Risk factors of necrotizing enterocolitis in twin preterm infants.

PURPOSE: This study was aimed to investigate the risk factors of necrotizing enterocolitis (NEC) in twin preterm infants. METHODS: The clinical data of 67 pairs of twin preterm infants admitted to the neonatal department of our hospital from January 2010 to December 2021 were retrospectively collected. One of the twins had NEC (Bell II and above) and the other twin without NEC. They were divided into NEC group and control group according to whether NEC occurred or not. RESULTS: Univariate analysis showed that NEC was associated with congenital heart disease, small for gestational age, mild asphyxia at birth and feeding intolerance (P < 0.05). CONCLUSION: Occurrence of NEC was associated with congenital heart disease, small for gestational age, and asphyxia at birth. For twin preterm infants with congenital heart disease, small for gestational age, or asphyxia at birth, special attention should be paid to the occurrence of NEC to minimize and avoid the occurrence of NEC.

Values of serum intestinal fatty acid-binding protein, fecal calprotectin, and fecal human ß-defensin 2 for predicting necrotizing enterocolitis.

BACKGROUND: This study aimed to assess the diagnostic potential of serum intestinal fatty acid-binding protein (I-FABP), fecal calprotectin (FC), and fecal human ß-defensin 2 (hBD2) in predicting necrotizing enterocolitis (NEC) in preterm infants. METHODS: A prospective cohort of neonates with a gestational age < 32 weeks, suspected of NEC, was enrolled between June 2021 and December 2022. Serum I-FABP, FC, and fecal hBD2 levels were measured upon NEC suspicion, and diagnosis was confirmed through radiological examination or surgical intervention. Diagnostic precision of serum I-FABP, FC, and fecal hBD2 was assessed using a logistic regression model with multiple variables. RESULTS: The study included 70 neonates (45 males, 25 females), with 30 developing NEC (40% Stage III, n = 12; 60% Stage II, n = 18) and 40 in the control group. NEC patients exhibited significantly higher serum I-FABP and FC levels (4.76 ng/mL and 521.56 µg/g feces, respectively) than those with other diagnoses (1.38 ng/mL and 213.34 µg/g feces, respectively; p ˂ 0.05 for both biomarkers). Stage II NEC neonates showed elevated fecal hBD2 levels (376.44 ng/g feces) than Stage III NEC neonates and controls (336.87 ng/g and 339.86 ng/g feces, respectively; p ˂ 0.05). No such increase was observed in infants progressing to Stage III NEC. Using a serum I-FABP threshold of > 2.54 ng/mL yielded 76.7% sensitivity, 87.5% specificity, 82.1% positive predictive value (PPV), and 83.3% negative predictive value (NPV). For FC (cutoff > 428.99 µg/g feces), corresponding values were 76.7% sensitivity, 67.5% specificity, 63.9% PPV, and 79.4% NPV. CONCLUSION: Serum I-FABP and FC levels are valuable for early NEC detection and provide insights into disease severity. Low fecal hBD2 levels suggest an inadequate response to luminal bacteria, potentially rendering these infants more susceptible to NEC development or exacerbation.

Cerebral and intestinal oxygen saturation of different volumes of red blood cell transfusion in preterm infants.

OBJECTIVES: The purpose of this study was to investigate and compare the effects of 20 ml/kg and 15 ml/kg red blood cell transfusion (RBCT) on cerebral and intestinal tissue oxygenation, the number of administered transfusions, and neonatal complications in premature infants with anemia. METHODS: This prospective, randomized, partially blinded observational study investigated anemic neonates of gestational age < 32 weeks (Registration ID: ChiCTR 1,900,026,672). The infants were randomly assigned to receive 15 or 20 ml/kg red blood cell transfusion. Cerebral and intestinal tissue oxygen saturation (cer rSO2 and int rSO2) were collected 2 h before transfusion, 2, 4, 6, 12, 24, and 48 h after the beginning of transfusion by Near-infrared spectroscopy (NIRS). We also collected vital signs including heart rate (HR), peripheral oxygen saturation (SpO2), and mean arterial blood pressure (MABP) 2 h before infusion, 2 h, and 6 h after the beginning of transfusion. Then we analyzed and compared regional oxygen saturation(rSO2), fractional tissue oxygen extraction (FTOE), and other outcome readouts (blood transfusion numbers, changes in hematocrit and hemoglobin, hospitalization days, HR, SpO2, MABP, and complications) between the two groups. The intraindividual comparisons of the above readouts before transfusion and those after transfusion were also evaluated within each group. RESULT: 73 newborns received 20 ml/kg (large volume group) and 78 newborns received 15 ml/kg transfusion (small volume group). There was no significant difference in cer rSO2, int rSO2, Cerebral fractional tissue oxygen extraction (cFTOE), and intestinal fractional tissue oxygen extraction (iFTOE) between the two groups. rSO2, MABP, and SpO2 increased; HR, cFTOE, and iFTOE decreased following transfusion in both groups. The transfusion number of the large volume group is significantly less than that of the small volume group (1.9 ± 0.3 vs. 2.6 ± 0.9, p < 0.01) and hospitalization days were also less than those in the low volume group (44.3 ± 8.2 vs. 47.6 ± 9.8, p < 0.05). The increases in hematocrit and hemoglobin were higher in the large volume group than those in small volume (hematocrit increment (%),10.7 ± 4.2 vs. 10.1 ± 5.9, p = 0.015; Hb concentration after blood transfusion (g/L) 132.3 ± 11.1 vs. 127.4 ± 15.4, p = 0.028). CONCLUSION: After the transfusion, cer rSO2 and int rSO2 increased significantly, FTOE decreased and vital signs improved in both the 15 ml/kg and 20 ml/kg groups, and these changes were not significantly different between the two groups. However, the larger group showed a more pronounced increase in hematocrit and hemoglobin, a reduction in the total number of transfusions, and a shorter duration of hospitalization after transfusion in preterm infants without increasing complications.

