Epidemiology, microbiology and antibiotic treatment of bacterial and fungal meningitis among very preterm infants in China: a cross-sectional study.

OBJECTIVE: Neonatal meningitis significantly contributes to neonatal morbidity and mortality, yet large-scale epidemiological data in developing countries, particularly among very preterm infants (VPIs), remain sparse. This study aimed to describe the epidemiology of meningitis among VPIs in China. DESIGN: Cross-sectional study using the Chinese Neonatal Network database from 2019 to 2021. SETTING: 79 tertiary neonatal intensive care units in China. PATIENTS: Infants with gestational age <32 weeks or birth weight <1500 g. MAIN OUTCOME MEASURES: Incidence, pathogen distribution, antimicrobial use and outcomes of bacterial and fungal meningitis. RESULTS: Of 31 915 VPIs admitted, 122 (0.38%) infants were diagnosed with culture-confirmed meningitis, with 14 (11.5%) being early-onset (≤6 days of age) and 108 (88.5%) being late-onset (>6 days of age). The overall in-hospital mortality was 18.0% (22/122). A total of 127 pathogens were identified, among which 63.8% (81/127) were Gram-negative bacteria, 24.4% (31/127) were Gram-positive bacteria and 11.8% (15/127) were fungi. In terms of empirical therapy (on the day of the first lumbar puncture), the most commonly used antibiotic was meropenem (54.9%, 67/122). For definitive therapy (on the sixth day following the first lumbar puncture, 86 cases with available antibiotic data), meropenem (60.3%, 35/58) and vancomycin (57.1%, 16/28) were the most used antibiotics for Gram-negative and Gram-positive bacterial meningitis, respectively. 44% of infants with Gram-positive bacterial meningitis and 52% with Gram-negative bacterial meningitis received antibiotics for more than 3 weeks. CONCLUSION: 0.38% of VPIs in Chinese neonatal intensive care units were diagnosed with meningitis, experiencing significant mortality and inappropriate antibiotic therapy. Gram-negative bacteria were the predominant pathogens, with fungi emerging as a significant cause.

Mortality and extrauterine growth restriction of necrotizing enterocolitis in very preterm infants with heart disease: a multi-center cohort study.

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6 weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC.     Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.

The performance of the practices associated with the occurrence of severe intraventricular hemorrhage in the very premature infants: data analysis from the Chinese neonatal network.

BACKGROUND: The occurrence of severe intraventricular hemorrhage (sIVH) was high in the very preterm infants (VPIs) in China. The management strategies significantly contributed to the occurrence of sIVH in VPIs. However, the status of the perinatal strategies associated with sIVH for VPIs was rarely described across the multiple neonatal intensive care units (NICUs) in China. We aim to investigate the characteristics of the perinatal strategies associated with sIVH for VPIs across the multiple NICUs in China. METHODS: This was a retrospective analysis of data from a prospective cohort of Chinese Neonatal Network (CHNN) dataset, enrolling infants born at 24+0-31+6 from 2019 to 2021. Eleven perinatal practices performed within the first 3 days of life were investigated including antenatal corticosteroids use, antenatal magnesium sulphate therapy, intubation at birth, placental transfusion, need for advanced resuscitation, initial inhaled gas of 100% FiO2 in delivery room, initial invasive respiratory support, surfactant and caffeine administration, early enteral feeding, and inotropes use. The performances of these practices across the multiple NICUs were investigated using the standard deviations of differences between expected probabilities and observations. The occurrence of sIVH were compared among the NICUs. RESULTS: A total of 24,226 infants from 55 NICUs with a mean (SD) gestational age of 29.5 (1.76) and mean (SD) birthweight of 1.31(0.32) were included. sIVH was detected in 5.1% of VPIs. The rate of the antenatal corticosteroids, MgSO4 therapy, and caffeine was 80.0%, 56.4%, and 31.5%, respectively. We observed significant relationships between sIVH and intubation at birth (AOR 1.52, 95% CI 1.13 to 1.75) and initial invasive respiratory support (AOR 2.47, 95% CI 2.15 to 2.83). The lower occurrence of sIVH (4.8%) was observed corresponding with the highest utility of standard antenatal care, the lowest utility of invasive practices, and early enteral feeding administration. CONCLUSIONS: The current evidence-based practices were not performed in each VPI as expected among the studied Chinese NICUs. The higher utility of the invasive practices could be related to the occurrence of sIVH.

Association of Antenatal Corticosteroids with Neonatal Outcomes among Very Preterm Infants Born to Mothers with Clinical Chorioamnionitis: A Multicenter Cohort Study.

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.

Early Antibiotic Exposure and Bronchopulmonary Dysplasia in Very Preterm Infants at Low Risk of Early-Onset Sepsis.

Importance: The overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities. Nevertheless, the association of early antibiotic exposure with bronchopulmonary dysplasia (BPD) remains equivocal. Objective: To evaluate the association of varying durations and types of early antibiotic exposure with the incidence of BPD in VPIs at low risk of EOS. Design, Setting, and Participants: This national multicenter cohort study utilized data from the Chinese Neonatal Network (CHNN) which prospectively collected data from January 1, 2019, to December 31, 2021. VPIs less than 32 weeks' gestational age or with birth weight less than 1500 g at low risk of EOS, defined as those born via cesarean delivery, without labor or rupture of membranes, and no clinical evidence of chorioamnionitis, were included. Data analysis was conducted from October 2022 to December 2023. Exposure: Early antibiotic exposure was defined as the total number of calendar days antibiotics were administered within the first week of life, which were further categorized as no exposure, 1 to 4 days of exposure, and 5 to 7 days of exposure. Main Outcomes and Measures: The primary outcome was the composite of moderate to severe BPD or mortality at 36 weeks' post menstrual age (PMA). Logistic regression was employed to assess factors associated with BPD or mortality using 2 different models. Results: Of the 27 176 VPIs included in the CHNN during the study period (14 874 male [54.7%] and 12 302 female [45.3%]), 6510 (23.9%; 3373 male [51.8%] and 3137 female [48.2.%]) were categorized as low risk for EOS. Among them, 1324 (20.3%) had no antibiotic exposure, 1134 (17.4%) received 1 to 4 days of antibiotics treatment, and 4052 (62.2%) received 5 to 7 days of antibiotics treatment. Of the 5186 VPIs who received antibiotics, 4098 (79.0%) received broad-spectrum antibiotics, 888 (17.1%) received narrow-spectrum antibiotics, and 200 (3.9%) received antifungals or other antibiotics. Prolonged exposure (5-7 days) was associated with increased likelihood of moderate to severe BPD or death (adjusted odds ratio [aOR], 1.23; 95% CI, 1.01-1.50). The use of broad-spectrum antibiotics (1-7 days) was also associated with a higher risk of moderate to severe BPD or death (aOR, 1.27; 95% CI, 1.04-1.55). Conclusions and Relevance: In this cohort study of VPIs at low risk for EOS, exposure to prolonged or broad-spectrum antibiotics was associated with increased risk of developing moderate to severe BPD or mortality. These findings suggest that VPIs exposed to prolonged or broad-spectrum antibiotics early in life should be monitored for adverse outcomes.

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..

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.

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..

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.

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.

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.

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.

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.

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.