[Influence of the coronavirus disease 2019 pandemic on maternal breastfeeding for very low birth weight infants]. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žç–«æƒ å¯¹æžä½Žå‡ºç”Ÿä½“é‡å„¿äº²æ¯æ¯ä¹³å–‚å »çš„å½±å“.

OBJECTIVES: To investigate the changes in the rate and volume of mother's own milk (MOM) feeding for very low birth weight infants (VLBWIs) hospitalized during the prevention and control of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective analysis was performed on the medical data of the VLBWIs with a gestational age of <32 weeks who were born and admitted to the Neonatal Intensive Care Unit of Nanjing Maternal and Child Health Hospital from January 2019 to December 2020. The changes in the rate and volume of MOM feeding for VLBWIs during hospitalization were examined. RESULTS: A total of 301 VLBWIs were enrolled. According to the timing of COVID-19 outbreak, these infants were divided into a pre-CIVID-19 group with 205 VLBWIs and a post-COVID-19 group with 96 VLBWIs. Compared with the pre-CIVID-19 group, the post-COVID-19 group had a significantly lower rate of MOM feeding within 28 days after birth and during hospitalization (P<0.05), a significantly lower volume of MOM feeding within 0-7 days, 0-14 days, and 0-28 days after birth (P<0.05), and significantly higher incidence rates of moderate-to-severe bronchopulmonary dysplasia and feeding intolerance (P<0.05). CONCLUSIONS: The COVID-19 pandemic has a significant impact on MOM feeding for VLBWIs, and there are significant reductions in the rate and volume of MOM feeding for VLBWIs within 28 days after birth, as well as a significant reduction in the rate of MOM feeding during hospitalization.

Prediction Models for Bronchopulmonary Dysplasia in Preterm Infants: A Systematic Review.

Objective: To provide an overview and critical appraisal of prediction models for bronchopulmonary dysplasia (BPD) in preterm infants. Methods: We searched PubMed, Embase, and the Cochrane Library to identify relevant studies (up to November 2021). We included studies that reported prediction model development and/or validation of BPD in preterm infants born at ≤32 weeks and/or ≤1,500 g birth weight. We extracted the data independently based on the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS). We assessed risk of bias and applicability independently using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Results: Twenty-one prediction models from 13 studies reporting on model development and 21 models from 10 studies reporting on external validation were included. Oxygen dependency at 36 weeks' postmenstrual age was the most frequently reported outcome in both development studies (71%) and validation studies (81%). The most frequently used predictors in the models were birth weight (67%), gestational age (62%), and sex (52%). Nearly all included studies had high risk of bias, most often due to inadequate analysis. Small sample sizes and insufficient event patients were common in both study types. Missing data were often not reported or were discarded. Most studies reported on the models' discrimination, while calibration was seldom assessed (development, 19%; validation, 10%). Internal validation was lacking in 69% of development studies. Conclusion: The included studies had many methodological shortcomings. Future work should focus on following the recommended approaches for developing and validating BPD prediction models.

[Clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation: a multicenter retrospective analysis].

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (n=1 184), tracheal intubation (n=166), and extensive cardiopulmonary resuscitation (ECPR; n=116). The three groups were compared in terms of general information and clinical outcomes. RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid (P < 0.05). As the intensity of resuscitation increased, the Apgar scores at 1 minute and 5 minutes gradually decreased (P < 0.05), and the proportion of infants with Apgar scores of 0 to 3 at 1 minute and 5 minutes gradually increased (P < 0.05). Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly higher mortality rate and incidence rates of moderate-severe bronchopulmonary dysplasia and serious complications (P < 0.05). The incidence rates of grade Ⅲ-Ⅳ intracranial hemorrhage and retinopathy of prematurity (stage Ⅲ or above) in the tracheal intubation group were significantly higher than those in the non-tracheal intubation group (P < 0.05). CONCLUSIONS: For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.

[Association of early nutrition deficiency with the risk of bronchopulmonary dysplasia: a Meta analysis].