Associations of elevated glucose levels at each time point during OGTT with fetal congenital heart diseases: a cohort study of 72,236 births.

BACKGROUND: It remains unclear how the condition of glucose metabolism during pregnancy affects fetal outcomes. This study aimed to investigate the associations of gestational diabetes mellitus (GDM) and elevated glucose levels at each time point during oral glucose tolerance test (OGTT) with congenital heart disease (CHD) risk in offspring. METHODS: We conducted a retrospective cohort study of mothers with singleton pregnancies of 20 weeks or more registered at Maternal and Child Health Centers in Fujian Province, China. The OGTT results and offspring CHD occurrence were collected. We used logistic regression to analyse the association between elevated blood glucose at each time point during OGTT and CHD. RESULTS: A total of 71,703 normal and 533 CHD fetuses were included. Compared to the corresponding normal group, women with GDM, elevated blood glucose at different time points in OGTT (0 h ≥ 5.1 mmol/L, 1 h ≥ 10 mmol/L, and 2 h ≥ 8.5 mmol/L) showed an increased risk of CHD in offspring (adjusted OR = 1.41, 1.36, 1.37, and 1.41, all P < 0.05, respectively). Compared to group 1 (normal OGTT 0 h, 1 h and 2 h), the risk of CHD was higher in group 3 (normal OGTT 0 h and abnormal OGTT 1 h or 2 h) and group 4 (abnormal OGTT 0 h, 1 h and 2 h), OR = 1.53 and 2.21, all P < 0.05, respectively. Moreover, we divided participants by advanced maternal age, multipara, assisted reproduction, fetal sex, and others, similar associations were observed in the subgroup analyses. CONCLUSION: Elevated blood glucose at different time points during OGTT was associated with CHD in offspring. Fetuses of pregnant women with GDM should be screened for a high risk of CHD.

Noninvasive high-frequency oscillatory ventilation versus bi-level positive pressure ventilation in premature infants with respiratory failure: A retrospective study.

Objectives: Noninvasive high-frequency oscillatory ventilation (nHFOV) is a novel respiratory support mode for premature infants. This retrospective study aimed to compare the effect of nHFOV and bi-level nasal continuous positive airway pressure (BiPAP) in premature infants with neonatal respiratory failure (NRF) as initial noninvasive ventilation (NIV) support mode. Methods: We retrospectively analyzed medical records of preterm infants admitted to the tertiary neonatal intensive care units (NICUs) of Fujian Maternal and Child Health Hospital from January 2019 to December 2020. Preterm infants with the gestational age of 25-34 weeks, diagnosed with NRF, used nHFOV or BiPAP as the initial respiratory support mode were analyzed. The rates of invasive mechanical ventilation (IMV) within the first seven days after birth and adverse outcomes were compared between the two groups. Results: Two hundred fifty-five preterm infants were analyzed (128 in nHFOV group,127 in BiPAP group). There was no significant difference in baseline characteristics between the two groups. Compared with the BiPAP group, the nHFOV group had significantly lower need for IMV within the first seven days after birth (18/128 vs. 33/127, p = 0.01) and PCO2 at 12 and 24 hours post-treatment (46.34±5.24mmHg vs. 51.18±4.83mmHg, P<0.01; 40.72±4.02mmHg vs. 42.50±3.86mmHg, P<0.01). The incidence of BPD, ROP, air leak syndromes, IVH≥ grade 3, PVL, NEC≥II stage, abdominal distension, and nasal trauma were similar between the two groups. Conclusion: nHFOV significantly reduced the need for IMV and improved the elimination of CO2 compared with BiPAP in preterm infants with NRF without increasing the incidence of adverse effects.

