Association between admission hypothermia and outcomes in very low birth weight infants in China: a multicentre prospective study.

BACKGROUND: The objective of this prospective, multicentre, observational cohort study was to evaluate the association between admission hypothermia and neonatal outcomes in very low-birth weight (VLBW) infants in multiple neonatal intensive care units (NICUs) in China. METHODS: Since January 1, 2018, a neonatal homogeneous cooperative research platform-Shandong Neonatal Network (SNN) has been established. The platform collects clinical data in a prospective manner on preterm infants with birth weights (BWs) < 1500 g and gestational ages (GAs) < 34 weeks born in 28 NICUs in Shandong Province. These infants were divided into normothermia, mild or moderate/severe hypothermia groups according to the World Health Organization (WHO) classifications of hypothermia. Associations between outcomes and hypothermia were tested in a bivariate analysis, followed by a logistic regression analysis. RESULTS: A total of 1247 VLBW infants were included in this analysis, of which 1100 infants (88.2%) were included in the hypothermia group, 554 infants (44.4%) in the mild hypothermia group and 546 infants (43.8%) in the moderate/severe hypothermia group. Small for gestational age (SGA), caesarean section, a low Apgar score at 5 min and intubation in the delivery room (DR) were related to admission hypothermia (AH). Mortality was the lowest when their admission temperature was 36.5 ~ 37.5 °C, and after adjustment for maternal and infant characteristics, mortality was significantly associated with AH. Compared with infants with normothermia (36.5 ~ 37.5 °C), the adjusted ORs of all deaths increased to 4.148 (95% CI 1.505-11.437) and 1.806 (95% CI 0.651-5.009) for infants with moderate/severe hypothermia and mild hypothermia, respectively. AH was also associated with a high likelihood of respiratory distress syndrome (RDS), intraventricular haemorrhage (IVH), and late-onset neonatal sepsis (LOS). CONCLUSIONS: AH is still very high in VLBW infants in NICUs in China. SGA, caesarean section, a low Apgar score at 5 min and intubation in the DR were associated with increased odds of hypothermia. Moderate/severe hypothermia was associated with mortality and poor outcomes, such as RDS, IVH, LOS.

Pathogens distribution and antimicrobial resistance in bloodstream infections in twenty-five neonatal intensive care units in China, 2017-2019.

BACKGROUND: Overcrowding, abuse of antibiotics and increasing antimicrobial resistance negatively affect neonatal survival rates in developing countries. We aimed to define pathogens and their antimicrobial resistance (AMR) of early-onset sepsis (EOS), hospital-acquired late-onset sepsis (HALOS) and community-acquired late-onset sepsis (CALOS) in 25 neonatal intensive care units (NICUs) in China. STUDY DESIGN: This retrospective descriptive study included pathogens and their AMR from all neonates with bloodstream infections (BSIs) admitted to 25 tertiary hospitals in China from January 1, 2017, and December 31, 2019. We defined EOS as the occurrence of BSI at or before 72 h of life and late-onset sepsis (LOS) if BSI occurred after 72 h of life. LOS were classified as CALOS if occurrence of BSI was ≤ 48 h after admission, and HALOS, if occurrence was > 48 h after admission. RESULTS: We identified 1092 pathogens of BSIs in 1088 infants from 25 NICUs. Thirty-two percent of all pathogens were responsible for EOS, 64.3% HALOS, and 3.7% CALOS. Gram-negative (GN) bacteria accounted for a majority of pathogens in EOS (56.7%) and HALOS (62.2%). The most frequent pathogens causing EOS were Escherichia coli (27.2%) and group B streptococcus (GBS; 14.6%) whereas in CALOS they were GBS (46.3%) and Staphylococcus aureus (41.5%). Klebsiella pneumoniae (27.9%), Escherichia coli (15.7%) and Fungi (12.8%) were the top three isolates in HALOS. Third-generation cephalosporin resistance rates in GN bacteria ranged from 9.7 to 55.6% in EOS and 26% to 63.3% in HALOS. Carbapenem resistance rates in GN bacteria ranged from 2.7 to 31.3% in HALOS and only six isolates in EOS were carbapenem resistant. High rates of multidrug resistance were observed in Klebsiella pneumoniae (60.7%) in HALOS and in Escherichia coli (44.4%) in EOS. All gram-positive bacteria were susceptible to vancomycin except for three Enterococcus faecalis in HALOS. All-cause mortality was higher among neonates with EOS than HALOS (7.4% VS 4.4%, [OR] 0.577, 95% CI 0.337-0.989; P = 0.045). CONCLUSIONS: Escherichia coli, Klebsiella pneumoniae and GBS were the leading pathogens in EOS, HALOS and CALOS, respectively. The high proportion of pathogens and high degree of antimicrobial resistance in HALOS underscore understanding of the pathogenesis and emphasise the need to devise effective interventions in developing countries.

