Using a new human milk fortifier to optimize human milk feeding among very preterm and/or very low birth weight infants: a multicenter study in China.

BACKGROUND: Human milk fortifier (HMF) composition has been optimized recently. But clinical evidence of its safety and efficacy is limited in Chinese population. The aim of this study was to evaluate effects of a new HMF in growth, nutritional status, feeding intolerance, and major morbidities among very preterm (VPT) or very low birth weight (VLBW) infants in China. METHODS: VPT/VLBW infants admitted from March 2020 to April 2021 were prospectively included in the experimental (new HMF, nHMF) group, who received a new powdered HMF as a breast milk feeding supplement during hospitalization. Infants in the control group (cHMF) admitted from January 2018 to December 2019, were retrospective included, and matched with nHMF group infants for gestational age and birth weight. They received other kinds of commercially available HMFs. Weight gain velocity, concentrations of nutritional biomarkers, incidence of major morbidities, and measures of feeding intolerance were compared between the two groups. RESULTS: Demographic and clinical characteristics of infants in nHMF and cHMF groups were comparable. Weight gain velocity had no significant difference between the nHMF (14.0 ± 3.5 g/kg/d) and the cHMF group (14.2 ± 3.8 g/kg/d; P = 0.46). Incidence of morbidities, including necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, culture-confirmed sepsis, and feeding intolerance during hospitalization between nHMF and cHMF, were similar (all P-values > 0.05). The time to achieve full enteral feeding [13.5 (10, 21) days] in the nHMF group was significantly shorter than that in the cHMF group [17 (12, 23) days, HR = 0.67, 95%CI: 0.49, 0.92; P = 0.01]. Compared with cHMF group, the decrease of blood urea nitrogen level over time in nHMF group was smaller (ß = 0.6, 95%CI:0.1, 1.0; P = 0.01). CONCLUSIONS: The new HMF can promote growth of preterm infants effectively without increasing the incidence of major morbidity and feeding intolerance. It can be used feasible in Chinese VPT/VLBW infants. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT04283799).

Incidence and Risk Factors for Retinopathy of Prematurity in a Tertiary Hospital in China.

Purpose: To investigate the incidence and risk factors for the retinopathy of prematurity (ROP) in the neonatal intensive care unit (NICU) of Obstetrics and Gynecology Hospital of Affiliated to Nanjing Medical University, China. Methods: This retrospective case-control study included 611 preterm infants with birth weight (BW)<1500 grams admitted to the Department of Neonatology, Obstetrics and Gynecology Hospital of Affiliated to Nanjing Medical University between January 2019 and December 2022. The incidence and risk factors for any stage and severe ROP were analyzed. Results: Within 611 infants, 245(40.1%) developed ROP; 160(26.2%) infants were stage 1, 54(8.8%) were stage 2, and 31(5.1%) were stage 3, no stage 4 and 5. Among them, 22(3.6%) infants needed treatment. Multivariate analysis showed a higher gestational age (GA) was protective, whereas twin birth and moderate-to-severe BPD increased the hazard of any stage ROP; higher BW and male gender were significant risk factors for severe ROP. Conclusion: Compared to other tertiary hospitals, the incidence of any stage ROP in our NICU was higher, but the rate of ROP needed treatment was lower. A higher GA was protective, whereas twin birth and moderate-to-severe BPD increased the hazard of any stage ROP; higher BW was protective, whereas male gender were risk factors for the development of severe ROP.

CircABPD1 alleviates oxidative lung injury of bronchopulmonary dysplasia through regulating miR-330-3p/HIF1α axis.