Glycyrrhizin treatment ameliorates post-traumatic stress disorder-like behaviours and restores circadian oscillation of intracranial serotonin.

Post-traumatic stress disorder (PTSD) has become a major disease that threatens human health. Neurotransmitters and the amygdala are found to be critical in the development and maintenance of PTSD. We aim to investigate the role of glycyrrhizin in treating PTSD. Contextual fear extinction and elevated plus maze test were applied to evaluate the anxiety and fear memory. Microdialysis and high-performance liquid chromatography were used to analyze the expression of amygdala neurotransmitters in PTSD animal models and to verify the effects of glycyrrhizin on major neurotransmitters. The protein levels of tryptophan hydroxylase 2 (TPH2) were examined by western bolt. Glycyrrhizin treatment significantly reduced anxiety and fear memory after 1 and 7 days of PTSD modelling. In addition, glycyrrhizin treatment restored the circadian rhythm changes of serotonin and TPH2. The present study found a significant circadian rhythm change of serotonin in the amygdala in PTSD rats. Besides, glycyrrhizin treatment restored the altered serotonin diurnal fluctuations, which raises important implications for PTSD treatment.

Glycyrrhizin Treatment Facilitates Extinction of Conditioned Fear Responses After a Single Prolonged Stress Exposure in Rats.

BACKGROUND/AIMS: Impaired fear memory extinction is widely considered a key mechanism of post-traumatic stress disorder (PTSD). Recent studies have suggested that neuroinflammation after a single prolonged stress (SPS) exposure may play a critical role in the impaired fear memory extinction. Studies have shown that high mobility group box chromosomal protein 1 (HMGB-1) is critically involved in neuroinflammation. However, the role of HMGB-1 underlying the development of impairment of fear memory extinction is still not known. METHODS: Thus, we examined the levels of HMGB-1 in the basolateral amygdala (BLA) following SPS using Western blot and evaluated the levels of microglia and astrocytes activation in the BLA after SPS using immunohistochemical staining. We then examined the effects of pre-SPS intra-BLA administration of glycyrrhizin, an HMGB1 inhibitor, or LPS-RS, a competitive TLR4 antagonist, on subsequent post-SPS fear extinction. RESULTS: We found that SPS treatment prolonged the extinction of contextual fear memory after the SPS. The impairment of SPS-induced extinction of contextual fear memory was associated with increased HMGB1 and Toll-like receptor 4 (TLR4) levels in the BLA. Additionally, the impairment of SPS-induced extinction of contextual fear memory was associated with increased activation of microglia and astrocyte in the BLA. Intra-BLA administrations of glycyrrhizin (HMGB-1 inhibitor) or LPS-RS (TLR4 antagonist) can prevent the development of SPS-induced fear extinction impairment. CONCLUSION: Taken together, these results suggested that SPS treatment may not only produce short term effects on the HMGB1/TLR4-mediated pro-inflammation, but alter the response of microglia and astrocytes to the exposure to fear associated contextual stimuli.

Reference intervals for thyroid function from the fifth to seventh day of life in twin-pregnancy preterm neonates: an 8-year retrospective study.

PURPOSE: The immature and developing hypothalamic-pituitary-thyroid axis leads to different levels of thyroid function in twin neonates, including free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) levels. No reference intervals for twins have been established until now. To compensate for this lack, we collected data and established this standard across different gestational ages (GAs) and sexes. METHODS: A total of 273 pairs of neonates admitted to the NICU in Southeast China from 2015 to 2022 were included. Each pair was divided into Neonate A (relatively heavy birth weight (BW)) and Neonate B (relatively light BW). Their thyroid functions were analyzed to establish reference intervals and comparisons were made stratified by GA and sex. RESULTS: The FT3, FT4, and TSH reference intervals in twin neonates with a GA of 26-36 weeks were as follows: Neonate A and B: 3.59 ± 0.99 and 3.57 ± 1.00 pmol/L; Neonate A and B: 17.03 ± 5.16 and 16.77 ± 5.29 pmol/L; and Neonate A and B: 4.097 ± 3.688 and 4.674 ± 4.850 mlU/L, respectively. There were significant differences between serum FT3 and FT4 reference intervals and GA (p < 0.05). The serum FT3 and FT4 reference intervals for male neonates were lower than those for female neonates in the 29-32-week group (p < 0.05). CONCLUSION: This was the first study, to our knowledge, to establish reference intervals for thyroid function in twin neonates from the fifth to seventh day of life, which will be beneficial for the diagnosis and management of congenital hypothyroidism.