OBJECTIVE: To systematically evaluate the association of early nutrition intake with the risk of bronchopulmonary dysplasia (BPD). METHODS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, and Weipu Periodical Database were searched for the observational studies on the association between early nutrition intake and BPD. RevMan 5.3 software was used to perform a Meta analysis of eligible studies. RESULTS: Eight observational studies were included, with 548 infants with BPD and 522 infants without BPD. The Meta analysis showed that the BPD group had a significantly lower caloric intake than the non-BPD group within the first week after birth and in the first 2 weeks after birth (P < 0.05). The BPD group had a significantly lower enteral nutrition intake than the non-BPD group (WMD=-18.27, 95%CI:-29.70 to -6.84, P < 0.05), as well as a significantly lower intake of carbohydrate, fat, and protein (P < 0.05). The BPD group had a significantly longer duration of parenteral nutrition than the non-BPD group (WMD=14.26, 95%CI:13.26-15.25, P < 0.05). CONCLUSIONS: Early nutrition deficiency may be associated with the development of BPD, and more attention should be paid to enteral feeding of infants at a high risk of BPD to achieve total enteral feeding as soon as possible.

[Influence of twin pregnancy by assisted reproductive technology on neonatal outcomes].

OBJECTIVE: To study the influence of twin pregnancy by assisted reproductive technology (ART) versus twin pregnancy by spontaneous conception (SC) on neonatal outcomes. METHODS: A retrospective analysis was performed for the clinical data of 3 356 live twins with a gestational age of ≥24 weeks who were born in Nanjing Maternal and Child Health Hospital from 2017 to 2019, with 2 006 twins (1 003 pairs) in the ART group and 1 350 (675 pairs) in the SC group. The two groups were compared in terms of the mother's general information and pregnancy comorbidities and the general information, diseases, and outcomes of neonates. RESULTS: Compared with the SC group, the ART group had a significantly higher maternal age (P < 0.05) and significantly higher rates of primiparity, cesarean section, and cervical cerclage (P < 0.05). Compared with the SC group, the ART group had significantly higher incidence rates of maternal pregnancy comorbidities including hypertension, gestational diabetes, and postpartum hemorrhage (P < 0.05). Compared with the SC group, the ART group had a significantly lower mean gestational age of neonates (P < 0.05) and a significantly higher proportion of very-low-birth-weight infants (6.8% vs 5.8%, P < 0.05), while ART did not increase the risks of preterm birth and low Apgar score. There were no significant differences between the two groups in the mortality rate of neonates and the incidence rates of neonatal diseases including respiratory distress syndrome, stage II/III necrotizing enterocolitis, bronchopulmonary dysplasia, and grade III-IV intracranial hemorrhage (P > 0.05). CONCLUSIONS: Compared with twin pregnancy by SC, twin pregnancy by ART does not increase the neonatal mortality rate and risk of adverse outcomes.

Profiles analysis reveals circular RNAs involving zebrafish physiological development.

Recent studies have found that known functions of circular RNAs (circRNAs) include sequestration of microRNAs (miRNAs) or proteins, modulation of transcription and interference with splicing, and even translation to produce polypeptides. The zebrafish model is also demonstrably similar to humans in many studies. To explore the changes in circRNAs during embryonic development and to further research the mechanism of action of circRNAs in development-related diseases, Zebrafish embryos at the blastula period, gastrula period, segmentation period, throat stage, and incubation period were collected. Illumina deep-sequencing technology and CircRNA Identifier (CIRI) algorithm were used to detect circRNAs. In total, we identified 1,028 circRNAs (junction reads ≥5 and p < 0.05). Considering that the function of circRNAs is related to host genes, a bioinformatics analysis revealed these differentially expressed host genes are involved in NOTCH signaling pathways, cardiovascular system development, retinal ganglion cell axon guidance, and so on. Moreover, circRNAs can participate in biological regulation through the function of miRNA sponges. TargetScan and miRanda were used to predict 73 miRNAs binding to circRNAs such as miR-19b, miR-124, and so on. Some miRNAs play important roles in embryogenesis. The peak expression of circRNAs is distributed at different time points, suggesting that it may be involved in embryogenesis at different stages. Our study provides a foundation for understanding the dynamic regulation of circRNA transcriptomes during embryogenesis and identifies novel key circRNAs that might control embryonic development in a zebrafish model.