In the NICU, bronchopulmonary dysplasia (BPD) is a concerning common respiratory complication in preterm and low birth-weight infants. Clinical studies have confirmed that human milk has an important nutritional role for children with BPD, therefore, dentification of beneficial components in human milk that prevent BPD is urgently needed. Our previous work showed that human milk exosomes (HM-Exos) could inhibit apoptosis of alveolar type II epithelial cells (AT II), and the circular RNA (circRNA)-circABPD1 were highly expressed in preterm colostrum milk exosomes. Exosomes transport circRNAs that are stable and may exert anti-inflammatory and immune effects attracted the attention of researchers, but the role and mechanism of human milk exosome-derived circABPD1 in BPD remains unclear. Here, we constructed BPD in vivo and in vitro models through exposure to hyperoxia, verified the effect of circABPD1 and revealed its mechanism through rescue experiments. We found that circABPD1 had circRNA properties, and overexpression of circABPD1 could improve reduced alveolar number, enlarged the alveolar linear intercept in vivo models of BPD, promote cell proliferation, reduce oxidative stress levels and alleviate lung epithelial cell damage in vivo and in vitro models. Mechanistically, circABPD1 targets miR-330-3p and regulates the expression of HIF1α. These results suggest that circABPD1 can improve the pathologoical changes of bronchopulmonary dysplasia, promote cell proliferation, inhibit oxidative stress level, and alleviate lung injury by targeting the miR-330-3p/HIF1α axis, which provides a new idea for the prevention and treatment of bronchopulmonary dysplasia.

Short-time mortality and severe complications of very premature infants-a multicenter retrospective cohort study from Jiangsu Province during 2019-2021.

Background: The short-term and long-term severe complications of preterm infants have brought serious psychological and economic burdens to the society and family. Therefore, our study aimed to investigate the risk factors for the mortality and serious complications in very premature infants less than 32 weeks of gestational age (GA), so as to guide the antenatal and postnatal care of very premature. Methods: The very premature infants from 1 January 2019 to 31 December 2021 from 15 member hospitals of the Neonatal Intensive Care Unit (NICU) Multi-center Clinical Research Collaboration Group in Jiangsu Province were recruited. In accordance with the plan of the intensive care unit for unified management, recruitment of premature infants is carried out on the day of admission, and discharge or death is the outcome indicator in 1-2 months by telephone follow-up. The research content mainly includes three aspects: clinical information of mother and infant, outcomes and complications. According to the final outcomes, very premature infants were divided into two categories: survival without severe complications, survival with severe complications and death. Then, univariate and multivariate logistic regression model and receiver operating characteristic (ROC) analyses were used to analyze the independent risk factors. Results: A total of 3,200 very premature infants with GA less than 32 weeks were recruited. The median GA is 30.00 (28.57, 31.14) weeks, the average birth weight is 1,350 (1,110, 1,590) g, among whom 375 premature infants survived with severe complications, and 2,391 premature infants survived without severe complications. Then, it was found that GA at birth was a protective factor for death and severe complications, whereas severe neonatal asphyxia and persistent pulmonary hypertension of the newborn (PPHN) were independent risk factors for death and severe complications in very premature infants born at less than 32 weeks of gestation. Conclusions: The prognosis of very premature infants in NICU treatment depends not only on GA, but also on various perinatal factors and their clinical management, such as preterm asphyxia and PPHN occurrence, so the next step is necessary for multicenter continuous quality improvement to improve outcomes in very preterm infants.

Inhaled nitric oxide in premature infants for preventing bronchopulmonary dysplasia: a meta-analysis.

