received at least one dose of narcotics or sedatives, 111 (1.2%) received only narcotics, 1,301 (13.8%) received sedatives solely, and 154 (1.6%) received both narcotics and sedatives during their hospital stay. Of 4,172 very preterm infants who underwent invasive mechanical ventilation, 1,117 (26.8%) received at least one dose of narcotics or sedatives, with 883 (21.2%) only received sedatives. Significant site variation of narcotics/sedatives use existed among hospitals, with the application rate ranging from 0-72.5% in individual hospital. The narcotics and/or sedatives use by very preterm infants was independently associated with increased risks for periventricular leukomalacia, severe retinopathy of prematurity, and bronchopulmonary dysplasia. Conclusions: Narcotic and/or sedative administration is relatively conservative for very preterm infants in Chinese neonatal intensive care units, with significant variation among hospitals. Since narcotic and sedative use might be related to adverse neonatal outcomes, a pressing and developing need for national quality improvement initiatives is seen with respect to pain/stress management for very preterm infants.

Status of the neonatal follow-up system in China: survey and analysis.

BACKGROUND: There is little information about neonatal follow-up programs (NFUPs) in China. This study aimed to conduct a survey of hospitals participating in the Chinese Neonatal Network (CHNN) to determine the status of NFUPs, including resources available, criteria for enrollment, neurodevelopmental assessments, and duration of follow-up. METHODS: We conducted a descriptive study using an online survey of all 72 hospitals participating in CHNN in 2020. The survey included 15 questions that were developed based on the current literature and investigators' knowledge about follow-up practices in China. RESULTS: Sixty-four (89%) of the 72 hospitals responded to the survey, with an even distribution of children's (31%), maternity (33%) and general (36%) hospitals. All but one (98%) hospital had NFUPs, with 44 (70%) being established after 2010. Eligibility criteria for follow-up were variable, but common criteria included very preterm infants < 32 weeks or < 2000 g birth weight (100%), small for gestational age (97%), hypoxic ischemic encephalopathy (98%) and postsurgery (90%). The average follow-up rate was 70% (range: 7.5%-100%). Only 12% of hospitals followed up with patients for more than 24 months. There was significant variation in neurodevelopmental assessments, follow-up schedule, composition of staff, and clinic facilities and resources. None of the staff had received formal training, and only four hospitals had sent staff to foreign hospitals as observers. CONCLUSIONS: There is significant variation in eligibility criteria, duration of follow-up, types of assessments, staffing, training and facilities available. Coordination and standardization are urgently needed.

Fungal infection and neurodevelopmental outcomes at 18-30 months in preterm infants.

Background: Invasive fungal infection (IFI) is associated with significant mortality and morbidity among preterm infants but there has been no population-based study of long-term neurodevelopmental outcomes. The objective of this study was to examine population-based incidence trends as well as mortality, short term in-hospital morbidity and long-term neurodevelopmental outcomes among preterm infants with IFI, non-fungal infections (NFI) and no infections in Canada. Methods: We conducted a retrospective cohort study of 8,408 infants born at <29 weeks gestational age (GA), admitted to Canadian Neonatal Network neonatal intensive care units (NICU) from April 2009 to December 2017, and followed up at 18-30 months corrected age (CA) in Canadian Neonatal Follow-Up Network clinics. We compared mortality, long term neurodevelopmental outcomes and short term in-hospital morbidity among 3 groups of infants (IFI, NFI, and no infections). Results: The incidence of IFI was 1.3%, non-IFI 26.9% and no infections 71.7%. IFI incidence varied between 0.93% and 1.94% across the study period with no significant trend over time. Infants of higher gestational age were significantly (p < 0.01) less likely to have IFI. Among infants with IFI, NFI and no infections, the incidence of the significant neurodevelopmental impairment (sNDI) was 44.26%, 21.63% and 14.84% respectively, while mortality was 50%, 25.35% and 22.25% respectively. Even after risk adjustment for confounders (GA, Score for Neonatal Acute Physiology Version II, ruptured membranes >24 h, maternal antibiotic treatment, antenatal steroid use, cesarean section), infants with IFI had significantly higher odds of sNDI than NFI (aOR: 2.19; 95% CI: 1.23, 3.91) or no infections (aOR: 2.97; 95% CI: 1.55, 5.71), and higher odds of mortality than NFI (aOR: 1.55; 95% CI: 1.07, 2.26) or no infections (aOR: 1.45; 95% CI: 0.97, 2.17). Conclusions: Preterm infants with invasive fungal infections have significantly higher incidence of mortality and adverse neurodevelopmental outcomes than those with non-invasive fungal infections and no infections.

