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A meta-analysis of the efficacy and safety of early high-dose recombinant human erythropoietin in the prevention of anemia in premature infants

Miaomiao HU ; 泰山医学院附属医院新生儿科 ; Ji QI ; Hui LI ; Li WEI ; Jing LI

Chinese Journal of Neonatology.2017;32(6):456-462. doi:10.3760/cma.j.issn.2096-2932.2017.06.013

Objective To evaluate the efficacy and safety of early use of high-dose rHu-EPO in the prevention of anemia in premature infants .Method Available data from clinical randomized controlled trials of early application of high-dose rHu-EPO to prevent premature infant anemia since database building till February 2017 were retrieved, which includes Pubmed, Embase, Cochrane Collaboration and CNKI , SinoMed, Wanfang, VIP.Premature infants less than gestational age of 37 weeks, with routine prevention of anemia as the control group and early combined use of high-dose rHu-EPO≥750 IU/( kg· w) as the treatment group.The relevant data from the literatures obtained were then screened and analyzed by the RevMan 5.3 software.Result A total of 1779 preterm infants from 21 articles including 898 cases of rHu-EPO treatment group and 881 cases in control group.Meta-analysis showed that rHu-EPO treatment group apparently increased the hemoglobin ( MD=27.42, 95%CI 20.01~34.84, P<0.001), hematocrit and reticulocyte count , reduced the blood transfusion. As to the risk of retinopathy of prematurity in rHu-EPO treatment group was significantly higher than that in the control group (RR=1.21, 95%CI 1.01~1.46, P=0.04), and reduced risks of bronchopulmonary dysplasia (RR=0.79, 95%CI 0.46 ~1.35, P =0.39) and patent ductus arteriosus ( RR =0.83, 95% CI 0.68 ~1.01, P=0.07) the difference, however, was not statistically significant, and there was no increasing risks of necrotizing enterocolitis , periventricular leukomalacia , intraventricular hemorrhage .Conclusion Early administration of high-dose of rHu-EPO can effectively prevent anemia in premature infants , but there is an increased risk of retinopathy of prematurity .

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Early targeted therapy treatment of patent ductus arteriosus with ibuprofen and hydrocortisone in premature infants with low cortisol level

Hanqiang CHEN ; Xia OUYANG ; Changyi YANG ; Baoquan ZHANG ; Huiying SHI

Chinese Journal of Neonatology.2017;32(6):420-425. doi:10.3760/cma.j.issn.2096-2932.2017.06.005

Objective To evaluate the role of ibuprofen and hydrocortisone in early treatment of patent ductus arteriosus ( PDA ) in premature infants with low cortisol level . Method A prospective randomized controlled trial on 144 very low birth weight infants in the Hospital within 24 hours after birth with gestational age of 28~32 weeks and birth weight of 1000~1499 grams,who had asymptomatic PDA diagnosed by echocardiography , introducing early administration of drugs including ibuprofen and /or hydrocortisone within the first 24 ~48 hours after birth.According to the baseline of serum cortisol level measured prior to the administration of drugs , the preterm were assigned into two groups .The low cortisol level group ( the cortisol level <150μg/L) were further subdivided into four groups each being allocated to hydrocortisone or ibuprofen or both of hydrocortisone and ibuprofen combined or placebo treatment .The high cortisol level group ( the cortisol level≥150μg/L) were allocated to either ibuprofen or placebo treatment in randomization.Diameter of ductus arteriosus and cortisol value were measured again after treatment , and the follow-ups were undertaken till discharge .All data was collected and analyzed by statistical software .Result A total of 91 cases were in low cortisol level group ( 22 cases of hydrocortisone , 23 cases of ibuprofen , 21 cases of both hydrocortisone and ibuprofen , and 25 cases of placebo ) and 53 cases in high cortisol level group (26 cases of placebo and 27 cases of Ibuprofen ).Low cortisol level group , combined therapy , closure of the ductus at a rate of 81.0%, was higher than other methods of therapy ( P<0.05);high cortisol level group, the ductus arteriosus closed in 20 patients of ibuprofen therapy ( 74.1%) and in 13 patients of placebo treatment (50.0%) (P<0.05).Early treatment did not significantly increase the drug adverse effects, including impaired renal function , gastrointestinal bleeding , hyperglycemia and others. After comparisons between laboratory changes in early targeted groups and non-early targeted groups after treatment, findings were as follows: decrease in the incidence of apnea , myocardial damage , feeding intolerance , intraventricular hemorrhage and reduce the duration of phototherapy .Conclusion This trial proved the efficacy and safety of early therapy with ibuprofen and hydrocortisone for closure of ductus arteriosus in premature infants with low cortisol level and the decreasing incidence of complications due to PDA without increasing the risk of adverse effects .

