Interfering with Rac1-activation during neonatal monocyte-macrophage differentiation influences the inflammatory responses of M1 macrophages.

Necrotizing enterocolitis (NEC) is a life-threatening, inflammatory disease affecting premature infants with intestinal necrosis, but the mechanism remains unclear. Neonatal macrophages are thought to play an important role in the pathogenesis of NEC through the production of proinflammatory cytokines. Restriction of cytokine expression in macrophages of NEC tissues may be beneficial. In adult macrophages, interfering with Rac1 has been shown to influence the expression of cytokines. Here, we investigated whether interfering with Rac1 in neonatal macrophages affects their inflammatory responses. First, we found that Rac1-activation was upregulated in the macrophages of rats with NEC model induction compared to controls. The M1 macrophages derived from human neonatal monocytes showed greater Rac1-activation than the M2 macrophages derived from the same monocytes. Inhibition of Rac1-activation by NSC23766 potently reduced the production of proinflammatory cytokines in these M1 macrophages. While neonatal monocytes differentiated into M1 macrophages in vitro, NSC23766 significantly altered cell function during the first six days of incubation with GM-CSF rather than during the subsequent stimulation phase. However, the same effect of NSC23766 was not observed in adult macrophages. Using mass spectrometry, Y-box binding protein 1 (YB1) was identified as being downregulated upon inhibition of Rac1-activation in the neonatal macrophages. Moreover, we found that inhibition of Rac1-activation shortens the poly A tail of PABPC1 mRNA, thereby reducing the translation of PABPC1 mRNA. Consequently, the downregulation of PABPC1 resulted in a reduced translation of YB1 mRNA. Furthermore, we found that TLR4 expression was downregulated in neonatal macrophages, while YB1 expression was reduced. Adding resatorvid (TLR4 signaling inhibitor) to the macrophages treated with NSC23766 did not further reduce the cytokine expression. These findings reveal a novel Rac1-mediated pathway to inhibit cytokine expression in neonatal M1 macrophages and suggest potential targets for the prevention or treatment of NEC.

Phototherapy: a new risk factor for necrotizing enterocolitis in very low birth weight preterm infants? a retrospective case-control study.

OBJECTIVE: To investigate the association between phototherapy (PT) and the development of necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. STUDY DESIGN: A retrospective case-control study was conducted on VLBW infants with or without NEC (stage IIA or greater) born at ≤35 weeks' gestation in a tertiary hospital over 7 years. Sample size calculation, trend test, as well as univariate and multiple logistic regression analyses were employed. RESULTS: A total of 824 VLBW infants were reviewed, with 74 cases and 122 controls finally enrolled. The odds of NEC increased with the duration and number of PT sessions. Exposure to >120 h and >4 instances of PT were significantly associated with NEC in multivariate analysis. CONCLUSION: This is the first study suggesting a potential association between PT and development of NEC in VLBW infants. This association needs further exploration.

Is intravenous immunoglobulin a risk factor for necrotizing enterocolitis in neonates with haemolytic disease of the newborn? A retrospective cohort study.

BACKGROUND AND OBJECTIVES: To assess whether the use of intravenous immunoglobulin (IVIG) in late-preterm and term newborns with haemolytic disease of the newborn (HDN) is associated with an increased risk of necrotizing enterocolitis (NEC). MATERIALS AND METHODS: A retrospective cohort study was conducted in a tertiary centre. Infants with HDN during early neonatal period (<7 days) who were of ≥34 weeks' gestation and born between January 2019 and October 2021 were included. Propensity score, interaction as well as univariate and multiple logistic regression analyses were employed. RESULTS: One-thousand two-hundred and fifty-nine infants with HDN were enrolled, of whom 192 (15.3%) received IVIG. NEC was diagnosed in 29 (2.3%) patients with 5 (2.6%) in the IVIG group and 24 (2.2%) in the non-IVIG group. No significant association between IVIG administration and confirmed NEC was observed using univariate analysis (p > 0.05). The possible predictors of NEC, as assessed by multivariate analysis, were caesarean delivery, haemoglobin on admission <130 g/L and patent ductus arteriosus (PDA). There was no interactive effect of IVIG against NEC for prematurity, low birth weight, caesarean delivery, haemoglobin on admission <130 g/L and PDA. CONCLUSIONS: In late-preterm and term infants with HDN, there was no evidence that the early use of IVIG led to the development of NEC.

[Risk factors for metabolic bone disease of prematurity in very/extremely low birth weight infants: a multicenter investigation in China].

