BackgroundPolymicrobial infections in adults and children are associated with increase in mortality, duration of intensive care and healthcare costs. Very few studies have characterized polymicrobial bloodstream infections in the neonatal unit. Considerable variation has been reported in incidence of polymicrobial infections and associated clinical outcomes. We characterized the risk factors and outcomes of polymicrobial bloodstream infections in our neonatal units in a tertiary hospital in North America.MethodsIn a retrospective case control study design, we identified infants in the neonatal intensive care unit with positive blood cultures at Texas Children’s Hospital, over a 16-year period from January 1, 1997 to December 31, 2012. Clinical data from online databases were available from January 2009 to December 2012. For each polymicrobial bloodstream infection (case), we matched three infants with monomicrobial bloodstream infection (control) by gestational age and birth weight.ResultsWe identified 2007 episodes of bloodstream infections during the 16 year study period and 280 (14%) of these were polymicrobial. Coagulase-negative Staphylococcus, Enterococcus, Klebsiella and Candida were the most common microbial genera isolated from polymicrobial infections. Polymicrobial bloodstream infections were associated with more than 3-fold increase in mortality and an increase in duration of infection. Surgical intervention was a significant risk factor for polymicrobial infection.ConclusionThe frequency and increased mortality emphasizes the clinical significance of polymicrobial bloodstream infections in the neonatal intensive care unit. Clinical awareness and focused research on neonatal polymicrobial infections is urgently needed.

Objective To investigate the effectiveness and safety of non-invasive high-frequency oscillatory ventilation (NHFOV) in post-extubation preterm infants. Methods This was a randomized, controlled trial. A total of 149 preterm infants aged between 25 to 34 weeks’ gestational age with a birth weight of <1500 g who required invasive mechanical ventilation on admission were included. After extubation, they were randomized to the NHFOV group (n = 47), nasal intermittent positive pressure ventilation (NIPPV) group (n = 51), or nasal continuous positive airway pressure (NCPAP) group (n = 51). We compared the effectiveness and safety among these three groups. Results A total of 139 preterm infants finally completed the study. The reintubation rate was significantly lower in the NHFOV group than in the other groups. The duration of non-invasive ventilation and the length of hospital stay in the NHFOV and NIPPV groups were significantly shorter than those in the NCPAP group. The incidence of bronchopulmonary dysplasia in the NHFOV and NIPPV groups was significantly lower than that in the NCPAP group. The NHFOV group had significantly less nasal injury than the NCPAP group. Conclusion As post-extubation respiratory support in preterm infants, NHFOV has a lower reintubation rate compared with NCPAP and NIPPV, without increasing the rate of complications.

for the Nasal Oscillation Post-Extubation (NASONE) Study Group IMPORTANCE Several respiratory support techniques are available to minimize the use of invasive mechanical ventilation (IMV) in preterm neonates. It is unknown whether noninvasive high-frequency oscillatory ventilation (NHFOV) is more efficacious than nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive pressure ventilation (NIPPV) in preterm neonates after their first extubation.OBJECTIVE To test the hypothesis that NHFOV is more efficacious than NCPAP or NIPPV in reducing IMV after extubation and until neonatal intensive care unit discharge among preterm neonates. DESIGN, SETTING, AND PARTICIPANTSThis multicenter, pathophysiology-based, assessor-blinded, 3-group, randomized clinical trial was conducted in 69 tertiary referral neonatal intensive care units in China, recruiting participants from December 1, 2017, to May 31, 2021. Preterm neonates who were between the gestational age of 25 weeks plus 0 days and 32 weeks plus 6 days and were ready to be extubated were randomized to receive NCPAP, NIPPV or NHFOV. Data were analyzed on an intention-to-treat basis. INTERVENTIONSThe NCPAP, NIPPV, or NHFOV treatment was initiated after the first extubation and lasted until discharge.MAIN OUTCOMES AND MEASURES Primary outcomes were total duration of IMV, need for reintubation, and ventilator-free days. These outcomes were chosen to describe the effect of noninvasive ventilation strategy on the general need for IMV.RESULTS A total of 1440 neonates (mean [SD] age at birth, 29.4 [1.8] weeks; 860 boys [59.7%]) were included in the trial. Duration of IMV was longer in NIPPV (mean difference, 1.2; 95% CI, 0.01-2.3 days; P = .04) and NCPAP (mean difference, 1.5 days; 95% CI, 0.3-2.7 days; P = .01) compared with NHFOV. Neonates who were treated with NCPAP needed reintubations more often than those who were treated with NIPPV (risk difference: 8.1%; 95% CI, 2.9%-13.3%; P = .003) and NHFOV (risk difference, 12.5%; 95% CI, 7.5%-17.4%; P < .001). There were fewer ventilator-free days in neonates treated with NCPAP than in those treated with NIPPV (median [25th-75th percentile] difference, −3 [−6 to −1] days; P = .01). There were no differences between secondary efficacy or safety outcomes, except for the use of postnatal corticosteroids (lower in NHFOV than in NCPAP group; risk difference, 7.3%; 95% CI, 2.6%-12%; P = .002), weekly weight gain (higher in NHFOV than in NCPAP group; mean difference, −0.9 g/d; 95% CI, −1.8 to 0 g/d; P = .04), and duration of study intervention (shorter in NHFOV than in NIPPV group; median [25th-75th percentile] difference, −1 [−3 to 0] days; P = .01).CONCLUSIONS AND RELEVANCE Results of this trial indicated that NHFOV, if used after extubation and until discharge, slightly reduced the duration of IMV in preterm neonates, and both NHFOV and NIPPV resulted in a lower risk of reintubation than NCPAP. All 3 respiratory support techniques were equally safe for this patient population.