Dynamic Change of Thyroid Hormones With Postmenstrual Age in Very Preterm Infants Born With Gestational Age <32 Weeks: A Multicenter Prospective Cohort Study.

Background: At present, the relationship between thyrotropin (TSH) and free thyroxine (FT4) in relation to postmenstrual age (PMA) in preterm infants is still unclear, and there is no reliable standard thyroid hormone reference ranges, resulting in different diagnostic criteria for congenital hypothyroidism been used by different newborn screening programs and different countries. Objectives: To investigate the relationship between TSH/FT4 and PMA in very preterm infants (VPIs) born with gestational age (GA) <32 weeks and to derive thyroid function reference charts based on PMA. Methods: A prospective cohort study was performed on VPIs born with GA<32 weeks and born in or transferred to the 27 neonatal intensive care units from January 1, 2019 to December 31, 2019. Serial TSH and FT4 values were measured at the end of each week during the first month after birth and also at PMA36 weeks, PMA40 weeks and at discharge, respectively. The 2.5th, 5th, 50th, 95th, and 97.5th percentiles of TSH and FT4 of different PMA groups were calculated to draw the percentile charts based on PMA. Results: 1,093 preterm infants were included in this study. The percentile charts of TSH and FT4 levels based on PMA were drawn respectively, and the result indicated that the percentile charts of TSH values were gradually increased initially and then decreased with increasing PMA. The 97.5th percentile chart reached the peak at PMA30 weeks (17.38µIU/ml), and then decreased gradually, reaching the same level as full-term infants (9.07µIU/ml) at PMA38-40 weeks. The 2.5th percentile chart of FT4 was at its lowest point at PMA26-27 weeks (5.23pmol/L), then increased slowly with PMA and reached the same level as full-term infants at PMA38-40 weeks (10.87pmol/L). At PMA36 weeks, the reference intervals of the 2.5th to 97.5th percentiles of TSH and FT4 were 1.18-12.3µIU/ml and 8.59-25.98pmol/L, respectively. Conclusion: The percentile charts of TSH and FT4 in VPIs showed characteristic change with PMA. The results prompt that age-related cutoffs, instead of a single reference range, might be more useful to explain the thyroid function of VPIs. And repeated screening is necessary for preterm infants.

Berberine reduces the occurrence of neonatal necrotizing enterocolitis by reducing the inflammatory response.

Necrotizing enterocolitis (NEC) is a life-threatening disease that occurs in premature infants. The aim of the present study was to investigate the effects of berberine, an isoquinoline alkaloid mainly used to treat digestive diseases, in a rat model of NEC. NEC models were established in newborn rats via inhalation of N2 for 90 sec every 4 h and oral administration of 4 mg/kg/day lipopolysaccharides on days 0 and 1. Berberine was administered via oral gavage. In the NEC model group, Toll-like receptor (TLR)4, nuclear factor NF-κB (NF-κB), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were upregulated. Symptoms of NEC in the berberine intervention group were significantly relieved, with a clear reduction in the incidence of NEC compared with the NEC group. TLR4, NF-κB, iNOS, TNF-α, IL-6 and IL-10 expression was decreased following berberine intervention. Furthermore, the expression of mucin-2 (MUC2) and RNA polymerase σ factor SigA (SIgA) were decreased in the NEC model group and increased following berberine intervention, when compared with the untreated group. It was also demonstrated that the incidence of NEC was reduced following berberine administration, possibly owing to changes in the inflammatory responses. The results of the current study support a potential therapeutic role of berberine for the treatment of NEC.