Early Antibiotic Use and Neonatal Outcomes Among Preterm Infants Without Infections.

OBJECTIVES: To determine whether use, duration, and types of early antibiotics were associated with neonatal outcomes and late antibiotic use in preterm infants without infection-related diseases. METHODS: This cohort study enrolled infants admitted to 25 tertiary NICUs in China within 24 hours of birth during 2015-2018. Death, discharge, or infection-related morbidities within 7 days of birth; major congenital anomalies; and error data on antibiotic use were excluded. The composite outcome was death or adverse morbidities. Late antibiotic use indicated antibiotics used after 7 days of age. Late antibiotic use rate was total antibiotic use days divided by the days of hospital stay after the first 7 days of life. RESULTS: Among 21 540 infants, 18 302 (85.0%) received early antibiotics. Early antibiotics was related to increased bronchopulmonary dysplasia (BPD) (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.05-1.56), late antibiotic use (aOR, 4.64; 95% CI, 4.19-5.14), and late antibiotic use rate (adjusted mean difference, 130 days/1000 patient-days; 95% CI, 112-147). Each additional day of early antibiotics was associated with increased BPD (aOR, 1.07; 95% CI, 1.04-1.10) and late antibiotic use (aOR, 1.41; 95% CI, 1.39-1.43). Broad-spectrum antibiotics showed larger effect size on neonatal outcomes than narrow-spectrum antibiotics. The correlation between early antibiotics and outcomes was significant among noncritical infants but disappeared for critical infants. CONCLUSIONS: Among infants without infection, early antibiotic use was associated with increased risk of BPD and late antibiotic use. Judicious early antibiotic use, especially avoiding prolonged duration and broad-spectrum antibiotics among noncritical infants, may improve neonatal outcomes and overall antibiotic use in NICUs.

Multinational Pharmaceutical Companies Shortchange Canada in Research and Development Investments: Is It Time to Pursue Other Options?

In 1987, the government passed legislation to protect brand-name pharmaceutical firms against competition from generic drug brands in exchange for economic investment in Canadian pharmaceutical research and development (R&D). Since 2002, brand-name pharmaceutical companies' R&D investments have fallen short of their commitment, while Canadians now pay the fourth highest drug prices of all the Organisation for Economic Co-operation and Development member countries. In this article, we examine the degree to which brand-name pharmaceutical companies have fallen short of their promises, discuss whether a patent policy is the best strategy to secure Canadian pharmaceutical R&D funding and propose practical alternatives to this arrangement.

Survey on human milk feeding and enteral feeding practices for very-low-birth-weight infants in NICUs in China Neonatal Network.

BACKGROUND: The breastfeeding rate in China is lower than that in many other countries and the extent of adoption of the "Feeding Recommendations for Preterm Infants and Low Birth Weight Infants" guideline in NICUs remains unclear. METHOD: A web-based survey about the current status of human milk feeding and enteral feeding practices at NICUs was sent to all China Neonatal Network's cooperation units on September 7, 2021, and the respondents were given a month to send their responses. RESULTS: All sixty NICUs responded to the survey, the reply rate was 100%. All units encouraged breastfeeding and provided regular breastfeeding education. Thirty-six units (60.0%) had a dedicated breastfeeding/pumping room, 55 (91.7%) provided kangaroo care, 20 (33.3%) had family rooms, and 33 (55.0%) routinely provided family integrated care. Twenty hospitals (33.3%) had their own human milk banks, and only 13 (21.7%) used donor human milk. Eight units (13.3%) did not have written standard nutrition management guidelines for infants with body weight < 1500 g. Most units initiated minimal enteral nutrition with mother's milk for infants with birth weight ˂1500 g within 24 h after birth. Fifty NICUs (83.3%) increased the volume of enteral feeding at 10-20 ml/kg daily. Thirty-one NICUs (51.7%) assessed gastric residual content before every feeding session. Forty-one NICUs (68.3%) did not change the course of enteral nutrition management during drug treatment for patent ductus arteriosus, and 29 NICUs (48.3%) instated NPO for 1 or 2 feeds during blood transfusion. CONCLUSION: There were significant differences in human milk feeding and enteral feeding strategies between the NICUs in CHNN, but also similarities. The data obtained would be useful in the establishment of national enteral feeding guidelines for preterm infants and quality improvement of cooperation at the national level.