BACKGROUND: The effectiveness of nitric oxide (NO) in reducing the risk of bronchopulmonary dysplasia (BPD) remains debatable. In this study, we performed a meta-analysis to guide clinical decision-making regarding the significance of inhaled NO (iNO) on the potential occurrence and outcomes of BPD in premature infants. METHODS: Data from clinical randomized controlled trials (RCTs) published in PubMed, Embase, Cochrane Library, Wanfang, China National Knowledge Infrastructure (CNKI) and Chinese Scientific Journal Database VIP databases for premature infants were searched from inception to March 2022. Review Manager 5.3 statistical software was used for heterogeneity analysis. RESULTS: Of the 905 studies retrieved, 11 RCTs met the screening criteria of this study. Our analysis showed that the iNO group was associated with a significantly lower incidence of BPD than the control group (relative risk [RR] = 0.91, 95% confidence interval (CI) 0.85-0.97, P = 0.006). We also observed no significant difference in the incidence of BPD between the two groups at the initial dose of 5 ppm (ppm) (P = 0.09) but those treated with 10 ppm iNO had a significantly lower incidence of BPD (RR = 0.90, 95%CI 0.81-0.99, P = 0.03). However, it should be noted that although the iNO group had an increased risk for necrotizing enterocolitis (NEC) (RR = 1.33, 95%CI 1.04-1.71, P = 0.03), cases treated with an initial dose of 10 ppm revealed no significant difference in the incidence of NEC compared with the control group (P = 0.41), while those treated with an initial dosage of 5 ppm of iNO had a significantly greater NEC rates than the control group (RR = 1.41, 95%CI 1.03-1.91, P = 0.03). Further, we observed no statistically significant differences in the incidence of in-hospital mortality, intraventricular hemorrhage (IVH) (Grade 3/4) or periventricular leukomalacia (PVL) and pulmonary hemorrhage (PH) between the two treatment groups. CONCLUSIONS: This meta-analysis of RCTs showed that iNO at an initial dosage of 10 ppm seemed more effective in reducing the risk of BPD than conventional treatment and iNO at an initial dosage of 5 ppm in preterm infants at a gestational age of ≤34 weeks who required respiratory support. However, the incidence of in-hospital mortality and adverse events between the overall iNO group and Control were similar.

The casein-derived peptide YFYPEL alleviates intestinal epithelial cell dysfunction associated with NEC by regulating the PI3K/AKT signaling pathway.

Necrotizing enterocolitis (NEC) is a life-threatening risk to the health of neonates, but thus far, there is no very effective treatment. Although many studies have confirmed the therapeutic role of peptides in diseases, the effect of peptides in NEC remains poorly understood. This study investigated the role of casein-derived peptide YFYPEL in NEC cells and animal models. We synthesized YFYPEL and analysed its protective effects on NEC both in vitro and in vivo. YFYPEL integration in the intestine increased rat survival and clinical conditions, lowered the incidence of NEC, alleviated bowel inflammation, and enhanced intestinal cell migration. Furthermore, YFYPEL significantly decreased interleukin 6 expression and increased intestinal epithelial cell migration. Moreover, YFYPEL alleviated intestinal epithelial cell dysfunction through the PI3K/AKT pathway, as demonstrated by western blotting and bioinformatics analysis. A selective PI3K activator reversed the protective effect of YFYPEL on lipopolysaccharide-stimulated intestinal epithelial cells. Our study showed that YFYPEL reduced inflammatory cytokine expression and enhanced migration by regulating the PI3K/AKT pathway. The use of YFYPEL may thus develop into a novel modality in NEC treatment.

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.

LncRNA and mRNA profiles of human milk-derived exosomes and their possible roles in protecting against necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is one of the most severe diseases commonly afflicting premature infants. Our previous studies suggests that human milk-derived exosomes (HM-Exos) have a potential therapeutic effect on NEC. In this study, we investigate the potentially therapeutic role of HM-Exos in an NEC animal model via comprehensive lncRNA and mRNA expression profiles. A rat model of NEC was induced through hypoxia, hypothermia and formula feeds. We extracted exosomes from the colostrum of healthy lactating mothers and identified their functions in an NEC animal model. Furthermore, high-throughput lncRNA and mRNA sequencings were explored to find the underlying mechanisms. Although both exosomes from term human breast milk (Term-Exos) and exosomes from preterm human breast milk (Pre-Exos) alleviated the severity of NEC, Pre-Exos seemed to better promote the proliferation of intestinal epithelial cells in vivo. We identified a total of 44 differentially expressed lncRNAs and 88 differentially expressed mRNAs between Term-Exos and Pre-Exos. Further GO and KEGG pathway analysis showed that the lncRNA-mRNA network of HM-Exos was associated with the JAK-STAT signaling pathway, bile secretion and the AMPK signaling pathway, which are predicted to be involved in the proliferation of cells. Therefore, this study reveals for the first time the important roles of human milk derived lncRNAs and mRNAs in protecting against necrotizing enterocolitis. These results provide new insight into the development of NEC.

Mechanical ventilation characteristics and their prediction performance for the risk of moderate and severe bronchopulmonary dysplasia in infants with gestational age <30 weeks and birth weight <1,500†g.