Changes in cytomegalovirus load in the breast milk of very/extremely premature infants and the effect of pasteurization and freeze-thawing on reducing viral load.

Objective: This study aimed to clarify the change in Cytomegalovirus (CMV) loads in breast milk (BM) of very/extremely premature infants (VPI/EPI) with birth weight < 1,500 g after birth, and to compare the effectiveness of pasteurization and freeze-thawing methods in reducing the CMV load of BM. Methods: Breast milk samples were collected and tested every 2 weeks by fluorescence quantitative polymerase chain reaction (FQ-PCR). We determined CMV load in BM before and after pasteurizing, and freeze-thawing. Results: Cytomegalovirus DNA can already be detected in colostrum. The viral load gradually increased in the first 4 weeks, peaked in the 4th to 6th weeks, and gradually decreased thereafter. The viral load gradually returned to the initial level approximately 10-12 weeks postpartum. During the peak period of the CMV load in BM, the viral load was higher in the EPI than the VPI (P < 0.05). The average CMV load (logarithmic [LG]) in the pasteurization group was significantly lower than that in the raw BM group. The average CMV load in the freeze-thawed BM group was significantly lower than that in the raw BM group. The mean CMV load in the pasteurized BM group was lower than that in the freeze-thawed BM group, but the difference was not statistically significant. The CMV-DNA clearance rate in pasteurized was higher than in freeze-thawed (P < 0.05). Conclusion: The CMV detoxification rate in BM is high and the peak load period is mainly between 4 and 6 weeks. The CMV load values detected are higher than the threshold values (7 × 103 copy number/mL) of CMV infection that are reported in the literature as a concern. Both the freeze-thaw and pasteurization techniques can effectively reduce the CMV load.

Non-invasive High-Frequency Oscillatory Ventilation as Initial Respiratory Support for Preterm Infants With Respiratory Distress Syndrome.

Objectives: The aim of this study was to investigate the safety and feasibility of nHFOV as initial respiratory support in preterm infants with RDS. Methods: This study retrospectively analyzed the clinical data of 244 premature infants with RDS who were treated in our hospital from January 2016 to January 2019 and divided into the nHFOV group (n = 115) and the BiPAP group (n = 129) based on the initial respiratory support method. Results: Respiratory outcomes showed that the rate of NIV failure during the first 72 hours of life in the nHFOV group was significantly lower than that in the BiPAP group. The time of NIV in the nHFOV group was significantly shorter than that in the BiPAP group. The time of supplemental oxygen in the nHFOV group was significantly shorter than that in the BiPAP group. The incidence of air leakage syndrome in the nHFOV group was significantly lower than that in the BiPAP group, and the length of hospital stay of the nHFOV group was also significantly shorter than that in the BiPAP group. Although the rate of infants diagnosed with BPD was similar between the two groups, the rate of severe BPD in the nHFOV group was significantly lower than that in the BiPAP group. Conclusion: This study showed that nHFOV as initial respiratory support for preterm infants with RDS was feasible and safe compared to BiPAP. Furthermore, nHFOV can reduce the need for IMV and reduce the incidence of severe BPD and air leak syndrome.

MicroRNA-149 sensitizes colorectal cancer to radiotherapy by downregulating human epididymis protein 4.

Human epididymis protein 4 (HE4) was significantly up-regulated in colorectal cancer (CRC), while the potential relevance to radiation resistance of this phenomenon is still elusive. Relative expressions of target genes were quantified by real-time PCR. The protein level was determined by Western blot. The regulatory effect of miR-149 on WFDC2 (gene encoding HE4 protein) expression was analyzed by luciferase reporter assay. The response to radiation was evaluated by clonogenic assay in vitro and xenograft growth in vivo. WFDC2 was aberrantly up-regulated and miR-149 was down-regulated in CRC. MiR-149 repressed WFDC2 expression via directly targeting its 3'UTR region. The ectopic expression of miR-149 significantly sensitized CRC to radiation both in vitro and in vivo. Likewise, we further demonstrated that WFDC2-deficiency remarkably improved the radiation resistance in CRC. Simultaneously, WFDC2 rescue completely abolished the radiation sensitivity imposed by miR-149. Our data suggested that miR-149 sensitized CRC to radiation via directly inhibiting WFDC2/HE4, which would hold great promise for future therapeutic exploitations.