Peptidomic Analysis of Amniotic Fluid for Identification of Putative Bioactive Peptides in Ventricular Septal Defect.

BACKGROUND: Ventricular septal defect (VSD) is one of the most common congenital heart diseases and to date the role of peptides in human amniotic fluid in the pathogenesis of VSD have been rarely investigated. METHODS: To gain insight into the mechanisms of protein and peptides in cardiovascular development, we constructed a comparative peptidomic profiling of human amniotic fluid between normal and VSD fetuses using a stable isobaric labeling strategy involving tandem mass tag reagents, followed by nano liquid chromatography tandem mass spectrometry. RESULTS: We identified and quantified 692 non-redundant peptides, 183 of which were differentially expressed in the amniotic fluid of healthy and VSD fetuses; 69 peptides were up regulated and 114 peptides were down regulated. These peptides were imported into the Ingenuity Pathway Analysis (IPA) and identified putative roles in cardiovascular system morphogenesis and cardiogenesis. CONCLUSION: We concluded that 35 peptides located within the functional domains of their precursor proteins could be candidate bioactive peptides for VSD. The identified peptide changes in amniotic fluid of VSD fetuses may advance our current understanding of congenital heart disease and these peptides may be involved in the etiology of VSD.

Effects of miR-19b overexpression on proliferation, differentiation, apoptosis and Wnt/ß-catenin signaling pathway in P19 cell model of cardiac differentiation in vitro.

MicroRNA (miR)-19b is part of the miR-17-92 cluster associated with cardiac development. Here, we investigated the effects of overexpressing miR-19b on proliferation, differentiation, apoptosis, and regulation of the Wnt/ß-catenin signaling pathway in the multipotent murine P19 cell line that can be induced to undergo cardiogenesis. P19 cells were transfected with the miR-19b plasmid or empty vector, and miR-19b overexpression was verified by Quantitative Real-Time PCR (qPCR). The miR-19b or vector control stable cell lines were selected using Blasticidin S HCl, and their proliferation, cell cycle, and apoptosis levels were analyzed using the Cell Counting Kit-8 and flow cytometry. P19 cell differentiation markers, apoptosis-related genes (bax, bcl-2), and Wnt/ß-catenin signaling pathway-related genes were detected by qPCR, the corresponding proteins by Western blot. Expression of the Wnt pathway and differentiation marker proteins was also verified by immunofluorescence. Morphological changes associated with apoptosis were observed by electron microscopy and Hoechst staining. On the basis of these results, we demonstrated that miR-19b overexpression promoted proliferation and differentiation but inhibited apoptosis in P19 cells; Wnt and ß-catenin expressions were decreased, while that of GSK3ß was increased with miR-19b overexpression. Overexpression of miR-19b inhibited activation of the Wnt/ß-catenin signaling pathway in P19 cells, which may regulate cardiomyocyte differentiation. Our findings may bring new insights into the mechanisms underlying cardiac diseases and suggest that miR-19b is a potential new therapeutic target for cardiovascular diseases.

ShRNA-mediated gene silencing of AHR promotes the differentiation of P19 mouse embryonic carcinoma cells into cardiomyocytes.

The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix (bHLH) transcription factor that is activated by environmental contaminants including polychlorinated biphenyls (PCBs). The AHR affects a variety of processes that are involved in cell growth and differentiation. In this study, we constructed a P19 embryonic carcinoma cell line with AHR gene silencing using the vector-based approach of short hairpin (sh)RNA interference that allows cells to differentiate into cardiac myocytes when treated with dimethyl sulfoxide (DMSO). The expression levels of the cardiac development-specific GATA4 and Nkx2.5 genes were measured using real-time quantitative polymerase chain reaction (qPCR). Our data showed that the expression levels of the GATA4 and Nkx2.5 genes were increased in the AHR-silenced P19 cells compared with the control groups. Four critical genes (ARNT, CYP1A1, GSK3ß and ß-catenin) expressed in the AHR and in the Wnt signaling pathway were also measured by qPCR. We found that the expression levels of ARNT, CYP1A1 and ß-catenin were suppressed, whereas GSK3ß expression was elevated in the AHR-silenced P19 cells. Therefore, it is possible that the silencing of AHR promotes the differentiation of P19 cells through the AHR and Wnt signal transduction pathway.