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Neonatal bacterial meningitis in 13 hospitals of Northern China: epidemiology, etiology and outcomes

network meningitis NEONATAL

Chinese Journal of Neonatology.2017;32(6):415-419. doi:10.3760/cma.j.issn.2096-2932.2017.06.004

Objective Bacterial meningitis is a major cause of mortality and morbidity in neonates . Large-scale epidemiology data on neonatal meningitis are scarce in China .This study aimed to investigate the incidence, etiology, and outcomes of neonatal meningitis in 13 hospitals of Northern China.Method We performed a one year prospective cohort study in 13 neonatal intensive care units from four provinces (Hebei, Shanxi, Henan, Shandong) in Northern China.The following information of neonatal bacterial meningitis was collected: blood and cerebrospinal fluid ( CSF ) culture findings , demographic characteristics, hematological and CSF parameters , and outcome.Result A total of 236 neonates were included in the study, male 149 (63.1%).The mean gestational age and birth weight were (38.0 ±2.9) weeks and ( 3082 ±746 ) g, respectively.Only 71 ( 30.9%) neonates had a positive blood culture . Positive CSF culture results were found in 30.5% ( 65/213 ) of the patients.Among the early-onset meningitis, Staphylococcus aureus ( 6 cases, 35.3%), E.coli ( 2 cases, 11.8%) were the main pathogens.Among the late onset meningitis, E.coli was the main pathogen (18 cases, 37.5%), followed by Staphylococcus haemolyticus ( 6 cases, 12.5%) .The median ( interquartile range ) white blood cell count in CSF was 330/mm3(838), with a range of 0~92512/mm3.67 (28.4%) patients had white blood cell count>1000/mm3 in CSF.The overall case mortality was 6.8% ( 16/236 ) .The case mortality was 33% for K.pneumoniae , and 25% for E.coli meningitis , but 0 for Gram-positive meningitis.E.coli was responsible for approximately one third of all deaths caused by meningitis .Conclusion This study provides essential information regarding the etiology , characteristics , and outcome of neonatal bacterial meningitis in Northern China.E.coli was the most common Gram-negative organism causing late onset meningitis with high case fatality.

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Monochorionic diamnionic twins: a study of perinatal outcomes

Xiaohong XI ; Ming ZHOU ; Xuefeng HU ; Jiangqin LIU

Chinese Journal of Neonatology.2017;32(6):411-414. doi:10.3760/cma.j.issn.2096-2932.2017.06.003

Objective To study the perinatal outcomes of monochorionic diamnionic ( MCDA ) twins.Method A retrospective study had been conducted to analyze the outcomes of MCDA twins delivered in Hospital from Jan 2011 to Dec 2012.According to whether complicated with twin to twin transfusion syndrome ( TTTS, n=14 ) and/or selective intrauterine growth restriction ( sIUGR, n=41 ) , the infants enrolled in the study were assigned into complicated group (n=55) and uncomplicated group (n=90).The infants with sIUGR were further subdivided into three groups .The outcomes of the neonates were compared between the groups.Result A total of 145 pairs of MCDA twins were delivered , 285 neonates (12 of them died after birth ) and 5 cases of stillbirth. The gestational age at delivery in complicated group were significantly lower than those in uncomplicated group (33.8 ±2.8weeks vs.35.5 ±1.6weeks, P<0.001);The birth weight in complicated group ( the birth weight of the bigger baby was 2072 ±460 g vs.2520 ± 383 g, the smaller one 1620 ±477 g vs.2320 ±373 g ) were significantly lighter than those in uncomplicated group;The incidence of fetal death in complicated MCDA twin pregnancies (7.3% vs.0) was significantly higher than controls .Neonatal outcomes of fetuses complicated with sIUGRⅠ ( n=23 ) were similar to controls.Neonates complicated with TTTS, sIUGRⅡ(n =6) or sIUGRⅢ (n =12) had significantly increased incidence of respiratory distress syndrome , asphyxia, cardiac disorders, retinopathy of prematurity and neonatal death compared with controls .Conclusion Neonates of MCDA with TTTS or sIUGR had more complications compared with uncomplicated MCDA twins .The fetuses with abnormal umbilical artery Doppler blood flow are more vulnerable to stillbirth , neonatal death and other serious adverse outcomes .