Introduction: Moderate and severe bronchopulmonary dysplasia (BPD) is a common pulmonary complication in premature infants, which seriously affects their survival rate and quality of life. This study aimed to describe the mechanical ventilation characteristics and evaluate their prediction performance for the risk of moderate and severe BPD in infants with gestational age <30 weeks and birth weight <1,500 g on postnatal Day 14. Methods: In this retrospective cohort study, 412 infants with gestational age <30 weeks and birth weight <1,500 g were included in the analysis, including 104 infants with moderate and severe BPD and 308 infants without moderate and severe BPD (as controls). LASSO regression was used to optimize variable selection, and Logistic regression was applied to build a predictive model. Nomograms were developed visually using the selected variables. To validate the model, receiver operating characteristic (ROC) curve, calibration plot, and clinical impact curve were used. Results: From the original 28 variables studied, six predictors, namely birth weight, 5 min apgar score, neonatal respiratory distress syndrome (≥Class II), neonatal pneumonia, duration of invasive mechanical ventilation (IMV) and maximum of FiO2 (fraction of inspiration O2) were identified by LASSO regression analysis. The model constructed using these six predictors and a proven risk factor (gestational age) displayed good prediction performance for moderate and severe BPD, with an area under the ROC of 0.917 (sensitivity = 0.897, specificity = 0.797) in the training set and 0.931 (sensitivity = 0.885, specificity = 0.844) in the validation set, and was well calibrated (P Hosmer-Lemeshow test = 0.727 and 0.809 for the training and validation set, respectively). Conclusion: The model included gestational age, birth weight, 5 min apgar score, neonatal respiratory distress syndrome (≥Class II), neonatal pneumonia, duration of IMV and maximum of FiO2 had good prediction performance for predicting moderate and severe BPD in infants with gestational age <30 weeks and birth weight <1,500 g on postnatal Day 14.

Peptide Tat(48-60) YVEEL protects against necrotizing enterocolitis through inhibition of toll-like receptor 4-mediated signaling in a phosphatidylinositol 3-kinase/AKT dependent manner.

Necrotizing enterocolitis (NEC) is a catastrophic disease largely occurring in preterm infants, and toll-like receptor 4 (TLR4) has been implicated in its pathogenesis. The current therapeutic strategies for NEC are, however, far from optimal. In the present study, a whey-derived antioxidative peptide conjugated with a cell-penetrating TAT [Tat (48-60) YVEEL] was prepared to endow it with enhanced cell uptake capability and bioavailability. The protective effect of Tat (48-60) YVEEL on experimental NEC was evaluated both in vitro and in vivo. Inhibition of TLR4-mediated signaling by Tat (48-60) YVEEL was assessed in FHC and IEC-6 enterocytes, neonatal rat model of NEC, and the mechanism underlying this effect was determined. Tat (48-60) YVEEL significantly inhibited TLR4-mediated expression of pro-inflammatory cytokines, p65 nuclear translocation and restored the impaired enterocyte migration in cultured enterocytes. In addition, Tat (48-60) YVEEL administration strikingly increased the survival rate, and reduced the severity of NEC in rats through inhibition of TLR4-mediated signaling. These protective effects of Tat (48-60) YVEEL occurred in a PI3K/AKT dependent manner, as administration of PI3K activator Ys49 abrogated its protective effects. Combined with liposomes, Tat (48-60) YVEEL demonstrated longer retention in the intestines that better for potential clinical applications. These data demonstrate that Tat (48-60) YVEEL protects against NEC through inhibition of TLR4-mediated signaling in a PI3K/AKT dependent manner, and offer a potential therapeutic approach to this disease.

[Antibiotic use in very low birth weight/extremely low birth weight infants in 15 hospitals in Jiangsu Province of China: a multicenter survey]. / 江苏省15家医院极低/è¶ ä½Žå‡ºç”Ÿä½“é‡å„¿æŠ—ç”Ÿç´ ä½¿ç”¨çŽ°çŠ¶è°ƒæŸ¥.