OBJECTIVE: To investigate the incidence rate and risk factors for metabolic bone disease of prematurity (MBDP) in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The medical data of 61 786 neonates from multiple centers of China between September 1, 2013 and August 31, 2016 were retrospectively investigated, including 504 VLBW/ELBW preterm infants who met the inclusion criteria. Among the 504 infants, 108 infants diagnosed with MBDP were enrolled as the MBDP group and the remaining 396 infants were enrolled as the non-MBDP group. The two groups were compared in terms of general information of mothers and preterm infants, major diseases during hospitalization, nutritional support strategies, and other treatment conditions. The multivariate logistic regression analysis was used to investigate the risk factors for MBDP. RESULTS: The incidence rate of MBDP was 19.4% (88/452) in VLBW preterm infants and 38.5% (20/52) in ELBW preterm infants. The incidence rate of MBDP was 21.7% in preterm infants with a gestational age of < 32 weeks and 45.5% in those with a gestational age of < 28 weeks. The univariate analysis showed that compared with the non-MBDP group, the MBDP group had significantly lower gestational age and birth weight, a significantly longer length of hospital stay, and a significantly higher incidence rate of extrauterine growth retardation (P < 0.05). Compared with the non-MBDP group, the MBDP group had significantly higher incidence rates of neonatal sepsis, anemia, hypocalcemia, and retinopathy of prematurity (P < 0.05). The MBDP group had a significantly lower mean feeding speed, a significantly higher age when reaching total enteral feeding, and a significantly longer duration of parenteral nutrition (P < 0.05). The use rate of caffeine citrate in the MBDP group was significantly higher, but the use rate of erythropoietin was significantly lower than that in the non-MBDP group (P < 0.05). The multivariate logistic regression analysis showed that gestational age < 32 weeks, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis were risk factors for MBDP (P < 0.05). CONCLUSIONS: A lower gestational age, hypocalcemia, extrauterine growth retardation at discharge, and neonatal sepsis may be associated an increased risk of MBDP in VLBW/ELBW preterm infants. It is necessary to strengthen perinatal healthcare, avoid premature delivery, improve the awareness of the prevention and treatment of MBDP among neonatal pediatricians, and adopt positive and reasonable nutrition strategies and comprehensive management measures for preterm infants.

[Risk factors for endotracheal intubation during resuscitation in the delivery room among very preterm infants].

OBJECTIVE: To explore the risk factors for endotracheal intubation during resuscitation in the delivery room among very preterm infants. METHODS: A retrospective analysis was performed for 455 very preterm infants who were admitted to the neonatal intensive care unit from January 2017 to December 2019. They were divided into an intubation group (n=79) and a non-intubation group (n=376) according to whether endotracheal intubation was performed during resuscitation. The risk factors for endotracheal intubation during resuscitation were evaluated by multivariate logistic regression analysis. RESULTS: The intubation rate was 17.4% (79/455). Compared with the intubation group, the non-intubation group had significantly higher gestational age, birth weight, and rates of caesarean birth, delayed cord clamping (DCC), resuscitation quality improvement, regular use of antenatal glucocorticoids in mothers and premature rupture of membranes > 18 hours (P < 0.05), but significantly lower rates of maternal gestational diabetes mellitus, placental abruption, placenta previa or placenta previa status, and maternal thyroid dysfunction (P < 0.05). Regular use of antenatal glucocorticoids in mothers (OR=0.368, P < 0.05) and DCC (OR=0.222, P < 0.05) were protective factors against intubation during resuscitation, while younger gestational age, birth weight < 750 g, maternal gestational diabetes mellitus, and placenta previa or placenta previa status were risk factors for intubation during resuscitation (P < 0.05). CONCLUSIONS: Very preterm infants with younger gestational age, birth weight < 750 g, maternal diabetes mellitus, placenta previa or placenta previa status may have a higher risk for endotracheal intubation after birth. The regular use of antenatal glucocorticoids and DCC can reduce the risk of intubation during resuscitation in very preterm infants.

Practical Experience of Establishing German Standard Level 1 Perinatal Center in Chongqing Health Care for Women and Children.

Germany, as a western developed country, has an advanced medical level, especially in the health care of very immature premature infants. We trace the medical history of perinatology to understand the development of perinatal centers in Germany. After analyzing the classification and function, hierarchical management and quality control systems of German perinatal centers, we established a German standard level 1 perinatal center in the Chongqing Health Center for Women and Children (CHCWC). During more than two years of practice, we changed concepts, continuously updated clinical knowledge and skills, developed a series of high-quality work processes and supervision systems and introduced advanced medical equipment. We believe that the experience of establishing a German standard level 1 perinatal center and perinatal center network in Chongqing is worthy of being promoted to the Chinese maternal and child health care system.

[Application of metabolomics in neonatal clinical practice].