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A study on the protective mechanisms of lipoxin A4 for hyperoxia-induced pulmonary epithelial cells injury in mice

Shujun LI ; Shenghua WU ; Bingjie LI ; Hongyan LU ; Yanyan LUO ; Xiaoqing CHEN

Chinese Journal of Neonatology.2017;32(6):468-472. doi:10.3760/cma.j.issn.2096-2932.2017.06.016

Objective To study the protective mechanisms of lipoxin A 4 ( LXA4 ) for hyperoxia-induced lung injury through modulation of let-7c/TGF-β1 signal pathway in mice.Method MLE-12 cells was transfected with let-7c mimic, mimic negative control ( NC) , let-7c inhibitor and inhibitor NC.The cells were assigned into hyperoxia group , LXA4 group, let-7c over-expression group, let-7c silence group, let-7c silence+LXA4 group, and all exposed to 85% oxygen.The mRNA level of the extracellular matrixα-smooth muscle actin (α-SMA) and collagen Ⅰ( COL-Ⅰ) , and the expression of related genes in TGF-β1 signaling pathway (Smad 2, Smad 3, Smad 4, TGF-βR1, TGF-βR2) were examined using qPCR.The protein expressions in TGF-β1 signaling pathway was examined using Western blot .Result The mRNA expressions of α-SMA, COL-Ⅰ, Smad 3, Smad 4, TGF-βR1 and TGF-βR2 in LXA4 group [(24.3 ±2.1), (14.6 ±0.2), (17.0 ±0.0), (14.9 ±0.1), (20.8 ±0.1), (9.0 ±0.0) ] and let-7c over-expression group [ ( 12.2 ±0.5 ) , ( 3.0 ±0.0 ) , ( 3.1 ±0.0 ) , ( 9.6 ±0.4 ) , ( 28.5 ±0.2 ) , ( 7.6 ± 0.1)] were decreased comparing with the hyperoxia group [(51.4 ±0.5), (32.0 ±0.1), (40.6 ±0.2), (16.3 ±0.1), (89.1 ±1.1), (19.3 ±0.2)].These expressions were increased in both let-7c silence group [(87.3 ±7.0), (38.5 ±0.3), (48.0 ±0.2), (56.5 ±0.2), (126.0 ±0.9), (33.1 ±1.0)] and let-7c silence +LXA4 group [(144.5 ±12.9), (86.3 ±3.0), (91.5 ±4.7), (86.5 ±3.3), (109.0 ±4.5), (45.6 ±1.6)].The protein levels of Smad 2, Smad 3, Smad 4, p-Smad 2, p-Smad 3 and TGF-βR1 of LXA4 group and let-7c over-expression group were decreased comparing with the hyperoxia group, while p-Smad 2, p-Smad 3 of let-7c silence+LXA4 group were increased(P<0.05).Conclusion LXA4 may play a protective role through let-7c /TGF-β1 signal pathway of lung epithelial cells for hyperoxia-induced lung injury in mice .

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A study on the roles and mechanisms of miR-20a in lipopolysaccharide-induced inflammation of A549 cells

Hui HONG ; 杭州市第一人民医院新生儿科 ; Xinqiao YU ; Beibei WANG ; Yaojun JIANG ; Yongjian GONG ; Yuan YANG ; Yang YANG ; Xiaoyu ZHOU ; Xiaoguang ZHOU ; Feng YANG

Chinese Journal of Neonatology.2017;32(6):463-467. doi:10.3760/cma.j.issn.2096-2932.2017.06.015

Objective To study the roles of miR-20a in lipopolysaccharide induced inflammation of A549 cells and the possible mechanisms.Method The miR-20a mimic/inhibitor were transfected into A549 cells, and the cells were stimulated using lipopolysaccharide for 24 h.Interleukin-6 ( IL-6) and IL-8 were detected at mRNA level and protein level using real-time PCR and ELISA method , respectively.Protein expression of apoptosis signal regulating kinase 1 (ASK1)、P38、P-P38、JNK and P-JNK were detected using Western blot. Result Compared to mimic negative control group , the levels of mRNA and protein expression of IL-6 and IL-8 in the mimic group were all significantly decreased ( P<0.05).Compared to inhibitor negative control group , the levels of mRNA and protein expression of IL-6 and IL-8 in the inhibitor group were all significantly increased (P<0.05).The levels of ASK1, P-P38 and P-JNK protein in the mimic group were significantly lower than the mimic negative control group (P<0.05);the level of protein expression of ASK1, P-P38 and P-JNK in the inhibitor group were all higher than the inhibitor negative control group (P<0.05).Conclusion The regulation of ASK1 by miR-20a may play an important role in the inflammation process of acute respiratory distress syndrome .