OBJECTIVES: To investigate the current status of antibiotic use in very low birth weight/extremely low birth weight infants in Jiangsu Province of China, and to provide a clinical basis for the quality and improvement of antibiotic management in the neonatal intensive care unit (NICU). METHODS: A retrospective analysis was performed on the data on general conditions and antibiotic use in the very low birth weight/extremely low birth weight infants who were admitted to 15 hospitals of Jiangsu Province from January 1, 2019 to December 31, 2020. A questionnaire containing 10 measures to reduce antibiotic use was designed to investigate the implementation of these intervention measures. RESULTS: A total of 1 920 very low birth weight/extremely low birth weight infants were enrolled, among whom 1 846 (96.15%) were treated with antibiotic, and the median antibiotic use rate (AUR) was 50/100 patient-days. The AUR ranged from 24/100 to 100/100 patient-days in the 15 hospitals. After adjustment for the confounding factors including gestational age, birth weight, and neonatal critical score, the Poisson regression analysis showed that there was a significant difference in the adjusted AUR (aAUR) among the hospitals (P<0.01). The investigation results showed that among the 10 measures to reduce antibiotic use, 8 measures were implemented in less than 50% of these hospitals, and the number of intervention measures implemented was negatively correlated with aAUR (rs=-0.564, P=0.029). CONCLUSIONS: There is a high AUR among the very low birth weight/extremely low birth weight infants in the 15 hospitals of Jiangsu Province, with a significant difference among hospitals. The hospitals implementing a relatively few measures to reduce antibiotic use tend to have a high AUR. It is expected to reduce AUR in very low birth weight/extremely low birth weight infants by promoting the quality improvement of antibiotic use management in the NICU.

Effects of a WeChat Mini-Program on Human Milk Feeding Rates in a Neonatal Intensive Care Unit During the COVID-19 Pandemic.

Objective: We investigated changes in maternal daily milk pumping frequency and milk volume per expression and their derived lactation indicators, as well as human milk (HM) feeding status with a focus on amount and rates in preterm infants admitted to the neonatal intensive care unit (NICU) after using a WeChat mini-program during the 2019 coronavirus (COVID-19) pandemic. Methods: The study was conducted with 482 mothers and their 544 babies. We prospectively enrolled mothers and infants with birth weight <1,500 g or gestational age <32 weeks born in 2020, and retrospectively included the same population in 2019. All study subjects were classified into three subgroups: pre-pandemic (PP, 2019), early pandemic (EP, January to April 2020), and late pandemic (LP, May to December 2020). From 1 January 2020, mothers recorded in an online pumping diary using the WeChat mini-program. We obtained the infants' feeding information from an online database for analysis. Results: Maternal lactation indicators did not change significantly. However, 56.7% (139/245) of mothers achieved milk volume ≥500 ml/day (CTV) in PP, 58.9% (33/156) in EP, and a slight increase to 60.7% (91/150) in LP. Maternal pumping frequency remained about eight times/day. In LP, daily milk volume was higher than the other two periods from day 4, and mothers achieved CTV by day 12, which was achieved in the other two groups by 13-14 days. There were several statistical differences in the amount and rates of feeding between the groups, particularly about HM and donor milk feeding, with the vast majority being decreased during EP, while during LP they returned to PP levels. Pleasingly, the median average daily dose of HM at 1-28 days was highest in LP (LP, 87.8 vs. PP, 75.5 or EP, 52.6 ml/kg/day, P corrected < 0.001). In addition, most categorical feeding indicators decreased in EP and recovered in LP. Conclusion: An education model based on the WeChat program could aid lactation education and management in mothers of preterm infants to maintain healthy lactation. The model, together with optimized management strategies, can ensure that the HM feeding rate is not compromised in vulnerable high-risk infants during NICU hospitalization in a public health emergency, like the COVID-19 pandemic.

[Preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and influencing factors for follow-up compliance: a multicenter investigation]. / äº§ç§‘å‡ºé™¢åŽå› ä¸¥é‡é«˜èƒ†çº¢ç´ è¡€ç—‡ä½é™¢æ–°ç”Ÿå„¿å ¥é™¢å‰éšè®¿æƒ å†µåŠéšè®¿ä¾ä»Žæ€§å½±å“å› ç´ çš„å¤šä¸­å¿ƒè°ƒæŸ¥.