Metabolomics is an emerging and popular subject in the post-genome era, and a large number of studies have been noted on the application of metabolomics in health evaluation, growth and development evaluation, disease diagnosis, and therapeutic efficacy evaluation. As a special period of life, the neonatal period is characterized by rapid cell renewing, consumption of a lot of energy and materials, and changes in metabolic pathways, all of which affect the level of metabolites. However, there is still no reference standard for metabolic level and profile in neonates. This article reviews the current status of metabolic research on neonatal growth and development and common diseases and related clinical application of metabolomics, so as to provide new ideas for nutrition guidance and evaluation, selection of therapeutic regimens, and new drug research in neonates.

[Prospective and controlled study on effect of fortified human milk feeding on infants with extremely and very low birth weight during hospital stay].

OBJECTIVE: To explore the effect of fortified human milk feeding on growth and complications of infants with extremely and very low birth weight (ELBW/VLBW) during hospital stay by a prospective, random and controlled study. METHODS: In the study, 122 ELBW/VLBW infants were enrolled and divided into two groups. The infants fed with human breast milk, combined with human milk fortification (HMF) during hospital stay were named HMF group (n=62), and those fed exclusively with premature formula were named premature formula feeding group (PF group, n=60). The data of the infants'growth (the velocity of increase on the weight, length, head circumference and upper arm circumference), the time of rebounding to birth weight, the time of needing intravenous nutrition, the time of hospitalizing, the proportion of extrauterine growth retardation (EUGR) during hospital stay, the level of hemoglobin, bone metabolism and incidence of complications were compared between the two groups. RESULTS: Among the 122 infants included, (1) the length increment in HMF group was higher than PF group [(0.89 ± 0.23) cm/week vs. (0.79 ± 0.34) cm/week, P=0.04]; there were no significant differences in the weight gain, head circumference increment and upper arm circumference increment (P>0.05); (2) the age of rebounding to birth weight [(10.13 ± 4.03) d vs. (8.03 ± 3.28) d, P=0.002] and the duration of intravenous nutrition [(16.77 ± 6.63) d vs. (14.23 ± 4.15) d, P=0.01] in HMF group were longer than that in PF group, there were no significant differences between the two groups in the hospital stay and age achieved feeding; (3) there were no significant differences between the two groups in the incidence rate of EUGR during hospital stay (P>0.05); (4) the level of calcium at birth in HMF group was lower than that in PF group [(2.19 ± 0.22) mmol/L vs.( 2.32 ± 0.27) mmol/L, P=0.005], and the level of alkaline phosphatase (AKP) in HMF group at discharge was higher than in PF group [(363.98 ± 122.49) mmol/L vs. (299.73 ± 117.39) mmol/L, P=0.004]; (5) the incidence of the feeding intolerance (6.5% vs. 18.3%, P=0.04) and sepsis (4.8% vs. 16.7%, P=0.03) in HMF group were less than in PF group, there were no significant differences between the two groups on the morbidity of necrotizing enterocditis, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD) (P>0.05). CONCLUSION: HMF for premature infants may ensure the same growth pattern as those fed by premature formula, promote the calcium absorption, decrease the incidence of sepsis and feeding intolerance, and does not increase the incidence of necrotizing enterocolitis.

[Prevalence and molecular analysis of ß-thalassemia in children of Han ethnicity in Chongqing city].

OBJECTIVE: To investigate the incidence and the gene mutation frequencies and patterns of ß-thalassemia (ß-Thal) in ethnic Han children in Chongqing city. METHOD: A total of 1726 children were screened by using automatic hemocytic analyzer, cellulose acetate electrophoresis and fetal hemoglobin alkali denaturation test. Samples with mean corpuscular volume (MCV) < 80 fl, cell hemoglobin content (MCH) < 27 pg and hemoglobin A2 (HbA2) levels >3.3%, fetal hemoglobin (HbF) >2% for ß-Thal screening indicators. The positive samples of screening indicators were detected and identified by PCR-reverse dot blot method for 18 common ß-Thal mutations in Chinese populations, unknown mutations samples were subjected to DNA sequencing analysis of the ß-globin gene. RESULT: Twenty-five cases of ß-Thal carriers were observed from the 1726 samples, with 24 cases of ß-Thal heterozygote and one case of double heterozygote. Therefore, the ß-Thal carrier rate was 1.51%. After 1726 peripheral venous blood samples analyzed by hematological parameters, 164 positive cases of ß-Thal screening indicators were found, with the positive rate being 9.50% (164/1726). A total of 6 different gene mutations were detected, the four most common mutations were as the following: CD41-42, IVS-II-654, CD17 and beta E. These four mutations as the major types in this area accounted for 88.00% of all the mutations. In addition, one rare mutation of 5 'UTR; + (43 -40) was found, and one case of the hemoglobin variant of Hb Zurich was reported in Chinese people for the first time. CONCLUSION: Chongqing is a high risk region of the ß-Thal. Epidemiological Data from the research was useul for the genetic counseling and the prevention of ß-Thal major.