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Effects of family integrated care in neonatal intensive care unit on physical and mental health of premature infants and their mothers

Ying WANG ; Ting YE ; Lin ZHANG ; Geqin MO ; Huaiyan WANG

Chinese Journal of Neonatology.2017;32(6):448-451. doi:10.3760/cma.j.issn.2096-2932.2017.06.011

Objective To study the effects of family integrated care ( FIcare ) in the neonatal intensive care unit ( NICU) on preterm infants and their mothers′physical and mental health.Method From Jan 2016 to Dec 2016, preterm infants(birth weight 1000~2000 g;gestational age 26~34 weeks stabilized in NICU were randomly assigned into two groups:FIcare group and control group .The incidences of major diseases in infants , their mothers′depression score and anxiety score were studied .Result A total of 40 infants were assigned into two groups respectively .No significant differences existed between the two groups in gender , gestational age , brith weight , age, breastfeeding rate and their mothers′depression score and anxiety score (P>0.05).At discharge, the breastfeeding rate (90.0%vs.52.5%) and weight gain [(2258 ±112) g vs.(2105 ±103) g] of the FIcare group were significantly higher than the control group, and the hospital stay duration [(42.0 ±15.7) d vs.(43.5 ±14.3) d], hospitalization expenses [(40,000 ±18,000) RMB vs.(44,000 ±19,000) RMB], oxygen therapy duration [(10.4 ±5.7) d vs. (11.7 ±7.9) d], CPAP duration [(7.2 ±4.3) d vs.(8.1 ±5.0) d], mothers′depression score [(48.7 ±3.0) vs.(57.6 ±2.7)] and anxiety score [(49.4 ±1.1) vs.(61.1 ±1.9)]of the FIcare group were significantly lower than the control group ( P <0.05 ) . Conclusion Family-integrated care is beneficial for the recovery of preterm infants and their mother′s physical and mental health .

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A clinical study on the efficacy of caffeine in premature infants receiving mechanical ventilation

Xiaomeng GENG ; Junli LIU ; Guifang LI ; Guo YAO ; Chengfang ZHANG ; Baohai SHI

Chinese Journal of Neonatology.2017;32(6):443-447. doi:10.3760/cma.j.issn.2096-2932.2017.06.010

Objective To study the clinical efficacy of caffeine in premature infants receiving mechanical ventilation and related complications .Method From January 2014 to September 2016, preterm infants (28w≤GA<33w) treated with nasal continuous positive airway pressure (NCPAP) or conventional mechanical ventilation ( CMV ) in neonatal intensive care unit were studied .They were randomly assigned into the caffeine group and the control group .The caffeine group received caffeine when NCPAP ventilation was applied or adjusting to synchronized intermittent mandatory ventilation ( SIMV) mode.The control group was injected with 5%glucose without caffeine .The t test andχ2 test were used to analyze the clinical efficacy and related complications .Result A total of 96 patients receiving NCPAP ventilation were collected ( birth weight between 1300~2100 g), including 51 cases in caffeine group and 45 cases in the control group. 84 cases received CMV ventilation (birth weight between 1000~1499 g), with 43 cases in the caffeine group and 41 cases the control group.Among the NCPAP infants, the incidence of failure to withdraw ventilator (0% vs.13.3%) and the incidence of bronchopulmonary dysplasia (3.9% vs.17.8%) were lower in the caffeine group than the control group .The duration of assisted ventilation and hospital stay in the caffeine group were shorter than the control group [(6.2 ±3.1) d vs.(8.2 ±3.2) d, (16.3 ±8.7) d vs. (19.5 ±9.2) d], the differences were statistically significant (P<0.05).Among the CMV infants, the incidence of failure of A/C to SIMV mode transition and bronchopulmonary dysplasia were lower in the caffeine group than the control group and the duration of assisted ventilation and hospital stay were shorter . The differences were statistically significant ( P <0.05 ) . No differences were found in the related complications in each group ( P>0.05) . Conclusion Caffeine can help reduce the incidences of withdrawal failure, bronchopulmonary dysplasia , ventilation duration and hospital stay when using NCPAP and CMV ventilation.