OBJECTIVES: To investigate the preadmission follow-up condition of neonates hospitalized due to severe hyperbilirubinemia after discharge from the department of obstetrics and the influencing factors for follow-up compliance. METHODS: A multicenter retrospective case-control study was performed for the cases from the multicenter clinical database of 12 units in the Quality Improvement Clinical Research Cooperative Group of Neonatal Severe Hyperbilirubinemia in Jiangsu Province of China from January 2019 to April 2021. According to whether the follow-up of neonatal jaundice was conducted on time after discharge from the department of obstetrics, the neonates were divided into two groups: good follow-up compliance and poor follow-up compliance. The multivariate logistic regression model was used to identify the influencing factors for follow-up compliance of the neonates before admission. RESULTS: A total of 545 neonates with severe hyperbilirubinemia were included in the study, with 156 neonates (28.6%) in the good follow-up compliance group and 389 (71.4%) in the poor follow-up compliance group. The multivariate logistic regression analysis showed that low gestational age at birth, ≥10% reduction in body weight on admission compared with birth weight, history of phototherapy of siblings, history of exchange transfusion of siblings, Rh(-) blood type of the mother, a higher educational level of the mother, the use of WeChat official account by medical staff to remind of follow-up before discharge from the department of obstetrics, and the method of telephone notification to remind of follow-up after discharge were associated with the increase in follow-up compliance (P<0.05). CONCLUSIONS: Poor follow-up compliance is observed for the neonates with severe hyperbilirubinemia after discharge from the department of obstetrics, which suggests that it is necessary to further strengthen the education of jaundice to parents before discharge and improve the awareness of jaundice follow-up. It is recommended to remind parents to follow up on time by phone or WeChat official account.

Transition From Parenteral to Enteral Nutrition and Postnatal Growth in Very Preterm Infants During Their First 28 Days of Life.

Background: Nutrition practices for preterm infants during the first few weeks of life can be divided into three phases: the parenteral nutrition (PN), enteral nutrition (EN), and transition (TN) phases; the TN phase includes both PN and EN. Our purpose was to analyze nutrition practices for very preterm infants during the TN phase and their association with the infants' growth during the first 28 days of life. Methods: Data from 268 very preterm infants <32 weeks old from six neonatal intensive care units were analyzed retrospectively. The TN phase was defined as enteral feedings of 30-120 ml/kg/d. Postnatal growth failure (PGF) was defined as a 28-day growth velocity <15 g/kg/d. Differences in protein and energy intake between the PGF and non-PGF groups during the TN phase were calculated, and risk factors for PGF were identified using multivariate regression analysis. Results: The total protein (parenteral + enteral) intake during the TN was 3.16 (2.89, 3.47) g/kg/d, which gradually decreased as the enteral feeding volume increased in the TN phase. The total energy (parenteral + enteral) intake during the TN phase was 115.72 (106.98, 122.60) kcal/kg/d. The PGF group had a lower total protein intake (parenteral + enteral) than the non-PGF group had [3.09 (2.85, 3.38) g/kg/d vs. 3.27 (3.06, 3.57) g/kg/d, P = 0.007, respectively]. No significant difference was found in energy intake during the TN phase. The variables associated with PGF included a lower total protein (parenteral + enteral) intake, a smaller day of age at the end of the TN phase, and a higher birth weight z-score. Conclusion: Increasing the total protein intake (parenteral + enteral) during the TN could reduce the incidence of PGF.

The role of polypeptide PDTLN1 in suppression of PI3K/AKT signaling causes cardiogenetic disorders in vitro and in vivo.