Differential expression profile of MicroRNAs during differentiation of cardiomyocytes exposed to polychlorinated biphenyls.

Exposure to persistent environmental pollutants, such as polychlorinated biphenyls (PCBs), is a risk factor for the development of congenital heart defects. MicroRNAs (miRNAs) have been shown to be involved in cardiac development. The objective of this study was to investigate changes in miRNA expression profiles during the differentiation of cardiomyocytes exposed to PCBs. For that purpose, PCBs (Aroclor 1254) at a concentration of 2.5 µmol/L were added on day 0 of differentiation of P19 mouse embryonal carcinoma cells into cardiac myocytes. The relative expression of miRNA genes was determined by miRNA microarray and real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) analyses. The microarray results revealed that 45 miRNAs, of which 14 were upregulated and 31 were downregulated, were differentially expressed in P19 cells treated with PCBs compared with control cells. The miRNA expression data was validated with real-time RT-PCR. The expression of certain potential target genes (Wnt1) was found to be reduced in P19 cells treated with PCBs, whereas the expression of other potential predicted target genes (GSK3ß) was increased. Our results demonstrate a critical role of miRNAs in mediating the effect of PCBs during the differentiation of P19 cells into cardiac myocytes.

[Effects of infant formula containing palm oil on the nutrient absorption and defecation in infants: a meta-analysis].

OBJECTIVE: To evaluate the effects of infant formula containing palm oil on the nutrient absorption and defecation in infants. METHODS: A search in Cochrane Library, PubMed, OVID, Springer, China National Knowledge Infrastructure, Vip Chinese Periodical Database, Wanfang Chinese Periodical Database and Chinese Bio-medicine Database was performed to identify relevant English and Chinese language articles between January 1990 and March 2009. Two reviewers independently performed data extraction and appraised using Jadad instrument. Double data were input and analyzed by software of Review Manager 4.2 recommended by Cochrane Collaboration. Intestinal nutrient absorption, electrolyte content of fecal excretion, in vivo calcium deposition, and defecation were included as the target outcomes. These outcomes were evaluated as the combined standardized mean difference (SMD) and relative risk (RR) value and 95% CI of them. RESULTS: Thirteen articles were included. Three articles meeting inclusion criteria were analyzed for the effects between infant formula containing palmitic acid at the Sn-2 positions and palmitic acid at the Sn-1, 3 positions; five articles were analyzed for the effects between infant formula containing palmitic acid at the Sn-1, 3 and without palmitic acid; another five articles were analyzed for the effects between infant formula containing palmitic acid at the Sn-2 positions and without palmitic acid. Absorption of fat and calcium was higher, the Ca(2+) of fecal excretion was lower when the infant formula provided palmitic acid at the Sn-2 positions or without palmitic acid than that determined when formula containing palmitic acid at the Sn-1 and Sn-3 positions was given (P < 0.01). The bone mineral content (BMC) and bone mineral density (BMD) increased at 3, 6 months when the infant formula without palmitic acid as compared with using the formula containing palmitic acid at the Sn-1 and Sn-3 positions (P < 0.01). The formation of calcium soaps in stool was reduced, the BMC increased when the infant formula provided palmitic acid at the Sn-2 positions as compared with using the infant formula without palmitic acid (P < 0.01). The incidence of soft stools was higher, and the incidence of hard stools was lower when the infant formula provided palmitic acid at the Sn-2 positions or without palmitic acid than that when formula containing palmitic acid at the Sn-1 and Sn-3 positions was used (P < 0.01). CONCLUSION: Absorption of fat and calcium was lower, the Ca(2+) of fecal excretion was higher, the BMC was reduced, the incidence of hard stools increased when the infant formula provided the palmitic acid at the Sn-1 and Sn-3 positions as compared with using formula contained palmitic acid at the Sn-2 positions or without palmitic acid. However, this conclusion should be used cautiously because of the limited quality of studies included into the analysis.