Sepsis and bronchopulmonary dysplasia as potential risk factors for parenteral nutrition-associated cholestasis in neonates: a meta-analysis of retrospective studies.

INTRODUCTION: The aim of this study was to evaluate whether sepsis and bronchopulmonary dysplasia (BPD) are risk factors for parenteral nutrition-associated cholestasis (PNAC) and to provide suggestions for the prevention of PNAC in infants. EVIDENCE ACQUISITION: Electronic databases (PubMed, EBSCO, Elsevier, Springer, Wiley, and Cochrane) were searched for studies published up to October 22, 2017. Associations between sepsis, BPD and PNAC were assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic, and subgroup analyses were performed. EVIDENCE SYNTHESIS: Nine studies incorporating a total of 2248 cases were included in the meta-analysis. Sepsis was significantly associated with PNAC (pooled OR=2.04; 95% CI: 1.23-2.85), but BPD was not (pooled OR=1.22; 95% CI: 0.65-1.78). In a subgroup analysis, BPD was not associated with PNAC in either the non-Asian group (pooled OR=1.38; 95% CI: 0.58-2.18) or the Asian group (pooled OR=1.05; 95% CI: 0.26-1.84). CONCLUSIONS: Sepsis, but not BPD, was a risk factor for PNAC in this meta-analysis. Further studies are needed to confirm the findings.

Association Between Antibiotic Overexposure and Adverse Outcomes in Very-Low-Birth-Weight Infants Without Culture-Proven Sepsis or Necrotizing Enterocolitis: A Multicenter Prospective Study.

OBJECTIVES: To explore the associations between higher antibiotic use rates (AURs) and adverse outcomes in very-low-birth-weight (VLBW) infants without culture-proven sepsis or necrotizing enterocolitis (NEC) in a multicenter of China. METHODS: A prospective cohort study was performed on VLBW infants admitted to 24 neonatal intensive care units from January 1, 2018, to December 31, 2018. AUR was calculated as calendar days of antibiotic therapy divided by total hospital days. The composite primary outcome was defined as mortality or severe morbidity, including any of the following: severe neurologic injury, bronchopulmonary dysplasia (BPD), and stage 3 or higher retinopathy of prematurity. RESULTS: A total of 1,034 VLBW infants who received antibiotics without culture-proven sepsis or NEC were included in this study. The overall AUR of eligible VLBW infants was 55%, and the AUR of each eligible VLBW infant ranged from 3 to 100%, with a median of 56% (IQR 33%, 86%). After generalized propensity score and logistic regression analysis of 4 groups of VLBW infants with different AUR range, infants in the higher quartile AUR, (Q3, 0.57~0.86) and (Q4, 0.87~1.00), had higher odds of composite primary outcome (adjusted OR: 1.81; 95% CI: 1.23-2.67; adjusted OR 2.37; 95% CI: 1.59-3.54, respectively) and BPD (adjusted OR: 3.09; 95% CI: 1.52-6.57; adjusted OR 3.17; 95% CI: 1.56-6.57, respectively) than those in the lowest AUR (Q1). CONCLUSIONS: Antibiotic overexposure in VLBW infants without culture-proven sepsis or NEC was associated with increased risk of composite primary outcome and BPD. Rational empirical antibiotic use in VLBW infants is urgently needed in China.

Initial respiratory support modality and outcome in preterm infants with less than 32 weeks of gestation in China: A multicentre retrospective cohort study.