AIMS: A new polypeptide, PDTLN1, derived from the human Talin-1 protein, which is highly expressed in both myocardial tissue and maternal peripheral blood of aborted fetuses with congenital heart disease (CHD). However, its role in cardiac developmental disorders has not been disclosed till now. In the present study, we aim to assess the functions of PDTLN1 in heart development of zebrafish and cellular viability, proliferation, and apoptosis of P19 cells. MAIN METHODS: Cellular viability was assessed by Cell Counting Kit-8, the EdU Kit was used to evaluate cellular proliferation, and apoptosic rate of P19 was examined using FITC Annexin-V staining followed by flow cytometry. The zebrafish embryos were divided into three groups: PEP group and NC group were microinjected with polypeptides, WT group without any intervention. The protein expression of PI3K/AKT were evaluated by western blotting. KEY FINDINGS: PDTLN1 could suppress the proliferation, and facilitate apoptosis. PDTLN1 caused abnormal heart development of zebrafish embryos and the PDTLN1 (50 µM)-injected group showed an aberrant expression pattern of vmhc, amhc and cmlc2. Compared to the CTL group and SC79 group of P19 cells, the PDTLN1 group had a lower phosphorylated PI3K/AKT proteins level, decreased cellular viability and lower proliferation activity. SIGNIFICANCE: PDTLN1 caused cardiac developmental defects in zebrafish, inhibited cellular viability, proliferation, and promoted apoptosis of P19 cells via suppressing the PI3K/AKT signaling pathway. Our findings provide a fresh perspective on the functional mechanism of human-derived peptides and may promote novel diagnostic biomarkers detection and therapeutic targets in CHD.

Differential Expression Profiles and Functional Prediction of circRNAs in Necrotizing Enterocolitis.

Circular RNAs (circRNAs), a novel type of noncoding RNAs, have been demonstrated to behave as microRNA (miRNA) sponges to exert their effects during pathological processes of diseases. However, the roles of circRNAs have not been explored in necrotizing enterocolitis (NEC). This study sought to identify differentially expressed circRNAs and predict their potential biological functions in NEC. circRNA expression profiles in terminal ileum from newborn rats with NEC and normal controls were explored using next-generation sequencing. In the NEC group, 53 circRNAs were significantly differentially expressed, including 9 upregulated and 44 downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted, and circRNA-miRNA interaction networks were generated to predict the potential roles of circRNAs in NEC progression. Further investigation revealed that most circRNAs include miRNA binding sites and that some are implicated in NEC development. In conclusion, this study's findings demonstrate that differentially expressed circRNAs are involved in NEC development via their interactions with miRNAs, making them prospective targets for NEC diagnosis and treatment.

Using a WeChat mini-program-based lactation consultant intervention to increase the consumption of mother's own milk by preterm infants in the neonatal intensive care unit: a study protocol for a cluster randomized controlled trial.

BACKGROUND: The benefits of mother's own milk (MOM) for preterm infants have been widely recognized. Many studies have shown that the rate of breastfeeding of premature infants remains very low. Although many studies use measures to promote breastfeeding, few high-quality cluster randomized controlled studies have evaluated the effectiveness of these measures. WeChat is an instant messaging software for smart terminals, and WeChat mini-programs have been widely used to promote health and self-management in China. Based on this background, we designed a randomized controlled study based on WeChat mini-programs to promote MOM feeding of premature infants in the neonatal intensive care unit (NICU). METHODS/DESIGN: This study will evaluate the effectiveness of WeChat mini-programs to increase the consumption of MOM feeding in twelve NICUs in Jiangsu Province, namely, six "intervention" NICUs and six "control" NICUs. The study process is as follows: (1) design and preparation, (2) NICU recruitment and training, (3) interpretation and analysis of baseline data, (4) quality control implementation process, and (5) data analysis feedback and publication of study reports. The primary outcome is the proportion of MOM feeding of premature infants during NICU hospitalization. The secondary outcomes are as follows: (1) time to initiation of MOM feeding (hours) and proportion of first-time MOM feeding (%), (2) duration of parenteral nutrition (days), (3) time to total gastrointestinal feeding (days), (4) hospitalization time and hospitalization cost, and (5) incidence of complications (necrotizing enterocolitis, bronchopulmonary dysplasia, feeding intolerance, late-onset sepsis, retinopathy of prematurity). DISCUSSION: This study is the first cluster randomized controlled trial on the intervention of using a WeChat mini-program-based lactation consultant for premature infants in the NICU in China. We hope this study can improve the consumption of MOM by NICU premature infants during hospitalization through the intervention of WeChat mini-programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04383379. Registered on May 5, 2020.