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Clinical characteristics of extremely and very low birth weight infants conceived with different methods of fertilization

Cong AN ; Qian ZHANG

Chinese Journal of Neonatology.2017;32(6):439-442. doi:10.3760/cma.j.issn.2096-2932.2017.06.009

Objective To study the differences of clinical characteristics of extremely and very low birth weight ( E/VLBW) infants conceived with assisted reproductive technology ( ART) and spontaneous conception ( SC) .Method From July 2014 to July 2016, preterm infants with birth weight less than 1500 g admitted to neonatal intensive care units of First Affiliated Hospital of Zhengzhou University were retrospectively studied.They were assigned into ART group and SC group according to their fertilization methods.Their general condition , major complications , respiratory support strategy , duration of hospital stay, hospitalization cost and mortality rate between the two groups were compared using t test, U test andχ2 test.Result A total of 527 preterm infants were included , with an average gestational age of ( 30.6 ± 2.0) weeks (25.4 to 36.0 weeks) and an average birth weight of (1198 ±202) g (500 to 1490 g). 88 infants were ELBW infants and 439 VLBW infants.156 infants were small for gestational age ( SGA ) infants and 371 appropriate for gestational age infants .According to their fertilization method , 81 infants were assigned into ART group and 446 infants SC group.The gestational age of ART group was lower than SC group, and the incidence of double/multiple birth was higher than SC group , the differences were statistically significant (P<0.05).Compared with SC group, the hospitalization duration and cost of ART group were significantly higher ( P <0.001 ) .The incidences of respiratory failure , bronchopulmonary dysplasia, sepsis, fungal infection, heart failure, disseminated intravascular coagulation and multiple organ dysfunction syndrome in ART group were higher than SC group ( 48.1% vs.34.8%, 50.6% vs.16.1%19.8%vs.7.0%, 8.6%vs.2.9%, 39.5%vs.17.7%, 22.2%vs.7.2%, 29.0%vs.15.0%) , and the incidence of hyperbilirubinemia was lower than SC group (81.5%vs.90.8%).The differences were all statistically significant (P<0.05).No significant difference existed in respiratory support strategy between the two groups ( P>0.05 ) .Conclusion Compared with spontaneous conception , ART method does not increase the risk of death among E/VLBW infants.However, ART conceived infants have potential risks of lower gestational age , higher double/multiple birth rates , higher complications incidences , longer hospitalization duration and higher hospitalization costs .Perinatal care and management are important for these infants.

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Clinical research of changes of oxygen saturation in intestinal tissues of preterm infants during erythrocyte infusion

Yunsu ZOU ; Yang YANG ; Yue WU ; Yan GUO ; Zhaolan CAO ; Xiaoguang ZHOU ; Rui CHENG

Chinese Journal of Neonatology.2017;32(6):435-438. doi:10.3760/cma.j.issn.2096-2932.2017.06.008

Objective To study the variability of oxygen saturation in intestinal tissue of preterm infants during erythrocyte infusion .Method Preterm infants aged over 5 days, hospitalized in our NICU from March 2016 to August 2016 were selected by computer random number generator . Near-infrared spectroscopy was applied to monitor splanchnic tissue oxygen saturation ( SrSO2 ) and cerebral tissue oxygen saturation(CrSO2)during erythrocyte transfusion.The duration of transfusion was 4 hours.The mean value and range of SrSO2 and CrSO2 during transfusion were analyzed.To analysis the average and variable range of SrSO2 and CrSO2 and to illuminate the correlation with post-conceptional age. Result A total of 34 premature infants were collected.The average of SrSO2 was (0.56 ±0.06) and the average of CrSO2 was (0.62 ±0.02) throughout transfusion, There was a significantly greater change in SrSO2 than in CrSO2 during the transfusion period (0.35 ±0.14 vs.0.18 ±0.09) (P<0.05).The changing range of CrSO2 was smaller as the post-conceptional age increased , and was significant different statistically ( P=0.006). While there was little change in the range of SrSO 2 (P=0.191).Conclusion The of SrSO2 change was more significant than CrSO 2 in preterm infants during erythrocyte transfusion , which may cause ischemia-reperfusion injury to the intestinal tissue .It should be more cautious to avoid transfusion-related necrotizing enterocolitis.

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