Changyi Yang

Importance: The Chinese Neonatal Network was established in 2018 and maintains a standardized national clinical database of very preterm or very low-birth-weight infants in tertiary neonatal intensive care units (NICUs) throughout China. National-level data on outcomes and care practices of very preterm infants (VPIs) in China are lacking. Objective: To assess the care practices in NICUs and outcomes among VPIs in China. Design, Setting, and Participants: A cohort study was conducted comprising 57 tertiary hospitals from 25 provinces throughout China. All infants with gestational age (GA) less than 32 weeks who were admitted to the 57 NICUs between January 1 and December 31, 2019, were included. Main Outcomes and Measures: Care practices, morbidities, and survival were the primary outcomes of the study. Major morbidities included bronchopulmonary dysplasia, severe intraventricular hemorrhage (grade ≥3) and/or periventricular leukomalacia, necrotizing enterocolitis (stage ≥2), sepsis, and severe retinopathy of prematurity (stage ≥3). Results: A total of 9552 VPIs were included, with mean (SD) GA of 29.5 (1.7) weeks and mean (SD) birth weight of 1321 (321) g; 5404 infants (56.6%) were male. Antenatal corticosteroids were used in 75.6% (6505 of 8601) of VPIs, and 54.8% (5211 of 9503)were born through cesarean delivery. In the delivery room, 12.1% of VPIs received continuous positive airway pressure and 26.7% (2378 or 8923) were intubated. Surfactant was prescribed for 52.7% of the infants, and postnatal dexamethasone was prescribed to 9.5% (636 of 6675) of the infants. A total of 85.5% (8171) of the infants received complete care, and 14.5% (1381) were discharged against medical advice. The incidences of the major morbidities were bronchopulmonary dysplasia, 29.2% (2379 of 8148); severe intraventricular hemorrhage and/or periventricular leukomalacia, 10.4% (745 of 7189); necrotizing enterocolitis, 4.9% (403 of 8171 ); sepsis, 9.4% (764 of 8171); and severe retinopathy of prematurity, 4.3% (296 of 6851) among infants who received complete care. Among VPIs with complete care, 95.4% (7792 of 8171) survived: 65.6% (155 of 236) at 25 weeks' or less GA, 89.0% (880 of 988) at 26 to 27 weeks' GA, 94.9% (2635 of 2755)at 28 to 29 weeks' GA, and 98.3% (4122 of 4192) at 30 to 31 weeks' GA. Only 57.2% (4677 of 8171) of infants survived without major morbidity: 10.5% (25 of 236) at 25 weeks' or less GA, 26.8% (48 of 179) at 26 to 27 weeks' GA, 51.1% (1409 of 2755) at 28 to 29 weeks' GA, and 69.3% (2904 of 4192) at 30 to 31 weeks' GA. Among all infants admitted, the survival rate was 87.6% (8370 of 9552)and survival without major morbidities was 51.8% (4947 of 9552). Conclusions and Relevance: The findings of this study suggest that survival and survival without major morbidity of VPIs in Chinese NICUs have improved but remain lower than in high-income countries. Comprehensive and targeted quality improvement efforts are needed to provide complete care for all VPIs, optimize obstetrical and neonatal care practices, and improve outcomes.

OBJECTIVE: To describe the incidence, case-fatality rate and pathogen distribution of late-onset sepsis (LOS) among preterm infants in China. To investigate risk factors and short-term outcomes associated with LOS caused by Gram-positive bacteria, Gram-negative bacteria and fungi. METHODS: This cohort study included all infants born at <34 weeks' gestation and admitted to 25 tertiary hospitals in 19 provinces in China from May, 2015 to April, 2018. Infants were excluded who died or were discharged within 3 days of being born. RESULTS: A total of 1199 episodes of culture-positive LOS were identified in 1133 infants, with an incidence of 4.4% (1133/25,725). Overall, 15.4% (175/1133) of infants with LOS died and 10.0% (113/1133) of infants died within 7 days of LOS onset. Among 1214 isolated pathogens, Gram-negative bacteria were the most common (51.8%, 629/1214) and fungi accounted for 17.1% (207/1214). Use of central lines, longer duration of antibiotics and previous carbapenem exposure were related to increased risk of fungal LOS compared with Gram-positive bacteria. Gram-negative bacteria LOS was independently associated with increased risk of death, periventricular leukomalacia, bronchopulmonary dysplasia, and necrotizing enterocolitis. Fungal LOS was independently associated with increased risk of periventricular leukomalacia, bronchopulmonary dysplasia and necrotizing enterocolitis. CONCLUSIONS: Late-onset sepsis was a significant cause of morbidity and mortality in Chinese neonatal intensive care units, with a distinct pathogen distribution from industrial countries. Clinical guidelines on the prevention and treatment of LOS should be developed and tailored to these LOS characteristics in Chinese neonatal intensive care units.