Epidemiologic survey on hospitalized neonates in China.

OBJECTIVE: To carry out a nationwide epidemiologic survey on the neonates in urban hospitals with an attempt to understand the disease spectrum and treatment outcomes of hospitalized neonates in China. METHODS: The clinical data of 43,289 hospitalized neonates from 86 hospitals in 47 Chinese cities (22 provinces) between January 1, 2005 and December 31, 2005 were retrospectively analyzed. RESULTS: The male:female ratio was 1.73:1. Premature infants accounted for 26.2% of the hospitalized neonates, which was higher than that reported in 2002 (19.7%). The top three diseases during the neonatal period were jaundice, pneumonia, and hypoxic-ischemic encephalopathy. The incidences of pneumonia, meconium aspiration syndrome, and bilirubin encephalopathy in term infants were higher than those in premature infants, while the incidences of asphyxia, respiratory distress syndrome, and pulmonary hemorrhage in term infants were lower than those in premature infants. The incidences of asphyxia, small for gestational age infant, and wet lung were higher in neonates whose mother had pregnancy induced hypertension. The outcomes of these hospitalized neonates included: recovered, 63.9%; improved, 27.3%; discharged due to the family's own decisions, 7.6%, and died, 1.2%. Nearly half (46.4%) of the neonatal death occurred within 24 hrs after admission. CONCLUSION: The incidence of premature birth shows an increasing trend among hospitalized neonates. Since the neonatal deaths mainly occur within 24 hrs after admission, monitoring during this period should be enhanced.

[Genotyping of major outer membrane protein gene of Chlamydia trachomatis by cleavase fragment length polymorphism analysis].

OBJECTIVE: To establish a methed of cleavage fragment length polymorphism (CFLP) analysis with a primer labeled at the 5'-end with digoxigenin for genotyping of Chlamydia trachomatis (Ct). The methods for detection of Ct by major outer membrane protein (MOMP) gene (ompl) with nested polymerase chain reaction (ompl-nPCR) were studied. The incidence of Ct infection in pregnant women, the common genotypes and vertical transmission rate of Ct in Chongqing area during the past one year was also investigated. METHODS: The samples were taken from cervical scrapes of parturient women and nasopharygeal swabs of their neonates from April 2003 to Feb. 2004 in Chongqing Women and Children's Health Care Institute. Totally 300 pairs (605 specimens) were detected by using ompl-nPCR, ompl-PCR (inside pair of primers was used directly) and plasmid-PCR. The results were judged by the modified gold standard (MGS). The ompl-nPCR amplified DNA was purified by recovery of DNA from agarose gel electroelution into dialysis bags. The DNA amplified from ompl-nPCR was sequenced by ABI PRISM 377 DNA sequencer. CFLP assay with a primer labeled at the 5'-end with digoxigenin was created for genotyping of Ct, and was primarily applied. RESULTS: The minimum detectable levels of ompl-nPCR and ompl-PCR corresponded to 2.5 elementary body (EB) and 25 EB, respectively. The sensitivity of ompl-nPCR was 10 times that of ompl-PCR. The positive rate of Ct in the samples from the pregnant women was 11% (33/300). The vertical transmission rate of Ct from mothers to their infants was 24.2% (8/33). The rate of Ct isolated from nasopharyngeal swabs 5 - 10 days after birth was 38.9% (7/18), which was significantly greater than that [3.0% (1/33)] detected within 24 hours after birth (chi(c)(2) = 8.79, P < 0.01). Of the 33 Ct-positive samples from pregnant women, 9 had vaginal delivery and 24 had caesarean section. The vertical transmission rates in vaginal delivery group and caesarean section group were 66.7% (6/9) and 8.3% (2/24), respectively (chi(c)(2) = 9.16, P < 0.01). Incidence of premature rupture of membrane in Ct-positive group was 30.3% (10/33), which was greater than that of Ct-negative groups (13.5%, 36/267, chi(2) = 6.40, P < 0.05). Four different patterns were observed in the 16 Ct-positive samples from 8 pregnant women and 8 matched maternal-infants by using CFLP, which were confirmed by DNA sequencing later. They were type E (3 pairs), type F (2 pairs), type H (2 pairs) and type D (1 pair). Each pair of matched maternal-infantile samples presented identical CFLP pattern. CONCLUSIONS: This study revealed the infection rate of Ct in pregnant women, vertical transmission rate of Ct and the common genotypes of Ct in Chongqing Women and Children's Health Care Institute. The CFLP assay by using a primer labeled at the 5'-end with digoxigenin was first used for genotyping of Ct. The assay showed a good sensitivity and reproducibility, no radioactive contamination, and is simple. Therefore the assay is a potential new method for Ct genotyping.