A multicenter retrospective study on survival rate and complications of very preterm infants. / æžæ—©äº§å„¿å­˜æ´»çŽ‡å’Œå¹¶å‘ç—‡çš„å¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To study the survival rate and the incidence of complications of very preterm infants and the factors influencing the survival rate and the incidence of complications. METHODS: The medical data of the very preterm infants with a gestational age of <32 weeks and who were admitted to the Department of Neonatology in 11 hospitals of Jiangsu Province in China from January 2018 to December 2019 were retrospectively reviewed. Their survival rate and the incidence of serious complications were analyzed. A multivariate logistic regression analysis was used to evaluate the risk factors for death and serious complications in very preterm infants. RESULTS: A total of 2 339 very preterm infants were enrolled, among whom 2 010 (85.93%) survived and 1 507 (64.43%) survived without serious complications. The groups with a gestational age of 22-25+6 weeks, 26-26+6 weeks, 27-27+6 weeks, 28-28+6 weeks, 29-29+6 weeks, 30-30+6 weeks, and 31-31+6 weeks had a survival rate of 32.5%, 60.6%, 68.0%, 82.9%, 90.1%, 92.3%, and 94.8% respectively. The survival rate tended to increase with the gestational age (P<0.05) and the survival rate without serious complications in each gestational age group was 7.5%, 18.1%, 34.5%, 52.2%, 66.7%, 75.7%, and 81.8% respectively, suggesting that the survival rate without serious complications increased with the gestational age (P<0.05). The multivariate logistic regression analysis showed that high gestational age, high birth weight, and prenatal use of glucocorticoids were protective factors against death in very preterm infants (P<0.05), and 1-minute Apgar score ≤3 was a risk factor for death in very preterm infants (P<0.05); high gestational age and high birth weight were protective factors against serious complications in very preterm infants who survived (P<0.05), while 5-minute Apgar score ≤3 and maternal chorioamnionitis were risk factors for serious complications in very preterm infants who survived (P<0.05). CONCLUSIONS: The survival rate is closely associated with gestational age in very preterm infants. A low 1-minute Apgar score (≤3) may increase the risk of death in very preterm infants, while high gestational age, high birth weight, and prenatal use of glucocorticoids are associated with the reduced risk of death. A low 5-minute Apgar score (≤3) and maternal chorioamnionitis may increase the risk of serious complications in these infants, while high gestational age and high birth weight may reduce the risk of serious complications.

Evaluation of nutrition status of very preterm infants in neonatal intensive care units using different growth indicators.

BACKGROUND:  Nutrition status of very preterm infants in the neonatal intensive care unit (NICU) is strongly associated with postnatal growth. This study aimed to develop indicators of nutrition status using growth data of very preterm infants during hospitalization. METHODS: The data of 596 newborns from eight NICUs were retrospectively analyzed. Inclusion criteria were birth at <32 weeks' gestation, NICU admission ≤24 h after delivery, and length of hospital stay ≥28 days. Three indicators were evaluated: (indicator I) prevalence of extrauterine growth restriction (EUGR); (indicator II) z-score for change in weight from birth to discharge, adjusted for birth weight z-score and gestational age; and (indicator III) change in weight z-score from birth to discharge, adjusted for birth weight z-score, gestational age, and time to regain birth weight. Using data from NICU 1 as the reference for the latter two indicators, we established linear regression models of the adjusted change in weight z-score from birth to discharge. The difference between the observed value and the baseline value (calculated by the two models) served as the nutrition indices. RESULTS: The prevalence of EUGR differed significantly between the eight NICUs (P = .009). Statistically significant differences were found between the mean indices calculated by the other two models (all P < .05). CONCLUSIONS: Indicator III, change in weight z-score from birth to discharge (adjusted for birth weight z-score, gestational age, and time to regain birth weight), appears to be the most accurate for evaluating the quality of nutrition in the NICU.