BACKGROUND: Oropharyngeal administration of colostrum (OAC) may provide immunoprotective and anti-inflammatory effects that potentially reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis and improve short-term outcomes. Our objective was to evaluate the role of OAC in the early prevention of NEC and late-onset sepsis in preterm infants with gestational age (GA) ≤ 32 weeks. METHODS: A pilot, single-center, 1:1 parallel randomized controlled trial was conducted in a 40-bed tertiary neonatal intensive care unit (NICU) in China from 1 January 2019 to 30 September 2020. Preterm infants were randomly divided into two groups with GA ≤ 32 weeks. The OAC group included preterm infants who received 0.4 ml of maternal colostrum via the oropharyngeal route every 3 h for 10 days beginning within the first 48 h after birth, and the control group included preterm infants who received normal saline instead. Data from the two groups were collected and compared. RESULTS: A total of 127 infants in the OAC group and 125 infants in the control group were enrolled. The incidence of NEC (Bell stage 2 or 3) and late-onset sepsis were lower in the OAC group [2.36% vs. 10.40%, relative risk (RR) 0.23 (95% confidence interval (CI) 0.07, 0.78), adjusted RR 0.23 (95% CI 0.06, 0.84); 4.72% vs. 13.60%, RR 0.35 (95% CI 0.14, 0.85), adjusted RR 0.36 (95% CI 0.14, 0.95)]. In addition, the incidence of proven sepsis and intraventricular hemorrhage (IVH) (stage 3 or 4) were lower in the OAC group [2.36% vs. 8.80%, RR 0.27 (95% CI 0.08, 0.94); 1.57% vs. 7.20%, RR 0.22 (95% CI 0.05, 0.99)], and the time to achieve full enteral feeding was shorter (23.13 ± 9.45 days vs. 28.50 ± 14.80 days). No adverse reactions were observed in either group. CONCLUSIONS: Oropharyngeal administration of colostrum is a safe and simple NICU procedure that may yield a potential effect in decreasing the incidences of NEC, late-onset sepsis, and severe IVH and shorten the time to achieve full enteral feeding in preterm infants with GA ≤ 32 weeks. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900023697 , Registered 8 June 2019, retrospectively registered.

The present study aims to analyze the risk factors for metabolic bone disease (MBD) of prematurity.A total of 238 preterm infants who were born at <34 weeks of gestation and were hospitalized for at least 6 weeks in the Department of Neonatology, Fujian Maternity and Children Hospital between January 1, 2011 and November 30, 2015 were enrolled in the study. Sixteen preterm infants diagnosed with MBD were selected as the case group, and 32 non-MBD preterm infants were matched 2:1 at admission into the study. The 2 groups were compared to examine the differences in maternal obstetric conditions, conditions during parturition, neonatal conditions, and neonatal diseases and treatments. The risk factors for MBD of prematurity were analyzed using t tests, χ tests, and a logistic regression model.The mean gestational age and birth weight of the case group were significantly lower (P < .05) than those of the control group. Compared with the control group, the case group had a significantly higher ratios of small-for-gestational-age infants, antenatal maternal corticosteroids use, sedative use, ventilator use, aminophylline use, diuretic use, liver function impairment, vitamin D (VitD) supplementation at more than 14 days of age, achievement of total enteral nutrition (TEN) beyond 28 days of age, and feeding intolerance.Logistic regression analysis showed that birth at <30 weeks of gestation, VitD supplementation at >14 days of age, and achievement of TEN beyond 28 days of age were independent risk factors for MBD (P < .05).Level of Evidence: IV.

To date, the genetic risk factors for neonatal hyperbilirubinemia remain unknown in Southeastern China. This case-control study aimed to identify the genetic risk factors for neonatal hyperbilirubinemia in Fujian, Southeastern China. A total of 286 hyperbilirubinemic newborns were enrolled as a case group, and 250 randomly selected newborns without jaundice or with a bilirubin level that was lower than the threshold required for phototherapy served as controls. The serum levels of total bilirubin, unconjugated bilirubin, and direct bilirubin were measured, and the common genetic loci in UGT1A1, OATP1B1, and HO-1 genes were genotyped. Higher incidence of ABO incompatibility and G6PD deficiency was detected in the case group compared to the control group ( P &lt; 0.01). There were significant differences in the frequencies of rs4148323 and rs1805173 genotypes between the case and control groups ( P &lt; 0.05). At the rs4148323 locus, the frequencies of GA heterozygotes and AA mutant homozygotes were higher in the case group than in the control group ( P &lt; 0.05), and at the rs1805173 locus, the frequencies of LS, MS, and SS genotypes were higher in the case group than in the control group ( P &lt; 0.05). A higher frequency of rs4148323 A allele and rs1805173 S allele was detected in the case group compared to the control group ( P = 0). Additionally, multivariate logistic regression analysis identified that the mutant genotype of rs4148323 in the UGT1A1 gene, ABO incompatibility, G6PD deficiency, and SS genotype at rs1805173 locus of the HO-1 gene were genetic risk factors of neonatal hyperbilirubinemia. Our data demonstrate that G211 mutation in the UGT1A1 gene, ABO incompatibility, G6PD deficiency, and the SS genotype of the repeats in the promoter region of the HO-1 gene are risk factors for neonatal hyperbilirubinemia in Fujian, Southeastern China.