Use of antenatal corticosteroids among infants with gestational age at 24 to 31 weeks in 57 neonatal intensive care units of China: a cross-sectional study.

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.

Discharge against medical advice among infants with 24-31 weeks' gestation admitted to Chinese neonatal intensive care units: A multicenter cohort study.

Background: Previous studies demonstrated high rates of discharge against medical advice (DAMA) among very preterm infants (VPIs) in China. Objectives: The aim of this study was to investigate the concurrent incidence, variation, and predictors of DAMA, along with the effect of DAMA on mortality of VPIs in China using data from the Chinese Neonatal Network (CHNN). Methods: All infants born at 24-31 completed weeks' gestation and admitted to 57 CHNN neonatal intensive care units (NICUs) in 2019 were included for this cohort study, excluding infants with major congenital anomalies. Patient information was prospectively collected using the CHNN database. Multivariable log-linear regression analysis was used to assess the association of perinatal factors and DAMA. Results: A total of 9,442 infants born at 24-31 completed weeks' gestation and admitted to 57 CHNN participating sites in 2019 were included in the study. Overall, 1,341 infants (14.2%) were discharged against medical advice. Rates of DAMA decreased with increasing gestational age (GA), and infants with lower GA were discharged earlier. DAMA infants had significantly higher rates of necrotizing enterocolitis, severe brain impairment, and bronchopulmonary dysplasia than non-DAMA infants. A total of 58.2% DAMA infants were predicted to die after discharge. The attributable risk percentage of mortality among DAMA infants was 92.4%. Younger maternal age, lower gestational age, small for gestational age, and Apgar score ≤3 at 5 min were independently associated with an increased risk of DAMA, while infants with antenatal steroids were less likely to be DAMA. Conclusion: The rate of DAMA in preterm infants between 24 and 31 weeks' gestation remained high in China with a significant impact on the mortality rates. Continuous efforts to reduce DAMA would result in substantial improvement of outcomes for VPIs in China.

Current epidemiology and factors contributing to postnatal growth restriction in very preterm infants in China.

BACKGROUND: Postnatal growth restriction (PGR) is common in very preterm infants (VPIs) and is associated with adverse short and long-term developmental outcomes. Postnatal growth status for VPIs in middle- or low-income countries remains unclear. AIMS: To evaluate PGR in VPIs and identify maternal and neonatal factors, clinical practice, and major neonatal morbidities associated with PGR in China. STUDY DESIGN: Prospective cohort study. SUBJECTS: We included 6085 infants born at <32 weeks gestation who were admitted at 57 hospitals in the Chinese Neonatal Network in 2019. OUTCOME MEASURES: Birth and discharge weights were converted to age-specific Z-scores. PGR was defined as a decrease in weight z-score from birth to discharge >2. RESULTS: The overall incidence of PGR was 19.9 %. The mean (standard deviation [SD]) weight Z-score was 0.12 (0.78) at birth and decreased to -1.36 (0.98) at discharge. About 4.0 % of VPIs were small for gestational age (SGA) at birth and 25.5 % of SGA infants had PGR. The incidence of PGR increased with decreasing gestational age except in the SGA subgroup. Each 1-unit increase in birthweight Z-score was associated with a 1.49-fold increased risk for PGR. Late initiation of enteral feeds and late achievement of full enteral feeds were positively associated with PGR. The common morbidities that influenced PGR were necrotizing enterocolitis ≥ stage II, patent ductus arteriosus requiring medical or surgical treatment, sepsis, bronchopulmonary dysplasia, and respiratory distress syndrome requiring surfactants. CONCLUSION: Nearly one fifth of VPIs were PGR, and one fourth of SGA had PGR, which warranted further study to investigate underlying causes by which to improve postnatal growth in very preterm infants in future.

Impact of maternal age on neonatal outcomes among very preterm infants admitted to Chinese neonatal intensive care units: a multi-center cohort study.