BACKGROUND: For initial respiratory management, continuous positive airway pressure (CPAP) is increasingly used for preterm infants, especially for gestational age less than 32 weeks. However, neonatologists are concerned about the potential risks of CPAP support failure. OBJECTIVES: To examine the association between different initial respiratory support modalities and the outcomes of preterm infants at <32 weeks of gestation across multiple neonatal intensive care units (NICU) in China. METHODS: This study was carried out over a period of 12 months in 2018. Unadjusted relative risks (RR) for demographic and clinical characteristics were calculated for CPAP failure and CPAP success in the total cohort using log-linear model based on generalised estimating equations for clustered observations. RESULTS: Among 1560 preterm infants delivered at <32 weeks, the incidence of CPAP failure was 10.3%. After adjustment for demographic and clinical factors, the relative risk of mortality (RR 7.54, 95% CI 5.56, 10.44), pneumothorax (RR 9.85, 95% CI 2.89, 61.53), pulmonary haemorrhage (RR 7.78, 95% CI 4.51, 14.64) and BPD (RR 3.65, 95% CI 3.65, 4.51) were considerably higher for infants in the CPAP failure group than those in the CPAP-S group. However, the risk of poor outcomes in CPAP failure infants was similar to that of those in the initial mechanical ventilation (MV) group. CONCLUSIONS: Continuous positive airway pressure failure was associated with an increased risk of mortality and major morbidities, including BPD, pulmonary haemorrhage and pneumothorax, and was comparable to the risk associated with initial MV.

Effect of electrode temperature on measurements of transcutaneous carbon dioxide partial pressure and oxygen partial pressure in very low birth weight infants. / 电极温度对极低出生体重儿经皮二氧化碳分压和氧分压监测的影响.

OBJECTIVES: To evaluate the accuracy and safety of measurements of transcutaneous carbon dioxide partial pressure (TcPCO2) and transcutaneous oxygen partial pressure (TcPO2) at electrode temperatures lower than the value used in clinical practice in very low birth weight infants. METHODS: A total of 45 very low birth weight infants were enrolled. TcPCO2 and TcPO2 measurements were performed in these infants. Two transcutaneous monitors were placed simultaneously for each subject. One electrode was set and maintained at 42℃ used in clinical practice for neonates (control group), and the other was successively set at 38℃, 39℃, 40°C, and 41℃ (experimental group). The paired t-test was used to compare the measurement results between the groups. A Pearson correlation analysis was used to analyze the correlation between the measurement results of the experimental group and control group, and between the measurement results of experimental group and arterial blood gas parameters. RESULTS: There was no significant difference in TcPCO2 between each experimental subgroup (38-41℃) and the control group. TcPCO2 in each experimental subgroup (38-41℃) was strongly positively correlated with TcPCO2 in the control group (r>0.9, P<0.05) and arterial carbon dioxide partial pressure (r>0.8, P<0.05). There were significant differences in TcPO2 between each experimental subgroup (38-41℃) and the control group (P<0.05), but TcPO2 in each experimental subgroup (38-41℃) was positively correlated with TcPO2 in the control group (r=0.493-0.574, P<0.05) and arterial oxygen partial pressure (r=0.324-0.399, P<0.05). No skin injury occurred during transcutaneous measurements at all electrode temperatures. CONCLUSIONS: Lower electrode temperatures (38-41℃) can accurately measure blood carbon dioxide partial pressure in very low birth weight infants, and thus can be used to replace the electrode temperature of 42°C. Transcutaneous measurements at the lower electrode temperatures may be helpful for understanding the changing trend of blood oxygen partial pressure.

Berberine Attenuates Neonatal Sepsis in Mice By Inhibiting FOXA1 and NF-κB Signal Transduction Via the Induction of MiR-132-3p.

Neonatal sepsis (NS) is a severe syndrome in newborns that is induced by infections, and the initiation and development of NS are closely associated with the function of miRs. In the current study, the effects of berberine, which is a functional component in traditional Chinese medicine (TCM), against NS were assessed by focusing on the interaction of berberine with miR-132-3p-mediated signaling. An NS model was induced using cecal slurry (CS) in vivo and LPS in vitro, and berberine treatment was applies. The changes in survival rate, intestinal structure, and systemic inflammation in mice and the viability, apoptosis, and inflammatory response in intestinal cells were measured. At the molecular level, miR-132-3p levels and the activities of the FOXA1 and NF-κB pathways were analyzed. The data showed that berberine increased the survival rates of CS-induced mice. The intestinal injuries induced by CS were also attenuated by berberine, which was associated with inhibition of the production of systemic IL-6, IL-1ß, and TNF-α. At the molecular level, the expression of miR-132-3p was upregulated, suppressing the expression of FOXA1, p-IκBα, and p65 while inducing the expression of IκBα. The effects of berberine on NS-induced impairments were blocked by the injection of the miR-132-3p antagomir, which exacerbated intestinal injuries, induced systemic inflammation, and reactivated the FOXA1 and NF-κB pathways. The findings in the in vivo model were validated with in vitro assays. Collectively, the findings outlined in the current study indicated that berberine had solid protective effects against NS-induced symptoms in newborn mice, and the effects depended on the upregulation of miR-132-3p.