Background:Globally, the proportion of child deaths that occur in the neonatal period remains a high level of 37–41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.Methods:All the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed.Results:A total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents’ concern about the long-term outcomes was the main reason of medical care withdrawal.Conclusions:Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.

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Articles Population Study nature publishing groupBackground: Uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene mutation was shown to be responsible for neonatal hyperbilirubinemia. This study aimed to investigate whether UGT1A1 gene mutation is associated with neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations. Methods: Two hundred and eighteen infants with hyperbilirubinemia (118 Heiyi Zhuang, 100 Han) and 190 control subjects (110 Heiyi Zhuang, 80 Han) were enrolled. Polymerase chain reaction and gene sequencing were used to detect the TATA-box and exon 1 of UGT1A1. results: (TA)7 insertion mutation, 211G>A (G71R), 686C>A (P229Q), and 189C>T (D63D) were detected. Logistic regression analysis showed odds ratios (OR) of 2.64 (95% confidence interval (CI) 1.64-4.24; P < 0.001) and 0.69 (95%CI 0.43-1.10; P = 0.115) for neonates who carried UGT1A1 G71R and (TA)7 insertion mutation, respectively. G71R homozygosity increased the odds of dangerous bilirubin levels by a factor 34.23, and G71R heterozygosity only by 2.10. conclusion: We found that UGT1A1 G71R mutation is a risk factor for neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations. Meanwhile, the UGT1A1 (TA)7 insertion mutation is not associated with neonatal hyperbilirubinemia in the two ethnic groups.

UDP-glucuronosyltransferases (UGTs) are the main phase II drug-metabolizing enzymes mediating the most extensive glucuronidation-binding reaction in the human body. The UGT1A family is involved in more than half of glucuronidation reactions. However, significant differences exist in the distribution of UGT1As in vivo and the expression of UGT1As among individuals, and these differences are related to the occurrence of disease and differences in metabolism. In addition to genetic polymorphisms, there is now interest in the contribution of epigenetics and noncoding RNAs (especially miRNAs) to this differential change. Epigenetics regulates UGT1As pretranscriptionally through DNA methylation and histone modification, and miRNAs are considered the key mechanism of posttranscriptional regulation of UGT1As. Both epigenetic inheritance and miRNAs are involved in the differences in sex expression and in vivo distribution of UGT1As. Moreover, epigenetic changes early in life have been shown to affect gene expression throughout life. Here, we review and summarize the current regulatory role of epigenetics in the UGT1A family and discuss the relationship among epigenetics and UGT1A-related diseases and treatment, with references for future research.

We aimed to investigate the effect of the genetic mutant G71R (c. 211G > A) in uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) on the glucuronidation of unconjugated bilirubin. The UGT1A1 wild-type and mutant G71R gene sequences were inserted into the lentiviral vector GV358 plasmid and then transfected into COS-7 cells. Real-time polymerase chain reaction and western blot analyses were used to determine mRNA and protein expression levels of UGT1A1, respectively. High-performance liquid chromatography was used to quantitate the levels of conjugated bilirubin. The results showed no significant difference in the mRNA and protein expression levels between the UGT1A1 wild-type and G71R homozygous and heterozygous mutants. The level of conjugated bilirubin reached a maximum in wild-type UGT1A1-transfected COS-7 cells. However, relative to the UGT1A1 wild-type, conjugated bilirubin concentrations were 71 and 22% with G71R heterozygous- and G71R homozygous-transfected COS-7 cells, respectively. In conclusion, we successfully established in vitro cell models of the UGT1A1 wild-type and the G71R homozygous and heterozygous mutants using a lentiviral vector. Furthermore, the catalytic activity for unconjugated bilirubin was lower in the mutant G71R than the UGT1A1 wild-type enzyme, and a weaker effect was observed in the homozygote.