Background: The percentage of advanced maternal age (aged over 35 years) mothers has been rising across the world, the evidence of maternal age on neonatal outcomes from low- and middle-income countries is scarce. Our objective was to evaluate the effect of maternal age on mortality and major morbidity among very preterm infants admitted to Chinese neonatal intensive care units. Methods: Data from a retrospective multi-center cohort of all complete care very preterm infants admitted to 57 neonatal intensive care units that participated in the Chinese Neonatal Network from January 1st to December 31st, 2019 were analyzed. Neonatal outcomes including mortality or any major morbidity, defined as necrotizing enterocolitis stage 2 or 3, moderate & severe bronchopulmonary dysplasia, severe intraventricular hemorrhage, cystic periventricular leukomalacia, severe retinopathy of prematurity, or sepsis. A multiple logistic regression model was constructed to analyze the independent association between maternal age and neonatal outcome. Results: Among 7,698 eligible newborns, 80.5% of very preterm infants were born to mothers between the ages of 21 and 35 years, with 18.0% born to mothers >35 years and 1.5% born to mothers <21 years. Higher rates of maternal hypertension, maternal diabetes, cesarean deliveries, antenatal steroid usage were noted as maternal age increased. The proportion of prenatal care, cesarean section, antenatal steroid usage and inborn for very preterm infants born to mothers <21 years was lower than those of mothers of other ages. Compared to the ages of 21-35 years group, the odds of severe intraventricular hemorrhage (adjusted odd ratio: 2.00, 95% CI: 1.08-3.71) was significantly higher in the ages of 15-20 years group. Increasing maternal age was associated with higher rates of small for gestational age and lower birth weight of very preterm infants, but no correlation between advanced maternal age and very preterm infants mortality or major morbidity. Conclusions: Among very preterm infants, increasing maternal age was associated with higher rates of small for gestational age but not neonatal mortality or major morbidity. Young maternal age may increase the risk of severe intraventricular hemorrhage of very preterm infants.

Neurodevelopmental Outcomes of Infants at <29 Weeks of Gestation Born in Canada Between 2009 and 2016.

OBJECTIVE: To evaluate changes in mortality or significant neurodevelopmental impairment (NDI) in children born at <29 weeks of gestation in association with national quality improvement initiatives. STUDY DESIGN: This longitudinal cohort study included children born at 220/7 to 286/7 weeks of gestation who were admitted to Canadian neonatal intensive care units between 2009 and 2016. The primary outcome was a composite rate of death or significant NDI (Bayley Scales of Infant and Toddler Development, Third Edition score <70, severe cerebral palsy, blindness, or deafness requiring amplification) at 18-24 months corrected age. To evaluate temporal changes, outcomes were compared between epoch 1 (2009-2012) and epoch 2 (2013-2016). aORs were calculated for differences between the 2 epochs accounting for differences in patient characteristics. RESULTS: The 4426 children included 1895 (43%) born in epoch 1 and 2531 (57%) born in epoch 2. Compared with epoch 1, in epoch 2 more mothers received magnesium sulfate (56% vs 28%), antibiotics (69% vs 65%), and delayed cord clamping (37% vs 31%) and fewer infants had a Score for Neonatal Acute Physiology, version II >20 (31% vs 35%) and late-onset sepsis (23% vs 27%). Death or significant NDI occurred in 30% of children in epoch 2 versus 32% of children in epoch 1 (aOR, 0.86; 95% CI, 0.75-0.99). In epoch 2, there were reductions in the need for hearing aids or cochlear implants (1.4% vs 2.6%; aOR, 0.50; 95% CI, 0.31-0.82) and in blindness (0.6% vs.1.4%; aOR, 0.38; 95% CI, 0.18-0.80). CONCLUSIONS: Among preterm infants born at <29 weeks of gestation, composite rates of death or significant NDI and rates of visual and hearing impairment were significantly lower in 2013-2016 compared with 2009-2012.

Chinese Neonatal Network: a national protocol for collaborative research and quality improvement in neonatal care.

INTRODUCTION: The objective of the Chinese Neonatal Network (CHNN) is to provide a platform for collaborative research, outcomes evaluation and quality improvement for preterm infants with gestational age less than 32 weeks in China. The CHNN is the first national neonatal network and has the largest geographically representative cohort from neonatal intensive care units (NICUs) in China. METHODS AND ANALYSIS: Individual-level data from participating NICUs will be collected using a unique database developed by the CHNN on an ongoing basis from January 2019. Data will be prospectively collected from all infants <32 weeks gestation or <1500 g birth weight at 58 participating NICUs. Infant outcomes and inter-institutional variations in outcomes will be examined and used to inform quality improvement measures aimed at improving outcomes. Information about NICU environmental and human resource factors and processes of neonatal care will also be collected and analysed for association with outcomes. Clinical studies, including randomised controlled trials will be conducted using the CHNN data platform. ETHICS AND DISSEMINATION: This study was approved by the ethics review board of Children's Hospital of Fudan University, which was recognised by all participating hospitals. Waiver of consent were granted at all sites. Only non-identifiable patient level data will be transmitted and only aggregate data will be reported in CHNN reports and publications.