Early Diagnosis of Brain Injury in Premature Infants Based on Amplitude-Integrated EEG Scoring System.

Analyzing and discussing the relationship between brain injury in preterm infants and related risk factors can provide evidence for perinatal prevention and early intervention of brain injury in preterm infants, thereby improving the quality of life of preterm infants. This paper selects term preterm infants diagnosed with preterm infant asphyxia in the NICU of a university's First Affiliated Hospital from January 2018 to February 2019 as the research object. In addition, healthy term infants born at the same time in the obstetric department of this hospital are selected as the control group. Both groups of premature infants were monitored for brain function within 6 hours after birth. The aEEG results range from background activity (continuous normal voltage, discontinuous normal voltage, burst suppression, continuous low voltage, and plateau) and sleep-wake cycle (no sleep-wake cycle, immature, and mature sleep-wake cycle) to epileptic activity (single seizures, recurrent seizures, and status epilepticus), three aspects to judge. Statistical analysis uses SPSS 17.0 software. Amplitude-integrated EEG is a simplified form of continuous EEG recording. The trace of the trace represents the voltage change signal of the entire EEG background activity, which can reflect the EEG amplitude, frequency, burst-inhibition, and other pieces of information. aEEG can reflect the degree of HIE lesions in premature infants and the long-term prognosis. It is easy to operate and effective in diagnosis and can be continuously monitored. It is worthy of clinical popularization. There is a good correlation between the expression of EEG and biomarkers. Combining multiple methods can diagnose HIE earlier and evaluate the prognosis.

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.

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.

Effects of Taurine Supplementation on Growth in Low Birth Weight Infants: A Systematic Review and Meta-Analysis.

OBJECTIVE: To summarize the available randomized controlled trials (RCTs) to evaluate the effect of taurine supplementation on growth in low birth weight infants (LBW). METHODS: PubMed, EmBase, and Cochrane Library electronic databases were searched for published articles through March 2017. Analysis was done to examine the effect of taurine supplementation on growth, and sensitivity analysis was performed by removing each individual study from meta-analysis. RESULTS: Results of 9 trials totaling 216 LBW infants in the present meta-analysis were collected and analyzed. The conclusion of included studies demonstrated that taurine supplementation significantly reduced length gain (WMD:-0.18; P < 0.001), plasma glycine (WMD:-106.71; P = 0.033), alanine (WMD:-229.30; P = 0.002), leucine (WMD:-64.76; P < 0.001), tyrosine (WMD:-118.11; P < 0.001), histidine (WMD:-52.16; P < 0.001), proline (WMD: -84.29; P = 0.033), and asparagine-glutamine (WMD:-356.30; P < 0.001). However, taurine supplementation was associated with higher levels of acidic sterols (WMD:0.61; P = 0.024), total fatty acids (WMD:7.94; P = 0.050), total saturated fatty acids (WMD:9.70; P < 0.001), and unsaturated fatty acids (WMD:6.63; P < 0.001). Finally, taurine supplementation had little or no significant effect on weight gain, head circumference gain, plasma taurine, threonine, serine, citrulline, valine, methionine, isoleucine, phenylalanine, ornithine, lysine, arginine, glutamate, hydroxyproline, aspartate, dietary cholesterol, endogenous neutral sterols, cholesterol synthesis, and medium-chain triglycerides. CONCLUSIONS: The findings suggest that although there are several significant differences in plasma indeces, no significant effect on growth in LBW infants was observed with taurine supplementation.